RESUMO
OBJECTIVES: We aimed to compare bare-metal stents (BMS), durable-polymer everolimus-eluting stents (DP-EES), and abluminal biodegradable-polymer sirolimus-eluting stents (ABP-SES) in the bifurcation model setup. BACKGROUND: The mechanism of thrombogenicity, which differs among second-generation stents implanted using double-kissing (DK) crush or culotte stenting techniques, remains unclear. We have shown previously that setting up a porcine arteriovenous shunt model is feasible and useful to assess thrombogenicity at vessel bifurcation points. METHODS: Six porcine shunt models were prepared for the comparison between DK crush and culotte stenting techniques using BMS, DP-EES, and ABP-SES. Intracoronary imaging with high-resolution optical coherence tomography (OCT) was performed to evaluate the thrombogenicity in different stent types in the bifurcation stenting model and was evaluated by a core lab. RESULTS: Culotte stenting demonstrated more thrombogenicity at the proximal main branch (MB) with DP-EES, side branch (SB) with BMS, and the bifurcation site irrespective of the stent type, while DK crush technique exhibited thrombogenicity only at SB with BMS and ABP-SES. OCT analysis revealed malapposition of DP-EES in the proximal MB with culotte stenting. Stent expansion was generally larger in ABP-SES than BMS and DP-EES. CONCLUSIONS: The study provides hypothesis-generating findings in distinct thrombogenicity of bifurcation stenting with DP- or ABP-coated drug-eluting stents.
Assuntos
Stents , Tomografia de Coerência Óptica , Animais , Everolimo , Humanos , Polímeros , Desenho de Prótese , Sirolimo , Suínos , Resultado do TratamentoRESUMO
Nitrate (NO3-) obtained from the diet is converted to nitrite (NO2-) and subsequently to nitric oxide (NO) within the body. Previously, we showed that porcine eye components contain substantial amounts of nitrate and nitrite that are similar to those in blood. Notably, cornea and sclera exhibited the capability to reduce nitrate to nitrite. To gain deeper insights into nitrate metabolism in porcine eyes, our current study involved feeding pigs either NaCl or Na15NO3 and assessing the levels of total and 15N-labeled NO3-/NO2- in various ocular tissues. Three hours after Na15NO3 ingestion, a marked increase in 15NO3- and 15NO2- was observed in all parts of the eye; in particular, the aqueous and vitreous humor showed a high 15NO3- enrichment (77.5 and 74.5%, respectively), similar to that of plasma (77.1%) and showed an even higher 15NO2- enrichment (39.9 and 35.3%, respectively) than that of plasma (19.8%). The total amounts of NO3- and NO2- exhibited patterns consistent with those observed in 15N analysis. Next, to investigate whether nitrate or nitrite accumulate proportionally after multiple nitrate treatments, we measured nitrate and nitrite contents after supplementing pigs with Na15NO3 for five consecutive days. In both 15N-labeled and total nitrate and nitrite analysis, we did not observe further accumulation of these ions after multiple treatments, compared to a single treatment. These findings suggest that dietary nitrate supplementation exerts a significant influence on nitrate and nitrite levels and potentially NO levels in the eye and opens up the possibility for the therapeutic use of dietary nitrate/nitrite to enhance or restore NO levels in ocular tissues.
