RESUMO
Hyperperfusion syndrome can complicate carotid revascularization, be it endarterectomy or carotid artery stenting (CAS). Although extensive effort has been devoted to reducing the incidence of ischemic stroke complicating CAS, little is known about the incidence, etiology, and prevention strategies for hyperperfusion following CAS. We report two cases (female patients 72 and 81 years) presenting severe internal carotid stenosis (> 90%), who underwent presurgical and therapeutic intervention with CAS. Both patients developed hyperperfusion symptoms at 2 hours and at 30 minutes, respectively, following stenting, in both cases unilateral hyperperfusion was CCT confirmed. Case 1 was presenting with acute edema of the right hemisphere, case 2 with distended focal edema (left fronto-temporoparietally). Hyperperfusion syndrome and neurological symptoms retroceded in both cases (conservative therapy) and both patients returned to full activity (case 2 within 48 hours).
Assuntos
Prótese Vascular/efeitos adversos , Estenose das Carótidas/complicações , Estenose das Carótidas/cirurgia , Transtornos Cerebrovasculares/etiologia , Stents/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falha de Prótese , SíndromeRESUMO
Non-invasive imaging techniques for the detection of graft patency after multivessel coronary revascularisation may be useful for follow-up after surgery. Forty consecutive asymptomatic patients (38 men, age 59.9+/-1.3 years) who had undergone coronary bypass surgery with at least three grafts were examined by spiral computed tomography or magnetic resonance angiography 24.9+/-0.3 months after surgery, using conventional angiography as reference. In total, 133 grafts (37 internal mammary artery, 96 venous grafts) were analysed. Spiral computed tomography studies were performed with a subsecond scanner; for magnetic resonance angiography, a three-dimensional contrast-enhanced gradient echo technique with ultrashort echo time during breath holding was used. For spiral computed tomography, sensitivities were 76% (internal mammary artery) and 100% (venous graft). This was compared with 100% (internal mammary artery) and 92% (venous graft) assessed by magnetic resonance angiography (P=ns). The positive predictive values were 100% for internal mammary artery and venous graft (spiral computed tomography) and 100% (internal mammary artery), 92% for venous grafts studied by magnetic resonance angiography (P=ns). Both subsecond spiral computed tomography and contrast-enhanced magnetic resonance angiography are highly accurate and relatively non-invasive approaches of assessing coronary graft patency after multivessel revascularisation and have potential for follow-up assessment in the long term.
Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Angiografia por Ressonância Magnética , Tomografia Computadorizada por Raios X , Grau de Desobstrução Vascular , Meios de Contraste , Humanos , Imageamento Tridimensional , Anastomose de Artéria Torácica Interna-Coronária , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Veia Safena/transplante , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In addition to its known properties as a competitive, nonselective beta and alpha-1 receptor blocker, carvedilol directly inhibits vascular myocyte migration and proliferation and exerts antioxidant effects that are considerably greater than those of vitamin E or probucol. This provides the basis for an evaluation of carvedilol for the prevention of coronary restenosis. METHODS AND RESULTS: In a prospective, double-blind, randomized, placebo-controlled trial, 25 mg of carvedilol was given twice daily, starting 24 hours before scheduled directional coronary atherectomy and continuing for 5 months after a successful procedure. The primary end point was the minimal luminal diameter as determined during follow-up angiography 26+/-2 weeks after the procedure. Of 406 randomized patients, 377 underwent attempted atherectomy, and in 324 (88.9%), a =50% diameter stenosis was achieved without the use of a stent. Evaluable follow-up angiography was available in 292 eligible patients (90%). No differences in minimal luminal diameter (1.99+/-0.73 mm versus 2.00+/-0.74 mm), angiographic restenosis rate (23.4% versus 23.9%), target lesion revascularization (16.2 versus 14.5), or event-free survival (79.2% versus 79.7%) between the placebo and carvedilol groups were observed at 7 months. CONCLUSIONS: The maximum recommended daily dose of the antioxidant and beta-blocker carvedilol failed to reduce restenosis after successful atherectomy. These findings are in contrast to those of the Multivitamins and Probucol Trial, which raises doubts regarding the validity of the interpretation that restenosis reduction by probucol was via antioxidant effects. The relationship between antioxidant agents and restenosis remains to be elucidated.
