Program Director (U.S) Japan Biodesign, Stanford Biodesign
Cardiovascular Medicine, Stanford University
Dr. Ikeno is a Research Associate, Cardiovascular Medicine, Stanford University. In this role, he is responsible for pre clinical studies including GLP for medical devices and also regenerative medicines for cardiovascular diseases. Currently, he is devoting himself to the international regulatory project between Japan and the United States, also known as "Harmonization by Doing", whose focus is to collaborate with regulatory agencies such as FDA, PMDA/MHLW, academia and industries for improving the regulatory process in the 2 largest medtech markets. Dr. Ikeno also devoted himself to found Japan biodesign program which is a collaborative program with University of Tokyo, Osaka University, Tohoku University, Japan Federation Medical Device Association, Ministry of Education Japan and Stanford biodesign program. Currently, Dr. Ikeno serves as the Program Director (US) for Japan Biodesign. Dr. Ikeno is co-founder and board member of US-Japan MedTech Frontier which is a non-profit cooperate to make a trans-pacific eco-system of medical device between Japan and USA.
After 9 years clinical practice as an interventional cardiologist and Family Doctor in rural areas of Japan, Dr. Ikeno came to Stanford as a Researcher and completed his Biodesign Certificate Program. Being part of the ecosystem in Silicon Valley, Dr. Ikeno participated in more than 200 medtech projects and 50 GLP studies as well as in the analysis of clinical trials for cardiovascular medicine (BARI2D, FAME, ReOPEN etc). His other academic consortium projects include Peripheral Academic Research Consortium, Global Consensus Working Group of Optical Coherence Tomography, and Japan-US consensus document for the treatment of critical limb ischemia.
Over the last decade, Dr. Ikeno has served as an advisor for medical device industries and currently serves as a chief medical officer of an incubation fund specific for medtech (Medventure Partners, Inc, Tokyo) as a spin-off from Innovation Network Corporation of Japan (INCJ) that is the largest government and private partnership fund in Japan. He is also serving as a chair of cardiovascular working group of APAN (Asian Pacific Advanced Network) that contributes the remote education, research activities, and tele-health using a specialized internet network. Dr.Ikeno is also serving as consulting faculty/lecturer roles in several universities in Japan including University of Tokyo, Osaka University, Tsukuba University etc. Dr. Ikeno has authored over 70 peer reviewed publications and textbooks and has been invited to lecture at international medical conferences. Dr. Ikeno is a council member of U.S.- Japan Council which is a non-profit organization by Japanese American. He is serving as a mentor for START-X MED which is an accelerating program for Stanford related entrepreneurs in medical fields.
Falk CVRC CV007
300 Pasteur Drive
Palo Alto, CA 94305-5406
Education & Certifications
PhD Candidate, Waseda University/Tokyo Women's Medical Collage, Biomedical Engineering (2018)
Certificate, Stanford Biodesign, Graduate Student, Biodesign Certificate Program · Stanford, California, Medical Device (2007)
M.D., Jichi Medical University, Japan, Medicine (1992)
Preclinical research of medical devices in cardiovascular medicine, regenerative medicine. Clinical research of cardiovascular medicine, Medical device development
Professional Affiliations and Activities
Co-founder, US-Japan MedTech Frontiers (2014 - Present)
Steering Committee member, U.S. - Japan Medical Device Harmonization by Doing (HBD) (2009 - Present)
Board Member, Japan Association of MedTech Innovation (2015 - Present)
Advisory Faculty, Japan Biodesign (2015 - Present)
Member, U.S-Japan Council (2015 - Present)
Board Member, Nihon Ikou Monozukuri Commons (2013 - Present)
Visiting Lecturer, University of Tokyo, Japan (2016 - Present)
Consulting Professor, Osaka University, Japan (2015 - Present)
Advisor, Kyushu University, California Office (2011 - Present)
Visiting Professor, Tsukuba University, Japan (2016 - Present)
Visiting Professor, Hiroshima University, Japan (2016 - Present)
Visiting Professor, Kyushu Institute of Technology, Japan (2016 - Present)
Visiting Professor, Shizuoka University, Japan (2016 - Present)
Visiting Lecture, Tottori University, Japan (2016 - Present)
Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.
2016; 280 (3): 826-836
Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article.
View details for DOI 10.1148/radiol.2016151150
View details for PubMedID 27332865
Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction.
2016; 280 (3): 815-825
Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.
View details for DOI 10.1148/radiol.2016140049
View details for PubMedID 27308957
Acute stent recoil and optimal balloon inflation strategy: an experimental study using real-time optical coherence tomography.
2016; 12 (2): e190-8
Our aim was to evaluate stent expansion and acute recoil at deployment and post-dilatation, and the impact of post-dilatation strategies on final stent dimensions.Optical coherence tomography (OCT) was performed on eight bare metal platforms of drug-eluting stents (3.0 mm diameter, n=6 for each) during and after balloon inflation in a silicone mock vessel. After nominal-pressure deployment, a single long (30 sec) vs. multiple short (10 sec x3) post-dilatations were performed using a non-compliant balloon (3.25 mm, 20 atm). Stent areas during deployment with original delivery systems were smaller in stainless steel stents than in cobalt-chromium and platinum-chromium stents (p<0.001), whereas subsequent acute recoil was comparable among the three materials. At post-dilatation, acute recoil was greater in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001), resulting in smaller final stent areas in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001). In comparison between conventional and latest-generation cobalt-chromium stents, stent areas were not significantly different after both deployment and post-dilatation. With multiple short post-dilatations, acute recoil was significantly improved from first to third short inflation (p<0.001), achieving larger final area than a single long inflation, despite stent materials/designs (p<0.001).Real-time OCT revealed significant acute recoil in all stent types. Both stent materials/designs and post-dilatation strategies showed a significant impact on final stent expansion.
View details for DOI 10.4244/EIJV12I2A32
View details for PubMedID 27290678
Quantitative precision of optical frequency domain imaging: direct comparison with frequency domain optical coherence tomography and intravascular ultrasound.
Cardiovascular intervention and therapeutics
2016; 31 (2): 79-88
No systematic validation study is available with optical frequency domain imaging (OFDI), directly compared with frequency domain optical coherence tomography (FD-OCT) and intravascular ultrasound (IVUS). Controversy also remains about the impact of different stent contour tracing methods by OFDI/FD-OCT. In vitro: coronary phantom models (1.51-5.04 mm) were imaged with OFDI, FD-OCT, and IVUS, demonstrating excellent quantitative precision with a slight overestimation of mean lumen diameter (difference 0.01-0.02 mm). In vivo: corresponding 64 OFDI/IVUS images of stented coronary segments from 20 swines were analyzed. Minimum lumen area by OFDI was larger than IVUS at baseline (P < 0.001), whereas it was smaller than IVUS at follow-up. When stent was traced at leading edges of struts by OFDI, minimum stent area was similar between OFDI and IVUS (P = 0.60). When traced at the highest intensity points of struts by OFDI, it was significantly larger in OFDI than in IVUS (P < 0.001). Three modalities have clinically acceptable precision across the wide range of lumen diameters. In vivo measurements by OFDI and IVUS could slightly be discrepant depending on the parameters and time points. In stent assessment by OFDI, the 2 methods led to a small but systematic difference; therefore, consistency in methodology is advised for comparative studies.
View details for DOI 10.1007/s12928-015-0349-x
View details for PubMedID 26271203
Transcatheter Alcohol-Mediated Perivascular Renal Denervation With the Peregrine System First-in-Human Experience
2016; 9 (6): 589-598
This study evaluated the first clinical use of a new endovascular approach to renal denervation, using chemical neurolysis, via periadventitial infusion of dehydrated alcohol (ethanol) to perform "perivascular" renal artery sympathetic denervation.Renal denervation remains a promising technology for the treatment of hypertension and other disorders.A novel 3-needle delivery device (Peregrine System Infusion Catheter, Ablative Solutions, Inc., Kalamazoo, Michigan) was introduced into the renal arteries of 18 subjects with refractory hypertension. Microdoses of alcohol were infused bilaterally via the 3 needles into to the adventitial space (0.30 ml/artery, 37 arteries). Renal artery angiography was performed at the time of the procedure and at 6 months (n = 16). The primary safety endpoints were complications associated with the catheter insertion and delivery of the neurolytic agent or any major vascular access complications. The secondary performance endpoint was a reduction in office-based systolic blood pressure at 6 months compared with baseline.Procedural success was achieved in 100% of subjects (N = 18) and arteries (N = 37). There were no study-related adverse clinical events at follow-up. One death of a subject was recorded but determined by the investigator and an independent medical monitor to be non-study related. There were no angiographic observations of renal artery stenosis, aneurysms, or other renal artery abnormalities at 6 months (32 renal arteries). Sixteen of the 18 subjects had a 6-month follow-up. The mean office systolic blood pressure decreased from 175 ± 17 mm Hg to 151 ± 26 mm Hg (-24 mm Hg). There was an average reduction of antihypertensive medications from 3.4 (baseline) to 2.0 per subject at 6 months.Chemical renal denervation using the infusion of very low doses of alcohol directly into the adventitial space appears to be feasible and safe. This approach may be a promising alternative approach to perform catheter-based renal denervation. These results need to be confirmed in larger scale clinical studies.
View details for DOI 10.1016/j.jcin.2015.11.041
View details for Web of Science ID 000372717900017
Serial changes of coronary endothelial function and arterial healing after paclitaxel-eluting stent implantation.
Cardiovascular intervention and therapeutics
2016; 31 (1): 21-28
Several studies have shown coronary endothelial dysfunction and delayed arterial healing associated with first-generation drug-eluting stents. However, it remains unclear whether those issues persist for a longer term. We thus evaluated serial changes in endothelial function and intra-stent condition after paclitaxel-eluting stents (PES) implantation. Eight patients with stable effort angina were assessed at 9 and over 24 months (1st and 2nd follow-up) after PES implantation. Endothelial function was evaluated with intracoronary infusion of acetylcholine (Ach). Vascular responses were quantitatively measured. Intra-stent condition was evaluated using angioscopy. We assessed (1) the degree of neointimal coverage over the stent (grade 0: no coverage to grade 3: full coverage); (2) presence of yellow intima inside the stent, and (3) existence of in-stent thrombus. Vasomotions proximal to the stent at 2nd follow-up significantly improved compared with 1st follow-up (p = 0.04), whereas vascular responses at the distal segment did not differ between 1st and 2nd follow-up (p = 0.19). From the angioscopic study, the average of coverage grading was comparable between the 2 points (0.9 ± 0.8 vs. 1.3 ± 1.0, p = 0.20). In addition, the incidence of yellow intima and in-stent thrombus did not differ between 1st and 2nd follow-up (yellow intima; 50 vs. 37.5 %, p = 1.0, thrombus; 75 vs. 50 %, p = 0.61). Endothelial dysfunction and delayed healing with PES could attenuate gradually, but these issues may persist over 24 months in some patients.
View details for DOI 10.1007/s12928-015-0341-5
View details for PubMedID 26113198
- Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model JOURNAL OF THE AMERICAN HEART ASSOCIATION 2015; 4 (7)
Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model.
Journal of the American Heart Association
2015; 4 (7)
The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts.Twelve adult swine underwent ischemia-reperfusion injury. Digital subtraction of MEMRI-negative myocardium (intrainfarct region) from delayed gadolinium enhancement MRI-positive myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI demonstrated an increased PIR viability signal compared with control. Direct PIR viability remained higher in hAMSC-treated hearts for >6 weeks. Increased PIR viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and hAMSC engraftment, as confirmed by immunocytochemistry. Increased MEMRI and positron emission tomography reporter gene signal in the intrainfarct region and the PIR correlated with sustained functional augmentation (global and regional) within the hAMSC group (mean change, left ventricular ejection fraction: hAMSC 85±60%, control 8±10%; P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume increase: hAMSC 24±8%, control 110±30%; P<0.05).The positron emission tomography reporter gene signal of hAMSC engraftment correlates with the improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real-time method of tracking PIR viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells.
View details for DOI 10.1161/JAHA.115.002044
View details for PubMedID 26215972
Optical Coherence Tomography of Pulmonary Arterial Walls in Humans and Pigs (Sus scrofa domesticus)
2015; 65 (3): 217-224
Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by progressive elevation of the pulmonary pressures that, in the absence of therapy, results in chronic right-heart failure and premature death. The vascular pathology of PAH is characterized by progressive loss of small (diameter, less than 50 μm) peripheral pulmonary arteries along with abnormal medial thickening, neointimal formation, and intraluminal narrowing of the remaining pulmonary arteries. Vascular pathology correlates with disease severity, given that hemodynamic effects and disease outcomes are worse in patients with advanced compared with lower-grade lesions. Novel imaging tools are urgently needed that demonstrate the extent of vascular remodeling in PAH patients during diagnosis and treatment monitoring. Optical coherence tomography (OCT) is a catheter-based intravascular imaging technique used to obtain high-resolution 2D and 3D cross-sectional images of coronary arteries, thus revealing the extent of vascular wall pathology due to diseases such as atherosclerosis and in-stent restenosis; its utility as a diagnostic tool in the assessment of the pulmonary circulation is unknown. Here we show that OCT provides high-definition images that capture the morphology of pulmonary arterial walls in explanted human lungs and during pulmonary arterial catheterization of an adult pig. We conclude that OCT may facilitate the evaluation of patients with PAH by disclosing the degree of wall remodeling present in pulmonary vessels. Future studies are warranted to determine whether this information complements the hemodynamic and functional assessments routinely performed in PAH patients, facilitates treatment selection, and improves estimates of prognosis and outcome.
