Publications (11)35.98 Total impact
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Article: Catheter-Based Endomyocardial Delivery of Mesenchymal Precursor Cells Using 3D Echo Guidance Improves Cardiac Function in a Chronic Myocardial Injury Ovine Model.
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ABSTRACT: Background: The administration of bone marrow-derived stem cells may provide a new treatment option for patients with heart failure. Trans-catheter cell injection may require multi-imaging modalities to optimize delivery. This study sought to evaluate whether endomyocardial injection of mesenchymal precursor cells (MPCs) could be guided by real-time 3D echocardiography (RT3DE) in treating chronic, post-infarction (MI) left ventricular (LV) dysfunction in sheep.Methods and Results: Four weeks after induction of an anterior wall myocardial infarction in 39 sheep, allogeneic MPCs in doses of either 25 x10⁶ (n=10), 75 x10⁶ (n=9) or 225x10⁶ (n=10) cells or non-conditioned control media (n=10) were administered intramyocardially into infarct and borderzone areas using an catheter designed for combined fluoroscopic and RT3DE-guided injections. LV function was assessed before and after injection. Infarct dimension and vascular density were evaluated histologically. RT3DE-guided injection procedures were safe. Compared to controls, the highest doses MPCs treatment led to increments in ejection fraction (3±3% in 225M MPCs vs. -5±4% in control group, p<0.01), the wall thickening in both infarct (4±4% in 225M MPCs vs. -3±6% in control group, p=0.02) and border zones (4±6% in 225M MPCs vs. -8±9% in control group, p=0.01). Histology analysis demonstrated significantly higher arteriole density in the infarct and border zones in the highest dose MPCs treated animals compared to the lower dose or control groups.Conclusions: Endomyocardial implantation of MPCs under RT3DE guidance was safe and without observed logistical obstacles. Significant increases in LV performance (ejection fraction and wall thickening) and neovascularization result from this technique, and have important implications in treating patients with post-ischemic LV dysfunction.Cell Transplantation 10/2012; · 5.13 Impact Factor -
Article: Evaluation of efficacy and dose response of different Paclitaxel-coated balloon formulations in a novel Swine model of iliofemoral in-stent restenosis.
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ABSTRACT: The authors aimed to validate a novel iliofemoral in-stent restenosis (ISR) model for the efficacy evaluation of paclitaxel-coated balloons (PCB) using the familial hypercholesterolemic swine (FHS). Most of the validation work regarding PCB technologies has been performed in the coronary territory of juvenile domestic swine. Although invaluable for safety evaluation, this model is not suited for the evaluation of the efficacy of peripheral PCB technologies. Twenty-four iliofemoral segments in 12 FHS underwent balloon injury and self-expanding stent placement. After 21 days, the resulting ISR lesions were treated with either 1 μg/mm(2) dose (n = 8), or 3 μg/mm(2) dose (n = 8) PCB (Cotavance, Bayer Pharma AG/MEDRAD, Indianola, Pennsylvania), or with an identical uncoated control balloon (n = 8). At termination (28 days after treatment), the percent diameter stenosis by quantitative vascular analysis in the control group was higher (31.2 ± 13.7%) compared with the 1 μg/mm(2) (19.3 ± 14.0%, 38% reduction) and 3 μg/mm(2) (8.6 ± 10.7%, 72% reduction) PCB groups. Intravascular ultrasound analysis showed 36% (1 μg/mm(2) dose, p = 0.04) and 55% (3 μg/mm(2) dose, p < 0.01) reductions in neointimal volume stenosis. In the histological analysis, the control group showed the highest degree of percent area stenosis (65 ± 14.3%). The reductions in percent area stenosis was 13.2% (p = 0.5) and 26% (p = 0.04) in the 1 μg/mm((2)) and 3 μg/mm(2) dose groups, respectively. The FHS model of iliofemoral ISR demonstrated a dose-dependent effect on the inhibition of neointimal proliferation of a clinically validated PCB technology. This model represents a positive step toward the efficacy evaluation of PCB in the peripheral vascular territory.10/2012; 5(10):1081-8. · 1.07 Impact Factor -
Article: Long term impact of balloon post-dilatation on neointimal formation: an experimental comparative study between 2(nd) generation self-expanding versus balloon-expandable stent technologies.