Assuntos
Suplementos Nutricionais , Nitratos , Nitritos , Animais , Nitratos/metabolismo , Suínos , Nitritos/metabolismo , Olho/metabolismo , Isótopos de Nitrogênio , Córnea/metabolismo , Dieta , Humor Aquoso/metabolismo , Corpo Vítreo/metabolismo , Óxido Nítrico/metabolismo , Ração Animal/análiseRESUMO
BACKGROUND: The aim of this pilot clinical study is to evaluate the safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-coated balloon (M.A. MedAlliance SA, Nyon, Switzerland) for improving the patency of failing arterio-venous fistulas (AVF) in hemodialysis patients. We also present herein a pre-clinical pharmacokinetic and safety evaluation of Selution™ to justify its first use in hemodialysis patients for endovascular access salvage. METHODS AND RESULTS: This is an investigator-initiated prospective single-center, non-blinded single-arm trial. Forty patients with clinically significant de novo or recurrent stenoses in a mature AVF circuit will be recruited. All stenotic lesions will be prepared with high pressure non-compliant conventional balloon angioplasty (CBA) prior to deployment of the Sustained-Release Selution™ sirolimus drug-eluting balloon. The primary efficacy endpoint is 6-month target lesion primary patency and the primary safety endpoint is freedom from localized or systemic serious adverse events through 30 days. Secondary endpoints of interest include technical and clinical success rates and circuit access patency at 3 and 6 months. Follow-up will occur for 2 years for those patients whose AVFs remain patent. Pharmacokinetic and histological animal safety studies performed with the Selution™ coating formulation showed prolonged arterial tissue retention of sirolimus with therapeutic levels up to 60 days and non-toxic and rapidly declining blood levels. Histological results in animal models demonstrated safety, freedom from intraluminal thrombus, reduction in restenosis by sirolimus elution compared to CBA, and no evidence of embolic phenomena indicative of adverse particulate effects. DISCUSSION: Long release sirolimus coated balloons may serve as a promising novel alternative therapy to paclitaxel-based technology for treating conduit stenosis secondary to neointimal hyperplasia. Pre-clinical pharmacokinetic and histological animal data are encouraging and provide suggestion of safety and efficacy in this setting. This single-center trial will provide a first step toward demonstration of efficacy and safety of this device for treatment of stenotic fistulas.
Assuntos
Angioplastia com Balão , Fístula Arteriovenosa , Humanos , Fístula Arteriovenosa/etiologia , Materiais Revestidos Biocompatíveis , Constrição Patológica/etiologia , Paclitaxel , Estudos Prospectivos , Diálise Renal/efeitos adversos , Sirolimo/efeitos adversos , Resultado do Tratamento , Grau de Desobstrução Vascular , Projetos PilotoRESUMO
OBJECTIVES: To evaluate the effect of a polymer-free Biolimus A9-eluting stent [BioFreedom (BF)], compared with that of a biodegradable polymer-based Biolimus A9-eluting stent [BioMatrix Flex (BMF)] and a bare metal stent (BMS) in balloon denuded and radiated hypercholesterolemic rabbit iliac arteries. METHODS: Rabbits were fed with 1% cholesterol diet (n = 14) for 14 days, both iliac arteries were balloon denuded and radiated, and then rabbits were switched to 0.15% cholesterol diet. After 4 weeks, BF (n = 8), BMF (n = 8), and BMS (n = 8) were deployed in denuded and radiated areas. Four weeks later animals were euthanized, arterial segments were processed for morphometry. RESULTS: The neointimal area in vessels implanted with BF stents was significantly less than that seen in vessels implanted with BMS (0.90 mm(2) ± 0.14 vs. 1.29 mm(2) ± 0.23, P <0.01). Percent fibrin and fibrin score were higher with BMF stents compared to BMS (P <0.03 and <0.04) and giant cell number was significantly higher with both BMF and BF stents (P < 0.01 for both). Percent endothelialization was significantly higher and % uncovered struts were lower with BMS compared to either BMF or BF stents (P < 0.05 for both). CONCLUSION: This study demonstrates that compared to BMS, BF stents significantly decreased neointimal hyperplasia.
Assuntos
Implantes Absorvíveis , Angioplastia com Balão/instrumentação , Aterosclerose/terapia , Fármacos Cardiovasculares/administração & dosagem , Stents Farmacológicos , Hipercolesterolemia/complicações , Artéria Ilíaca/patologia , Metais , Polímeros , Sirolimo/análogos & derivados , Stents , Animais , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Constrição Patológica , Modelos Animais de Doenças , Fibrina/metabolismo , Hiperplasia , Artéria Ilíaca/metabolismo , Artéria Ilíaca/efeitos da radiação , Inflamação/patologia , Masculino , Neointima , Placa Aterosclerótica , Desenho de Prótese , Coelhos , Sirolimo/administração & dosagem , Fatores de TempoRESUMO
BACKGROUND/PURPOSE: Coronary artery bypass graft (CABG) in the presence of metallic permanent stents may be challenging. We explored the feasibility of performing CABG in 1-year Magmaris resorbable scaffold implants in healthy Yucatan pigs. METHODS/MATERIALS: One animal received Magmaris 3.0 × 20.0-mm scaffolds in the left anterior descending (LAD), left circumflex (LCx), and right coronary arteries (RCA) under fluoroscopy. After 376 days, the animal underwent off-pump CABG at the scaffold site, including a single "end-to-side" anastomosis involving the right internal mammary artery (RIMA) to the LAD. The LAD was grafted in the territory of the previous scaffold as demonstrated by angiogram and the D1 and D2 landmarks. RESULTS: Digital radiography of the intact heart showed all degraded scaffolds widely expanded and uniformly positioned in the vessel wall in their expected locations. The proximal and distal radiopaque markers were clearly visible. The anastomosis was clearly identified by titanium branch clips, and the RIMA bypass was surrounded by connective tissue, which was further dissected before micro-computed tomography (CT) imaging. On the micro-CT images, calcification of the device was rare. The anastomosis site appeared intact, and the LAD at treatment site was widely open. CONCLUSIONS: Our limited early feasibility study in a healthy animal demonstrates the practicality of CABG in a Magmaris scaffold after 1 year despite the persistence of visible degradation product, suggesting that the prior coronary device implant does not preclude future coronary surgery.