View details for Web of Science ID 000357147100007
Evaluation and Treatment of Patients With Lower Extremity Peripheral Artery Disease Consensus Definitions From Peripheral Academic Research Consortium (PARC)
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2015; 65 (9): 931-941
The lack of consistent definitions and nomenclature across clinical trials of novel devices, drugs, or biologics poses a significant barrier to accrual of knowledge in and across peripheral artery disease therapies and technologies. Recognizing this problem, the Peripheral Academic Research Consortium, together with the U.S. Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, has developed a series of pragmatic consensus definitions for patients being treated for peripheral artery disease affecting the lower extremities. These consensus definitions include the clinical presentation, anatomic depiction, interventional outcomes, surrogate imaging and physiological follow-up, and clinical outcomes of patients with lower-extremity peripheral artery disease. Consistent application of these definitions in clinical trials evaluating novel revascularization technologies should result in more efficient regulatory evaluation and best practice guidelines to inform clinical decisions in patients with lower extremity peripheral artery disease.
View details for DOI 10.1016/j.jacc.2014.12.036
View details for Web of Science ID 000350216700011
View details for PubMedID 25744011
Efficacy and Safety of Novel Multi-Lumen Catheter for Chronic Total Occlusions: From Preclinical Study to First-in-Man Experience
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2015; 85 (3): E70-E75
To report our initial animal and human experience with a new multi-lumen catheter called MultiCross™ (Roxwood Medical, Inc.) in a porcine coronary model and patients with a chronic total occlusion (CTO).Preclinical safety study was done in the coronary vasculature of a porcine model. In a clinical setting, patients with a CTO of a coronary artery (n = 5) were enrolled. After an initial unsuccessful attempt using a conventional guidewire, operators could use the MultiCross system. The primary efficacy endpoint was successful recanalization (technical success) and the primary safety endpoint was serious adverse events through 30 days post-procedure.The MultiCross catheter was used for all patients after failure of the initial attempt with a guidewire. Successful recanalization was achieved in all CTOs attempted (100%). No patients reported any adverse events at 30 days post-procedure.In this first-in-man experience, the MultiCross catheter has the potential to enhance crossing of CTOs.
View details for DOI 10.1002/ccd.25711
View details for Web of Science ID 000349962400002
View details for PubMedID 25331940
Echocardiographic and Electrocardiographic Characteristics of Male and Female Squirrel Monkeys (Saimiri spp.)
JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
2015; 54 (1): 25-28
Cardiomyopathy is a leading cause of mortality in aging squirrel monkeys (Saimiri spp.). However, data regarding echocardiographic measures obtained from clinically healthy nonsedated squirrel monkeys have not been published, and few electrocardiographic data are available. Here we obtained echocardiographs without sedation and electrocardiographs with minimal sedation from 63 clinically healthy squirrel monkeys that ranged from 3 to 20 y in age. 2D and M-mode echocardiography were performed on nonsedated monkeys to determine the left ventricular internal diameters at systole and diastole and the ejection fraction. Electrocardiography was performed under sedation with ketamine (15 mg/kg). Parameters evaluated included heart rate; P-wave duration; lengths of the PR, QRS, and QT intervals; R-wave amplitude, and P-wave amplitude. Initial physical examination, electrocardiography, and echocardiography indicated normal cardiac function for all monkeys. The objectives of this study were to provide reference values for nonsedated echocardiography and ketamine-sedated electrocardiography of clinically normal squirrel monkeys and to determine correlates of age and sex in these values.
View details for Web of Science ID 000349577700005
- Dichloroacetate prevents restenosis in preclinical animal models of vessel injury NATURE 2014; 509 (7502): 641-?
Dichloroacetate prevents restenosis in preclinical animal models of vessel injury.
2014; 509 (7502): 641-644
Despite the introduction of antiproliferative drug-eluting stents, coronary heart disease remains the leading cause of death in the United States. In-stent restenosis and bypass graft failure are characterized by excessive smooth muscle cell (SMC) proliferation and concomitant myointima formation with luminal obliteration. Here we show that during the development of myointimal hyperplasia in human arteries, SMCs show hyperpolarization of their mitochondrial membrane potential (ΔΨm) and acquire a temporary state with a high proliferative rate and resistance to apoptosis. Pyruvate dehydrogenase kinase isoform 2 (PDK2) was identified as a key regulatory protein, and its activation proved necessary for relevant myointima formation. Pharmacologic PDK2 blockade with dichloroacetate or lentiviral PDK2 knockdown prevented ΔΨm hyperpolarization, facilitated apoptosis and reduced myointima formation in injured human mammary and coronary arteries, rat aortas, rabbit iliac arteries and swine (pig) coronary arteries. In contrast to several commonly used antiproliferative drugs, dichloroacetate did not prevent vessel re-endothelialization. Targeting myointimal ΔΨm and alleviating apoptosis resistance is a novel strategy for the prevention of proliferative vascular diseases.
View details for DOI 10.1038/nature13232
View details for PubMedID 24747400
Histological characteristics of myocardial bridge with an ultrasonic echolucent band. Comparison between intravascular ultrasound and histology.
2014; 78 (2): 502-504
View details for PubMedID 24172077
Patient access to medical devices-what about Japan, the second largest medical device market?
Cardiovascular intervention and therapeutics
2014; 29 (1): 1-3
Patients' access to innovative medical devices in Japan still shows the gap between the other countries. The cause of this device gap is researched from the prior published data. We searched the review time of new innovative devices by the Pharmaceuticals and Medical Devices Agency (PMDA) and the submission time lag compared with the US and EU from the prior published data. The average review time was 9.5 months and the total time from PMDA to introduction of the device to patients in Japan is almost similar to the US and the four European countries. However, the time lag of the file submission between Japan and the US was 2.42 years, on average, between 2001 and 2009. The review time for new innovative medical devices by the PMDA has been improving year after year. On the contrary, the pre-submission delay still exists in Japan.
View details for DOI 10.1007/s12928-013-0202-z
View details for PubMedID 23975639
- Response to letter regarding article, "fractional flow reserve assessment of left main stenosis in the presence of downstream coronary stenoses". Circulation. Cardiovascular interventions 2013; 6 (4)
The Role of Large Animal Studies in Cardiac Regenerative Therapy Concise Review of Translational Stem Cell Research
KOREAN CIRCULATION JOURNAL
2013; 43 (8): 511-518
Animal models have long been developed for cardiovascular research. These animal models have been helpful in understanding disease, discovering potential therapeutics, and predicting efficacy. Despite many efforts, however, translational study has been underestimated. Recently, investigations have identified stem cell treatment as a potentially promising cell therapy for regenerative medicine, largely because of the stem cell's ability to differentiate into many functional cell types. Stem cells promise a new era of cell-based therapy for salvaging the heart. However, stem cells have the potential risk of tumor formation. These properties of stem cells are considered a major concern over the efficacy of cell therapy. The translational/preclinical study of stem cells is essential but only at the beginning stages. What types of heart disease are indicated for stem cell therapy, what type of stem cell, what type of animal model, how do we deliver stem cells, and how do we improve heart function? These may be the key issues that the settlement of which would facilitate the transition of stem cell research from bench to bedside. In this review article, we discuss state-of-the-art technology in stem cell therapies for cardiovascular diseases.
View details for DOI 10.4070/kcj.2013.43.8.511
View details for Web of Science ID 000342388400001
View details for PubMedID 24044009
Global Cardiovascular Device Innovation: Japan-USA Synergies - Harmonization by Doing (HBD) Program, a Consortium of Regulatory Agencies, Medical Device Industry, and Academic Institutions -
2013; 77 (7): 1714-1718
Global medical devices have become more popular, but investment money for medical device development is not easily available in the market. Worldwide health-care budget constraints mean that efficient medical device development has become essential. To achieve efficient development, globalization is a key to success. Spending large amounts of money in different regions for medical device development is no longer feasible.In order to streamline processes of global medical device development, an academic, governmental, and industrial consortium, called the Harmonization by Doing program, has been set up. The program has been operating between Japan and the USA since 2003. The program has 4 working groups: (1) Global Cardiovascular Device Trials; (2) Study on Post-Market Registry; (3) Clinical Trials; and (4) Infrastructure and Methodology Regulatory Convergence and Communication. Each working group has as its goals the achievement of speedy and efficient medical device development in Japan and the USA. The program has held multiple international meetings to deal with obstacles against efficient medical device development.This kind of program is very important to deliver novel medical devices. Involvement of physicians in this type of activity is also very helpful to achieve these goals.
View details for DOI 10.1253/circj.CJ-12-1431
View details for Web of Science ID 000321405000013
View details for PubMedID 23538483
Fractional Flow Reserve Assessment of Left Main Stenosis in the Presence of Downstream Coronary Stenoses
2013; 6 (2): 161-165
Several studies have shown that fractional flow reserve (FFR) measurement can aid in the assessment of left main coronary stenosis. However, the impact of downstream epicardial stenosis on left main FFR assessment with the pressure wire in the nonstenosed downstream vessel remains unknown.Variable stenoses were created in the left main coronary arteries and downstream epicardial vessels in 6 anaesthetized male sheep using balloon catheters. A total of 220 pairs of FFR assessments of the left main stenosis were obtained, before and after creation of a stenosis in a downstream epicardial vessel, by having a pressure-sensor wire in the other nonstenosed downstream vessel. The apparent left main FFR in the presence of downstream stenosis (FFR(app)) was significantly higher compared with the true FFR in the absence of downstream stenosis (FFR(true); 0.80±0.05 versus 0.76±0.05; estimate of the mean difference, 0.035; P<0.001). The difference between FFR(true) and FFR(app) correlated with composite FFR of the left main plus stenosed artery (r=-0.31; P<0.001) indicating that this difference was greater with increasing epicardial stenosis severity. Among measurements with FFR(app) >0.80, 9% were associated with an FFR(true) of <0.75. In all instances, the epicardial lesion was in the proximal portion of the stenosed vessel, and the epicardial FFR (combined FFR of the left main and downstream stenosed vessel) was ≤0.50.A clinically relevant effect on the FFR assessment of left main disease with the pressure wire in a nonstenosed downstream vessel occurs only when the stenosis in the other vessel is proximal and very severe.
View details for DOI 10.1161/CIRCINTERVENTIONS.112.000104
View details for Web of Science ID 000330361600015
View details for PubMedID 23549643
SUSTAINED RESTORATION OF LV FUNCTION IN A PORCINE ISCHEMIA-REPERFUSION INJURY MODEL USING HUMAN PLACENTAL MESENCHYMAL STEM CELLS AND MANGANESE-ENHANCED MRI
ELSEVIER SCIENCE INC. 2013: E1142-E1142
View details for Web of Science ID 000316555201247
VALIDATION OF INFARCT CHARACTERIZATION IN A PORCINE ISCHEMIA REPERFUSION INJURY MODEL
ELSEVIER SCIENCE INC. 2013: E617-E617
View details for Web of Science ID 000316555200617
IMPACT OF POST-DILATATION STRATEGIES AND STENT MATERIALS ON CHRONIC STENT AREA PRESERVATION: AN EXPERIMENTAL STUDY USING OPTICAL COHERENCE TOMOGRAPHY
ELSEVIER SCIENCE INC. 2013: E1657-E1657
View details for Web of Science ID 000316555201762
PLAQUE ASSESSMENT WITH A NOVEL HIGH-DEFINITION 60-MHZ IVUS IMAGING SYSTEM: COMPARISON WITH CONVENTIONAL 40 MHZ IVUS AND OPTICAL COHERENCE TOMOGRAPHY
ELSEVIER SCIENCE INC. 2013: E1878-E1878
View details for Web of Science ID 000316555202082
Clinical and Angiographic Risk Stratification and Differential Impact on Treatment Outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial
2012; 126 (17): 2115-?
The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial assigned patients with type 2 diabetes mellitus to prompt coronary revascularization plus intensive medical therapy versus intensive medical therapy alone and reported no significant difference in mortality. Among patients selected for coronary artery bypass graft surgery, prompt coronary revascularization was associated with a significant reduction in death/myocardial infarction/stroke compared with intensive medical therapy. We hypothesized that clinical and angiographic risk stratification would affect the effectiveness of the treatments overall and within revascularization strata.An angiographic risk score was developed from variables assessed at randomization; independent prognostic factors were myocardial jeopardy index, total number of coronary lesions, prior coronary revascularization, and left ventricular ejection fraction. The Framingham Risk Score for patients with coronary disease was used to summarize clinical risk. Cardiovascular event rates were compared by assigned treatment within high-risk and low-risk subgroups. Overall, no outcome differences between the intensive medical therapy and prompt coronary revascularization groups were seen in any risk stratum. The 5-year risk of death/myocardial infarction/stroke was 36.8% for intensive medical therapy compared with 24.8% for prompt coronary revascularization among the 381 coronary artery bypass graft surgery-selected patients in the highest angiographic risk tertile (P=0.005); this treatment effect was amplified in patients with both high angiographic and high Framingham risk (47.3% intensive medical therapy versus 27.1% prompt coronary revascularization; P=0.010; hazard ratio=2.10; P=0.009). Treatment group differences were not significant in other clinical-angiographic risk groups within the coronary artery bypass graft surgery stratum, or in any subgroups within the percutaneous coronary intervention stratum.Among patients with diabetes mellitus and stable ischemic heart disease, a strategy of prompt coronary artery bypass graft surgery significantly reduces the rate of death/myocardial infarction MI/stroke in those with extensive coronary artery disease or impaired left ventricular function.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.