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ABSTRACT: BACKGROUND: Self-expanding stents (SES) are reemerging as therapeutic alternatives to treat coronary artery disease. It has been proposed that SES can improve clinical outcomes by inducing less injury at implantation and achieving better vessel wall apposition. To date, little data exists comparing the vascular response to both methods of deployment in a controlled experimental setting. OBJECTIVE: To quantify differences in vascular injury and healing between second-generation SES and balloon-expandable stents (BES) and the effects of balloon post-dilation in a porcine coronary model. METHODS: 75 bare SES (AXXESS or vProtect) and 42 BES (Vision) were implanted in porcine coronaries. A subset of these received balloon post-dilation (SES+D=22, BES+D=20). Follow-up was scheduled at 30 (BES=10, BES+D=6, SES=19, SES+D=8), 90 (BES=6, BES+D=8, SES=19, SES+D=8) and 180 days (BES=6, BES+D=6, SES=15, SES+D=6). RESULTS: In vivo imaging and histological analysis showed that neointimal formation peaks early (30 days) in BES. Conversely, for SES, the peak occurred later (90 days). However, the neointimal formation achieved in either group equalized at 180 days. For SES, post-dilation shortened the peak of neointimal formation to 30 days. Conversely, for BES, post-dilation delayed the peak of neointimal formation to 90 days. At 30 days, histology showed that SES had significantly less injury. However, at 90 days, injury scores tended to be higher for SES. By 180 days, injury scores were comparable between both groups. CONCLUSIONS: The mechanism of stent expansion influences the degree of vascular injury and healing. The synergistic use of balloon post-dilation changes the dynamics of healing and may impact the potential beneficial effects inherent to SES technologies. © 2012 Wiley Periodicals, Inc.Catheterization and Cardiovascular Interventions 04/2012; · 2.29 Impact Factor -
Article: Long-term effects on vascular healing of bare metal stents delivered via paclitaxel-coated balloons in the porcine model of restenosis.
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ABSTRACT: Clinical trials have consistently demonstrated benefits of Paclitaxel-coated balloons (PCB) in particular clinical situations such as in-stent restenosis and peripheral vascular interventions. However, the long-term vascular effects of bare metal stents (BMS) delivered via PCB (PCB+BMS) are still unknown. The aim of this study was to assess the long-term effects of PCB+BMS on vascular healing and neointimal formation (NF). A total of 208 stents: 56 BMS crimped on PCB, 50 BMS crimped on uncoated balloons (UCB+BMS), 52 Taxus and 50 Cypher stents were implanted in normal coronary arteries of 104 pigs using 1.2:1.0 stent-to-artery ratio. Follow-up occurred at 3, 7, 28, 90, and 180 days. Vascular effects were assessed based on angiographic and histological analysis. Endothelialization was evaluated using an anti von-Willebrand Factor stain. At 28 days, delivery of a BMS using a PCB led to a significant reduction in NF compared to the UCB+BMS and the Taxus stent (P < 0.01). Between 28 and 180 days, the progression of NF tended to be lower in the PCB+BMS compared to all DES groups. At 90 days, the PCB+BMS (2.56 ± 0.43) and the Taxus stents (2.60 ± 0.59) had a trend toward higher inflammatory scores compared to the UCB+BMS group (1.85 ± 1.13, P = 0.09). By 180 days, inflammation and NF had completely normalized between the groups. Expression of peristrut vWF was comparable among all tested groups at 28 days. The long-term pattern of vascular healing occurring following PCB+BMS deployment appears to be comparable to what has been reported with DES technologies. © 2012 Wiley Periodicals, Inc.Catheterization and Cardiovascular Interventions 04/2012; 80(4):603-10. · 2.29 Impact Factor -
Article: Controlled reperfusion with intravenous bivalirudin and intracoronary abciximab combination therapy in the porcine myocardial infarction model.
