Дисертації з теми "Angioplasty"

Aim: To investigate the nature of psychological adjustment following angioplasty and to assess the relative contributions of illness cognitions and coping in the context of the Self-Regulation Model (Leventhal, Meyer & Nerenz, 1980). Design: A longitudinal, prospective within-groups, multi-factorial study. Method: 120 participants were recruited from an opportunity sample of patients approached during admission to the Manchester Heart Centre for angioplasty. Questionnaires addressing illness beliefs, coping and psychological outcomes were presented at two time points; during admission and three months post-procedure. Results: Analysis revealed that angioplasty is followed by clinically and statistically significant psychological gains. Perceptions of the illness as serious, and having a cyclical time-course, together with a general difficulty in making sense of the illness, were associated with increased anxiety at the time of treatment, and in most cases also at three months. Higher levels of emotional representation were also strongly associated with anxiety and quality of life outcomes at both time points. Problem-focused and maladaptive coping also showed associations with psychological outcome at treatment and at three months. Illness beliefs were demonstrated to significantly predict psychological well-being, explaining a substantial proportion of variance, with emotional representation the strongest independent predictor. Coping was not found to mediate the relationship between illness beliefs, and psychological distress and quality of life. Conclusion: This research has demonstrated the utility of illness beliefs, and to an extent the Self Regulation Model in predicting psychological outcome in angioplasty. Cognitive factors may therefore serve as useful clinical indicators to help identity those patients at greatest risk of impaired recovery, which in the future may enable targeting with further support, and evidence permitting, psychological interventions. [Abstract taken from Section B: Research Report (Option 1)]

Cardiovascular disease is the commonest cause of death in the western world and atherosclerosis is the commonest cause of cardiovascular disease. It is characterised by the deposition of intra-luminal plaque leading to arterial stenosis. Balloon angioplasty offers a minimally invasive method of dilating peripheral and coronary arterial stenosis. The results of angioplasty are improved by stenting. However, a significant percentage of these patients have restenosis of their arteries with clinical and resource implications. Restenosis is caused by neointimal hyperplasia (NIH) and negative remodelling the combined effects of which result in vessel re-narrowing. It has previously been shown in animal models that photodynamic therapy (PDT) reduces the restenosis when used as an adjuvant to angioplasty. PDT involves the interaction of light at a particular wavelength with a pre-administered photosensitive agent to produce cell death by apoptosis in the presence of oxygen. The aims of this thesis are two fold. 1. to optimise the effects of PDT in preventing in-stent restenosis 2. to conduct a randomised controlled trial to show the clinical benefits of PDT in preventing post-angioplasty restenosis.

Coronary artery disease is a leading cause of morbidity and mortality in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is an important treatment option when intervention is required; namely for patients with relatively severe occlusions. However, adverse events including recurrence of angina pectoris and restenosis of the treated artery limit patient prognosis, with subsequent re-vascularisation often necessary. Platelet activation accompanies PTCA, with platelet adhesion and aggregation involved in thrombus formation during restenosis. During platelet activation, highly coagulant platelet-derived microparticles (PMPs) are formed, and it is likely that these PMPs will also be produced during PTCA. While platelet aggregation inhibitors used during PTCA limit platelet aggregation and decrease the incidence of restenosis, they do not prevent PMPs being formed. PMPs are capable of adhesion and aggregation, and adhere to PTCA treated arteries in an animal model. Therefore, in order to understand the phenomenon of restenosis and its improved limitation, it is necessary to investigate PMP formation during PTCA. The field of PMP study is in its infancy, with conflicting results from the substantial inequities in methods of PMP measurement, which may be exacerbated by PMP heterogeneity. The current literature on this topic is reviewed in Chapter 2, where the PMP surface and possible functions are considered, and the PMP size and morphology examined. To conclude, the relationship between PMPs and PTCA is explored, with a focus on the potential role of PMPs in restenosis. The knowledge deficiencies in this field are highlighted at the conclusion of this chapter. Very little is known regarding the production of PMPs with PTCA. The level of PMPs during PTCA was monitored in paired arterial blood samples obtained from seventy-five patients undergoing the procedure (Chapter 3). A significant increase in PMPs from baseline to completion of PTCA was clearly demonstrated for the first time. This indicated that procoagulant PMPs are produced during PTCA and may contribute to subsequent restenosis. Furthermore, administration of the platelet aggregation inhibitor abciximab to a group of thirty-eight high risk patients limited PMP formation; given that abciximab patients required