View details for DOI 10.1161/CIRCULATIONAHA.112.092973
View details for Web of Science ID 000310365500021
View details for PubMedID 23008442
Clinical Feasibility of Higher-Frequency IVUS for Quantitative Measurements of Native Coronary Lesions: First-in-Human Experience with 60MHz versus 40MHz IVUS Imaging
ELSEVIER SCIENCE INC. 2012: B81-B82
View details for Web of Science ID 000310210101088
Microfluidic Single-Cell Analysis Shows That Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation
2012; 111 (7): 882-893
Induced pluripotent stem cells (iPSCs) hold great promise for the development of patient-specific therapies for cardiovascular disease. However, clinical translation will require preclinical optimization and validation of large-animal iPSC models.To successfully derive endothelial cells from porcine iPSCs and demonstrate their potential utility for the treatment of myocardial ischemia.Porcine adipose stromal cells were reprogrammed to generate porcine iPSCs (piPSCs). Immunohistochemistry, quantitative PCR, microarray hybridization, and angiogenic assays confirmed that piPSC-derived endothelial cells (piPSC-ECs) shared similar morphological and functional properties as endothelial cells isolated from the autologous pig aorta. To demonstrate their therapeutic potential, piPSC-ECs were transplanted into mice with myocardial infarction. Compared with control, animals transplanted with piPSC-ECs showed significant functional improvement measured by echocardiography (fractional shortening at week 4: 27.2±1.3% versus 22.3±1.1%; P<0.001) and MRI (ejection fraction at week 4: 45.8±1.3% versus 42.3±0.9%; P<0.05). Quantitative protein assays and microfluidic single-cell PCR profiling showed that piPSC-ECs released proangiogenic and antiapoptotic factors in the ischemic microenvironment, which promoted neovascularization and cardiomyocyte survival, respectively. Release of paracrine factors varied significantly among subpopulations of transplanted cells, suggesting that transplantation of specific cell populations may result in greater functional recovery.In summary, this is the first study to successfully differentiate piPSCs-ECs from piPSCs and demonstrate that transplantation of piPSC-ECs improved cardiac function after myocardial infarction via paracrine activation. Further development of these large animal iPSC models will yield significant insights into their therapeutic potential and accelerate the clinical translation of autologous iPSC-based therapy.
View details for DOI 10.1161/CIRCRESAHA.112.269001
View details for Web of Science ID 000308868800015
View details for PubMedID 22821929
Evaluation of the peri-strut low intensity area following sirolimus- and paclitaxel-eluting stents implantation: Insights from an optical coherence tomography study in humans
INTERNATIONAL JOURNAL OF CARDIOLOGY
2012; 157 (1): 38-42
Recent pathological studies have demonstrated that peri-strut low intensity area (PLIA) seen on optical coherence tomography (OCT) imaging represents the presence of fibrinogen and/or extracellular matrix. We sought to assess the clinical prevalence of PLIA and its relation to neointimal proliferation after the implantation of sirolimus- (SES) and paclitaxel-eluting stents (PES) in humans.Seventy patients underwent 6-months follow-up OCT after SES (43 stents) or PES (37 stents) implantation. PLIA was defined as a region around stent struts with homogenous lower intensity than surrounding tissue on OCT images without signal attenuation. The incidence of stent struts with PLIA (+PLIA struts) was calculated as the number of +PLIA struts/number of all struts (%).PES showed a higher incidence of stents with PLIA than SES (86% vs. 58%; p=0.005) with a higher prevalence of +PLIA struts (27.8±21.9% vs. 10.9±11.0%; p=0.0008). SES with PLIA showed a significantly greater neointimal thickness (NIT) than SES without PLIA (p=0.02), while PES showed a similar tendency (p=0.19). In a detailed strut basis analysis, average NIT on +PLIA struts were significantly greater than that on -PLIA struts in both SES and PES. In addition, average NIT was positively correlated with the prevalence of +PLIA struts (SES: Rho=0.73; p<0.0001, PES: Rho=0.58, p=0.0005) in both stents.The prevalence of PLIA was significantly higher in PES than in SES. The presence and extent of PLIA might be associated with intimal thickening after 1st-generation DES implantation.
View details for DOI 10.1016/j.ijcard.2010.11.006
View details for Web of Science ID 000303206800015
View details for PubMedID 21168926
Impact of Completeness of Revascularization on Long-Term Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus Results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D)
2012; 5 (2): 166-173
Patients with diabetes have more extensive coronary disease than those without diabetes, resulting in more challenging percutaneous coronary intervention or surgical (coronary artery bypass graft) revascularization and more residual jeopardized myocardium. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial provided an opportunity to examine the long-term clinical impact of completeness of revascularization in patients with diabetes.This is a post hoc, nonrandomized analysis of the completeness of revascularization in 751 patients who were randomly assigned to early revascularization, of whom 264 underwent coronary artery bypass graft surgery and 487 underwent percutaneous coronary intervention. The completeness of revascularization was determined by the residual postprocedure myocardial jeopardy index (RMJI). RMJI is a ratio of the number of myocardial territories supplied by a significantly diseased epicardial coronary artery or branch that was not successfully revascularized, divided by the total number of myocardial territories. Mean follow-up for mortality was 5.3 years. Complete revascularization (RMJI=0) was achieved in 37.9% of patients, mildly incomplete revascularization (RMJI >0≤33) in 46.6%, and moderately to severely incomplete revascularization (RMJI >33) in 15.4%. Adjusted event-free survival was higher in patients with more complete revascularization (hazard ratio, 1.14; P=0.0018).Patients with type 2 diabetes mellitus and less complete revascularization had more long-term cardiovascular events.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.
View details for DOI 10.1161/CIRCINTERVENTIONS.111.963512
View details for Web of Science ID 000311705400009
View details for PubMedID 22496082
IMPACT OF POST-DILATATION STRATEGIES ON ACUTE STENT EXPANSION: AN EXPERIMENTAL STUDY USING OPTICAL COHERENCE TOMOGRAPHY
ELSEVIER SCIENCE INC. 2012: E153-E153
View details for Web of Science ID 000302326700154
Consensus Standards for Acquisition, Measurement, and Reporting of Intravascular Optical Coherence Tomography Studies A Report From the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2012; 59 (12): 1058-1072
The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease.Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ~10 ?m, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results.The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings.Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text.This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.
View details for DOI 10.1016/j.jacc.2011.09.079
View details for Web of Science ID 000301443000003
View details for PubMedID 22421299
Preclinical Derivation and Imaging of Autologously Transplanted Canine Induced Pluripotent Stem Cells
JOURNAL OF BIOLOGICAL CHEMISTRY
2011; 286 (37): 32697-32704
Derivation of patient-specific induced pluripotent stem cells (iPSCs) opens a new avenue for future applications of regenerative medicine. However, before iPSCs can be used in a clinical setting, it is critical to validate their in vivo fate following autologous transplantation. Thus far, preclinical studies have been limited to small animals and have yet to be conducted in large animals that are physiologically more similar to humans. In this study, we report the first autologous transplantation of iPSCs in a large animal model through the generation of canine iPSCs (ciPSCs) from the canine adipose stromal cells and canine fibroblasts of adult mongrel dogs. We confirmed pluripotency of ciPSCs using the following techniques: (i) immunostaining and quantitative PCR for the presence of pluripotent and germ layer-specific markers in differentiated ciPSCs; (ii) microarray analysis that demonstrates similar gene expression profiles between ciPSCs and canine embryonic stem cells; (iii) teratoma formation assays; and (iv) karyotyping for genomic stability. Fate of ciPSCs autologously transplanted to the canine heart was tracked in vivo using clinical positron emission tomography, computed tomography, and magnetic resonance imaging. To demonstrate clinical potential of ciPSCs to treat models of injury, we generated endothelial cells (ciPSC-ECs) and used these cells to treat immunodeficient murine models of myocardial infarction and hindlimb ischemia.
View details for DOI 10.1074/jbc.M111.235739
View details for Web of Science ID 000294726800078
View details for PubMedID 21719696
Dual Manganese-Enhanced and Delayed Gadolinium-Enhanced MRI Detects Myocardial Border Zone Injury in a Pig Ischemia-Reperfusion Model
2011; 4 (5): 574-582
Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn(2+))-enhanced MRI (MEMRI) denotes specific Mn(2+) uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo.Sixty-minute left anterior descending coronary artery IR injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn(2+) contrast agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with 2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI, r=0.78; DEMRI, r=0.75; P<0.004). MEMRI infarct volume percentage was significantly lower than that of DEMRI (14±4% versus 23±4%; P<0.05). BZ MEMRI signal-to-noise ratio (SNR) was intermediate to remote and core infarct SNR (7.5±2.8 versus 13.2±3.4 and 2.9±1.6; P<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct SNR (8.4±5.4 versus 3.3±0.6 and 14.3±6.6; P>0.05). Tissue electron microscopy analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement.The dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.
View details for DOI 10.1161/CIRCIMAGING.110.960591
View details for Web of Science ID 000295030600017
View details for PubMedID 21719779
Fundamental Wire Technique and Current Standard Strategy of Percutaneous Intervention for Chronic Total Occlusion With Histopathological Insights
2011; 4 (9): 941-951
Currently, successful treatment of chronic total occlusion (CTO) seems markedly improved, due to several new techniques and dedicated device developments. However, this improved success rate is often limited to procedures performed by skilled, highly experienced operators. To improve the overall success rate of percutaneous coronary intervention of CTO from a worldwide perspective, a deeper understanding of CTO histopathology might offer insights into the development of new techniques and procedural strategies. In this review, CTO histopathology and wire techniques are discussed on the basis of the fundamental concepts of antegrade and retrograde approaches. Although details pertaining to wire manipulation are very difficult to explain objectively, we tried to describe this as best as possible in this article. Finally, a systematic review of the current standard CTO strategy is provided. Hopefully, this article will enhance the understanding of this complex procedure and, consequently, promote safe and effective CTO-percutaneous coronary intervention for patients who present with this challenging lesion subset.
View details for DOI 10.1016/j.jcin.2011.06.011
View details for Web of Science ID 000295602800001
View details for PubMedID 21939933
Comparison of Drug-Eluting Versus Bare Metal Stents in Cardiac Allograft Vasculopathy
AMERICAN JOURNAL OF CARDIOLOGY
2011; 108 (5): 665-668
Although not a definitive treatment, percutaneous coronary intervention offers a palliative benefit to patients with cardiac allograft vasculopathy. Given the superior outcomes with drug-eluting stents (DESs) over bare metal stents (BMSs) in native coronary artery disease, similar improvements might be expected in transplant patients; however, the results have been mixed. Consecutive cardiac transplantation recipients at a single center receiving a stent for de novo cardiac allograft vasculopathy from 1997 to 2009 were retrospectively analyzed according to receipt of a DES versus a BMS. The angiographic and clinical outcomes were subsequently evaluated at 1 year. The baseline clinical and procedural characteristics were similar among those receiving DESs (n = 18) and BMSs (n = 16). Quantitative coronary angiography revealed no difference in the reference diameter, lesion length, or pre-/postprocedural minimal luminal diameter. At the 12-month angiographic follow-up visit, the mean lumen loss was significantly lower in the DES group than in the BMS group (0.19 ± 0.73 mm vs 0.76 ± 0.97 mm, p = 0.02). The DES group also had a lower rate of in-stent restenosis (12.5% vs 33%, p = 0.18), as well as a significantly lower rate of target lesion revascularization (0% vs 19%, p = 0.03). At 1 year, DESs were associated with a lower composite rate of cardiac death and nonfatal myocardial infarction (12% vs 38%, p = 0.04). In conclusion, DESs are safe and effective in the suppression of neointimal hyperplasia after percutaneous coronary intervention for cardiac allograft vasculopathy, resulting in significantly lower rates of late lumen loss and target lesion revascularization, as well as a reduced combined rate of cardiac death and nonfatal myocardial infarction.
View details for DOI 10.1016/j.amjcard.2011.04.014
View details for Web of Science ID 000294751000009
View details for PubMedID 21684511
BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways
JOURNAL OF CELL BIOLOGY
2011; 192 (1): 171-188
We present a novel cell-signaling paradigm in which bone morphogenetic protein 2 (BMP-2) consecutively and interdependently activates the wingless (Wnt)-?-catenin (?C) and Wnt-planar cell polarity (PCP) signaling pathways to facilitate vascular smooth muscle motility while simultaneously suppressing growth. We show that BMP-2, in a phospho-Akt-dependent manner, induces ?C transcriptional activity to produce fibronectin, which then activates integrin-linked kinase 1 (ILK-1) via ?4-integrins. ILK-1 then induces the Wnt-PCP pathway by binding a proline-rich motif in disheveled (Dvl) and consequently activating RhoA-Rac1-mediated motility. Transfection of a Dvl mutant that binds ?C without activating RhoA-Rac1 not only prevents BMP-2-mediated vascular smooth muscle cell motility but promotes proliferation in association with persistent ?C activity. Interfering with the Dvl-dependent Wnt-PCP activation in a murine stented aortic graft injury model promotes extensive neointima formation, as shown by optical coherence tomography and histopathology. We speculate that, in response to injury, factors that subvert BMP-2-mediated tandem activation of Wnt-?C and Wnt-PCP pathways contribute to obliterative vascular disease in both the systemic and pulmonary circulations.
View details for DOI 10.1083/jcb.201008060
View details for Web of Science ID 000287778600015
View details for PubMedID 21220513
The Representative Porcine Model for Human Cardiovascular Disease
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY
To improve human health, scientific discoveries must be translated into practical applications. Inherent in the development of these technologies is the role of preclinical testing using animal models. Although significant insight into the molecular and cellular basis has come from small animal models, significant differences exist with regard to cardiovascular characteristics between these models and humans. Therefore, large animal models are essential to develop the discoveries from murine models into clinical therapies and interventions. This paper will provide an overview of the more frequently used large animal models, especially porcine models for preclinical studies.