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ABSTRACT: The reperfusion injury (RI) remains a significant limitation of primary PCI, therefore we evaluated the role of intracoronary abciximab and bivalirudin for anticoagulation on myocardial salvage and RI in the porcine model of ischemia/reperfusion. Myocardial infarction was induced in 23 pigs by 60-minute over-the-wire (OTW) balloon occlusion of the LAD. Animals received intravenous bivalirudin and then five minutes prior to reperfusion, either a coronary downstream infusion of abciximab (n=11) or saline (n=12) through the central lumen of an OTW catheter. All animals were followed for 48 hours. Histological analysis showed that infarct area (IA) and area at risk (AAR) were comparable between groups (IA/AAR%: 57.6 ± 8% vs. 57.1 ± 7%, p=0.8). Confirming this trend, biochemical markers (troponin I, TNF-alpha, IL-6, hsCRP, adiponectin, and VCAM) and left ventricular ejection fraction were also similar at 48 hours. Adhesion markers like ICAM and P-selectin were significantly decreased in the study group, nevertheless histological evidence of leukocyte extravasation was similar. The enhancement of apoptosis by TUNEL was comparable in both groups. The number of hemorrhagic infarctions confirmed by micro and macroscopic evaluation tended to be higher in the study group (70% vs. 20%, p=0.07). Despite lowered concentrations of adhesion molecules, intracoronary abciximab with peripheral bivalirudin is not superior to bivalirudin unaided in terms of myocardial salvage caused by RI in the porcine ischemia/reperfusion model. This might be due to local hemorrhage caused by abciximab.Thrombosis Research 11/2011; 130(2):265-72. · 2.44 Impact Factor -
Article: Vascular response to zotarolimus-coated balloons in injured superficial femoral arteries of the familial hypercholesterolemic Swine.
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ABSTRACT: Background: Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine. METHODS AND RESULTS: A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation was performed in all superficial femoral artery segments, followed by balloon angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 μg/cm(2)) were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue) after ZCB inflation. In the safety and efficacy study, superficial femoral artery segments were randomized to either high-dose (600 μg/cm(2), n=16), low-dose (300 μg/cm(2), n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low-dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was similar among all tested groups. Histological analysis demonstrated a reduction in neointimal formation in both ZCB groups compared with controls (high-dose ZCB 44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no evidence of delayed arterial healing or vascular toxicity in any of the ZCB groups. CONCLUSIONS: The single delivery of zotarolimus via coated balloon is feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology appears to be effective in the reduction of neointimal proliferation in the superficial femoral artery of the familial hypercholesterolemic swine.Circulation Cardiovascular Interventions 09/2011; 4(5):447-55. · 6.06 Impact Factor -
Article: Paclitaxel-iopromide coated balloon followed by "bail-out" bare metal stent in porcine iliofemoral arteries: first report on biological effects in peripheral circulation.
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ABSTRACT: Despite recent abundance of data on drug-coated balloon technology, the biological effects of paclitaxel coated balloon (PCB) treatment followed by bare metal stent (BMS) implantation in peripheral arteries (simulating bail-out stenting, a common clinical scenario), have not been published. PCB technology containing a paclitaxel-iopromide coating and identical iopromide-coated controls (without paclitaxel) were used in 16 porcine ilio-femoral arteries. The biological effects of inflating one (PCBx1) or two sequential (PCBx2) paclitaxel coated balloons before BMS implantation were compared to the single application of a control balloon (CCBx1; contrast coated balloons). At 30 days PCBx2 displayed significantly reduced late lumen loss by angiography (58% reduction vs. CCBx1; p=0.04) and neointimal area by histomorphometry (35% reduction vs. CCBx1 and 30% vs. PCBx1; p=0.02). Similarly, percent area stenosis in the PCBx2 group was reduced by 45% as compared to CCBx1 and PCBx1 (p=0.04). At this time, all parameters of vessel wall healing (including injury score, inflammation, and endothelialisation) following drug coated balloon treatment were comparable to the control group. Paclitaxel delivery to porcine ilio-femorals using PCB followed by BMS implantation effectively decreased neointimal proliferation. More extensive and prolonged proliferative response of the vessel after stenting (necessitating higher drug dose) could potentially explain the undetectable effect of PEBx1 relative to CCBx1 in this pilot study. Histological analysis confirmed the safety and biocompatibility of PCB technology.EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 07/2011; 7(3):362-8. · 3.29 Impact Factor -
Article: Comparison of adverse cardiovascular events and bleeding complications of loading dose of clopidogrel 300 mg versus 600 mg in stable patients undergoing elective percutaneous intervention (from the CADICE study).