Assuntos
Magnésio , Artéria Torácica Interna , Animais , Ponte de Artéria Coronária , Suínos , Resultado do Tratamento , Microtomografia por Raio-XRESUMO
Nitric oxide (NO) signaling has been studied in the eye, including in the pathophysiology of some eye diseases. While NO production by nitric oxide synthase (NOS) enzymes in the eye has been characterized, the more recently described pathways of NO generation by nitrate (NO3-) and nitrite (NO2-) ions reduction has received much less attention. To elucidate the potential roles of these pathways, we analyzed nitrate and nitrite levels in components of the eye and lacrimal glands, primarily in porcine samples. Nitrate and nitrite levels were higher in cornea than in other eye parts, while lens contained the least amounts. Lacrimal glands exhibited much higher levels of both ions compared to other organs, such as liver and skeletal muscle, and even to salivary glands which are known to concentrate these ions. Western blotting showed expression of sialin, a known nitrate transporter, in the lacrimal glands and other eye components, and also xanthine oxidoreductase, a nitrate and nitrite reductase, in cornea and sclera. Cornea and sclera homogenates possessed a measurable amount of nitrate reduction activity. These results suggest that nitrate ions are concentrated in the lacrimal glands by sialin and can be secreted into eye components via tears and then reduced to nitrite and NO, thereby being an important source of NO in the eye.
Assuntos
Córnea/metabolismo , Aparelho Lacrimal/metabolismo , Nitratos/metabolismo , Nitritos/metabolismo , Esclera/metabolismo , Animais , Feminino , Masculino , Nitrato Redutase/metabolismo , Óxido Nítrico/metabolismo , Nitrito Redutases/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Transdução de Sinais , Suínos , Simportadores/metabolismo , Xantina Desidrogenase/metabolismoRESUMO
BACKGROUND: Double kissing (DK) crush stenting has been reported as a superior bifurcation stenting strategy compared to culotte stenting. However, the mechanism associated with the reduction of clinical events by DK crush stenting remains unclear. We therefore investigated the thrombogenicity of DK crush stenting and culotte stenting with both bare-metal stents (BMS) and drug-eluting stents (DES) and the feasibility of a novel porcine arteriovenous shunt model. METHODS: High-resolution intracoronary imaging with optical coherence tomography (OCT) evaluated the bifurcation stenting models for thrombogenicity. RESULTS: All porcine models retained continuous circulation without blood leakage. Thrombus was macroscopically demonstrated around the bifurcation in all settings. The volume of thrombus (mm3) with BMS using DK crush/culotte and DES using DK crush/culotte were 1.38/1.19 and 0.09/0.15, respectively. Culotte stenting had more thrombus in the proximal main branch, and DK crush stenting had more at the bifurcation. Unlike DK crush stenting, culotte stenting showed malapposition in the proximal main branch and bifurcation segments. CONCLUSION: The feasibility of a porcine arteriovenous shunt model to assess thrombogenicity by OCT in bifurcation stenting technique was confirmed. OCT detected less thrombogenicity in DES when used in the bifurcation model when compared to BMS.
