Dual platelet antiaggregation therapy after myocardial revascularization surgery.

Coronary artery bypass graft (CABG) is a consolidated treatment in patients with coronary artery disease (CAD) for both symptom control and improvement of prognosis. The patency of venous grafts is still the most vulnerable point of the surgical treatment since it presents a high prevalence of occlusion both in the immediate postoperative period and in the long-term follow-up. Aspirin plays a well-established role in this setting, and for a long time, clopidogrel use has been restricted to patients allergic to aspirin. Recently, subgroup analyses of studies with different anti-platelet therapies have shown reduced mortality and cardiovascular events in patients on dual anti-platelet antiplatelet therapy (DAPT) undergoing CABG, although such studies have not been designed to evaluate this patient profile. However, there is still an insufficient number of randomized studies using DAPT in this context, resulting in a disagreement between the European and American cardiology societies guidelines regarding their indication and generating doubts in clinical practice.

Dual platelet antiaggregation therapy after myocardial revascularization surgery

SUMMARY Coronary artery bypass graft (CABG) is a consolidated treatment in patients with coronary artery disease (CAD) for both symptom control and improvement of prognosis. The patency of venous grafts is still the most vulnerable point of the surgical treatment since it presents a high prevalence of occlusion both in the immediate postoperative period and in the long-term follow-up. Aspirin plays a well-established role in this setting, and for a long time, clopidogrel use has been restricted to patients allergic to aspirin. Recently, subgroup analyses of studies with different anti-platelet therapies have shown reduced mortality and cardiovascular events in patients on dual anti-platelet antiplatelet therapy (DAPT) undergoing CABG, although such studies have not been designed to evaluate this patient profile. However, there is still an insufficient number of randomized studies using DAPT in this context, resulting in a disagreement between the European and American cardiology societies guidelines regarding their indication and generating doubts in clinical practice.

RESUMO A cirurgia de revascularização miocárdica (CRM) é tratamento fundamental em pacientes com doença arterial coronariana (DAC) tanto para controle de sintomas quanto para melhora do prognóstico. A patência dos enxertos venosos ainda hoje é o ponto mais vulnerável do tratamento cirúrgico, por apresentar alta prevalência de oclusão tanto no pós-operatório imediato como no seguimento em longo prazo. A aspirina tem papel bem estabelecido neste cenário e, por muito tempo, o uso do clopidogrel ficou restrito a pacientes alérgicos a aspirina. Recentemente, análises de subgrupos de estudos com diferentes terapias antiplaquetárias demonstraram redução de mortalidade e eventos cardiovasculares em pacientes em uso de dupla antiagregação plaquetária (Dapt) submetidos à CRM, ainda que tais estudos não tenham sido desenhados para avaliar este perfil de pacientes. Contudo, há ainda uma quantidade insuficiente de estudos randomizados com uso de Dapt nesse contexto, resultando em uma discordância entre as diretrizes europeia e americana de cardiologia quanto à sua indicação e gerando dúvidas na prática clínica.

Rapamycin Combined with α-Cyanoacrylate Contributes to Inhibiting Intimal Hyperplasia in Rat Models / Rapamicina em Combinação com α-Cianoacrilato Contribui à Inibição de Hiperplasia Intimal em Modelos em Ratos

Abstract Background: Vein graft restenosis has an adverse impact on bridge vessel circulation and patient prognosis after coronary artery bypass grafting. Objectives: We used the extravascular supporter α-cyanoacrylate (α-CA), the local application rapamycin/sirolimus (RPM), and a combination of the two (α-CA-RPM) in rat models of autogenous vein graft to stimulate vein graft change. The aim of our study was to observe the effect of α-CA, RPM, and α-CA-RPM on vein hyperplasia. Methods: Fifty healthy Sprague Dawley (SD) rats were randomized into the following 5 groups: sham, control, α-CA, RPM, and α-CA-RPM. Operating procedure as subsequently described was used to build models of grafted rat jugular vein on carotid artery on one side. The level of endothelin-1 (ET-1) was determined by enzyme-linked immunosorbent assay (ELISA). Grafted veins were observed via naked eye 4 weeks later; fresh veins were observed via microscope and image-processing software in hematoxylin-eosin (HE) staining and immunohistochemistry after having been fixed and stored" (i.e. First they were fixed and stored, and second they were observed); α-Smooth Muscle Actin (αSMA) and von Willebrand factor (vWF) were measured with reverse transcription-polymerase chain reaction (RT-PCR). Comparisons were made with single-factor analysis of variance and Fisher's least significant difference test, with p < 0.05 considered significant. Results: We found that intimal thickness of the α-CA, RPM, and α-CA-RPM groups was lower than that of the control group (p < 0.01), and the thickness of the α-CA-RPM group was notably lower than that of the α-CA and RPM groups (p < 0.05). Conclusion: RPM combined with α-CA contributes to inhibiting intimal hyperplasia in rat models and is more effective for vascular patency than individual use of either α-CA or RPM.