more rigorous PTCA, the protective benefit of this medication for PMP production is underlined. Although few patients in this study experienced restenosis, it is interesting to note that of those treated with abciximab, all patients suffering subsequent restenosis were revascularised using PTCA. This demonstrates that their occlusions were comparatively mild as the need for coronary artery bypass grafting was avoided, and suggests that minimisation of PMP levels may assist in limiting the progression of severe restenosis. The increased peripheral level of PMPs predicated investigation of the coronary circulation to determine local events. Although the level of PMPs increased significantly within the coronary arteries of PTCA patients, there was no corresponding increase in the coronary sinus (Chapter 4). This important finding indicated that significant levels of PMPs remained within the coronary circulation, where their ability to adhere, aggregate and accelerate haemostasis may allow them to contribute directly to restenosis. During the time when increased levels of PMPs were being formed, there was no evidence of platelet lysis, which refuted the hypothesis that PMPs are merely membrane fragments of lysed platelets. A wide variation in reported PMP sizes has contributed to the hypothesis that PMPs are heterogeneous. As morphological information can assist in understanding physiology, the final study was designed to investigate platelet morphology from PTCA patients (Chapter 5). Most platelets were activated prior to and following PTCA, with a slight decrease in body size occurring due to PTCA, presumably due to loss of cytoplasm in PMPs being shed as reported in the previous chapter. Importantly, platelet distal pseudopod buds were observed, and these did not alter significantly with PTCA. These buds were probably unformed PMPs, although the exact mechanism of PMP formation remains undetermined. The platelet pseudopods were longer and significantly thinner distally with PTCA, which may be due to movement of cytoplasm into these terminal swellings. In addition, buds or swellings directly on the platelet body were smaller following PTCA, and it is likely these may also be PMPs prior to detachment from the parent platelet. This work has contributed substantially to knowledge of PMPs produced during PTCA. The level of PMPs increased significantly in peripheral arterial samples, with the platelet aggregation inhibitor abciximab preventing this occurrence. This may indicate that functional aggregation receptors are an essential requirement for PMP formation under these conditions. However, it is possible for PMPs to be formed when aggregation is inhibited, and therefore the molecular mechanisms of PMP formation remain unconfirmed. The examination of PMPs from the coronary circulation provided valuable data indicating that PMPs are produced during PTCA but remain within the coronary circulation. As PMPs are capable of adhesion and aggregation, this strongly suggests that PMPs within the coronary circulation would contribute directly to pathogenesis of restenosis, although further investigation on PMPs with PTCA is necessary to confirm this association. The examination of platelet morphology during PTCA indicated that platelets possessed terminal pseudopod swellings, and cell surface swellings. Importantly, the terminal swellings, which are likely to be unformed PMPs, were observed for the first time during PTCA.

Coronary artery disease is a leading cause of morbidity and mortality in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is an important treatment option when intervention is required; namely for patients with relatively severe occlusions. However, adverse events including recurrence of angina pectoris and restenosis of the treated artery limit patient prognosis, with subsequent re-vascularisation often necessary. Platelet activation accompanies PTCA, with platelet adhesion and aggregation involved in thrombus formation during restenosis. During platelet activation, highly coagulant platelet-derived microparticles (PMPs) are formed, and it is likely that these PMPs will also be produced during PTCA. While platelet aggregation inhibitors used during PTCA limit platelet aggregation and decrease the incidence of restenosis, they do not prevent PMPs being formed. PMPs are capable of adhesion and aggregation, and adhere to PTCA treated arteries in an animal model. Therefore, in order to understand the phenomenon of restenosis and its improved limitation, it is necessary to investigate PMP formation during PTCA. The field of PMP study is in its infancy, with conflicting results from the substantial inequities in methods of PMP measurement, which may be exacerbated by PMP heterogeneity. The current literature on this topic is reviewed in Chapter 2, where the PMP surface and possible functions are considered, and the PMP size and morphology examined. To conclude, the relationship between PMPs and PTCA is explored, with a focus on the potential role of PMPs in restenosis. The knowledge deficiencies in this field are highlighted at the conclusion of this chapter. Very little is known regarding the production of PMPs with PTCA. The level of PMPs during PTCA was monitored in paired arterial blood samples obtained from seventy-five patients undergoing the procedure (Chapter 3). A significant increase in PMPs from baseline to completion of PTCA was clearly demonstrated for the first time. This indicated that procoagulant PMPs are produced during PTCA and may contribute to subsequent restenosis. Furthermore, administration