Assuntos
Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Stents , Trombose/diagnóstico por imagem , Tomografia de Coerência Óptica , Animais , Artérias Carótidas/cirurgia , Stents Farmacológicos , Estudos de Viabilidade , Veias Jugulares/cirurgia , Metais , Modelos Animais , Valor Preditivo dos Testes , Estudo de Prova de Conceito , Desenho de Prótese , Sus scrofa , Trombose/etiologia , Fatores de TempoRESUMO
AIMS: The present study aimed to investigate whether the Magmaris resorbable magnesium scaffold (RMS) has platelet-repelling properties by comparing its acute thrombogenicity with an equivalent stainless steel stent in an arteriovenous shunt model. METHODS AND RESULTS: An ex vivo porcine carotid jugular arteriovenous shunt was established and connected to Sylgard tubing containing the Magmaris RMS with sirolimus-eluting PLLA coating and an equivalent 316L stainless steel stent with sirolimus-eluting PLLA coating. Six shunts (two shunt runs per pig) were run comparing the two scaffolds (n=9) in alternating order. Nested generalised linear mixed models were employed to compare variables between scaffold groups. Confocal fluorescent microscopy containing CD61/CD42b demonstrated that the 316L equivalent stent had significantly greater platelet coverage of the total scaffold compared with Magmaris (5.8% vs. 2.8%, adjusted rate ratio 2.21 [1.41, 3.47], p=0.012). Scanning electron microscopy demonstrated significantly greater thrombus deposition on the 316L equivalent stent as a percentage of the total scaffold compared with Magmaris (8.0% vs. 5.3%, p=0.009). Magmaris also had significantly less CD14 positive monocyte deposition and a trend towards less PM-1 positive neutrophil compared with the 316L equivalent stent. CONCLUSIONS: Magmaris has less thrombogenicity and inflammatory cell deposition compared with the equivalent 316L stainless steel (in geometry and design) stent in a porcine arteriovenous shunt model. These data suggest that resorbable magnesium scaffolds may have inherent properties that reduce adhesion of platelets and inflammatory cells.
Assuntos
Fístula Arteriovenosa , Trombose , Animais , Magnésio , Aço Inoxidável , Stents , SuínosRESUMO
OBJECTIVE: We aimed to evaluate an effective dosage and safety profile of pimecrolimus as an anti-inflammatory drug for drug-eluting stents. METHODS: In the dose finding study, coronary arteries of 20 domestic swine were randomly implanted with bare metal stents (ProKinetic and Guidant Vision), the ProKinetic stent with polylactic acid (PLLA), and pimecrolimus-eluting stents (32, 75, and 120 microg) over a period of 4 weeks. In addition, pimecrolimus (75 microg) and ProKinetic stents were randomly implanted into six swine over 3 months. In the safety study, the ProKinetic stent, the ProKinetic stent with PLLA, mid- (45 microg) and high-dose pimecrolimus (120 microg), and overlapping mid-dose stents were implanted over a period of 4 weeks. Mid-dose, ProKinetic stent, and ProKinetic stent with PLLA were implanted over a period of 3 months. RESULTS: The dose finding study revealed excellent luminal patency with low percent occlusion (approximately 29% vs. approximately 41%), injury (0.53-0.59 vs. 1.25), and inflammation (0.78-0.97 vs. 1.08) for the pimecrolimus group compared with the vision group. The safety study arm showed similar angiographic results for all tested groups, with a significantly larger minimal lumen diameter for pimecrolimus stents compared to PLLA stents. Except for the high-dose group and overlapping area of the overlapping group, promising morphometric results were found for pimecrolimus compared to bare metal stents. CONCLUSIONS: Present data suggest that pimecrolimus-eluting stents are safe and have a similar healing profile to bare metal stents. They may suppress inflammation, leading to a reduced intimal response and a milder inflammatory reaction in a porcine model.