Resumo Fundamento: Reestenose de enxertos venosos tem um impacto adverso na circulação de pontagens e no prognóstico de pacientes após a cirurgia de revascularização miocárdica. Objetivos: Nós utilizamos α-cianoacrilato (α-CA) como suporte extravascular, rapamicina/sirolimus (RPM) como aplicação local e a combinação dos dois (α-CA-RPM) em modelos de enxerto venoso autógeno em ratos para estimular mudança no enxerto venoso. O objetivo do nosso estudo foi observar o efeito de α-CA, RPM e α-CA-RPM na hiperplasia venosa. Métodos: Cinquenta ratos Sprague Dawley (SD) saudáveis foram randomizados nos 5 grupos seguintes: sham, controle, α-CA, RPM e α-CA-RPM. O procedimento operacional descrito subsequentemente foi utilizado para construir modelos de enxertos da veia jugular na artéria carótida em ratos, em um lado. O nível de endotelina-1 (ET-1) foi determinado por ensaio de imunoabsorção enzimática (ELISA). As veias enxertadas foram observadas a olho nu 4 semanas após; as veias frescas foram observadas via microscópio e software de processamento de imagem com coloração hematoxilina-eosina (HE) e imuno-histoquímica depois de serem fixadas e armazenadas; α-actina do músculo liso (αSMA) e o fator de von Willebrand (vWF) foram medidos com reação em cadeia da polimerase-transcriptase reversa (RT-PCR). Realizaram-se as comparações com análise de variância de fator único (ANOVA) e o teste de diferença mínima significativa (LSD) de Fisher, com p < 0,05 sendo considerado estatisticamente significante. Resultados: Nós achamos que a espessura intimal nos grupos α-CA, RPM e α-CA-RPM era menor que no grupo controle (p < 0,01) e a espessura no grupo α-CA-RPM era notavelmente menor que nos grupos α-CA e RPM (p < 0,05). Conclusão: A combinação de RPM e α-CA contribui à inibição de hiperplasia em modelos em ratos e é mais efetivo para patência vascular que uso individual de α-CA ou RPM.

Rapamycin Combined with α-Cyanoacrylate Contributes to Inhibiting Intimal Hyperplasia in Rat Models.

BACKGROUND: Vein graft restenosis has an adverse impact on bridge vessel circulation and patient prognosis after coronary artery bypass grafting. OBJECTIVES: We used the extravascular supporter α-cyanoacrylate (α-CA), the local application rapamycin/sirolimus (RPM), and a combination of the two (α-CA-RPM) in rat models of autogenous vein graft to stimulate vein graft change. The aim of our study was to observe the effect of α-CA, RPM, and α-CA-RPM on vein hyperplasia. METHODS: Fifty healthy Sprague Dawley (SD) rats were randomized into the following 5 groups: sham, control, α-CA, RPM, and α-CA-RPM. Operating procedure as subsequently described was used to build models of grafted rat jugular vein on carotid artery on one side. The level of endothelin-1 (ET-1) was determined by enzyme-linked immunosorbent assay (ELISA). Grafted veins were observed via naked eye 4 weeks later; fresh veins were observed via microscope and image-processing software in hematoxylin-eosin (HE) staining and immunohistochemistry after having been fixed and stored" (i.e. First they were fixed and stored, and second they were observed); α-Smooth Muscle Actin (αSMA) and von Willebrand factor (vWF) were measured with reverse transcription-polymerase chain reaction (RT-PCR). Comparisons were made with single-factor analysis of variance and Fisher's least significant difference test, with p < 0.05 considered significant. RESULTS: We found that intimal thickness of the α-CA, RPM, and α-CA-RPM groups was lower than that of the control group (p < 0.01), and the thickness of the α-CA-RPM group was notably lower than that of the α-CA and RPM groups (p < 0.05). CONCLUSION: RPM combined with α-CA contributes to inhibiting intimal hyperplasia in rat models and is more effective for vascular patency than individual use of either α-CA or RPM.