of the platelet aggregation inhibitor abciximab to a group of thirty-eight high risk patients limited PMP formation; given that abciximab patients required more rigorous PTCA, the protective benefit of this medication for PMP production is underlined. Although few patients in this study experienced restenosis, it is interesting to note that of those treated with abciximab, all patients suffering subsequent restenosis were revascularised using PTCA. This demonstrates that their occlusions were comparatively mild as the need for coronary artery bypass grafting was avoided, and suggests that minimisation of PMP levels may assist in limiting the progression of severe restenosis. The increased peripheral level of PMPs predicated investigation of the coronary circulation to determine local events. Although the level of PMPs increased significantly within the coronary arteries of PTCA patients, there was no corresponding increase in the coronary sinus (Chapter 4). This important finding indicated that significant levels of PMPs remained within the coronary circulation, where their ability to adhere, aggregate and accelerate haemostasis may allow them to contribute directly to restenosis. During the time when increased levels of PMPs were being formed, there was no evidence of platelet lysis, which refuted the hypothesis that PMPs are merely membrane fragments of lysed platelets. A wide variation in reported PMP sizes has contributed to the hypothesis that PMPs are heterogeneous. As morphological information can assist in understanding physiology, the final study was designed to investigate platelet morphology from PTCA patients (Chapter 5). Most platelets were activated prior to and following PTCA, with a slight decrease in body size occurring due to PTCA, presumably due to loss of cytoplasm in PMPs being shed as reported in the previous chapter. Importantly, platelet distal pseudopod buds were observed, and these did not alter significantly with PTCA. These buds were probably unformed PMPs, although the exact mechanism of PMP formation remains undetermined. The platelet pseudopods were longer and significantly thinner distally with PTCA, which may be due to movement of cytoplasm into these terminal swellings. In addition, buds or swellings directly on the platelet body were smaller following PTCA, and it is likely these may also be PMPs prior to detachment from the parent platelet. This work has contributed substantially to knowledge of PMPs produced during PTCA. The level of PMPs increased significantly in peripheral arterial samples, with the platelet aggregation inhibitor abciximab preventing this occurrence. This may indicate that functional aggregation receptors are an essential requirement for PMP formation under these conditions. However, it is possible for PMPs to be formed when aggregation is inhibited, and therefore the molecular mechanisms of PMP formation remain unconfirmed. The examination of PMPs from the coronary circulation provided valuable data indicating that PMPs are produced during PTCA but remain within the coronary circulation. As PMPs are capable of adhesion and aggregation, this strongly suggests that PMPs within the coronary circulation would contribute directly to pathogenesis of restenosis, although further investigation on PMPs with PTCA is necessary to confirm this association. The examination of platelet morphology during PTCA indicated that platelets possessed terminal pseudopod swellings, and cell surface swellings. Importantly, the terminal swellings, which are likely to be unformed PMPs, were observed for the first time during PTCA.

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A doença renal crônica (DRC) é caracterizada por uma perda progressiva da função renal e suas principais causas são hipertensão arterial sistêmica (HAS) e diabete melito. Entre as causas de HAS podemos destacar a doença renal aterosclerótica (DRA), que acomete principalmente idosos e muitas vezes não é diagnosticada. Existe uma alta incidência de complicações cardiovasculares em pacientes com DRA quando comparados com indivíduos da mesma idade, mas com artérias renais normais. Uma explicação seria a presença de aterosclerose em outros vasos, como artérias coronarianas e cerebrais. Outra hipótese seria o efeito deletério causado pela ativação do sistema renina angiotensina aldosterona secundária à isquemia renal. O desenvolvimento de DRC nos pacientes com DRA parece ser decorrente não apenas do acometimento das artérias renais principais, mas também da microcirculação renal, o que pode justificar o fato de o sucesso do procedimento não garantir uma melhora da evolução da DRC. Até o presente momento não existe evidência de benefício da angioplastia em relação ao tratamento clínico exclusivo nos pacientes com DRA. O presente trabalho procurou identificar algum subgrupo de pacientes com DRA que se beneficiaria da angioplastia com implante de endoprótese. Foram incluídos inicialmente 136 pacientes com diagnóstico arteriográfico de estenose de artéria renal superior a 60% do diâmetro do vaso uni ou bilateralmente, com idade superior a 18 anos identificados no Hospital das Clínicas da Faculdade de Medicina de Botucatu. Os critérios de exclusão foram: pacientes com menos de cinco medidas de creatinina antes ou após o procedimento, pacientes com estenose não aterosclerótica e aqueles submetidos a mais de uma angioplastia renal. Foi calculado o coeficiente de inclinação da reta de regressão do inverso da creatinina antes e após o procedimento angiográfico. Oitenta e quatro pacientes...