Assuntos
Anti-Inflamatórios/administração & dosagem , Doença das Coronárias/terapia , Vasos Coronários/efeitos dos fármacos , Stents Farmacológicos , Tacrolimo/análogos & derivados , Cicatrização/efeitos dos fármacos , Análise de Variância , Animais , Angiografia Coronária , Doença das Coronárias/patologia , Vasos Coronários/patologia , Modelos Animais de Doenças , Distribuição Aleatória , Estatísticas não Paramétricas , Suínos , Tacrolimo/administração & dosagem , Fatores de Tempo , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologia , Ultrassonografia de Intervenção , Grau de Desobstrução VascularRESUMO
BACKGROUND: A comparison in acute thrombogenicity between the Magmaris sirolimus-eluting bioabsorbable magnesium scaffold and the Absorb bioresorbable vascular scaffold has not been performed. This study assessed acute thrombogenicity of Magmaris compared with Absorb and the Orsiro hybrid drug-eluting stent in a porcine arteriovenous shunt model. METHODS AND RESULTS: An ex vivo porcine carotid jugular arteriovenous shunt was established and connected to SYLGARD tubing containing the Magmaris, Absorb, and Orsiro scaffolds/stents and allowed to run in the shunt for a maximum of 1 hour. Twelve shunts (2 shunt runs per pig) were run comparing the 3 scaffolds in alternating order. Nested generalized linear mixed models were used to compare variables between scaffold groups while adjusting for variability between shunt runs. Confocal fluorescent microscopy costaining CD61/CD42b demonstrated that both Magmaris (3.0%) and Orsiro (4.6%) had less platelet coverage of the total scaffold compared with Absorb (21.8%). Scanning electron microscopy demonstrated significantly less thrombus deposition to Magmaris as a percentage of the total scaffold compared with Absorb (5.0% versus 16.1%, P=0.02). Magmaris had significantly less PM-1-positive neutrophil and CD14-positive monocyte adherence compared with both Orsiro and Absorb. Orsiro had significantly less monocyte deposition compared with Absorb. CONCLUSIONS: Despite a similar scaffold strut thickness, the Magmaris sirolimus-eluting bioabsorbable magnesium scaffold was significantly less thrombogenic compared with the Absorb bioresorbable vascular scaffold in an ex vivo porcine arteriovenous shunt model. Further studies are needed to determine whether the reduced thrombogenicity of Magmaris will result in reductions in major cardiovascular events.
Assuntos
Stents Farmacológicos/efeitos adversos , Magnésio , Trombose/etiologia , Alicerces Teciduais/efeitos adversos , Animais , Adesão Celular , Microscopia Eletrônica de Varredura , Suínos , Trombose/patologiaRESUMO
BACKGROUND: Everolimus is an orally active derivative of sirolimus. Oral administration of rapamycin is efficacious in the reduction of neointima formation and clinical restenosis; however, its optimal dose and duration have not been determined. METHODS: New Zealand White rabbits were divided into three groups. The first (low-dose) group received 1.5 mg/kg everolimus 1 day before stenting, followed by 0.75 mg/kg/day everolimus for 28 days. The second (high-dose) group received 6 mg/kg everolimus 1 day before, on the day of, and on the day after stenting, followed by 2 mg/kg/day for 4 days. The third (placebo) group received a matching volume of vehicle similar to that of Group 2. Twenty-eight days after stenting, animals were euthanized and morphometry was performed. RESULTS: In the high-dose group, circulating everolimus levels corresponded with administrated dose levels; by Day 12, no circulating everolimus could be detected. In the low-dose everolimus group, levels remained constant up to 28 days. When compared with placebo, low-dose everolimus was associated with a significant reduction in medial thickness (32%), neointimal area (60%), and percent stent stenosis (33%); however, high-dose everolimus had no significant effect. CONCLUSIONS: In conclusion, oral everolimus suppresses in-stent neointimal growth in rabbit iliac arteries. Four weeks of low-dose everolimus is more effective than 7 days of high-dose everolimus.