View details for DOI 10.1155/2011/195483
View details for Web of Science ID 000286229500001
View details for PubMedID 21253493
Detection of Injured Border Zone Myocardium Using Manganese-Enhanced and Delayed-Enhanced MRI in a Pig Ischemia-Reperfusion Model
LIPPINCOTT WILLIAMS & WILKINS. 2010
View details for Web of Science ID 000208231600841
CCR2 Antagonist Inhibits Neointimal Proliferation Post CoronaryStent Deployment
LIPPINCOTT WILLIAMS & WILKINS. 2010
View details for Web of Science ID 000208231602333
Sustained Inhibition of epsilon Protein Kinase C Inhibits Vascular Restenosis After Balloon Injury and Stenting
LIPPINCOTT WILLIAMS & WILKINS. 2010: S170-S178
protein kinase C (?PKC) is involved in vascular smooth muscle cell (VSMC) activation, but little is known about its function in vascular pathology. We aimed at assessing the role of ?PKC in the development of restenosis.Rat models of aortic balloon injury with or without subsequent stenting were used. Rats were treated with the selective ??PKC activator ? receptor for activated protein kinase C (??RACK), the selective ?PKC inhibitor ?V1-2, or saline. Both down-stream cascades of the platelet-derived growth factor receptor via extracellular signal-regulated kinase and Akt, respectively, were evaluated in vivo and in VSMC cultures. Intimal hyperplasia with luminal obliteration developed in saline-treated balloon-injured rat aortas (20.3±8.0%), and ??RACK significantly promoted neointima development (32.4±4.9%, P=0.033), whereas ?V1-2 significantly inhibited luminal narrowing (9.2±4.3%, P=0.039). ?PKC inhibition led to significantly reduced VSMC extracellular signal-regulated kinase phosphorylation in vivo, whereas Akt phosphorylation was not markedly affected. Neointimal proliferation in vivo and platelet-derived growth factor-induced VSMC proliferation/migration in vitro were significantly inhibited by ?V1-2. The inhibition of the platelet-derived growth factor pathway was mediated by inhibiting down-stream extracellular signal-regulated kinase and Akt phosphorylation. In vitro, ?V1-2 showed inhibitory properties on endothelial cell proliferation, but that did not prevent reendothelialization in vivo. ?V1-2 showed proapoptotic effects on VSMC in vitro. After stent implantation, luminal restenosis (quantified by optical coherence tomography imaging) was significantly reduced with ?V1-2 (8.0±2.0%) compared with saline (20.2±9.8%, P=0.028).?PKC seems to be centrally involved in the development of neointimal hyperplasia. We suggest that ?PKC inhibition may be mediated via inhibition of extracellular signal-regulated kinase and Akt activation. ?PKC modulation may become a new therapeutic target against vascular restenosis.
View details for DOI 10.1161/CIRCULATIONAHA.109.927640
View details for Web of Science ID 000282294800025
View details for PubMedID 20837910
3 ',4-Dihydroxyflavonol reduces infarct size in a porcine acute myocardial ischaemia-reperfusion model
OXFORD UNIV PRESS. 2010: 493-494
View details for Web of Science ID 000281531903177
CCR2 antagonist inhibits neointimal proliferation post coronary stent deployment
OXFORD UNIV PRESS. 2010: 368-368
View details for Web of Science ID 000281531902268
Fractional Flow Reserve Versus Angiography for Guiding Percutaneous Coronary Intervention in Patients With Multivessel Coronary Artery Disease 2-Year Follow-Up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Study
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2010; 56 (3): 177-184
The purpose of this study was to investigate the 2-year outcome of percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) in patients with multivessel coronary artery disease (CAD).In patients with multivessel CAD undergoing PCI, coronary angiography is the standard method for guiding stent placement. The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study showed that routine FFR in addition to angiography improves outcomes of PCI at 1 year. It is unknown if these favorable results are maintained at 2 years of follow-up.At 20 U.S. and European medical centers, 1,005 patients with multivessel CAD were randomly assigned to PCI with drug-eluting stents guided by angiography alone or guided by FFR measurements. Before randomization, lesions requiring PCI were identified based on their angiographic appearance. Patients randomized to angiography-guided PCI underwent stenting of all indicated lesions, whereas those randomized to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was
0.80, the rate of myocardial infarction was 0.2% and the rate of revascularization was 3.2 % after 2 years.Routine measurement of FFR in patients with multivessel CAD undergoing PCI with drug-eluting stents significantly reduces mortality and myocardial infarction at 2 years when compared with standard angiography-guided PCI. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774).
View details for DOI 10.1016/j.jacc.2010.04.012
View details for Web of Science ID 000279520200002
View details for PubMedID 20537493
Intriguing Pen-Strut Low-Intensity Area Detected by Optical Coherence Tomography After Coronary Stent Deployment
2010; 74 (6): 1257-1259
Although peri-strut low-intensity area (PLIA) is frequently observed on post-stenting optical coherence tomography (OCT) images, the histology associated with PLIA is undocumented.The 36 porcine coronary lesions treated with bare-metal (BMS: n=16) or drug-eluting (DES: n=20) stents were assessed by OCT and histology at 28 days. DES showed a significantly higher incidence of PLIA than BMS. Also, +PLIA stents had greater neointima than PLIA stents. Histological analysis revealed the existence of fibrinoid and proteoglycans at the site of PLIA.PLIA might be represented by the presence of fibrinoid and proteoglycans, and associated with neointimal proliferation after stenting.
View details for DOI 10.1253/circj.CJ-10-0189
View details for Web of Science ID 000278211900036
View details for PubMedID 20453394
3 ', 4-Dihydroxyflavonol Reduces Infarct Size in a Porcine Acute Myocardial Infarction-Reperfusion Model
LIPPINCOTT WILLIAMS & WILKINS. 2009: S1174-S1174
View details for Web of Science ID 000271831504351
Evaluation of the Peri-strut Low Intensity Area Following Sirolimus- and Paclitaxel-Eluting Stents Implantation: Insights From an Optical Coherence Tomography Study in Humans
LIPPINCOTT WILLIAMS & WILKINS. 2009: S1000-S1000
View details for Web of Science ID 000271831503408
Safety and Efficacy of Drug Eluting Stents for Treatment of Cardiac Allograft Vasculopathy: A Prospective Clinical and Angiographic Study
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2009: 138D-138D
View details for Web of Science ID 000269981600385
Black spot surrounding stent struts observed by optical coherence tomography; what do these represent?
OXFORD UNIV PRESS. 2009: 848-848
View details for Web of Science ID 000208702607007
Development of Animal Model for Calcified Chronic Total Occlusion
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2009; 74 (3): 468-475
Chronic total coronary occlusion (CTO) remains a major problem for percutaneous revascularization, with relatively low primary success rates and a high incidence of restenosis and reocclusion compared with those of subtotal stenoses. No reproducible animal model simulating human CTOs has previously been developed. We hypothesized that an apatite-coated bioabsorbable polymer sponge could be implanted to produce calcified CTO lesions in animal coronary arteries/peripheral arteries. A total of 10 swine and six rabbits were used for this study. The apatite-coated bioabsorbable polymer sponges were implanted into a preselected segment of coronary and peripheral arteries. Four weeks after implantation, both angiography and histopathology were performed to document the presence or absence of CTO lesions. We could reproducibly develop CTO lesions in animal coronary/peripheral arteries that mimic human CTO lesions. These lesions were found to have microvascular channels and microcalcification similar to those of human older CTO lesions and demonstrate the development of adventitial arterioles, a consistent finding in human CTO. This CTO model might provide a platform for evaluating future CTO technologies as well as contributing to a better understanding of CTOs in both educational and practical terms.
View details for DOI 10.1002/ccd.22024
View details for Web of Science ID 000269389200019
View details for PubMedID 19360862
Imaging Gene Expression in Human Mesenchymal Stem Cells: From Small to Large Animals
2009; 252 (1): 117-127
To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning.Animal protocols were approved by the Institutional Administrative Panel on Laboratory Animal Care. Transduction of human MSCs by using different doses of adenovirus that contained a cytomegalovirus (CMV) promoter driving the mutant herpes simplex virus type 1 thymidine kinase reporter gene (Ad-CMV-HSV1-sr39tk) was characterized in a cell culture. A total of 2.25 x 10(6) transduced (n = 5) and control nontransduced (n = 5) human MSCs were injected into the myocardium of 10 rats, and reporter gene expression in human MSCs was visualized with micro-PET by using the radiotracer 9-(4-[fluorine 18]-fluoro-3-hydroxymethylbutyl)-guanine (FHBG). Different numbers of transduced human MSCs suspended in either phosphate-buffered saline (PBS) (n = 4) or matrigel (n = 5) were injected into the myocardium of nine swine, and gene expression was visualized with a clinical PET-CT. For analysis of cell culture experiments, linear regression analyses combined with a t test were performed. To test differences in radiotracer uptake between injected and remote myocardium in both rats and swine, one-sided paired Wilcoxon tests were performed. In swine experiments, a linear regression of radiotracer uptake ratio on the number of injected transduced human MSCs was performed.In cell culture, there was a viral dose-dependent increase of gene expression and FHBG accumulation in human MSCs. Human MSC viability was 96.7% (multiplicity of infection, 250). Cardiac FHBG uptake in rats was significantly elevated (P < .0001) after human MSC injection (0.0054% injected dose [ID]/g +/- 0.0007 [standard deviation]) compared with that in the remote myocardium (0.0003% ID/g +/- 0.0001). In swine, myocardial radiotracer uptake was not elevated after injection of up to 100 x 10(6) human MSCs (PBS group). In the matrigel group, signal-to-background ratio increased to 1.87 after injection of 100 x 10(6) human MSCs and positively correlated (R(2) = 0.97, P < .001) with the number of administered human MSCs.Reporter gene imaging in human MSCs can be translated to large animals. The study highlights the importance of co-administering a "scaffold" for increasing intramyocardial retention of human MSCs.
View details for DOI 10.1148/radiol.2513081616
View details for Web of Science ID 000268362900015
View details for PubMedID 19366903
A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease
NEW ENGLAND JOURNAL OF MEDICINE
2009; 360 (24): 2503-2515
Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established.We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention.At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003).Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.)
View details for DOI 10.1056/NEJMoa0805796
View details for Web of Science ID 000266813800005
View details for PubMedID 19502645
A Prospective, Multicenter, Randomized Trial to Assess Efficacy of Pioglitazone on In-Stent Neointimal Suppression in Type 2 Diabetes POPPS (Prevention of In-Stent Neointimal Proliferation by Pioglitazone Study)
2009; 2 (6): 524-531
The aim of this study was to clarify whether pioglitazone suppresses in-stent neointimal proliferation and reduces restenosis and target lesion revascularization (TLR) after percutaneous coronary intervention (PCI).Previous single-center studies have demonstrated the anti-restenotic effect of a peroxisome proliferator-activated receptor gamma agonist, pioglitazone, after PCI.A total of 97 patients with type 2 diabetes mellitus (T2DM) undergoing PCI (bare-metal stents only) were enrolled. After PCI, patients were randomly assigned to either the pioglitazone group (n = 48) or the control group (n = 49). Angiographical and intravascular ultrasound (IVUS) imaging were performed at baseline and repeated at 6-month follow-up. Primary end points included angiographical restenosis and TLR at 6 months follow-up. Secondary end point was in-stent neointimal volume by IVUS.Baseline glucose level and glycosylated hemoglobin (HbA1c) level were similar between the pioglitazone group and the control group. Angiographical restenosis rate was 17% in the pioglitazone group and 35% in control group (p = 0.06). The TLR was significantly lower in pioglitazone group than in control group (12.5% vs. 29.8%, p = 0.04). By IVUS (n = 56), in-stent neointimal volume at 6 months showed a trend toward smaller in the pioglitazone group than in the control group (48.0 +/- 30.2 mm(3) vs. 62.7 +/- 29.0 mm(3), p = 0.07). Neointimal index (neointimal volume/stent volume x 100) was significantly smaller in the pioglitazone group than in the control group (31.1 +/- 14.3% vs. 40.5 +/- 12.9%, p = 0.01).Pioglitazone treatment might suppress in-stent neointimal proliferation and reduce incidence of TLR after PCI in patients with T2DM.
View details for DOI 10.1016/j.jcin.2009.04.007
View details for Web of Science ID 000278971200008
View details for PubMedID 19539256
The Pre-Clinical Animal Model in the Translational Research of Interventional Cardiology
2009; 2 (5): 373-383
Scientific discoveries for improvement of human health must be translated into practical applications. Such discoveries typically begin at "the bench" with basic research, then progress to the clinical level. In particular, in the field of interventional cardiology, percutaneous cardiovascular intervention has rapidly evolved from an experimental procedure to a therapeutic clinical setting. Pre-clinical studies using animal models play a very important role in the evaluation of efficacy and safety of new medical devices before their use in human clinical studies. This review provides an overview of the emerging role, results of pre-clinical studies and development, and evaluation of animal models for percutaneous cardiovascular intervention technologies for patients with symptomatic cardiovascular disease.
View details for DOI 10.1016/j.jcin.2009.03.004
View details for Web of Science ID 000278971000001
View details for PubMedID 19463458
Intraoperative Fluorescence Imaging System for On-Site Assessment of Off-Pump Coronary Artery Bypass Graft
2009; 2 (5): 604-612
The aim of this study was to evaluate the intraoperative fluorescence imaging (IFI) system in the real-time assessment of graft patency during off-pump coronary artery bypass graft.Intraoperative fluorescence imaging is an intraoperative angiography-like imaging modality using fluorescent indocyanine green excited with laser light. Recently, assessment of graft patency using the IFI system was introduced into clinical use. The feasibility and efficacy of IFI technology in off-pump coronary artery bypass graft has not been systematically compared with other conventional diagnostic modalities.Patients undergoing off-pump coronary artery bypass graft received IFI analysis, intraoperative transit time flowmetry, and postoperative X-ray angiography. In off-line IFI analysis, the graft washout was classified based on the number of heartbeats required for indocyanine green washout: fast washout (
15 beats).A total of 507 grafts in 137 patients received IFI analysis. Of all the IFI analyses, 379 (75%) grafts were visualized clearly up to the distal anastomosis. With regard to anastomosis location, anterior location was associated with a higher percentage of fully analyzable images (90%). More than 80% of images were analyzable, irrespective of graft type. Six grafts with acceptable transit time flowmetry results were diagnosed with graft failure by IFI, which required on-site graft revision. All revised grafts' patency was confirmed by post-operative X-ray angiography. Conversely, 21 grafts with unsatisfactory transit time flowmetry results demonstrated acceptable patency with IFI. Graft revision was considered unnecessary in these grafts, and 20 grafts (95%) were patent by post-operative X-ray angiography. Compared with slow washout, fast washout was associated with a higher preoperative ejection fraction, use of internal mammary artery grafts, and anterior anastomosis location.The IFI system enables on-site assessment of graft patency, providing both morphologic and functional information. This technique may help reduce procedure-related, early graft failures in off-pump bypass patients.