Chronic kidney disease (CKD) is characterized by an irreversible loss of kidney function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension, atherosclerotic renal disease (ARD) is one of them, which mainly affects the elderly and is often not diagnosed. There is a high incidence of adverse cardiovascular events in patients with ARD compared with individuals of the same age but with normal renal arteries. One explanation is the presence of atherosclerosis in other vessels. Another hypothesis is the deleterious effects caused by activation of the rennin angiotensin aldosterone system secondary to renal ischemia. The development of CKD in patients with ARD happens not only by the involvement of the main renal arteries, but also by the involvement of the microcirculation, what may explain the fact that the success of the procedure does not guarantee an improvement in the development of CKD. To date there is no evidence of benefit of angioplasty compared to medical treatment alone in patients with ARD. This study sought to identify a subgroup of patients with ARD that would benefit from angioplasty with stent implantation. We included 136 patients initially diagnosed with arteriographic renal artery stenosis greater than 60% of the vessel diameter uni-or bilaterally, aged over 18 years identified in the hospital of Botucatu Medical School. Patients with less than five measures of creatinine before or after the procedure, patients with no atherosclerotic stenosis and those subjected to more than one renal angioplasty were excluded from the study. Among the 136 patients, 52 were selected and divided into two groups. Group 1 consisted of patients with progressive worsening of renal function and group 2 patients with stable renal function. Patients from group 1 who underwent renal angioplasty formed the subgroup 1A and patients who didn’t formed the subgroup 1NA. The same ...

Orientador: Ana Terezinha Guillaumon
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Objetivos: Analisar a distribuição temporal de sinais de microembolias (SM) ao longo de diferentes estágios da endarterectomia carotídea (EC) e da angioplastia carotídea (AC) e as variáveis associadas com a ocorrência destes sinais, além de avaliar as mudanças na velocidade média aferida na artéria cerebral média (ACM) durante os dois tipos de intervenção. Material e métodos: Trinta e três pacientes com estenose carotídea foram submetidos ou a EC (17) ou a AC (16). Os SM bem como as velocidades médias na ACM foram adquiridas utilizando o US doppler transcraniano (DTC) e esses dados então analisados e associados a diferentes estágios cirúrgicos (pré-proteção, durante a proteção e pós-proteção), tipos de intervenção (EC ou AC) e diferentes variáveis para encontrar potenciais fatores de risco para embolização. Para análise estatística, foram usados os testes de Qui-quadrado, de Fisher e de Mann-Whitney, além de análise por medidas repetidas das variâncias com transformação por postos (ANOVA), seguido de teste de perfil por contrastes e análise de regressão linear múltipla ajustada para o grupo. Resultados: Uma diferença significativa foi encontrada para o número de SM em ambos os grupos. Houve, em média, 89,8 (± 171,4) sinais por procedimento no grupo EC, enquanto a média no grupo AC foi de 597,5 (± 343,3) sinais por procedimento. A média da velocidade média na ACM foi, em ambos os grupos, significantemente menor no estágio durante a proteção. Anestesia local correlacionou-se positivamente (p=0,003) com aumento dos SM, e, associado a isso, o histórico de tabagismo importante (desde que houvesse a cessação do vício há mais de um ano) correlacionou-se negativamente (0,014) com a ocorrência de SM. Conclusão: EC por semi-eversão, à luz do DTC, provocou uma menor incidência de SM por procedimento do que AC com filtro distal, em todos os estágios cirúrgicos. A média da velocidade média na ACM se comportou de maneira similar em ambos os grupos (EC e AC). Anestesia geral e histórico de tabagismo importante (desde que o paciente houvesse cessado por menos um anos antes da intervenção) foram as únicas duas variáveis no estudo que se correlacionaram significativamente (negativamente) com a ocorrência de SM
Abstract: Objectives: To analyze the temporal distribution of microembolic signals throughout the different stages of both the semi-eversion carotid endarterectomy (CEA) and the carotid artery stenting (CAS) procedures and the variables associated with occurrence of them and to evaluate changes in mean blood flow velocity, for both CAS and CEA, within the ipsilateral middle cerebral artery (MCA). Methods: Thirty three patients with carotid stenosis underwent either a CEA (17) or a CAS (16). Microembolic signals, as well as mean blood flow velocity, were acquired using a Transcranial Doppler scan (TCD) and these data were then analyzed and associated to different surgical stages (pre-protection, during protection, and post-protection), types of procedure (CAS or CEA) and different variables to find potential risk factors. To statistical analysis, chi-squared test, Fisher test, Mann-Whitney test, repeated measures analysis of variance with rank transformation (ANOVA) followed by contrast test