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ABSTRACT: In large clinical trials enrolling patients with acute coronary syndromes, a high loading dose of clopidogrel (600 mg) has been found to be more effective compared to a low loading dose (300 mg). However, the applicability of these data to stable patients who undergo elective percutaneous coronary intervention is still unclear. A total of 400 patients who underwent elective PCI were prospectively randomized to receive either 600 mg (n = 200) or 300 mg (n = 200) of clopidogrel, followed by a daily maintenance dose of 75 mg. The primary end point was the presence of major adverse cardiovascular events (combined death, myocardial infarction, acute neurologic event, stent thrombosis, and need for percutaneous or surgical revascularization of the target vessel) during hospitalization and at 30 days. The secondary end point was periprocedural vascular complications, major bleeding, and cardiac enzyme elevation. There were no differences in the primary end point among the groups immediately after the procedure (3.5% of patients in the 300-mg group vs 4.5% of those in the 600-mg group, p = 0.799) or at 30 days (6% vs 5%, respectively, p = 0.826). The rates of periprocedural vascular complications (2.5% vs 3%, respectively, p = 1.00), bleeding complications (9% vs 8.5%, respectively, p = 1.00), and cardiac enzyme elevation (11% vs 15.5%, respectively, p = 0.317) were similar between the 2 groups. In conclusion, adverse cardiovascular events and bleeding complications during the initial hospitalization and at 30-day follow-up were similar when a 600-mg loading dose of clopidogrel was used compared to the conventional dose of 300 mg.The American journal of cardiology 01/2011; 107(1):6-9. · 3.58 Impact Factor -
Article: Coronary bare metal stent implantation in homozygous LDL receptor deficient swine induces a neointimal formation pattern similar to humans.
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ABSTRACT: To date, most of all new developments in stent technologies are tested in normal animals. Although invaluable in the evaluation of device safety, the juvenile domestic swine (DS) do not follow the biological healing response occurring in humans following coronary stent implantation. By using a novel swine breed afflicted with familial hypercholesterolemia (FHS), we aimed to analyse the vascular response occurring following bare metal stent (BMS) implantation by comparing in vivo endovascular imaging and histological data. A total of 26 swine were included in this study (12 FHS and 14 DS). Sixty eight BMS (FHS=28 versus DS=40) were implanted using a 10% overstretch ratio. Imaging evaluation (IVUS and OCT) was conducted in all animals at 30 (n=14) or 90 (n=12) days following stent implantation. After imaging, the stented coronary segments were harvested for histological evaluation. At 30 days, the degree of neointimal formation analysed by OCT (%AS=DS 21.9 ± 10% versus FHS 25.4 ± 12%; p=0.18) and histology (DS 24.6 ± 10% versus FHS 23.58 ± 10%; p=0.8) was similar between both animal groups. At 90 days, the degree of neointimal formation in the DS group decreased in all analysed variables (-40% in IVUS neointimal volume, -57% in OCT %AS, and -30% in %AS by histology) compared to the progression of neointimal formation observed in the FHS group (+29% in IVUS neointimal volume, +27% in OCT %AS and +43% in %AS by histology). The pattern of neointimal formation following BMS implantation in the FHS follows a progressive course that does not occur in the DS. Therefore, by providing a progressive neointimal biological response to BMS implantation, the FHS could serve as an ideal efficacy model for the validation of drug eluting stent technologies.Atherosclerosis 09/2010; 213(2):518-24. · 3.79 Impact Factor -
Article: Development of a novel prohealing stent designed to deliver sirolimus from a biodegradable abluminal matrix.