Assuntos
Oclusão de Enxerto Vascular/prevenção & controle , Artéria Ilíaca/efeitos dos fármacos , Imunossupressores/administração & dosagem , Sirolimo/análogos & derivados , Stents , Túnica Íntima/efeitos dos fármacos , Administração Oral , Animais , Implante de Prótese Vascular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Everolimo , Oclusão de Enxerto Vascular/sangue , Oclusão de Enxerto Vascular/fisiopatologia , Artéria Ilíaca/metabolismo , Artéria Ilíaca/patologia , Artéria Ilíaca/cirurgia , Imunossupressores/sangue , Masculino , Coelhos , Sirolimo/administração & dosagem , Sirolimo/sangue , Fatores de Tempo , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Túnica Íntima/cirurgia , Túnica Média/efeitos dos fármacos , Túnica Média/cirurgia , Grau de Desobstrução Vascular/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVES: Secreted growth factors and cell-to-cell contact are both required to elicit cellular functions. We tested the hypothesis that bone-marrow-derived growth factors, together with cell-to-cell contact between bone-marrow-derived stem cells and cardiomyocytes or myoblasts, promote the proliferation of cardiomyocytes and myoblasts. METHODS: Human cardiomyocytes or skeletal myoblasts were cultured for 4 days in the presence of low and high concentrations of bone-marrow-derived mononuclear cell conditioned medium (MNC-CM) or marrow stromal cell conditioned medium (MSC-CM). The concentrations of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), hepatocyte growth factor (HGF), and insulin-like growth factor-1 in their respective conditioned media were assayed by enzyme-linked immunosorbent assay. Stem cells were mixed with cardiomyocytes or skeletal myoblasts at a 1:1 ratio and cultured for 7 days to assess the proliferation of these cells. In parallel experiments, equal numbers of various cell types were cultured alone. RESULTS: The concentrations of VEGF, MCP-1, and HGF increased in MNC-CM and MSC-CM. MNC-CM showed no effect on cardiomyocyte proliferation. A low concentration of MSC-CM increased cardiomyocyte proliferation by 60% (P<.05). Low concentrations of MNC-CM or MSC-CM showed a trend toward an increased proliferation of myoblasts. A high concentration of either conditioned medium showed a toxic effect. In contact coculture, the proliferation of cardiomyocytes and MNC showed no synergistic effect; instead, there was some evidence of inhibition. The proliferation of cardiomyocytes and stromal cells showed an additive effect. Myoblasts in contact coculture with MNC or MSC showed no synergistic effect. CONCLUSION: These in vitro results suggest that paracrine effects may be the mechanism by which stromal cells become beneficial in cardiac therapy. MNC do not induce the proliferation of cardiomyocytes. Stem-cell-secreted growth factors induce the proliferation of myoblasts, which is not influenced by cell-to-cell contact.
Assuntos
Células da Medula Óssea/metabolismo , Mioblastos Esqueléticos/fisiologia , Miócitos Cardíacos/fisiologia , Células-Tronco/metabolismo , Análise de Variância , Células Cultivadas , Quimiocina CCL2/metabolismo , Ensaio de Imunoadsorção Enzimática , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Técnicas In Vitro , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Mioblastos Esqueléticos/metabolismo , Miócitos Cardíacos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
INTRODUCTION: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia-reperfusion murine myocardial infarction model. METHODS: Mice underwent ischemia-reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. RESULTS: The mean size of the liposomes was 100nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163±31% vs. 13±14%, p=0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. CONCLUSIONS: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.
Assuntos
Albuminas/farmacocinética , Meios de Contraste/farmacocinética , Corantes Fluorescentes/farmacocinética , Gadolínio DTPA/farmacocinética , Imageamento por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Miocárdio/metabolismo , Imagem Óptica/métodos , Fosfatidiletanolaminas/farmacocinética , Albuminas/administração & dosagem , Animais , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Corantes Fluorescentes/administração & dosagem , Gadolínio DTPA/administração & dosagem , Imuno-Histoquímica , Injeções Intravenosas , Lipossomos , Masculino , Camundongos , Microscopia de Fluorescência , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Nanopartículas , Tamanho da Partícula , Fosfatidiletanolaminas/administração & dosagem , Distribuição TecidualRESUMO
The aim of this retrospective, observational analysis was to compare the efficacy and safety of 3 antithrombotic regimens: bivalirudin, eptifibatide plus heparin, and heparin alone, with emphasis on preventing interventional procedural creatinine kinase-MB fraction (CK-MB) release, and consequently, myocardial necrosis.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Hirudinas/análogos & derivados , Isquemia Miocárdica/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Peptídeos/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Eptifibatida , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Heparina/administração & dosagem , Heparina/efeitos adversos , Hirudinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Fragmentos de Peptídeos/efeitos adversos , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We investigated the effect of contrast media on bone marrow-derived cell viability, growth factor secretion, and myoblast viability. Bone marrow was exposed to contrast media, mononuclear cells were isolated, viability was assessed by Trypan blue exclusion or cultured for 4 weeks, and conditioned medium was assayed for vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1). Skeletal myoblasts viability was assessed after exposing them to contrast media. In separate experiments, bone marrow or bone marrow-derived mononuclear cells were exposed to contrast media, cultured for 40 hr, then assessed for viability. None of the contrast media tested had any effect on bone marrow-derived cell viability. Hypaque or Hexabrix increased myoblasts viability by 8-10%. VEGF and MCP-1 concentrations in the conditioned medium increased in a time-related manner. These findings support the concept that for cell therapy, bone marrow cells or myoblasts may be mixed with contrast media and injected into ischemic myocardium without compromise in viability or function.