and multiple linear regression analysis were used. Results: A significant difference was found for the number of microembolic signals in both groups. There were, on average, 89.8 (± 171.4) signals per procedure in the CEA group, while the average in the CAS group was 597.5 (± 343.3) signals per procedure. The average blood flow in the MCA was, in both groups, significantly lower during the stage of protection. Local anesthesia correlated positively (p= .003) with increase in microembolic signals and history of prolonged tobacco use having dropped the addiction for over a year correlated negatively (p= -.014) with the frequency of microembolic signals. Conclusion: Semi-eversion CEA, in light of our TCD findings, evoked a smaller incidence of hyperintense microemboli per procedure than CAS with a distal filter in all the protection stages. The average of the mean blood flow velocity within the MCA has behaved similarly between both groups (CAS and CEA). General anesthesia and the history of tobacco use (as long as the patient had quit for a year or more prior to surgery) were the only two variables in the study that correlated significantly (negatively) with the frequency of microembolic signals
Mestrado
Fisiopatologia Cirúrgica
Mestre em Ciências

Orientador: Luis Cuadrado Martin
Coorientador: Vanessa dos Santos Silva
Banca: José Nery Praxedes
Banca: Fábio Cardoso de Carvalho
Resumo: A doença renal crônica (DRC) é caracterizada por uma perda progressiva da função renal e suas principais causas são hipertensão arterial sistêmica (HAS) e diabete melito. Entre as causas de HAS podemos destacar a doença renal aterosclerótica (DRA), que acomete principalmente idosos e muitas vezes não é diagnosticada. Existe uma alta incidência de complicações cardiovasculares em pacientes com DRA quando comparados com indivíduos da mesma idade, mas com artérias renais normais. Uma explicação seria a presença de aterosclerose em outros vasos, como artérias coronarianas e cerebrais. Outra hipótese seria o efeito deletério causado pela ativação do sistema renina angiotensina aldosterona secundária à isquemia renal. O desenvolvimento de DRC nos pacientes com DRA parece ser decorrente não apenas do acometimento das artérias renais principais, mas também da microcirculação renal, o que pode justificar o fato de o sucesso do procedimento não garantir uma melhora da evolução da DRC. Até o presente momento não existe evidência de benefício da angioplastia em relação ao tratamento clínico exclusivo nos pacientes com DRA. O presente trabalho procurou identificar algum subgrupo de pacientes com DRA que se beneficiaria da angioplastia com implante de endoprótese. Foram incluídos inicialmente 136 pacientes com diagnóstico arteriográfico de estenose de artéria renal superior a 60% do diâmetro do vaso uni ou bilateralmente, com idade superior a 18 anos identificados no Hospital das Clínicas da Faculdade de Medicina de Botucatu. Os critérios de exclusão foram: pacientes com menos de cinco medidas de creatinina antes ou após o procedimento, pacientes com estenose não aterosclerótica e aqueles submetidos a mais de uma angioplastia renal. Foi calculado o coeficiente de inclinação da reta de regressão do inverso da creatinina antes e após o procedimento angiográfico. Oitenta e quatro pacientes ...
Abstract: Chronic kidney disease (CKD) is characterized by an irreversible loss of kidney function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension, atherosclerotic renal disease (ARD) is one of them, which mainly affects the elderly and is often not diagnosed. There is a high incidence of adverse cardiovascular events in patients with ARD compared with individuals of the same age but with normal renal arteries. One explanation is the presence of atherosclerosis in other vessels. Another hypothesis is the deleterious effects caused by activation of the rennin angiotensin aldosterone system secondary to renal ischemia. The development of CKD in patients with ARD happens not only by the involvement of the main renal arteries, but also by the involvement of the microcirculation, what may explain the fact that the success of the procedure does not guarantee an improvement in the development of CKD. To date there is no evidence of benefit of angioplasty compared to medical treatment alone in patients with ARD. This study sought to identify a subgroup of patients with ARD that would benefit from angioplasty with stent implantation. We included 136 patients initially diagnosed with arteriographic renal artery stenosis greater than 60% of the vessel diameter uni-or bilaterally, aged over 18 years identified in the hospital of Botucatu Medical School. Patients with less than five measures of creatinine before or after the procedure, patients with no atherosclerotic stenosis and those subjected to more than one renal angioplasty were excluded from the study. Among the 136 patients, 52 were selected and divided into two groups. Group 1 consisted of patients with progressive worsening of renal function and group 2 patients with stable renal function. Patients from group 1 who underwent renal angioplasty formed the subgroup 1A and patients who didn't formed the subgroup 1NA. The same ...