New Regenerative Vascular Grafts for Hemodialysis Access: Evaluation of a Preclinical Animal Model.

The purpose of this study was to evaluate a suitable animal model for the in vivo evaluation of patency and vascular tissue regeneration in small intestinal submucosa (SIS) vascular grafts for hemodialysis access. First, a 4-mm U-shaped SIS vascular graft was implanted between the internal carotid artery (CA) and the external jugular vein (JV) in five sheep and six swine. The U-shape grafts remained functional for 53 ± 4 days in sheep and 32 ± 2 days in swine. The sheep model presented exaggerated inflammation, so the swine model was selected for the in vivo study. Based on these initial results, a 4-mm C-shape SIS vascular graft with SIS circumferential reinforcement was developed to mechanically improve the vascular graft and manage complications identified during surgery in both sheep and swine. The C-shape vascular graft was implanted in a swine model (n = 3) between the CA and JV. GORE-TEX® vascular grafts were used as controls in the contralateral side of the neck. C-shape grafts remained patent for 47 ± 4 days, whereas the GORE-TEX® grafts were patent for 30 ± 15 days. The C-shape vascular graft was easier to handle during surgery, and its circumferential reinforcement improved in vivo patency, avoiding kinks in the graft after implantation. Histological results showed neovascularization and some regeneration with the alignment of endothelial cells in the vascular wall of the grafts. The model developed may be helpful in other research involving in vivo studies of vascular grafts for hemodialysis access.

Coronary stent stenosis in acute myocardial infarction.

Acute myocardial infarction (AMI) represents one of the major mortality causes in the world. Treatment of AMI is widely known; however, in developing countries some medications are not so easily available yet. We present a case of a 49-year-old black male patient who suffered an AMI and 2 weeks after stent angioplasty evolved to a new ischaemic episode with a stent thrombosis. The patient did not use the prescribed medications.

Vascular access in haemodialysis: strengthening the Achilles' heel.

Despite all the progress achieved since Scribner first introduced the arteriovenous (AV) shunt in 1960 and Cimino and Brescia introduced the native AV fistula in 1962, we have continued to face a conundrum in vascular access for dialysis, in that dialysis vascular access is at the same time both the 'lifeline' and the 'Achilles' heel' of haemodialysis. Indeed, findings from a multitude of published articles in this area, unfortunately mainly observational studies, reflect both our frustration and our limited knowledge in this area. Despite improved understanding of the pathophysiology of stenosis and thrombosis of the vascular access, we have unfortunately not been very successful in translating these advances into either improved therapies or a superior process of care. As a result, we continue to face an epidemic of arteriovenous fistula (AVF) maturation failure, a proliferation of relatively ineffective interventions such as angioplasty and stent placement, an extremely high incidence of catheter use, and more doubts rather than guidance with regard to the role (or lack thereof) of surveillance. An important reason for these problems is the lack of focused translational research and robust randomized prospective studies in this area. In this Review, we will address some of these critical issues, with a special emphasis on identifying the best process of care pathways that could reduce morbidity and mortality. We also discuss the potential use of novel therapies to reduce dialysis vascular access dysfunction.

Transhepatic venous approach for balloon-assisted cervical collateral venous access.

Central venous catheter placement is indicated in many situations, and an increasing number of patients require temporary and long-term central catheters. Frequently, patients who have undergone multiple central veins catheterizations develop complete and diffuse venous occlusion, and this constitutes a difficult-to-manage clinical problem. We report a case of a 20-year-old patient who was referred to our department for central venous line placement who manifested bilateral femoral, jugular, and subclavian veins occlusion. A central venous catheter was implanted through a cervical collateral vein, targeting on and puncturing an angioplasty balloon, and advanced into the collateral vein through a transhepatic venous access.