View details for DOI 10.1016/j.jcmg.2008.12.028
View details for Web of Science ID 000287653200013
View details for PubMedID 19442948
Preserved coronary endothelial function by inhibition of delta protein kinase C in a porcine acute myocardial infarction model
INTERNATIONAL JOURNAL OF CARDIOLOGY
2009; 133 (2): 256-259
Previous studies demonstrate impairment of endothelial-dependent vasodilation after ischemia/reperfusion (I/R). Though we have demonstrated that inhibition of delta protein kinase C (delta PKC) at reperfusion reduces myocyte damage and improves cardiac function in a porcine acute myocardial infarction (AMI) model, impact of the selective delta PKC inhibitor on epicardial coronary endothelial function remains unknown.Either delta PKC inhibitor (delta V1-1, n=5) or saline (n=5) was infused into the left anterior descending artery at the last 1 min of the 30-min ischemia by balloon occlusion. In vivo responses to bradykinin (endothelium-dependent vasodilator) or nitroglycerin (endothelium-independent vasodilator) were analyzed at 24 h after I/R using intravascular ultrasound. Vascular responses were calculated as the ratio of vessel area at each time point (30, 60, 90 and 120 s after the infusion), divided by values at baseline (before the infusion).In control pigs, endothelial-dependent vasodilation following bradykinin infusion in infarct-related epicardial coronary artery was impaired, whereas in delta PKC inhibitor-treated pigs the endothelial-dependent vasodilation was preserved. Nitroglycerin infusion caused similar vasodilatory responses in the both groups.This is the first demonstration that a delta PKC inhibitor preserves vasodilator capacity in epicardial coronary arteries in an in vivo porcine AMI model. Because endothelial dysfunction correlates with worse outcome in patients with AMI, this preserved endothelial function in epicardial coronary arteries might result in a better clinical outcome.
View details for DOI 10.1016/j.ijcard.2007.11.021
View details for Web of Science ID 000264284500023
View details for PubMedID 18242734
Black Spot Surrounding Stent Struts Observed by Optical Coherence Tomography; What Do These Represent?
ELSEVIER SCIENCE INC. 2009: A90-A90
View details for Web of Science ID 000263864200371
Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention
NEW ENGLAND JOURNAL OF MEDICINE
2009; 360 (3): 213-224
In patients with multivessel coronary artery disease who are undergoing percutaneous coronary intervention (PCI), coronary angiography is the standard method for guiding the placement of the stent. It is unclear whether routine measurement of fractional flow reserve (FFR; the ratio of maximal blood flow in a stenotic artery to normal maximal flow), in addition to angiography, improves outcomes.In 20 medical centers in the United States and Europe, we randomly assigned 1005 patients with multivessel coronary artery disease to undergo PCI with implantation of drug-eluting stents guided by angiography alone or guided by FFR measurements in addition to angiography. Before randomization, lesions requiring PCI were identified on the basis of their angiographic appearance. Patients assigned to angiography-guided PCI underwent stenting of all indicated lesions, whereas those assigned to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80 or less. The primary end point was the rate of death, nonfatal myocardial infarction, and repeat revascularization at 1 year.The mean (+/-SD) number of indicated lesions per patient was 2.7+/-0.9 in the angiography group and 2.8+/-1.0 in the FFR group (P=0.34). The number of stents used per patient was 2.7+/-1.2 and 1.9+/-1.3, respectively (P<0.001). The 1-year event rate was 18.3% (91 patients) in the angiography group and 13.2% (67 patients) in the FFR group (P=0.02). Seventy-eight percent of the patients in the angiography group were free from angina at 1 year, as compared with 81% of patients in the FFR group (P=0.20).Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. (ClinicalTrials.gov number, NCT00267774.)
View details for Web of Science ID 000262434500004
View details for PubMedID 19144937
Imaging in-stent restenosis: an inexpensive, reliable, and rapid preclinical model.
Journal of visualized experiments : JoVE
Preclinical models of restenosis are essential to unravel the pathophysiological processes that lead to in-stent restenosis and to optimize existing and future drug-eluting stents. A variety of antibodies and transgenic and knockout strains are available in rats. Consequently, a model for in-stent restenosis in the rat would be convenient for pathobiological and pathophysiological studies. In this video, we present the full procedure and pit-falls of a rat stent model suitable for high throughput stent research. We will show the surgical procedure of stent deployment, and the assessment of in-stent restenosis using the most elegant technique of OCT (Optical Coherence Tomography). This technique provides high accuracy in assessing plaque CSAs (cross section areas) and correlates well with histological sections, which require special and time consuming embedding and sectioning techniques. OCT imaging further allows longitudinal monitoring of the development of in-stent restenosis within the same animal compared to one-time snapshots using histology.
View details for DOI 10.3791/1346
View details for PubMedID 19752856
The Importance of Pre-Clinical Animal Testing in Interventional Cardiology
ARQUIVOS BRASILEIROS DE CARDIOLOGIA
2008; 91 (5): 321-332
View details for Web of Science ID 000262436700010
The importance of pre-clinical animal testing in interventional cardiology.
Arquivos brasileiros de cardiologia
2008; 91 (5): 348-360
The treatment of cardiovascular disease has changed dramatically over the past 2 decades, allowing patients to live longer and better quality lives. The introduction of new therapies has contributed much to this success. Nowhere has this been more evident than in interventional cardiology, where percutaneous cardiovascular intervention has evolved in the past 2 decades from a quirky experimental procedure to a therapeutic cornerstone for patients with symptomatic cardiovascular disease. The development of these technologies from the earliest stages requires preclinical experiments using animal models. Once introduced into the clinical arena, an understanding of therapeutic mechanisms of these devices can be ascertained through comparisons of animal model research findings with clinical pathological specimens. This review provides an overview of the emerging role, results of preclinical studies and development, and evaluation of animal models for percutaneous cardiovascular intervention technologies for patients with symptomatic cardiovascular disease.
View details for PubMedID 19142381
Development of Animal Model for Calcified Chronic Total Occlusion (CTO)
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2008: 108I-108I
View details for Web of Science ID 000260094700252
Effect of Pioglitazone on Plaque Regression in Diabetic Patients with Coronary Artery Disease following Bare Metal Stent Implantation: Results from the POPPS Trial
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2008: 232I-232I
View details for Web of Science ID 000260094700584
- Tissue Sirolimus Levels of Distal Vessel, Stented Myocardium, and Distal Myocardium JACC-CARDIOVASCULAR INTERVENTIONS 2008; 1 (5): 595-595
Introducing the first polymer-free leflunomide eluting stent
2008; 200 (1): 126-134
We here describe the pharmacological characteristic, in vivo efficacy, and in vitro mechanisms of a polymer-free leflunomide eluting stent in comparison to its rapamycin-coated equivalent.Stents were coated with 40 mM solutions of leflunomide (L) or rapamycin (R) or were left uncoated (BM). Neointima formation was assessed 6 weeks after implantation into Sprague Dawley rats by optical coherence tomographies (OCT) and histopathology. In vitro proliferation assays were performed using isolated endothelial and smooth-muscle-cells from Sprague Dawley rats to investigate the cell-specific pharmacokinetic effect of leflunomide and rapamycin.HPLC-based drug release kinetics revealed a similar profile with 90% of the drug being released after 12.1+/-0.2 (L) and 13.0+/-0.2 days (R). After 6 weeks, OCTs showed that in-stent luminal obliteration was less for the coated stents (L:12.0+/-9.4%, R:13.3+/-13.1%) when compared to identical bare metal stents (BM:26.4+/-4.7%; p
View details for DOI 10.1016/j.atherosclerosis.2007.12.055
View details for Web of Science ID 000259549800017
View details for PubMedID 18295768
Development of animal model of calcified Chronic Total Occlusion (CTO)
OXFORD UNIV PRESS. 2008: 632-632
View details for Web of Science ID 000208702503229
In Vivo Comparison Between Optical Coherence Tomography and Intravascular Ultrasound for Detecting Small Degrees of In-Stent Neointima After Stent Implantation
2008; 1 (2): 168-173
The purpose of this study was to evaluate optical coherence tomography (OCT) for detecting small degrees of in-stent neointima (ISN) after stent implantation compared with intravascular ultrasound (IVUS).The importance of detecting neointimal coverage of stent struts has grown with the appreciation of the increased risk for late stent thrombosis after drug-eluting stent (DES) implantation. Intravascular ultrasound, the current standard for evaluating the status of DES, lacks the resolution to detect the initial neointimal coverage. Optical coherence tomography has greater resolution but has not yet been compared with IVUS in vivo with histological correlation for validation.Intravascular ultrasound and OCT were performed with motorized pullback imaging in 6 pigs across 33 stents, 1 month after implantation. Each pig was euthanized, and histological measurements of vessel, stent, and lumen dimensions were performed in 3 sections of each stent. A small degree of ISN was defined as occupying <30% of the stent area measured with histology. The IVUS, OCT, and histological assessment of ISN were compared in matched cross-sections of the stents with a small degree of ISN.Eleven stents had a small degree of ISN (average ISN area: 1.26 +/- 0.46 mm(2), and percent area obstruction: 21.4 +/- 5.2%). Compared with histology, the diagnostic accuracy of OCT (area under the receiver operating characteristic curve [AUC] = 0.967, 95% confidence interval [CI] 0.914 to 1.019) was higher than that of IVUS (AUC = 0.781, 95% CI 0.621 to 0.838).Optical coherence tomography detects smaller degrees of ISN more accurately than IVUS and might be a useful method for identifying neointimal coverage of stent struts after DES implantation.
View details for DOI 10.1016/j.jcin.2007.12.007
View details for Web of Science ID 000207586100011
View details for PubMedID 19463295
The Porcine Restenosis Model Using Thermal Balloon Injury: Comparison with the Model by Coronary Stenting
JOURNAL OF INVASIVE CARDIOLOGY
2008; 20 (3): 142-146
Percutaneous coronary intervention (PCI) continues to revolutionize the treatment of coronary atherosclerosis and technologic advances require a preclinical coronary stenosis model. The purpose of this study was to systematically evaluate a porcine restenosis model of thermal balloon injury compared to stent overstretching.To evaluate this injury model, 22 swine were utilized. For the induction of coronary stenoses, the thermal balloon-to-artery ratio was equal to the range of 1.2-1.3 and was placed at a desired location in the coronary arteries, inflated with 2 atm, and heated to 80 degrees C for 80 seconds. Quantitative coronary angiography was analyzed at baseline, immediately postprocedure, and 4 weeks at harvest. Quantitative coronary ultrasound analysis and histopathologic evaluation were also performed at 4 weeks postprocedure.A total of 54 coronary arteries (thermal balloon injury [Thermo]; n = 43, coronary stenting [Stent]; n = 11) from a total of 18 animals were analyzed for this study. At 4 weeks postprocedure, significantly greater coronary stenoses were observed in the Thermo Group versus the Stent Group (minimum lumen diameter: 1.00 % 0.63 mm vs. 1.58 % 0.44 mm; p = 0.009, % diameter stenosis [DS]: 66.2 +/- 21.6% vs. 48.1 +/- 11.4%; p = 0.02). There were significant linear correlations between the balloon-to-artery ratio, post %DS and %DS at 4 weeks (balloon-to-artery ratio; r = 0.538; p = 0.0012, post %DS; r = -0.744; p < 0.0001, respectively).This methodology may provide reproducible and consistent coronary stenoses. This model can be useful fnot only for the evaluation of medical devices, but also for technical training in PCI and development of coronary imaging technologies.
View details for Web of Science ID 000207738600011
View details for PubMedID 18316831
- Reporter gene imaging following percutaneous delivery in swine - Moving toward clinical applications JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2008; 51 (5): 595-597
In vivo porcine model of reperfused myocardial infarction: In situ double staining to measure precise infarct area/area at risk
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2008; 71 (1): 100-107
The aim of this study is to evaluate a catheter-based porcine model for reperfused myocardial infarction and investigate the appropriate location and duration of the occlusion.A balloon catheter was placed in the left descending coronary artery (LAD) in 78 swine, and used to occlude the LAD. To evaluate this model, left ventricular ejection fraction (LVEF), infarct size, incidence of ventricular fibrillation (VF), and mortality was compared among three groups: 60-min proximal LAD occlusion (60P), 60-min mid LAD occlusion (60M), and 30-min proximal LAD occlusion (30P).In 72 of the 78 pigs, the procedures were successfully completed. Both mortality and incidence of VF were highest in the 60P group (66.7% and 91.7%, respectively). Myocardial infarction was successfully induced in all 72 animals and in situ double-staining with Evans blue dye and 2,3,5-triphenyltetrazolium chloride was performed to delineate area at risk for ischemia and infarcted myocardium. There was no difference in infarct size, expressed as a percentage of the area at risk, between the 60P and 60M groups (49.5% +/- 3.9% vs. 45.4% +/- 13.3%, respectively). Serial changes in LVEF of the 60M group demonstrated that until 14 days after reperfusion, LVEF improved naturally over time (36.4% +/- 6.6% at 24 hr, and 47.3% +/- 10.1% at 14 days).This model and methodology could provide a reproducible and consistent infarct size. The current study demonstrated that 60-min mid LAD occlusion can be the most feasible to serve as a porcine reperfused myocardial infarction model.