Assuntos
Células da Medula Óssea/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Meios de Contraste/farmacologia , Mioblastos Esqueléticos/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Células da Medula Óssea/metabolismo , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Suínos , Fatores de TempoRESUMO
Aortic valve annular complex was rediscovered after the introduction of transcatheter aortic valve replacement; and imaging has been crucial in determining the annular geometry. Although the procedure has evolved, complications related to the annular mechanical response following valve implantation, such as aortic insufficiency, still occur in practice. We documented the feasibility of invasive assessment of aortic valve annular complex and the detection of induced aortic insufficiency via intravascular ultrasound with ChromaFlo® technology in a porcine model.
Assuntos
Insuficiência da Valva Aórtica/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Cateterismo Cardíaco/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Ultrassonografia de Intervenção/métodos , Animais , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/fisiopatologia , Cateterismo Cardíaco/instrumentação , Modelos Animais de Doenças , Estudos de Viabilidade , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/instrumentação , Valor Preditivo dos Testes , SuínosRESUMO
BACKGROUND: Injection of bone marrow cells (BMC) and endothelial progenitor cells (EPC) or application of stem-cell-mobilizing factors has been associated both with reduction or exacerbation of atherosclerosis and with unstable plaque phenotype. The discrepancies may reflect the cell type, dosing, duration, and route of administration of cells in these studies. The aim of this study was to determine the effects of peripheral-blood-derived endothelial progenitor cells (PBEPC) or unfractionated BMC obtained from inbred siblings on neointimal formation and inflammation in cholesterol-fed, balloon-denuded, and radiated rabbit iliac arteries. METHODS: Rabbits were fed a 1.0% cholesterol diet for 14 days, followed by endothelial denudation in both iliac arteries, and continued on a 0.15% cholesterol diet. On day 42, denuded areas were radiated, and animals were randomized. The first group received PBEPC (n=5), the second group received BMC (n=4), and the third group received heparinized (20 IU) saline (Control; n=3). PBEPC were characterized by flow cytometry. Cells (5x10(6)) or saline was administered twice through the ear vein: the first time at 1 h after radiation and the second time at 2 weeks after radiation. Four weeks after radiation, the animals were sacrificed, and arterial segments were processed for morphometry. RESULTS: Administration of BMC or PBEPC from inbred siblings had no adverse effect. Lumen area (0.93+/-0.53 mm(2)), neointimal area (0.65+/-0.29 mm(2)), percent stenosis (44+/-21), and macrophage score (0.6+/-0.3) in controls were similar to those in cell-treated groups. CONCLUSION: This study demonstrates that, in the current animal model, either PBEPC or BMC failed to affect neointimal formation or inflammation.
Assuntos
Aterosclerose/prevenção & controle , Transplante de Medula Óssea , Células Endoteliais/transplante , Transplante de Células-Tronco Hematopoéticas , Artéria Ilíaca/patologia , Inflamação/prevenção & controle , Túnica Íntima/patologia , Angioplastia com Balão/efeitos adversos , Animais , Aterosclerose/etiologia , Aterosclerose/patologia , Células Cultivadas , Colesterol/administração & dosagem , Constrição Patológica , Modelos Animais de Doenças , Hiperplasia , Artéria Ilíaca/lesões , Artéria Ilíaca/efeitos da radiação , Inflamação/etiologia , Inflamação/patologia , Macrófagos/patologia , Masculino , Coelhos , Túnica Íntima/lesões , Túnica Íntima/efeitos da radiaçãoRESUMO
BACKGROUND: Biocorrodible iron stents carry the potential to overcome limitations, such as chronic inflammation and premature recoil, posed by biodegradable polymer and magnesium alloy stents. This study aimed to test the safety and efficacy of biocorrodible iron stents in porcine coronary arteries. METHODS: Iron stents and cobalt chromium stents were randomly deployed in the coronary arteries of juvenile domestic pigs. Animals were sacrificed at 28 days, and the vessels were fixed and processed for histochemistry. RESULTS: At 28 days, iron stents started to show signs of degradation without evidence of stent particle embolization or thrombosis without traces of excess inflammation, or fibrin deposition. At 28 days, the surface of the iron stent struts was black to brown and the vascular wall adjacent to the iron stent had a brownish tinge. There were no statistically significant differences in any of the measured parameters between segments implanted with iron and cobalt chromium stents. There were also no adverse effects in the persistent areas. CONCLUSION: The current study demonstrates that stents made of biocorrodible iron are safe. In some of the measured parameters, such as intimal thickness, intimal area, and percentage occlusion, there was a trend in favor of the iron stents.