Emerging drugs for coronary restenosis: the role of systemic oral agents the in stent era.

Introduction of drug eluting stents (DES) during percutaneous coronary interventions significantly reduces the rate of angiographic restenosis, target lesion and vessel revascularization. In spite of these benefits, other clinical hard end points such as death or myocardial infarction were not reduced and, furthermore, new concerns associated with the presence of late and very late stent thrombosis have been raised. The requirement of long-term dual antiplatelet therapy is another limitation associated with DES. Conversely, in this decade, other options to DES have been simultaneously discussed in observational and randomized studies. Several registries and randomized trials using the systemic approach with anti-inflammatory, immunosuppressive or antiplatelet therapies have been identified and discussed in this manuscript. In spite of all randomized studies with oral therapies in the bare metal stent (BMS) era demonstrating positive reductions in coronary restenosis, this practice has not been introduced clinically. Furthermore, a recent randomized trial comparing oral sirolimus plus BMS versus DES demonstrated that the first approach was cost saving and of comparable efficacy to DES. Conclusive evidence of high incidence of late and very late stent thrombosis with DES, together with clinical limitations for its widespread use, has opened up a large opportunity to search for alternative therapies in coronary restenosis prevention.

Avaliação do leito arterial distal em revascularização de membros inferiores: estudo comparativo entre ecografia-doppler, arteriografia e medidas diretas do fluxo no intra-operatório / Arterial distal bed evaluation in revascularization of the lower extremities: comparative study enter doppler echography, arteriography and intra operative direct measures flow

A cirurgia de restauração circulatória aterial no paciente portador de isquemia crítica de membros inferiores apresenta indicações clínicas e técnica operatória já bastante estudadas e definidas. Ainda hoje, no entanto, um considerável número de enxertos evolui para oclusão. Entre as causas relacionadas à falência precoce, podemos destacar a resistência do leito distal receptor do enxerto. Interessou-nos estudar a existência de correlação hemodinâmica entre a Ecografia-Dopller, a Arteriografia pré-operatória e medidas diretas intra-operatórias de resistência do leito arterial receptor de enxerto. Foram estudadas 68 operações de revascularização de membros inferiores portadores de isquemia crítica . A Ecografia-Dopller foi considerada tenicamente satisfatória em 93,2%. Foi verificada a presença de correlação hemodinâmica positiva entre os métodos descritos acima (Teste de Pearson), particularmente para artéria a ser revascularizada pode auxiliar no estudo hemodinâmico do leito arterial receptor do enxerto e dessa forma auxiliar na definição do prognóstico do enxerto e no estabelecimento da melhor estratégia terapêutica a ser tomada ainda no período pré-operatório.

EPR study of radiation stability of organic plastic scintillator for cardiovascular brachytherapy Sr90-Y90 beta dosimetry.

Nowadays, more than one million percutaneous transluminal coronary angioplasties are being performed annually throughout the world. Restenosis is a significant problem associated with these angioplasty procedures. Radiation treatment with catheter-based beta-emitter sources is currently under clinical trial to prevent this problem. Due to fast and worldwide introduction of beta-sources for intravascular application, there is a growing interest in the dosimetry aspects. However, accurate dosimetry of beta-radiation is more difficult than that of gamma-radiation. Suitable detectors are not yet available with accuracy down to a tenth of a millimeter. Conventional measuring systems are not capable of such spatial resolution, except radiochromic film. However, film dosimeters have limited sensitivity and their radiation characteristics are different than those of tissue; therefore dose measurements require corrections. An alternative is to use water-equivalent plastic scintillators. In this work, organic plastic scintillator (BCF-10) dosimetry is studied using the Monte Carlo (MC) technique PENELOPE, and its radiation stability, after irradiation, is experimentally studied through electron paramagnetic resonance (EPR). Depth dose and dose profile are measured and compared to film dosimetry results. The EPR technique shows that the recovery time is dose independent in this kind of fiber and shows good stability.