View details for DOI 10.1002/ccd.21329
View details for Web of Science ID 000252139500016
View details for PubMedID 17985383
Real-time MRI of peripheral chronic total occlusion interventions: Visualization of devices ex vivo in animals and lesions in vivo pre/post intervention in patients
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2007: 224L-224L
View details for Web of Science ID 000250393900571
Optical coherence tomography compared to intravascular ultrasound for detecting small degrees of neointimal hyperplasia
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2007: 143L-143L
View details for Web of Science ID 000250393900359
Comparison of nonuniform strut distribution between two drug-eluting stent platforms.
journal of invasive cardiology
2007; 19 (6): 244-246
To compare the difference of strut distribution between two clinically available drug-eluting stent platforms (Bx Velocity and Express II stents) using intravascular ultrasound (IVUS).Nonuniform strut distribution (NSD) has been shown to be associated with increased intimal hyperplasia after drug-eluting stent implantation.IVUS imaging was performed on Bx Velocity (n = 6) and Express II stents (n = 6) after inflation pressures of 10, 16, and 26 atm in a bench test model. Percent NSD was defined as the length of segments with NSD (interstrut angle > 90 degrees) divided by stent length. NSD was also assessed in postprocedure IVUS images in 53 clinical cases (32 Cypher, 21 Taxus) using 3-dimensional IVUS analysis.Frequency of NSD segment and %NSD were lower in Bx Velocity stents than in Express II stents at the inflation pressures of 16 and 26 atm (%NSD: 16 atm, 0% vs. 13.8 +/- 9.4%; p < 0.005; 26 atm, 1.1 +/- 2.6% vs. 19.9 +/- 6.9% p < 0.0001). In postprocedural images from clinical cases, the frequency of NSD segment and %NSD were lower in Cypher stents than in Taxus stents (%NSD: 0.5 +/- 1.6 vs. 6.8 +/- 7.2; p < 0.0001).NSD segment was observed less in Bx Velocity stents than in Express II stents.
View details for PubMedID 17541122
Arteriotomy closure device application following percutaneous coronary intervention may prevent bleeding complications in patients with acute myocardial infarction
INTERNATIONAL JOURNAL OF CARDIOLOGY
2007; 117 (1): 131-132
The current study was performed to determine whether application of arteriotomy closure devices (ACDs) affect bleeding complications as compared to manual compression in patients with ST-elevated acute myocardial infarction (STEMI) who undergo primary or rescue percutaneous intervention (PCI). 314 consecutive cases of STEMI treated with PCI were retrospectively evaluated. Overall, 82.8% of patients received ACDs with total bleeding rate of 4.2% vs. 11.1% in patients who had manual compression, p=0.042. This difference in bleeding rates did not correlate with any clinical characteristic or utilization of GPIIb/IIIa inhibitors. Accordingly, ACDs can improve the acute results of PCI in STEMI patients.
View details for DOI 10.1016/j.ijcard.2006.03.082
View details for Web of Science ID 000245839200019
View details for PubMedID 16935367
Novel stent system for accurate placement in aorto-ostial renal artery disease: preclinical study in porcine renal artery model.
Cardiovascular revascularization medicine : including molecular interventions
2007; 8 (2): 99-102
Treatment of aorto-ostial renal artery stenosis has been associated with a lower procedural success and higher complication and restenosis rate, as compared to nonostial lesions. The design and delivery of currently available stent systems in ostial lesions can result in inaccurate stent positioning and placement leading to stent protrusion into the parent vessel lumen or geographic miss. A novel stent system (SquareOne Inc., Campbell, CA, USA) has been designed specifically for aorto-ostial lesions in the renal artery. This stent system aims to provide both tactile and visual confirmation of the ostium at the aorta, allow for improved accuracy during stent positioning and placement, provide complete scaffolding of the lesion at the aortic junction to the native vessel, and enable future vessel reaccess.Stents (n=12) were implanted in both renal arteries of six swine. For histology, two animals were euthanized immediately after stent implantation, and each two animals were then followed up at 2 and 4 weeks, respectively. Intravascular ultrasound (IVUS) studies were performed immediately after stent implantation and at follow-up.Proper stent positioning and implantation was obtained in all animals. Angiographic and IVUS assessments indicated no dissection or thrombus formation. Histology demonstrated good apposition and endothelialization of the stent strut surface.The unique flared shape of this novel ostial stent system allows for improved accuracy during stent positioning and placement, as well as complete apposition and coverage/scaffolding of the similarly-shaped luminal ostium. Future studies will determine if this novel stent system fulfills the unmet clinical need in aorto-ostial stenoses.
View details for PubMedID 17574168
Mechanism of luminal gain with plaque excision in atherosclerotic coronary and peripheral arteries: assessment by histology and intravascular ultrasound.
Journal of interventional cardiology
2007; 20 (2): 107-113
Using intravascular ultrasound (IVUS) and histology, the purpose of this study was to evaluate the occurrence of arterial wall overstretch and Dotter effect following revascularization with a plaque excision (PE) catheter compared with balloon angioplasty.Previous studies have demonstrated the safety and feasibility of plaque excision for the treatment of de novo coronary and peripheral atherosclerotic disease. However, whether mechanical vessel dilatation related to catheter insertion contributes to gains in the final luminal diameter is uncertain.Treatment with PE was assessed in both a porcine model (6 lesions treated with balloon angioplasty or PE) using histology and in humans with IVUS. In the latter part of the study, IVUS study was performed before and immediately following PE in 21 patients with either coronary artery disease (N = 13) or femoral artery disease (N = 8). Ultrasound measures in the femoral artery group were then compared with a control group of atherosclerotic lesions treated with conventional angioplasty that was matched according to lesion location and vessel diameter.Among individuals with coronary and peripheral arterial lesions treated with PE, the relative increases in luminal area secondary to reductions in plaque volume were 89% and 83%, respectively, with minimal increase in vessel diameter. In contrast, balloon angioplasty was associated with significantly greater vessel expansion and less plaque volume reduction. Vessel dissection also tended to occur less frequently and to a lesser extent with PE.Improvement in luminal dimensions using PE is principally due to a reduction in plaque volume rather than mechanical vessel expansion. The potential to increase luminal area while minimizing arterial dissection and barotrauma merits further clinical study with this method of revascularization.
View details for PubMedID 17391218
Impaired perfusion after myocardial infarction is due to reperfusion-induced delta PKC-mediated myocardial damage
2007; 73 (4): 699-709
To improve myocardial flow during reperfusion after acute myocardial infarction and to elucidate the molecular and cellular basis that impedes it. According to the AHA/ACC recommendation, an ideal reperfusion treatment in patients with acute myocardial infarction (AMI) should not only focus on restoring flow in the occluded artery, but should aim to reduce microvascular damage to improve blood flow in the infarcted myocardium.Transgenic mouse hearts expressing the deltaPKC (protein kinase C) inhibitor, deltaV1-1, in their myocytes only were treated with or without the deltaPKC inhibitor after ischemia in an ex vivo AMI model. deltaV1-1 or vehicle was also delivered at reperfusion in an in vivo porcine model of AMI. Microvascular dysfunction was assessed by physiological and histological measurements.deltaPKC inhibition in the endothelial cells improved myocardial perfusion in the transgenic mice. In the porcine in vivo AMI model, coronary flow reserve (CFR), which is impaired for 6 days following infarction, was improved immediately following a one-minute treatment at the end of the ischemic period with the deltaPKC-selective inhibitor, deltaV1-1 ( approximately 250 ng/kg), and was completely corrected by 24 h. Myocardial contrast echocardiography, electron microscopy studies, and TUNEL staining demonstrated deltaPKC-mediated microvascular damage. epsilonPKC-induced preconditioning, which also reduces infarct size by >60%, did not improve microvascular function.These data suggest that deltaPKC activation in the microvasculature impairs blood flow in the infarcted tissue after restoring flow in the occluded artery and that AMI patients with no-reflow may therefore benefit from treatment with a deltaPKC inhibitor given in conjunction with removal of the coronary occlusion.
View details for DOI 10.1016/j.cardiores.2006.12.011
View details for Web of Science ID 000245301800012
View details for PubMedID 17234167
Novel stent and delivery systems for the treatment of bifurcation lesions: porcine coronary artery model.
Cardiovascular revascularization medicine : including molecular interventions
2007; 8 (1): 38-42
In percutaneous treatment of bifurcation coronary lesions, side-branch restenosis remains a significant limitation in current therapeutic approaches. Coronary stents with a side aperture and a sleeve may be clinically advantageous to maintain access to side branch, stabilize the side-branch orifice, and deliver the appropriate drug to the side-branch ostium.A novel stent system (PETAL stent; Advanced Stent Technologies, Pleasanton, CA), incorporating a side aperture with deployable struts, was compared within porcine coronary model to the prior stent version having only the side aperture (SLK-View stent). In six pigs, each stent was implanted either in the left anterior descending coronary artery or the left circumflex coronary artery with adjunctive kissing balloon dilatation. At 28-day follow-up, coronary angiography was performed.A total of six SLK-View stents and six PETAL stents were implanted in coronary arteries without any complication, and adjunctive kissing balloon dilatations were successful in all lesions. Quantitative coronary angiography (QCA) data at 28 days showed that PETAL stents exhibited superior QCA in mean diameter compared with SLK-View stents for side branch, inferring efficacy of PETAL ostial struts.AST-PETAL stent has the potential to be a new solution for treatment of bifurcation lesions. Antirestenosis drug elution should be considered with this successful platform.
View details for PubMedID 17293267
Comparison of nonuniform rotational distortion between mechanical IVUS and OCT using a phantom model
ULTRASOUND IN MEDICINE AND BIOLOGY
2007; 33 (1): 67-73
Optical coherence tomography (OCT) is an optical analog of mechanical intravascular ultrasound (M-IVUS) with much higher spatial resolution. However, no data exist regarding the nonuniform rotational distortion (NURD) with OCT. The aim of the study was to investigate whether OCT generates less NURD relative to M-IVUS. A coronary artery phantom model was constructed with a rubber ring (3.68 mm in diameter), located at the distal end of the phantom. This model was also composed of eight equally spaced steel wires and an additional marker-wire. Two types of vascular phantoms were used, mild curve (90 degrees ) and acute curve (near 180 degrees ). Subsequent M-IVUS (n = 6) and OCT (n = 6) imaging was performed. Eight angles between eight wires, except the marker-wire, were measured from each image. These angles, measured with M-IVUS and OCT, were compared with those of high-resolution optical photography as a gold standard. The average in angle differences was significantly smaller in OCT compared with M-IVUS in the mild curve model (3.2 +/- 1.0 degrees vs, 6.9 +/- 2.1 degrees , p < 0.01). Compared with the latter model, the average in angle differences was exaggerated in the acute curve model with M-IVUS (9.1 +/- 0.9 degrees vs. 6.9 +/- 2.1 degrees , p < 0.05) but not with OCT (3.5 +/- 0.8 degrees vs. 3.2 +/- 1.0 degrees , p= not significant). OCT generates significantly less NURD compared with M-IVUS, especially in tortuous situation.
View details for DOI 10.1016/j.ultrasmedbio.2006.07.020
View details for Web of Science ID 000243243700008
View details for PubMedID 17189048
The conversion in application of percutaneous coronary intervention following the introduction of drug eluting stents
INTERNATIONAL JOURNAL OF CARDIOLOGY
2006; 113 (2): 279-280
In order to determine the changes in the pattern of techniques applied during elective coronary intervention, data from 688 patients prior to Sirolimus. Drug-Eluting Stents (DES) approval was compared to 438 patients who underwent coronary intervention after DES approval. There was increased intervention to higher risk lesions, including smaller vessels and re-stenotic lesions after DES approval. Total number of stents per patient significantly decreased, despite longer stent length per patient or per lesion after DES approval. No significant difference was found in multivessel interventions.
View details for DOI 10.1016/j.ijcard.2005.09.038
View details for Web of Science ID 000242312500031
View details for PubMedID 16318883
Optical coherence tomography: In-vivo correlation withhistology
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2006: 93M-93M
View details for Web of Science ID 000241442800218
Novel intra-operative fluorescence imaging system for on-site assessment of off-pump coronary artery bypass graft
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2006: 247M-248M
View details for Web of Science ID 000241442800631
- Endovascular intervention for infrainguinal artery disease requires additional evidence regarding selection of devices JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 2006; 17 (9): 1545-1545
Long-term histopathologic and IVUS evaluations of a novel coiled sheet stent in porcine carotid arteries
CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
2006; 29 (3): 413-419
Carotid angioplasty with stent placement has been proposed as an alternative method for revascularization of carotid artery stenosis. A novel stent with a laser-cut, rolled sheet of Nitinol (EndoTex Interventional Systems, Inc., Cupertino, CA) has been developed to customize treatment of stenotic lesions in carotid arteries utilizing a single stent, designed to adapt to multiple diameters and to tapered or nontapered configurations. The purpose of this study is to evaluate the conformability and vascular response to a novel stent in a chronic porcine carotid model using serial three-dimensional intravascular ultrasound (IVUS) analysis as well as histological examination. Ten Yucatan pigs underwent stent implantation in both normal carotid arteries with adjunctive balloon angioplasty. Three-dimensional IVUS analysis was performed before stent implantation, after adjunctive balloon angioplasty, and at follow-up [1 month (n = 6), 3 months (n = 6), or 6 months (n = 8)]. Histological examination (injury score, percent plaque obstruction, and qualitative analysis) was also performed. All stents were successfully deployed and well apposed in different sized vessels (lumen area range: 19-30 mm(2)). Volumetric IVUS analysis showed no significant difference between the lumen areas before stent implantation and after adjunctive balloon angioplasty and no stent area change at each follow-up point compared to immediately postprocedure. Histological examination revealed minimal injury and neointimal hyperplasia at each follow-up point. In the chronic porcine carotid model, the novel stent system demonstrated good conformability, resulting in minimal vessel injury and neointimal formation.