Assuntos
Antagonistas Adrenérgicos/uso terapêutico , Antioxidantes/uso terapêutico , Aterectomia Coronária , Carbazóis/uso terapêutico , Doença das Coronárias/prevenção & controle , Doença das Coronárias/terapia , Propanolaminas/uso terapêutico , Antagonistas Adrenérgicos/efeitos adversos , Idoso , Antioxidantes/efeitos adversos , Carbazóis/efeitos adversos , Carvedilol , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propanolaminas/efeitos adversos , Prevenção Secundária , Falha de TratamentoRESUMO
Revascularization by percutaneous transluminal coronary angioplasty is limited in the long-term by restenosis, which is luminal renarrowing in the first 6 months after the procedure. Smooth muscle cell proliferation is thought to be an important factor in restenosis; this leads to neointima formation and arterial lumen narrowing. Local therapy delivered perivascularly may have an effect on events in the neointima and reduce restenosis. The effect of delivering expression vector plasmids for senescent cell-derived inhibitor SDI-1, which regulates cell proliferation, and its antisense, into the perivascular tissue of injured arteries was investigated in a porcine arterial injury model using a needle injection catheter. Transfection efficiency, biological effect and plasmid dissemination were evaluated in arterial and organ tissue sections between 2 days and 4 months. A limited number of adventitial, medial and neointimal cells were transfected up to 4 months. sdi gene transfer did not result in a change in neointima. Transfer of antisense sdi resulted in an increase in neointima after 3 weeks. No DNA plasmid was detected in control tissues. Liposomally-mediated adventitial local gene delivery is feasible and safe using the needle injection catheter in a porcine model. A limited number of cells was transfected, with expression of transfected genes up to 4 months after delivery. A transient biological effect with increased neointima was observed after delivery of the antisense sdi gene.
Assuntos
Terapia Genética/métodos , Músculo Liso Vascular/citologia , Plasmídeos/administração & dosagem , Túnica Íntima/citologia , Análise de Variância , Animais , Sequência de Bases , Western Blotting , Cateterismo , Ciclo Celular , Divisão Celular , Células Cultivadas , DNA/análise , Modelos Animais de Doenças , Artéria Femoral/citologia , Artéria Femoral/lesões , Expressão Gênica , Humanos , Imuno-Histoquímica , Injeções Intralesionais/instrumentação , Dados de Sequência Molecular , Plasmídeos/genética , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Suínos , Porco Miniatura , Fatores de TempoRESUMO
The restenosis rate in vein bypass grafts is higher than in native coronary arteries, and both the cascade of regulatory factors and the vessel reaction may be altered. In this study, vein bypass atherectomy specimens were classified as primary (n = 10) or restenotic (n = 12). Immunohistochemistry with 11 primary antibodies showed low levels of proliferation in both tissues and similar amounts of extracellular matrix components in both primary and restenotic specimens at the time points at which tissue was removed for clinical reasons. Inflammation appeared increased in restenotic specimens. Using in situ hybridization, transforming growth factor-beta1 messenger RNA was detected in both primary and restenotic tissue, with a trend to higher expression in restenosis (8.4 +/- 5.3 vs. 9.4 +/- 7.4 grains/nucleus) and further increased expression in multiple compared with single restenoses (15.1 +/- 6.1 vs. 5.6 +/- 5.1 grains/nucleus, P < 0.05). Hence, there were no great differences in cell proliferation or extracellular matrix formation between primary and restenosis vein graft tissue, in contrast to previously described findings in arterial tissue. This suggests that primary vein graft tissue is already in a chronic 'restenosis-like' state and subsequent injury creates minimal additional upregulation.