Prevención de reestenosis post implante de stents coronarios / The restenosis prevention post coronary stent implantation

Los stent coronarios fueron grandes optimizadores de la angioplastia coronaria con balón. Los estudios stress, benestent 1 y 2 evidenciaron reducciones importantes en las tasas de reestenosis coronaria. El proceso de reestenosis fue afectado por los stents en el sentido de reducir el retroceso elástico precoz y el remodelamiento negativo, pero el proceso de hiperplasia neoíntimal sólo no fue modificado sino que exagerado. En el sentido de minimizar la hiperplasia debemos establecer formas de reducir la injuria durante el implante del stent, reducir el proceso inflamatorio, inhibir la migración y proliferación celular y favorecer el proceso de endotelización del stent. Varias opciones farmacológicas han sido discutidas y presentaremos los resultados con dichas drogas tales como: actinomocina, tacrolimus, taxol y sirolimus

Aterectomía coronaria: rol actual / Endovascular coronary atherectomy: present role

La aterectomía coronaria endovascular representa a un conjunto de técnicas de remoción de placa que fueron altamente utilizadas durante la angioplastia previo a la introducción de stents. En esa época, aunque comparadas con la angioplastia con balón no ofrecían beneficio en cuanto a la incidencia de reestenosis, permitían un procedimiento más seguro que el tratamiento de las lesiones complejas. Sin embargo, posterior al advenimiento de los stents su uso se restringió a situaciones exepcionales. En los últimos años nuevamente se plantea un rol de la aterectomía para ser usada previa al implante de los stents, con el propósito de disminuir la incidencia de reestenosis. Los resultados de los estudios preliminares hasta ahora disponibles sugieren que si bien esta tecnología puede no ser necesaria en la mayoría de los casos, frente a la dilatación de placas seleccionadas que tienen una conocida mayor incidencia de reestenosis, podría ser útil la aterectomía previa al implante de los stents

Intravascular brachytherapy: a model for the calculation of the dose

In this study we present the radiation dose distribution for a theoretical model with Montecarlo simulation, and based on an experimental model developed for the study of the prevention of restenosis post-angioplasty employing intravascular brachytherapy. In the experimental in vivo model, the atherosclerotic plaques were induced in femoral arteries of male New Zealand rabbits through surgical intervention and later administration of cholesterol enriched diet. For the intravascular irradiation we employed a 32P source contained within the balloon used for the angioplasty. The radiation dose distributions were calculated using the Monte Carlo code MCNP4B according to a segment of a simulated artery. We studied the radiation dose distribution in the axial and radial directions for different thickness of the atherosclerotic plaques. The results will be correlated with the biologic effects observed by means of histological analysis of the irradiated arteries

Sustained suppression of neointimal proliferation by sirolimus-eluting stents: one-year angiographic and intravascular ultrasound follow-up.

BACKGROUND: We have previously reported a virtual absence of neointimal hyperplasia 4 months after implantation of sirolimus-eluting stents. The aim of the present investigation was to determine whether these results are sustained over a period of 1 year. METHODS AND RESULTS: Forty-five patients with de novo coronary disease were successfully treated with the implantation of a single sirolimus-eluting Bx VELOCITY stent in São Paulo, Brazil (n=30, 15 fast release [group I, GI] and 15 slow release [GII]) and Rotterdam, The Netherlands (15 slow release, GIII). Angiographic and volumetric intravascular ultrasound (IVUS) follow-up was obtained at 4 and 12 months (GI and GII) and 6 months (GIII). In-stent minimal lumen diameter and percent diameter stenosis remained essentially unchanged in all groups (at 12 months, GI and GII; at 6 months, GIII). Follow-up in-lesion minimal lumen diameter was 2.28 mm (GIII), 2.32 mm (GI), and 2.48 mm (GII). No patient approached the >/=50% diameter stenosis at 1 year by angiography or IVUS assessment, and no edge restenosis was observed. Neointimal hyperplasia, as detected by IVUS, was virtually absent at 6 months (2+/-5% obstruction volume, GIII) and at 12 months (GI=2+/-5% and GII=2+/-3%). CONCLUSIONS: This study demonstrates a sustained suppression of neointimal proliferation by sirolimus-eluting Bx VELOCITY stents 1 year after implantation.