Assuntos
Materiais Biocompatíveis/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/patologia , Compostos de Ferro , Stents , Animais , Cromo , Cobalto , Reestenose Coronária/etiologia , Trombose Coronária/etiologia , Fibrina , Inflamação/etiologia , Stents/efeitos adversos , SuínosRESUMO
BACKGROUND: Absorbable metallic stents (AMS) composed of magnesium alloy were designed to complete degradation within 90-120 days. Among the potential advantages of these stents, when compared to conventional stents, are the elimination of late stent thrombosis, chronic inflammation, and artifacts during noninvasive imaging. METHODS: Magnesium-based AMS were deployed in juvenile domestic pig coronary arteries. Angiography, optical coherence tomography (OCT), and intravascular ultrasound (IVUS) were performed before and after implant and then at 28 days and 3 months following stenting. The animals were sacrificed at 28 days or 3 months following stent implantation. Stented vessels were harvested and analyzed by histomorphometry. RESULTS: Over time, OCT, IVUS, and histologic images revealed a progressive degradation of the stents. Mean stent strut width in the OCT images after implantation was 0.24+/-0.032 mm, then decreased to 0.12+/-0.007 mm (P<.0001) at 28 days and to 0.151+/-0.032 mm at 3 months (P<.0001 vs. implant, P=.078 vs. 28 days). CONCLUSION: Magnesium-based AMS degrade over a 3-month time period in a porcine model. Its structure is not apparent by angiography but is well-visualized by OCT and IVUS. OCT allowed quantitative assessment of stent degradation.
Assuntos
Implantes Absorvíveis , Ligas , Angioplastia Coronária com Balão/instrumentação , Vasos Coronários/patologia , Magnésio , Stents , Tomografia de Coerência Óptica , Ultrassonografia de Intervenção , Animais , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Teste de Materiais , Modelos Animais , Desenho de Prótese , Sus scrofa , Fatores de TempoRESUMO
BACKGROUND: Platelet-derived peptide and nonpeptide growth factors are known to play pivotal roles in neointimal proliferation. Along with its antiplatelet activity of reducing P-selectin and hs-CRP, clopidogrel has also been shown to have anti-inflammatory properties. The aim of this study is to find out by modulating inflammation if clopidogrel can affect neointima formation in balloon-denuded iliac arteries of hypercholesterolemic rabbits. METHODS AND RESULTS: Rabbits were fed with 1% cholesterol diet with (n = 20) or without (n = 20) clopidogrel (10 mg/kg body weight) for 7 days followed by balloon-denudation of endothelial layer in both the iliac arteries and continued on 0.15% cholesterol diet with or without clopidogrel. Four weeks later, the denuded area in both iliac arteries was radiated (n = 11, cholesterol-only group; n = 9, clopidogrel group) or sham treated (n = 10 from each group). Four weeks after radiation, animals were sacrificed and arterial segments were processed for morphometry. In the sham-treated clopidogrel group, neointimal area, percent stenosis, and macrophage score were 39% (P = 0.01), 32% (P = 0.02), and 50% (P = 0.02) smaller, respectively, when compared to the cholesterol-only group (0.48 +/- 0.18, 32.42 +/- 13.04, and 1.5 +/- 0.83). There were no differences in the radiated group (0.89 +/- 0.32, 50.34 +/- 13.00, and 1.88 +/- 1.27 vs. 0.93 +/- 0.38, 59.41 +/- 11.41, and 2.00 +/- 0.74, respectively). CONCLUSION: This study demonstrates that clopidogrel reduces inflammation and neointimal formation in balloon-denuded iliac arteries of hypercholesterolemic rabbits.