Assuntos
Arteriopatias Oclusivas/patologia , Oclusão de Enxerto Vascular/patologia , Veias/transplante , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Arteriopatias Oclusivas/cirurgia , Aterectomia , Divisão Celular , Matriz Extracelular/metabolismo , Humanos , Imuno-Histoquímica , Hibridização In Situ , Inflamação/patologia , Proteínas/metabolismo , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta/genética , Regulação para CimaRESUMO
Low-density lipoprotein (LDL) apheresis is a potent treatment for patients with coronary heart disease and severe hereditary forms of LDL hypercholesterolemia not adequately responsive to drug treatment. Until now, the beneficial effect of aggressive reduction of LDL cholesterol by LDL apheresis on the course of coronary heart disease has been demonstrated in one 3-year study and several studies lasting 2 years. We now report on the clinical course, lipoprotein concentrations, coronary angiograms, and side effects in patients undergoing LDL apheresis for as long as 8.6 years. Thirty-four patients (21 men and 13 women) with coronary heart disease and heterozygous familial hypercholesterolemia (FH) not adequately responsive to lipid-lowering drugs received weekly (four patients biweekly) LDL apheresis for 4.6 +/- 2.6 years under diet and lipid-lowering drug therapy; after 0.5 to 3 years, simvastatin in the maximal tolerable dose was added. The baseline LDL cholesterol concentration was 6.9 +/- 1.6 mmol/L. Combined treatment in the steady state yielded a pretreatment and posttreatment LDL cholesterol concentration of 4.8 +/- 0.9 and 1.8 +/- 0.4 mmol/L, respectively. The calculated interval mean LDL cholesterol was 3.3 +/- 0.6 mmol/L. Evaluation of the coronary angiographies revealed a definite regression of coronary lesions in four patients (11.8%); in 19 patients, there was a cessation of progression. Two patients developed atheromatous lesions in bypass grafts (L.H., 60% stenosis; S.M., occlusion). Of 23 patients eligible for the scoring of anginal symptoms, five (21.7%) reported a reduction of the frequency and severity of angina pectoris. The mean coronary symptom score in 23 patients changed from 1.65 +/- 0.83 at baseline to 1.39 +/- 0.66 at the end of the study. During the whole observation period, we observed three sudden deaths, one nonfatal myocardial infarction, and five patients requiring hospital admission because of unstable angina pectoris, one of which was followed by a transluminal coronary angioplasty. Aggressive reduction of LDL cholesterol with combined LDL apheresis and drugs induced regression of coronary lesions in four of 34 patients and prevented progression in 29 patients for as long as 8.6 years. The effect on LDL and high-density lipoprotein (HDL) cholesterol and lipoprotein(a) [Lp(a)] was comparable with all three apheresis techniques. Therefore, no obvious difference between the three techniques was found regarding changes in coronary lesions.
Assuntos
Ponte de Artéria Coronária , Doença das Coronárias/terapia , Vasos Coronários/metabolismo , Hiperlipoproteinemia Tipo II/terapia , Lipoproteínas LDL/sangue , Plasmaferese , Adulto , Angiografia Coronária/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Doença das Coronárias/sangue , Doença das Coronárias/cirurgia , Feminino , Seguimentos , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/cirurgia , Lipoproteínas LDL/genética , Masculino , Pessoa de Meia-Idade , Plasmaferese/efeitos adversos , Fatores de TempoRESUMO
PURPOSE: To determine the value of non-electrocardiographically triggered contrast material-enhanced magnetic resonance (MR) angiography in assessing the patency of venous and internal thoracic artery (ITA) grafts after coronary bypass surgery. MATERIALS AND METHODS: Twenty-seven patients with 76 coronary bypass grafts (48 venous, 28 ITA) were examined 26.5 months +/- 5.8 after surgery with MR angiography and conventional angiography. MR angiography was performed with a three-dimensional gradient-echo sequence after automated injection of contrast material; contrast agent administration was based on measurement of the individual transit time of the agent. Results of MR angiography were interpreted by two independent observers and compared with results of conventional angiography. RESULTS: The independent interpretations of the MR angiograms agreed with the results of conventional angiography in 96% and 91% of the grafts. After a final consensus reading, sensitivity was 95% for all grafts, 94% for venous grafts, and 96% for ITA grafts. Specificity was 85% for venous grafts and 67% for ITA grafts. Positive predictive value was 95% for all grafts, 94% for venous grafts, and 96% for ITA grafts. CONCLUSION: Non-electrocardiographically triggered contrast-enhanced MR angiography allows reliable assessment of the patency of venous and arterial coronary bypass grafts.