Mestre

The development of a new angioplasty balloon is a time consuming process. This thesis aims at reducing the amount of time and materials spent on the experimental stage of the development of new angioplasty balloons. This can be achieved by building a nonlinear neural network model of the balloon forming process and implementing an off-line cycle-to-cycle controller. The controller can learn from the previous experiments and provide better input parameters for improving the quality of the next balloons formed in the process. It is shown in the experimental test results that the neural network model can provide accurate estimates of the process outputs. The neural network model combined with a cycle-to-cycle control strategy has the potential to replace the trial-and-error approach to balloon development that is commonly applied today.

Thrombolysis remains the predominant reperfusion strategy for ST segment elevation myocardial infarction (STEMI) in the United Kingdom. Although primary angioplasty may offer superior outcomes, the logistics of delivering this therapy in the UK have not been investigated. This thesis describes the development of a pilot primary angioplasty service in North East London. Outcomes are compared with the thrombolytic strategy, and platelet activation is explored as a possible biological mechanism determining reperfusion. The impact of the thrombolytic strategy on revascularisation following STEMI in North East London was first investigated. Thrombolytic delivery was effective, but necessitated frequent early revascularisation, leading to prolonged hospital stay. A primary angioplasty service was developed at the cardiac centre, and expanded to serve six network hospitals. Within the limitations of a daytime pilot, the service improved clinical outcomes, and was associated with a substantial reduction in hospital stay. Two admission strategies were compared - direct access to the cardiac centre following pre-hospital diagnosis by ambulance crews, and transfer of patients presenting to network emergency (A&E) departments after upstream administration of abciximab and clopidogrel. Direct access significantly reduced reperfusion times. Upstream anti-platelet therapy improved angiographic reperfusion prior to primary angioplasty, possibly compensating for inter hospital transfer delays. A subgroup of STEMI patients underwent platelet activation studies. Lower baseline platelet monocyte aggregate (PMA) levels predicted improved angiographic reperfusion following primary angioplasty, supporting the concept that PMAs may reflect plaque rupture severity, and may promote microvascular 2 dysfunction. Early anti-platelet therapy reduced PMAs following intervention, which may explain the benefit of early abciximab observed in clinical trials. In summary this thesis has demonstrated that primary angioplasty can be del ivered safely and eff ectively in North East London. The eff icacy of reperf usion may be determined by mechanisms involving platelet activation. Delivery of a 24 hour seven day service should now be addressed.

Introdução: Um dos fatores mais comuns de falha do procedimento das angioplastias vasculares periféricas é a estenose recorrente (reestenose). A inflamação vascular após angioplastia e implante de stent desempenha papel importante na proliferação de células do músculo liso vascular e posterior crescimento de neoíntima hipertrófica. Diversos estudos têm sugerido que a superfície dos stents, quando impregnada com determinadas moléculas, pode limitar a reestenose de forma eficaz. O carbono diamante, polímero de hidrocarboneto amorfo, pode ser usado para essa finalidade, reduzindo liberação de íons metálicos e a trombogenicidade. Diversos mediadores têm sido implicados na resposta inflamatória vascular, como o sistema calicreína-cinina (SCC), as citocinas, proteína C reativa (PCR) e o óxido nítrico (NO). Portanto, estudos clínicos específicos correlacionando o implante do stent aos níveis séricos destes possíveis marcadores podem contribuir no entendimento desse processo. Objetivo: Estudar a perviedade do dispositivo e a evolução clínica de doentes submetidos a angioplastia com stents impregandos de carbono no território vascular periférico, assim como o comportamento de mediadores séricos envolvidos nas fases mais precoces do processo inflamatório pós angioplastia. População e Método: Estudo prospectivo envolvendo 32 pacientes submetidos à angioplastia com stent no segmento ilíacofêmoro-poplíteo, selecionados no Ambulatório de Cirurgia Vascular e Endovascular do HCFMRP/USP. Foram tratadas lesões estenosantes ou oclusivas com angioplastia e colocação de stents de nitinol, com superfície impregnada de carbono (Carbostent®). Foram estudados os seguintes marcadores: SCC - com quantificação dos substratos (cininogênio de alto e baixo peso molecular - CAPM / CBPM) e das enzimas calicreína plasmática e tecidual, além da quantificação da cininase II; a determinação dos níveis de nitrito e nitratos para a avaliação de óxido nítrico; dosagem sérica de PCR e citocinas (IL-1 beta, IL-6, IL-8, IL-10, TNF-alfa e TGFbeta). Também foi realizado a dosagem dos leucócitos. Amostras séricas