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ABSTRACT: We aimed to demonstrate that, by separating endothelial progenitor cell capture from sirolimus delivery through the application of drug to the abluminal surface of the stent, the degree of endothelialization can be enhanced. Stainless steel R Stents, with biodegradable SynBiosys polymer coating with sirolimus abluminally applied and surface modified with anti-CD34 antibody were prepared at 2 dosages (low-dose sirolimus [LD-Combo, 2.5 microg sirolimus/mm] and full-dose sirolimus [Combo, 5 microg sirolimus/mm). These Combo stents and the Cypher stent (10 microg sirolimus/mm) were deployed in 98 normal porcine arteries and harvested for pharmacokinetic analysis at 0.25, 1, 3, 7, 14, 28, and 35 days. The LD-Combo stents showed faster early release (50%total dose in 72 hours) than the Combo and Cypher. At 30 days, drug release was near complete with both Combo stents, whereas 20% of drug remained on the Cypher stents. To assess efficacy, a total of 50 stents (Xience V=8, Cypher=8, Genous bioengineered R stent=6, LD-Combo=14, and Combo=14) were implanted in 18 pigs for 14 and 28 days. Optical coherence tomography was performed, and stents were harvested for histology. At 28 days, there was less neointimal thickness with Combo (0.173+/-0.088 mm) compared with Cypher (0.358+/-0.225 mm), LD-Combo (0.316+/-0.228 mm), and Xience V (0.305+/-0.252 mm; P<0.00001). Immunohistochemical analysis of endothelialization showed that Genous bioengineered R stent had the highest degree of platelet endothelial cell adhesion molecule expression (87%) followed by the Combo (75%), LD-Combo (65%), and Cypher (58%). Both optical coherence tomography and histology demonstrate that anti-CD34 sirolimus-eluting stents promote endothelialization while reducing neointimal formation and inflammation.Circulation Cardiovascular Interventions 06/2010; 3(3):257-66. · 6.06 Impact Factor -
Article: Effects of local intracoronary paclitaxel delivery using the Remedy transport catheter on neointimal hyperplasia after stent implantation in a porcine model.
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ABSTRACT: To assess the effects of local paclitaxel delivery using the Remedy catheter on neointimal hyperplasia in a porcine model and compare these results to commercially available BMS and biodegradable polymer-coated paclitaxel-eluting stents (BP-PES). A total of 31 stents were implanted into coronary arteries of 15 domestic swine including eight BMS, six BP-PES, and 17 BMS after intravasal paclitaxel delivery at doses of 250 μg (LPD250; n=9) and 500 μg (LPD500, n=6). All stents were implanted under quantitative coronary angiography (QCA) guidance to achieve a balloon/artery diameter ratio of 1.15:1.0. Twenty-eight days after the procedure, follow-up coronary angiography was performed, the animals were euthanized, and the coronary arteries harvested for histopathological analysis. At follow-up, QCA analysis revealed that lumen loss was significantly worse in BMS and in both LPD groups in comparison to BP-PES stents (P=.02). Histomorphometric analysis showed that the LPD500 group presented the highest percentage of area stenosis, achieving a statistically significant difference in comparison to BMS and BP-PES stents. Our study demonstrates that local paclitaxel delivery using the Remedy transport catheter in the two studied doses (250 and 500 μg) is not effective at neointimal hyperplasia inhibition.Cardiovascular revascularization medicine: including molecular interventions 12(2):82-9.
Top Journals
Institutions
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2012
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Cardiovascular Research Foundation
New York City, NY, USA
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2011
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Instituto Cardio Neuro Vascular
Medellín, Departamento de Antioquia, Colombia
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