Assuntos
Meios de Contraste , Ponte de Artéria Coronária , Doença das Coronárias/diagnóstico , Gadolínio DTPA , Oclusão de Enxerto Vascular/diagnóstico , Angiografia por Ressonância Magnética/métodos , Adulto , Idoso , Artérias/transplante , Doença das Coronárias/cirurgia , Vasos Coronários/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Ventilação Pulmonar/fisiologia , Sensibilidade e Especificidade , Veias/transplanteRESUMO
Appropriately sized arteries in small animals may be possible models for studying the remodeling process as occurs after arterial balloon injury in humans. Magnetic resonance imaging (MRI) is able to noninvasively image tissue in vivo. To date, small animal angiography models have mostly used research-dedicated instruments and resolution, which are not universally available. Experiments were carried out on a rat aorta model of remodeling in vivo (n=40). Arteries were injured by oversized balloon dilation; control arteries were uninjured. Angiography imaging was performed immediately before sacrifice with an unmodified clinical MRI unit, a 1.5 Tesla MR tomograph with a 20-cm-diameter coil. Longitudinal MRI pictures of the aorta and morphometry of tissue sections to measure luminal and arterial wall areas were analyzed with use of computer-assisted techniques. Comparison of dimensions demonstrated correlation between MRI and histology measurements of the lumen. MRI and morphometry showed a gradual increase in mean luminal area over 6 weeks following injury. The lumen increase correlated with total arterial area and thickness. In this rat aorta model, remodeling documented at histology was followed-up in vivo. The use of such clinical MRI scanners has potential to reduce animal numbers needed to follow-up the remodeling process after therapeutic intervention.
Assuntos
Angioplastia com Balão/efeitos adversos , Aorta/lesões , Angiografia por Ressonância Magnética , Animais , Aorta/patologia , Modelos Animais de Doenças , Tecido Elástico/lesões , Tecido Elástico/patologia , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Angiografia por Ressonância Magnética/instrumentação , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Ratos , Ratos Sprague-Dawley , Análise de Regressão , CicatrizaçãoAssuntos
Vasoespasmo Coronário/diagnóstico , Eletrocardiografia , Doença Mista do Tecido Conjuntivo/diagnóstico , Infarto do Miocárdio/diagnóstico , Escleroderma Sistêmico/diagnóstico , Diagnóstico Diferencial , Endotelinas/sangue , Dedos/irrigação sanguínea , Humanos , Isquemia/diagnóstico , Masculino , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Pele/irrigação sanguíneaRESUMO
No systemic pharmacological treatment has been convincingly shown to reduce the incidence of restenosis after angioplasty in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates post-angioplasty and following stent implantation, as documented in dozens of clinical trials, has encouraged the development of new biotechnological approaches to the treatment of restenosis. Gene therapy and other agents, including antibodies, fusion toxins and ribozymes, have the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation. Mechanical methods of preventing restenosis, for example sophisticated local drug delivery strategies and biodegradable stents using new materials, in combination with novel therapeutic agents or radiation, may also be of use.
RESUMO
No systemic pharmacological treatment has been shown to convincingly reduce the incidence of restenosis after angioplasty in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates post-angioplasty and following stent-implementation shown in dozens of clinical trials has encouraged the development of new technological approaches as treatment. Gene therapy has the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation. Mechanical methods of preventing restenosis, such as sophisticated local drug delivery strategies and biodegradable stents using new materials in combination with gene therapy, may be of use to maximize safety and efficiency.
RESUMO
Late outcome after coronary artery bypass grafting (CABG) mainly depends on the status of graft patency. The recent generation of spiral computed tomography (SCT) scanners may have potential in the long-term follow-up of CABG. In this study, graft patency in patients with internal mammary (IMA) and venous CABG was investigated using SCT and angiography. Forty-nine consecutive patients (age 61 +/- 8 years, 45 men) who had undergone CABG were examined by SCT and angiography 22 +/- 6 months after CABG. In total, 134 bypass grafts (42 IMA and 92 venous grafts) were analyzed. The angiographically determined patency rate of grafts was 86% for IMA (n = 36 of 42) and 74% for venous grafts (n = 68 of 92). By SCT, 32 IMA and 64 venous grafts were diagnosed correctly as patent. Sensitivity was 89% (IMA) and 94% (venous); overall sensitivity was 92%. None of the truly occluded venous grafts was diagnosed falsely patent by SCT (specificity 100%), whereas the specificity of IMA graft visualization was somewhat lower (88%, p = NS [overall 97%]). The accuracy for a patent graft was 88% (IMA) and 96% (venous CABG, p = NS). Compared with previous studies, these data suggest that SCT using one of the recent generation scanners (single scan time 0.75 second) is a highly accurate and relatively noninvasive approach for assessing not only saphenous vein graft patency, but also IMA graft patency. To date, this technique has only limited use in visualizing graft stenosis or distal anastomosis site patency.