foram coletadas antes, 24 horas e 6 meses após o implante do stent. Os pacientes foram seguidos por um ano, para avaliação da perviedade nesse período. Resultados: Dos 27 pacientes que completaram seis meses de estudo, houve apenas uma reestenose (3,7%) e nenhuma oclusão (96,3% de perviedade). No período de um ano, quatro pacientes perderam seguimento e todos os 23 doentes avaliados, mantiveram a perviedade dos stents, com exceção do paciente no qual houve reestenose no tempo seis meses. Houve redução significativa das concentrações das citocinas inflamatórias (IL-1 beta, IL-6, IL-8 e TNF-?) no tempo 24 horas e seis meses quando comparado com o pré-procedimento (p<0,05); exceto a IL-8 no tempo 24 horas. As citocinas anti-inflamatórias (IL10 e TGF-beta) comportaram-se de maneira antagônica, com elevação do TGF-beta no tempo 24 horas e elevação, tanto do TGF-beta quanto da IL-10, no tempo 6 meses versus pré-tratamento e 6 meses versus 24 horas (P<0,05). A PCR apresentou queda no tempo seis meses em relação ao tempo 24h (p<0,05). Os níveis de NO não se alteraram entre os tempos; os de leucócitos elevaram-se no tempo 24 horas e reduziram-se no tempo seis meses em relação ao tempo 24 horas (p<0,05). Conclusão: No presente estudo a taxa de reestenose precoce foi de 3,7% nos primeiros 6 meses e 5% em 12 meses de seguimento. O comportamento dos marcadores inflamatórios evidenciou sua correlação direta com o processo de angioplastia e implante de carbostent, em especial o SCC, as citocinas, PCR e os leucócitos. Contudo, não foi possível relacionar a variação dos seus níveis séricos com o processo de reestenose.
Background: One of the most common factors of failure of the peripheral vascular angioplasty procedure is recurrent stenosis (restenosis). Vascular inflammation following angioplasty and stent implantation plays an important role in vascular smooth muscle cell proliferation and subsequent hypertrophic neointimal growth. Several studies have suggested that the surface of stents, when impregnated with certain molecules, can limit restenosis effectively. Diamond carbon, amorphous hydrocarbon polymer, can be used for this purpose, reducing release of metal ions and thrombogenicity. Several mediators have been implicated in the vascular inflammatory response, such as the kallikrein-kinin system (SCC), cytokines, C-reactive protein (CRP) and nitric oxide (NO). Therefore, specific clinical studies correlating stent implantation with serum levels of these possible markers may contribute to the understanding of this process. Objective: To study the patency of the device and the clinical evolution of patients undergoing angioplasty with carbon-impregnated stents in the peripheral vascular territory, as well as the behavior of serum mediators involved in the earlier stages of the inflammatory process after angioplasty. Population and Method: Prospective study involving 32 patients submitted to angioplasty with stent in the iliac-femoro-popliteal segment, selected at the HCFMRP / USP Outpatient Vascular and Endovascular Outpatient Clinic. Stenosis or occlusive lesions were treated with angioplasty and placement of nitinol stents with a carbon impregnated surface (Carbostent®). The following markers were studied: SCC - with quantification of substrates (high and low molecular weight cincinogens - HMWC / LMWC) and plasma and tissue kallikrein enzymes, besides quantification of kininase II; determination of nitrite and nitrate levels for the evaluation of nitric oxide; serum levels of CRP and cytokines (IL-1 beta, IL-6, IL-8, IL-10, TNF-a and TGF-b). Leucocytes were also dosed. Serum samples were collected before, 24 hours and 6 months after stent implantation. The patients were followed for one year to assess the patency in this period. Results: Of the 27 patients who completed six months of study, there was only one restenosis (3.7%) and no occlusion (96.3% of patency). In one year, four patients lost follow-up and all 23 patients evaluated, maintained stent patency, with the exception of the patient who had restenosis over time for six months. There was a significant reduction in the concentrations of inflammatory cytokines (IL-1 b, IL-6, IL-8 and TNF-a) in the time 24 hours and six months when compared with the pre-procedure (p <0.05); except for IL-8 in the 24 hour time. Anti-inflammatory cytokines (IL10 and TGF-b) behaved in an antagonistic manner, with TGF-b elevation in the 24 hour time and elevation of both TGF-b and IL-10, at 6 months versus pre- treatment and 6 months versus 24 hours (P <0.05). CRP showed a decrease in time six months in relation to time 24h (p <0.05). NO levels did not change between the times; the leukocytes increased in time 24 hours and reduced in time six months in relation to time 24 hours (p <0.05). Conclusion: In the present study, the rate of early restenosis was 3.7% in the first 6 months and 5% in 12 months of follow-up. The behavior of the inflammatory markers showed its direct correlation with the angioplasty and carbostent implantation process, especially SCC, cytokines, CRP and leukocytes. However, it was not possible to relate the variation of their serum levels to the restenosis process.