View details for DOI 10.1007/s00270-005-0137-6
View details for Web of Science ID 000236751300014
View details for PubMedID 16502176
Drug-eluting stent strut distribution: a comparison between Cypher and Taxus by optical coherence tomography.
journal of invasive cardiology
2006; 18 (3): 111-114
The purpose of this study is to compare the stent strut distribution between Cypher and Taxus stents by using optical coherence tomography (OCT) in a phantom model.Previous studies demonstrated that the distribution of stent struts might affect amount of neointima proliferation after drug-eluting stent (DES) implantation.We developed experimental models made of silicon tubing angled at 0 degrees, 30 degrees, and 60 degrees. Testing was performed on two types of stents, Cypher and Taxus, which represent current FDA-approved DES. After deployment, OCT was performed and measurements were obtained as follows at two cross sections; maximum and minimum numbers of visualized stent strut sites: (1) number of visualized stent struts; (2) angle between stent struts (interstrut angle); (3) mean interstrut angle; (4) the delta mean angle was defined as the margin between each value of the interstrut angle and mean interstrut angle.In the Cypher stent, both the interstrut angle and the delta mean angle were significantly better than all other stents evaluated (all comparisons between stents; p < 0.05, respectively).The present study found that the stent strut distribution of two stents, Cypher and Taxus, which represent current FDA-approved drug-eluting systems, were significantly different and suggested that the Cypher stent maintained a more regular strut distribution despite expansion in various anatomical situations, and therefore would provide the most regular and predictable drug delivery.
View details for PubMedID 16598109
Novel intra-operative fluorescence imaging system for on-site assessment of off-pump coronary artery bypass graft
ELSEVIER SCIENCE INC. 2006: 178A-178A
View details for Web of Science ID 000235530401084
Acute and long-term outcomes of the novel side access (SLK-View (TM)) stent for bifurcation coronary lesions: A multicenter nonrandomized feasibility study
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2006; 67 (2): 198-206
To evaluate technical feasibility and procedural safety of SLK-View stent for treating bifurcation lesions.Percutaneous treatment of coronary bifurcation lesions represents a technical challenge. Several stenting techniques and dedicated devices have proven unsuccessful, with high rates of side branch occlusion at index procedure and follow-up.Eighty one patients with 84 de novo coronary artery lesions involving a major side branch underwent SLK-View (Advanced Stent Technologies, Inc., Pleasanton, CA) stent implantation with subsequent kissing balloon post dilatation. SLK-View stent is a new scaffolding device incorporating a side aperture that allows access to the side-branch of a bifurcation after deployment of the stent in main vessel. All patients underwent angiographic follow-up at 6 months. Procedural, in-hospital, and 6-month follow-up outcomes were examined.The lesions were located in left main (n = 11), left anterior descending (n = 50), left circumflex (n = 8), right coronary artery (n = 7), and 1 ramus intermedius. The most frequent lesions (44.1%) were true bifurcations. Successful stent delivery to bifurcation was accomplished in 82/84 of the cases (97.6%). Technical success was obtained in 99 and 94% of main vessel and side branches, respectively. Stenting in side-branch was performed in 21 lesions (25%). Side-branches were accessed effectively in 100% of bifurcations postprocedurally. Binary restenosis rate at 6-month follow-up was 28.3% and 37.7% for main vessel and side-branch, respectively. TLR rate at 6-month follow-up was 21% and CABG rate of 6%.In this consecutive multicenter series of patients with coronary bifurcation lesions, this novel side-branch access stent proved feasible, with a high procedural success rate, while maintaining side-branch access.
View details for DOI 10.1002/ccd.20556
View details for Web of Science ID 000235145100005
View details for PubMedID 16404749
Augmentation of tissue perfusion by a novel compression device increases neurologically intact survival in a porcine model of prolonged cardiac arrest
2006; 68 (1): 109-118
This study was performed to determine the potential efficacy of an automated device with a load-distributing band (AutoPulse, Revivant Corporation), in improving neurologically intact survival after cardiac arrest.Randomized, controlled trial.University animal laboratory.Forty-four swine (18-23 kg).Eight minutes after induction of untreated ventricular fibrillation, pigs were randomized to AutoPulse-CPR (A-CPR, n = 22), conventional cardiopulmonary resuscitation (CPR) with 20% anterior-posterior chest displacement (C-CPR20, n = 10) or 30% chest displacement (C-CPR30, n = 12), followed by resuscitation protocol with ventilation, defibrillation and intravenous epinephrine (adrenaline).Aortic and right atrium blood pressure was measured with micromanometers. Regional blood flows were measured with microspheres. Coronary perfusion pressure during A-CPR was significantly higher as compared to C-CPR without epinephrine (A-CPR versus C-CPR20 versus C-CPR30; 16 +/- 1 mmHg versus 7 +/- 2 mmHg versus 11 +/- 2 mmHg, p < 0.05). A-CPR improved both myocardial flow without epinephrine (A-CPR versus C-CPR20 versus C-CPR30; 23% versus 0% versus 4%; percent of baseline, p < 0.05) and cerebral blood flow (40% versus 4% versus 19%, percent of baseline, p < 0.05). Sixteen of 22 animals receiving A-CPR regained spontaneous circulation and survived; 14/22 had normal cerebral performance (CPC 1). Four of 12 animals receiving C-CPR30 regained spontaneous circulation and survived, but only one animal had normal neurological function (14/22 versus 1/12, p < 0.0001). No animal receiving C-CPR20 achieved spontaneous circulation. At necropsy, 67% of C-CPR30 had rib fracture and 33% showed lung injury, while A-CPR and C-CPR20 resulted in no detectable injuries.Improved hemodynamics with AutoPulse performed CPR results in improved neurologically intact survival without subsequent thoracic or pulmonary injuries in this porcine model of prolonged cardiac arrest.
View details for DOI 10.1016/j.resuscitation.2005.05.024
View details for Web of Science ID 000234960400013
View details for PubMedID 16325982
Double balloon occlusion system superior to single balloon occlusion for selective interstitial retrograde venous delivery
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2005: 40H-40H
View details for Web of Science ID 000232725200083
Drug-Eluting Stents strut distribution; A comparison of 3 stent designs by optical coherence tomography
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2005: 182H-182H
View details for Web of Science ID 000232725200464
Long-term histopathologic and IVUS evaluations of a novel coiled sheet stent in porcine carotid arteries
OXFORD UNIV PRESS. 2005: 5-5
View details for Web of Science ID 000233987100011
Effect of lumen narrowing within coronary stents on proximal and distal vessel segments following bare metal stent implantation
AMERICAN JOURNAL OF CARDIOLOGY
2005; 96 (3): 376-378
Adjacent reference vessel response to smaller lumens at stented segments was examined with 3-dimensional intravascular ultrasound analysis. In 128 patients after bare metal stent implantation, minimal lumen area (MLA) within the stent and average lumen area at distal/proximal adjacent reference segments (5 mm) were obtained at baseline and follow-up. In the smaller in-stent MLA group (MLA <3 mm2), lumen area decreased significantly at the distal edge compared with the larger in-stent MLA group (MLA > or =3 mm2), although no significant difference was seen at the proximal edge. In-stent lumen patency may influence vascular responses at adjacent reference segments after bare metal stent implantation.
View details for DOI 10.1016/j.amjcard.2005.03.079
View details for Web of Science ID 000231057000011
View details for PubMedID 16054461
Cardioprotection by epsilon-protein kinase C activation from ischemia - Continuous delivery and antiarrhythmic effect of an epsilon-protein kinase C-activating peptide
2005; 111 (1): 44-50
We previously showed that a selective activator peptide of epsilon-protein kinase C (PKC), psi(epsilon)RACK, conferred cardioprotection against ischemia-reperfusion when delivered ex vivo before the ischemic event. Here, we tested whether in vivo continuous systemic delivery of psi(epsilon)RACK confers sustained cardioprotection against ischemia-reperfusion in isolated mouse hearts and whether psi(epsilon)RACK treatment reduces infarct size or lethal arrhythmias in porcine hearts in vivo.After psi(epsilon)RACK was systemically administered in mice either acutely or continuously, hearts were subjected to ischemia-reperfusion in an isolated perfused model. Whereas psi(epsilon)RACK-induced cardioprotection lasted 1 hour after a single intraperitoneal injection, continuous treatment with psi(epsilon)RACK induced a sustained preconditioned state during the 10 days of delivery. There was no desensitization to the therapeutic effect, no downregulation of epsilonPKC, and no adverse effects after sustained psi(epsilon)RACK delivery. Porcine hearts were subjected to ischemia-reperfusion in vivo, and psi(epsilon)RACK was administered by intracoronary injection during the first 10 minutes of ischemia. psi(epsilon)RACK treatment reduced infarct size (34+/-2% versus 14+/-1%, control versus psi(epsilon)RACK) and resulted in fewer cases of ventricular fibrillation during ischemia-reperfusion (87.5% versus 50%, control versus psi(epsilon)RACK).The epsilonPKC activator psi(epsilon)RACK induced cardioprotection both in vivo and ex vivo, reduced the incidence of lethal arrhythmia during ischemia-reperfusion, and did not cause desensitization or downregulation of epsilonPKC after sustained delivery. Thus, psi(epsilon)RACK may be useful for patients with ischemic heart disease. In addition, the psi(epsilon)RACK peptide should be a useful pharmacological agent for animal studies in which systemic and sustained modulation of epsilonPKC in vivo is needed.
View details for DOI 10.1161/01.CIR.0000151614.22282.F1
View details for Web of Science ID 000226065300008
View details for PubMedID 15611364
Novel percutaneous adventitial drug delivery system for regional vascular treatment
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2004; 63 (2): 222-230
A novel intracoronary microsyringe system (MicroSyringe) was developed for regulated drug injection into the adventitial space. In this report, the feasibility, safety, and distribution pattern of vascular treatment with this modality were tested in 17 swine by delivering Oregon green-labeled paclitaxel (OGP) and tacrolimus. Coronaries were harvested 0.5-96 hr postinjection and analyzed for drug by fluorescence histochemistry (OGP) and liquid chromatography-mass spectrometry (tacrolimus). Histopathological analysis was subsequently performed. The microsyringe deliveries were performed safely in all cases. In the OGP-injected group, within 2 hr postprocedure there was intense staining of the adventitia, media, and endothelium around the injection site, and by 23 hr staining extended distally by 27.5 mm. With tacrolimus, similar longitudinal drug distribution was seen; furthermore, by 48 hr there was detectable drug over 40 mm proximal and distal to the injection site. Significant levels of tacrolimus were detectable in coronaries at 96 hr. Percutaneous adventitial delivery is safe, feasible, and provides consistent dosing for complete treatment of a vascular territory.
View details for DOI 10.1002/ccd.20167
View details for Web of Science ID 000224240100018
View details for PubMedID 15390346
Impact of lumen reduction at stented segment on vessel responses in adjacent reference segments after bare metal stent implantation: Serial 3-dimensional intravascular ultrasound analysis
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2004: 163E-164E
View details for Web of Science ID 000224406500350
Intracoronary versus percutaneous endomyocardial delivery of porcine mesenchymal stem cells to areas of myocardial infarction.
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2004: 91E-91E
View details for Web of Science ID 000224406500199
AST-PETAL: novel stent and delivery systems for the treatment of bifurcation
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2004: 182E-183E
View details for Web of Science ID 000224406500390
Initial experience with the novel 6 Fr-compatible system for debulking De Novo coronary arterial lesions
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2004; 62 (3): 308-317
The purpose of this study was to determine the efficacy of a novel system for debulking of de novo native coronary arterial lesions. The Helixciser De Novo system is a novel 6 Fr-compatible catheter with a cutter encased in a slotted-orifice housing to excise atheromatous plaque. The cutter rotates at 15,000 rpm, debulking the plaque as it tracks through the lesion over a straight wire or a self-expanding nitinol helical-shaped wire. The tissue is aspirated via an Archimedes screw pump to vacuum collection chamber. The device was evaluated in a porcine toxic coronary stent model of chronic occlusion and in five patients with focal de novo native coronary arterial lesions. Procedural variables along with outcomes were reviewed. Quantitative angiography (QCA) and volumetric intravascular ultrasound (IVUS) analysis were performed. In a porcine model of chronic occlusion, QCA demonstrated pretreatment minimal lumen diameter (MLD) increased from 0.77 +/- 0.59 to 1.88 +/- 0.25 mm postdebulking. IVUS analysis demonstrated pretreatment lumen volume (LV) increased from 15.8 +/- 22.2 to 46.4 +/- 28.9 mm(3) postdebulking. In human clinical feasibility cases, QCA demonstrated pretreatment MLD increased from 0.96 +/- 0.40 to 2.04 +/- 0.19 mm postdebulking. IVUS analysis demonstrated pretreatment LV increased from 38.40 +/- 12.78 to 52.05 +/- 15.68 mm(3) postdebulking. Preliminary results document the feasibility of Helixcision De Novo for treatment of focal de novo native coronary arterial lesions. Quantitative angiographic and IVUS analysis indicate that this system can effectively debulk plaque from selected noncalcified atherosclerotic lesions and thus may represent an alternative treatment strategy for coronary artery disease.
View details for DOI 10.1002/ccd.20085
View details for Web of Science ID 000222407900008
View details for PubMedID 15224296
Six- and twelve-month results from first human experience using everolimus-eluting stents with bioabsorbable polymer
2004; 109 (18): 2168-2171
Everolimus, an active immunosuppressive and antiproliferative agent of the same family as sirolimus (rapamycin), has demonstrated significant reduction of neointimal proliferation in animal studies. The First Use To Underscore restenosis Reduction with Everolimus (FUTURE) I trial was the first in-human experience to evaluate the safety and efficacy of everolimus-eluting stents (EES), coated with a bioabsorbable polymer, compared with bare metal stents (BMS).FUTURE I was a prospective, single-blind, randomized trial that enrolled 42 patients with de novo coronary lesions (EES 27, BMS 15). Patient and lesion characteristics were comparable between the groups. Major adverse cardiac event rates were low at 30 days and 6 months, without any early or late stent thrombosis for either group (P=NS). Between 6 and 12 months, there were no additional reports of major adverse cardiac events. The 6-month angiographic in-stent restenosis rate was 0% versus 9.1% (1 patient) (P=NS), with an associated late loss of 0.11 mm versus 0.85 mm (P<0.001), and the in-segment restenosis rate was 4% (1 patient) and 9.1% (1 patient) (P=NS) for EES and BMS, respectively. Intravascular ultrasound analysis revealed a significant reduction of percent neointimal volume in EES compared with BMS (2.9+/-1.9 mm3/mm versus 22.4+/-9.4 mm3/mm, P<0.001). There was no late stent malapposition in either group. The safety and efficacy of the EES appeared to be sustained at 12 months.In this initial clinical experience, EES with bioabsorbable polymer demonstrated a safe and efficacious method to reduce in-stent neointimal hyperplasia and restenosis.