Assuntos
Ponte de Artéria Coronária , Vasos Coronários/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Grau de Desobstrução Vascular , Idoso , Angiografia Coronária , Feminino , Humanos , Anastomose de Artéria Torácica Interna-Coronária , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Spherocytosis is the most common of the hereditary hemolytic anemias, with characteristically shaped erythrocytes. An unusually large amount of arterial thrombus was documented in a dissected artery after angioplasty in a patient with spherocytosis. It is hypothesized that the excessive arterial thrombus may have been linked to the spherocytosis.
Assuntos
Trombose Coronária/etiologia , Esferocitose Hereditária/complicações , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angiografia Coronária , Doença das Coronárias/complicações , Doença das Coronárias/terapia , Trombose Coronária/diagnóstico por imagem , Feminino , Humanos , Fatores de RiscoRESUMO
There is increasing experimental evidence that oxidation of LDL plays a major role in the pathogenesis of coronary artery disease (CAD). However, results from clinical studies on LDL oxidation and CAD are not consistent. In most studies only single plasma factors of LDL oxidation have been determined. We studied 207 patients who underwent coronary angiography. They were divided into subjects with CAD (n = 137) and those without CAD (n = 70). We determined the susceptibility of LDL to in vitro oxidation (lag phase), potential prooxidative and antioxidative plasma factors (plasma vitamin E, LDL vitamin E, ascorbate, iron, copper, ferritin, and ceruloplasmin), and markers of in vivo LDL oxidation (autoantibodies to malondialdehyde-modified LDL, oxidized LDL, and thiobarbituric acid-reactive substances), plasma lipids and lipoproteins, smoking habits, and other coronary risk factors in both groups. The lag phase was significantly shorter in patients with CAD than in patients without CAD (101 +/- 38.6 versus 119 +/- 40.6 minutes, P < .01). There was no correlation between the lag phase and the other oxidation parameters or the coronary risk factors. In multivariate regression analyses the lag phase remained significant in all tested models. Our data suggest that a short lag phase of LDL oxidation might be an independent risk factor of CAD.
Assuntos
Ácido Ascórbico/metabolismo , Doença das Coronárias/metabolismo , Metabolismo dos Lipídeos , Lipoproteínas LDL/metabolismo , Lipoproteínas/metabolismo , Vitamina E/metabolismo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Oxirredução , Fatores de TempoRESUMO
Intimal proliferation and functional changes involving vascular smooth muscle cells are key events in the development of atherosclerosis, including restenosis after percutaneous transluminal angioplasty. Nonmuscle myosin (NMM) is required for cytokinesis and has been shown in cultures of vascular smooth muscle cells to undergo changes of isoform expression depending on the stage of proliferation and differentiation. The purpose of this study was to examine the differential expression of the two most recently identified nonmuscle myosin heavy chain isoform II (NMMHC-II) isoforms A and B in atherosclerotic plaque. Primary atherosclerotic and restenotic atherectomy specimens and non-atherosclerotic controls, were analyzed by Western Blot analysis, immunohistochemistry and in situ hybridization. Nonmuscle myosin heavy chain isoform IIA (NMMHC-IIA) was equally expressed in all types of tissue specimens both at the protein and mRNA levels. In contrast, NMMHC-IIB protein was found in restenotic specimens and normal artery but was at very low levels in primary atherosclerotic plaque. By in situ hybridization NMMHC-IIB mRNA levels were significantly greater in restenotic versus primary atherosclerotic lesions. NMMHC-IIB expression is associated with vascular restenosis but is downregulated in stable atherosclerotic lesions, whereas NMMHC-IIA is expressed in both. These results indicate that these new myosin isoforms have different functions and should be regarded separately with respect to smooth muscle proliferation and restenosis. They should prove to be useful molecular markers for the study of atherosclerosis and restenosis.