Cardiovascular disease is the leading cause of death in industrialized nations. Angioplasty is performed on millions of patients every year. It is, therefore, essential to constantly explore and investigate new approaches to study and improve the outcomes of this minimally-invasive procedure. In this thesis, novel applications of intravascular optical coherence tomography (IVOCT) are proposed, namely, monitoring, characterization, simulation, and control of balloon inflation.High-resolution IVOCT images lead to a detailed assessment of microstructures. Using image analysis techniques, IVOCT characterization of balloon deformation is presented as a method to validate the performance of balloons. IVOCT characterization of the deformation of artery phantoms is proposed as a method to study the tissue's response to various balloon sizes, various balloon folding strategies and various inflation strategies.In addition, IVOCT characterization of deformation is proposed as a method to validate simulation results. This thesis provides a comparison between finite-element simulation results and experimental results for two case studies, which investigate the effects of variation of mechanical properties as well as balloon unfolding and inflation process.Finally, in this thesis, methods are proposed to control the balloon inflation. During balloon inflation, the luminal diameter of an artery could be estimated in real-time and used in a feedback loop to control the inflation. The experimental relevance of this method is demonstrated when the balloon is inflated in an artery phantom, in an artery of an excised porcine heart and in an artery of a beating porcine heart.The methods and the results, provided in this thesis, could benefit the developers of angioplasty devices, cardiovascular research, and clinical users.
Les maladies cardiovasculaires sont la principale cause de décès dans les pays industrialisés. L'angioplastie est réalisée sur des millions de patients chaque année. Il est donc essentiel de constamment explorer et étudier de nouvelles approches pour étudier et améliorer les résultats de cette procédure peu invasive. Dans cette thèse, de nouvelles applications de la tomographie par cohérence optique intravasculaire (IVOCT) sont proposées, à savoir, la surveillance, la caractérisation, la simulation et le contrôle du gonflement du ballon.Des images haute résolution IVOCT mènent à une évaluation détaillée des microstructures. En utilisant des techniques d'analyse d'image, la caractérisation de la déformation du ballon est présentée comme une méthode pour valider la performance de ballons. La caractérisation de la déformation des fantômes est proposée comme une méthode pour étudier la réponse des tissus à des tailles différentes de ballons, et diverses stratégies de pliage et de gonflement du ballon. En outre, la caractérisation de la déformation est proposée pour valider les résultats de simulation. Une comparaison est fournie entre les résultats de la simulation par éléments finis et des résultats expérimentaux pour les deux études de cas, qui étudient les effets de la variation des propriétés mécaniques ainsi que le processus de déploiement et de gonflement du ballon. Enfin, dans cette thèse, des méthodes sont proposées pour contrôler le gonflement du ballon. Pendant le gonflement du ballon, le diamètre luminal de l'artère peut être estimé en temps réel et utilisé dans une boucle de rétroaction pour contrôler le gonflement. La pertinence expérimentale de cette méthode est démontrée lorsque le ballon est gonflé dans un fantôme, dans les artères porcines d'un cœur excisé et d'un cœur battant. Les méthodes et les résultats fournis dans cette thèse pourraient bénéficier aux développeurs de dispositifs d'angioplastie, à la recherche cardiovasculaire et aux utilisateurs cliniques.