View details for DOI 10.1161/01.CIR.0000128850.84227.FD
View details for Web of Science ID 000221322600003
View details for PubMedID 15123533
Protection against reperfusion injury-induced microvascular damage by inhibition of is an element of ' protein kinase C
LIPPINCOTT WILLIAMS & WILKINS. 2004: E38-E38
View details for Web of Science ID 000221272700235
Magnetic resonance angiography detects in-stent thrombosis and thrombolysis
ELSEVIER SCIENCE INC. 2004: 322A-322A
View details for Web of Science ID 000189388501364
Evaluation of high-pressure retrograde coronary venous delivery of FGF-2 protein
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2004; 61 (3): 422-428
Delivery of angiogenic factors to ischemic myocardium remains a practical challenge. We evaluated the efficiency and efficacy of delivery of fibroblast growth factor-2 (FGF-2) protein via high-pressure retrograde injection into the anterior interventricular vein (AIV) in a porcine model of chronic myocardial ischemia. Labeled FGF-2 protein was delivered to the myocardium of three pigs via the AIV and the left anterior descending (LAD) coronary artery in three others. At 1 hr, the amount of protein in the left ventricle and the LAD region was quantified. Copper stents were implanted in the LAD of 25 pigs, resulting in chronic myocardial ischemia. At 4 weeks, microsphere-derived myocardial blood flow was assessed at rest and during pacing. In eight pigs (AIV FGF), FGF-2 protein (6 microg/kg) was delivered via high-pressure retrograde injection into the AIV. Six pigs (intracoronary FGF) received the same amount of FGF-2 by intracoronary delivery. Five pigs (AIV saline) received a placebo injection into the AIV and six pigs (control) served as controls. Four weeks later, myocardial blood flow was reassessed. At 1 hr, significantly more FGF remained in the left ventricle (1.3 vs. 0.82 microg; P < 0.04) and in the LAD region (1.2 vs. 0.64 microg; P = 0.03) after AIV compared to intracoronary delivery. Four weeks after treatment, resting LAD blood flow (normalized to right ventricular flow) improved slightly in the AIV FGF and intracoronary FGF arms (1.32-1.37 for both; P = 0.11), while it decreased significantly in the AIV saline (1.32-1.23; P = 0.02) and the control arms (1.32-1.19; P = 0.0004). Pacing LAD blood flow decreased significantly in the control arm (1.30-1.23; P < 0.05), but did not change significantly in the other three arms. High-pressure retrograde injection into the AIV may represent an efficient and effective means for delivering angiogenic factors to ischemic myocardium.
View details for DOI 10.1002/ccd.10790
View details for Web of Science ID 000220022500027
View details for PubMedID 14988909
Early experience with a novel plaque excision system for the treatment of complex coronary lesions
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2004; 61 (1): 35-43
The use of directional coronary atherectomy (DCA) in current practice has been limited. The SilverHawk System is a newly developed plaque excision device that aims to overcome the drawbacks of prior DCA platforms. The device was evaluated in a porcine coronary model and in a series of patients. Procedural variables along with outcomes were reviewed. Quantitative angiography (QCA) was performed and excised tissue fragments were weighed and examined histologically. In porcine cases, pretreatment MLD increased from 0.51 +/- 0.26 to 2.36 +/- 0.59 mm postdebulking and 19.9 +/- 7.6 mg of tissue was retrieved. In human cases, pretreatment MLD increased from 0.8 +/- 0.4 to 2.2 +/- 0.5 mm postdebulking and 15.2 +/- 7.8 mg of tissue was retrieved without complications. These data show that the SilverHawk System may offer significant utility in treating a wide variety of complex coronary lesions.
View details for DOI 10.1002/ccd.10727
View details for Web of Science ID 000187802300008
View details for PubMedID 14696157
Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo
2003; 108 (19): 2304-2307
Current treatment for acute myocardial infarction (AMI) focuses on reestablishing blood flow (reperfusion). Paradoxically, reperfusion itself may cause additional injury to the heart. We previously found that delta-protein kinase C (deltaPKC) inhibition during simulated ischemia/reperfusion in isolated rat hearts is cardioprotective. We focus here on the role for deltaPKC during reperfusion only, using an in vivo porcine model of AMI.An intracoronary application of a selective deltaPKC inhibitor to the heart at the time of reperfusion reduced infarct size, improved cardiac function, inhibited troponin T release, and reduced apoptosis. Using 31P NMR in isolated perfused mouse hearts, we found a faster recovery of ATP levels in hearts treated with the deltaPKC inhibitor during reperfusion only.Reperfusion injury after cardiac ischemia is mediated, at least in part, by deltaPKC activation. This study suggests that including a deltaPKC inhibitor at reperfusion may improve the outcome for patients with AMI.
View details for DOI 10.1161/01.CIR.0000101682.24138.36
View details for Web of Science ID 000186475200003
View details for PubMedID 14597593
Real-time, bright-blood, and black-blood magnetic resonance angiography detect in-stent thrombosis
LIPPINCOTT WILLIAMS & WILKINS. 2003: 453-453
View details for Web of Science ID 000186360602139
In-stent neointimal hyperplasia distribution and edge effect following mycophenolic acid (MPA) eluting stent implantation: A 3D IVUS substudy of the IMPACT trial
LIPPINCOTT WILLIAMS & WILKINS. 2003: 463-463
View details for Web of Science ID 000186360602184
Magnetic resonance Imaging detects in-stent thrombosis and enhances with fibrin-binding magnetic resonance contrast agent
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2003: 200L-200L
View details for Web of Science ID 000185385600476
Novel stent and delivery systems for the treatment of bifurcation lesions
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2003: 212L-212L
View details for Web of Science ID 000185385600506
Segmental occlusion of the anterior intraventricular vein significantly improves regional delivery after high-pressure retroperfusion
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2003: 105L-105L
View details for Web of Science ID 000185385600237
Coronary vasodilation by noninvasive transcutaneous ultrasound - An in vivo canine study
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2003; 41 (9): 1623-1627
We evaluated the coronary vasodilatory effects of transcutaneous low-frequency (27-kHz) ultrasound (USD).Ultrasound has been shown to affect vascular function.Ultrasound energy was administered transcutaneously to 12 dogs. Coronary arterial dimensions were assessed using intravascular coronary ultrasound (IVUS) and quantitative coronary angiography (QCA).The IVUS mid-left anterior descending (LAD) luminal area was 6.77 +/- 1.27 mm(2) at baseline. After 30 s of ultrasound, this area increased by 9% (7.40 +/- 1.44 mm(2), p < 0.05), after 3 min by 19% (8.05 +/- 1.72 mm(2), p < 0.05) and after 5 min increased by 21% (8.16 +/- 1.29 mm(2), p < 0.05). The mean coronary diameter (2.69 +/- 0.33 mm) at baseline (QCA of three segments of LAD and three segments of left circumflex coronary artery) increased by 19.3% (3.21 +/- 0.28 mm) after 5 min of USD exposure. After a 90-min observation period there was a return to baseline values (p = NS). Intracoronary nitroglycerin (NTG) administered to five dogs revealed a similar magnitude of vasodilation as USD.Noninvasive, transthoracic low-frequency USD energy results in coronary artery vasodilation within seconds of exposure. The vasodilation is reversible and is similar in magnitude to that induced by NTG. Further evaluation is needed to assess its potential applications in humans.
View details for DOI 10.1016/S0735-1097(03)00412-1
View details for Web of Science ID 000182631800030
View details for PubMedID 12742306
Noninvasive transcutaneous ultrasound augments thrombolysis in the left circumflex coronary artery - an in vivo canine study
2003; 110 (2-3): 149-158
Ultrasound has the potential to augment chemical thrombolysis.Thrombotic occlusions in the left circumflex artery (LCx) were induced in 27 dogs. Sixty minutes later, tissue-type plasminogen activator (t-PA) was given intravenously over 90 min. Thrombotic occlusions (n = 20) were treated with concomitant transcutaneous low frequency (27 kHz), continuous wave (CW) (n = 10) or pulsed wave (PW) (n = 10) ultrasound. Tissue-type plasminogen activator plus ultrasound (n = 20) vs. tissue-type plasminogen activator alone (n=7) resulted in more frequent Thrombolysis in Myocardial Infarction (TIMI) 3 flow (90% vs. 43%, P = 0.024) and less reocclusion (11% vs. 67%, P = 0.080). At 60 min, median TIMI grade flow for tissue-type plasminogen activator alone was 2 (mean: 1.43 +/- 1.40) compared to 3 (mean: 2.70 +/- 0.95) for tissue-type plasminogen activator plus continuous as well as pulsed wave ultrasound (P = 0.035). Continuous wave and pulsed wave ultrasound were equally effective in augmenting thrombolysis. Histologically, no ultrasound-mediated injury to the myocardium or coronary arteries occurred.Both transcutaneous low frequency continuous wave ultrasound and pulsed wave ultrasound enhance tissue-type plasminogen activator-mediated thrombolysis of the posterior circulation with higher TIMI 3 flow rates and less reocclusion than with tissue-type plasminogen activator alone. In addition, at the energy levels used, low frequency ultrasound appears safe.
View details for DOI 10.1016/S0049-3848(03)00335-9
View details for Web of Science ID 000184729400011
View details for PubMedID 12893030
Percutaneous endocardial versus selective coronary various cellular delivery: Comparisons of transplant efficiency, distribution, and efficacy in reducing infarct size and improving myocardial function
ELSEVIER SCIENCE INC. 2003: 67A-67A
View details for Web of Science ID 000181669500289
Inhibition of delta protein kinase C protects vascular injury and microcirculation from reperfusion injury in myocardial infarction
ELSEVIER SCIENCE INC. 2003: 373A-373A
View details for Web of Science ID 000181669501624
Efficacy and feasibility of helixcision for debulking neointimal hyperplasia for in-stent restenosis
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2002; 57 (4): 460-466
The Helixcision system is a novel 6 Fr-compatible catheter designed to debulk tissue for in-stent restenosis lesions. The purpose of this study was to determine the efficacy and feasibility of this new system for removing neointimal hyperplasia. A total of 32 in-stent restenosis lesions in 32 patients were treated with helixcision followed by balloon angioplasty. Debulking efficacy was assessed with serial baseline intravascular ultrasound (IVUS) in a subset of 18 lesions. To investigate longitudinal efficacy, 3D analysis was also performed in 12 lesions with automated pullback to calculate average cross-sectional areas across the stent. Prior to procedure, the angiographic reference diameter was 2.60 +/- 0.46 mm. Immediately after procedure, minimum lumen diameter improved from 0.84 +/- 0.33 to 2.19 +/- 0.41 mm (P < 0.0001). IVUS showed a significant reduction of intimal area (IA) after helixcision (from 4.95 +/- 2.04 to 2.88 +/- 1.48 mm(2); P < 0.001). Adjunctive balloon angioplasty further improved lumen area (LA) mainly by stent expansion rather than IA reduction at the site of minimum lumen area. The degrees of IA reduction and LA improvement were closely similar in volumetric analysis. Thirty-day and 6-month clinical follow-up were available in 97% (n = 31) and 72% (n = 23) of the enrolled patients, respectively. At 30-day follow-up, no major adverse cardiac event was reported except for periprocedural CK elevation in two patients (6%). Target legion revascularization within 6 months was performed in six patients (26%). Preliminary results of helixcision indicate that this system is safe and feasible for the treatment of in-stent restenosis. The concordant results between 2D and 3D IVUS analyses suggest that this unique technology can achieve uniform longitudinal debulking throughout the stent. The long-term outcomes appeared to be favorable, considering the relatively diffuse lesion morphology.
View details for DOI 10.1002/ccd.10352
View details for Web of Science ID 000182814400006
View details for PubMedID 12455079
Myocardial delivery of labeled fibroblast growth factor-2 protein by high pressure, retrograde coronary venous injection is more efficient than intracoronary administration
LIPPINCOTT WILLIAMS & WILKINS. 2002: 656-656
View details for Web of Science ID 000179142703274
Cut to the future: Early experience with a new atherectomy device - The ReFORM debulking catheter system.
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2002: 109H-109H
View details for Web of Science ID 000178077400271
High pressure, retrograde, coronary venous delivery of FGF-2 protein improves coronary blood flow in a porcine model of myocardial ischemia
ELSEVIER SCIENCE INC. 2002: 10A-10A
View details for Web of Science ID 000174106700043
A novel inhibitor of protein kinase-C as a therapeutic for ischemic reperfusion injury in acute coronary syndromes
ELSEVIER SCIENCE INC. 2002: 445A-445A
View details for Web of Science ID 000174106702000
- Drug-eluting stents for the prevention of restenosis: In quest for the holy grail CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS 2002; 55 (3): 409-417
A comparison of angiographic and physiologic correlates to myocardial perfusion
LIPPINCOTT WILLIAMS & WILKINS. 2001: 580-580
View details for Web of Science ID 000171895002723
Experimental results with the novel 6Fr compatible Helixicison System for debulking de novo coronary arterial lesions.
EXCERPTA MEDICA INC. 2001: 2G-2G
View details for Web of Science ID 000170893600006
- Will there always be an edge to radiation for the prevention of restenosis? CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS 2001; 54 (1): 49-50