Assuntos
Artérias/química , Arteriosclerose/metabolismo , Cadeias Pesadas de Miosina/análise , Idoso , Especificidade de Anticorpos , Arteriosclerose/terapia , Aterectomia , Western Blotting , Células Cultivadas , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Músculo Liso Vascular/química , Cadeias Pesadas de Miosina/imunologia , Subfragmentos de Miosina/imunologia , RecidivaRESUMO
Calcium antagonists affect the arterial wall and blood components in many ways: these include their classical vasomotor functions, as well as newly-documented effects on platelet aggregation, rheology, the platelet membrane receptor glycoprotein IIb/IIIa complex and on tissue factor, a glycoprotein that initiates the clotting cascade. Calcium antagonists slow atherogenesis in animals, perhaps through inhibiting calcium incorporation, lowering heart rate or reducing thrombus formation, although no benefits were shown in prospective clinical studies of stenosis progression. However, it has been possible to attenuate proliferation in in vitro and in vivo experimental models. These discoveries are leading to novel calcium antagonist applications in revascularization. They have the potential to act synergistically in thrombolysis, but so far there has been very little evaluation of this. During coronary intervention, the myocardial protective action of calcium antagonists could be of benefit against stunning and in the no-reflow phenomenon. Their action on vasomotor tone and thrombus formation might affect acute closure or restenosis, although clinical studies have not yet shown this, perhaps because systemic administration of calcium antagonists does not achieve a high enough local concentration. Local drug delivery into the arterial wall may have potential. Calcium antagonists could be of use in cardiac surgery by preventing spasm or providing myocardial protection.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Vasos Coronários/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Animais , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Vasos Coronários/fisiopatologia , Humanos , Isquemia Miocárdica/fisiopatologia , Revascularização Miocárdica/métodosAssuntos
Angioplastia Coronária com Balão , Doença das Coronárias/terapia , Angioplastia Coronária com Balão/instrumentação , Divisão Celular/fisiologia , Terapia Combinada , Doença das Coronárias/patologia , Vasos Coronários/patologia , Desenho de Equipamento , Matriz Extracelular/patologia , Técnicas de Transferência de Genes , Substâncias de Crescimento/fisiologia , Humanos , Recidiva , StentsRESUMO
BACKGROUND: The effectiveness of local endovascular photodynamic therapy (PDT) in preventing tissue hyperplasia was evaluated in a vascular injury model. METHODS: Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries (n = 180). Animals (n = 72) were randomly allocated to unidirectional injury only (Group 1), injury followed by drug delivery of photosensitizer with a porous balloon (Group 2), or by local exposure to monochromatic light (Group 3). In Group 4, injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (PDT). Up to 21 days after treatment, all experimental vessels were excised, fixed and processed for histology, immunohistochemistry and transmission electron microscopy. RESULTS: After vascular injury an inflammatory and myoproliferative response was observed in Groups 1, 2 and 3 (mean tissue hyperplasia/media ratio 1.0 +/- 0.5 at 21 days; area tissue hyperplasia: 1.57 +/- 0.9 mm2). Proliferation in injured vascular segments (Group 1-3) reached a maximum at 7 days, with 6%. Only in Group 4, after injury followed by photodynamic therapy, was there no significant vascular response (mean tissue hyperplasia/media ratio 0.3 +/- 0.2: area tissue hyperplasia: 0.1 +/- 0.05 mm2 p < 0.001, proliferating cells 0.3%). CONCLUSION: Vascular response after unidirectional injury was suppressed only by endovascular photodynamic therapy.
Assuntos
Artérias Carótidas , Artéria Femoral , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Doenças Vasculares/tratamento farmacológico , Animais , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/ultraestrutura , Lesões das Artérias Carótidas , Cateterismo Periférico , Divisão Celular/efeitos dos fármacos , Modelos Animais de Doenças , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/lesões , Artéria Femoral/ultraestrutura , Hiperplasia/patologia , Hiperplasia/prevenção & controle , Imuno-Histoquímica , Microscopia Eletrônica , Microscopia de Fluorescência , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/administração & dosagem , Suínos , Doenças Vasculares/patologiaRESUMO
Local photodynamic therapy may have potential in preventing myointimal hyperplasia after angioplasty. In this study, the effect of photodynamic therapy was evaluated in an experimental model of restenosis. Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries. Animals were randomly allocated to four groups: group 1, unidirectional injury only; group 2, injury followed by local delivery of photosensitizer; group 3, injury followed by local exposure to monochromatic light; and group 4, where injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (photodynamic therapy). Seven, 14 or 21 days after treatment, all experimental vessels were excised, fixed and processed for histology. An inflammatory and myoproliferative response was observed after injury in vessels from groups 1, 2 and 3. In group 4, after injury followed by photodynamic therapy, the myoproliferative response was significantly reduced. Thus, in this study, tissue hyperplasia after unidirectional injury was effectively suppressed by photodynamic therapy.