RESUMO
BACKGROUND: Three-month studies of stent-delivered brachytherapy in the rabbit model show reduced neointimal growth. However, intimal healing is delayed, raising the possibility that intimal inhibition is merely delayed rather than prevented. The purpose of this study was to explore the long-term histological changes after placement of beta-emitting radioactive stents in normal rabbit iliac arteries. METHODS AND RESULTS: Three-millimeter beta-emitting (32)P stents (6, 24, and 48 microCi) were placed in normal rabbit iliac arteries with nonradioactive stents as controls. Animals were euthanatized at 6 and 12 months, and histological assessment, morphometry, and analysis of endothelialization were performed. Morphometric measurements demonstrated a >50% reduction in intimal growth and percent lumen stenosis within 24- and 48-microCi stents versus control nonradioactive stents at both 6 and 12 months. However, the 24- and 48-microCi stents also showed delayed healing of the intimal surface, characterized by persistent fibrin thrombus with nonconfluent areas of matrix, incomplete endothelialization, and increased intimal cellular proliferation. Stent edge stenosis was present at 12 months in the 24- and 48-microCi stent groups, characterized by both intimal thickening and negative arterial remodeling. CONCLUSIONS: Inhibition of intimal growth is maintained 6 and 12 months after (32)P beta-emitting stent placement. However, delayed arterial healing, incomplete endothelialization, and edge effects are present.
Assuntos
Artéria Ilíaca/efeitos da radiação , Stents , Animais , Arteriosclerose/patologia , Divisão Celular/efeitos da radiação , Endotélio Vascular/patologia , Endotélio Vascular/efeitos da radiação , Endotélio Vascular/ultraestrutura , Fibrina/metabolismo , Fibrina/efeitos da radiação , Artéria Ilíaca/patologia , Masculino , Microscopia Eletrônica de Varredura , Radioisótopos de Fósforo/farmacologia , Coelhos , Fatores de Tempo , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Túnica Íntima/efeitos da radiaçãoRESUMO
BACKGROUND: Subclinical episodes of plaque disruption followed by healing are considered a mechanism of increased plaque burden. Detailed pathological studies of healed ruptures, however, are lacking. METHODS AND RESULTS: We identified acute and healed ruptures from 142 men who died of sudden coronary death and performed morphometric measurements of plaque burden, luminal stenosis, and smooth muscle cell phenotype. Healed ruptures were found in 61% of hearts and were associated with healed myocardial infarction, increased heart weight, dyslipidemia, and diabetes. Multiple healed rupture sites with layering were frequently found in segments with acute and healed rupture; the percent area luminal narrowing increased with increased numbers of healed sites of previous rupture. The underlying percent luminal narrowing for acute ruptures (mean 79+/-15%) exceeded that for healed ruptures (mean 66+/-14%, P:=0.0001), and the area within the internal elastic lamina was significantly less in healed ruptures than in acute ruptures, when segments were grouped by distance from the ostium. Healed ruptures favored the accumulation of immature smooth muscle cells at repair sites, with a cellular proliferation index of 0.40+/-0.09%, significantly higher than the index at the sites of rupture (P:=0.008). CONCLUSIONS: These data provide evidence that silent plaque rupture is a form of wound healing that results in increased percent stenosis. Healed ruptures occur in arteries with less cross-sectional area luminal narrowing than acute ruptures and are a frequent finding in men who die suddenly with severe coronary atherosclerosis.
Assuntos
Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Morte Súbita Cardíaca/patologia , Diferenciação Celular , Divisão Celular , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Demografia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/patologia , Tamanho do Órgão , Fatores de Risco , Ruptura Espontânea , CicatrizaçãoRESUMO
BACKGROUND: Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored. METHODS AND RESULTS: Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 microgram of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 microgram of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 microgram) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 microgram of paclitaxel CONCLUSIONS: CSG coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days.
Assuntos
Inibidores da Angiogênese/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Paclitaxel/farmacologia , Stents , Inibidores da Angiogênese/farmacocinética , Animais , Divisão Celular/efeitos dos fármacos , Sulfatos de Condroitina , Relação Dose-Resposta a Droga , Fibrina/efeitos dos fármacos , Fibrina/metabolismo , Gelatina , Hemorragia/induzido quimicamente , Hemorragia/patologia , Artéria Ilíaca/efeitos dos fármacos , Artéria Ilíaca/metabolismo , Artéria Ilíaca/patologia , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Paclitaxel/sangue , Paclitaxel/farmacocinética , Polímeros , Coelhos , Fatores de Tempo , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/metabolismo , Túnica Íntima/patologiaRESUMO
BACKGROUND: Neither clinical prediction models nor noninvasive imaging tests that detect coronary artery calcification identify all patients who experience acute coronary events. Variations in culprit plaque morphology may account for these inaccuracies. METHODS AND RESULTS: We compared the 10-year Framingham risk index, histologic coronary calcification, and culprit plaque morphology in 79 consecutive adults with sudden cardiac death. There was a modest relationship between the Framingham risk index and the extent of histologic coronary calcification (r=0.35, P=0.002). Agreement in risk classification between the histologic calcification score and the Framingham risk index occurred in 50 of 79 cases (63.3%, P=0. 039). Either a focus of coronary artery calcification >/=40 micromol/L (62% of cases) or a Framingham risk index score >/= average risk for age (62% of cases) were present in 66 of 79 (83.5%) cases. Cases with plaque erosion (n=22) had significantly less coronary calcification (P=0.003) and lower Framingham risk index (P=0.001) scores than stable (n=27) or ruptured (n=30) plaques. Fourteen of 22 (63.6%) cases of plaque erosion were classified as low risk by both the Framingham risk index and the histologic calcification score. CONCLUSIONS: The prediction of sudden cardiac death using the Framingham risk index and the measurement of coronary calcification are distinct methods of assessing risk for sudden cardiac death. Excessive reliance on either method alone will produce errors in risk classification, particularly for patients at risk of plaque erosion, but their combination may be complementary.
Assuntos
Calcinose/complicações , Doença das Coronárias/complicações , Morte Súbita Cardíaca/etiologia , Adulto , Idoso , Algoritmos , Doença das Coronárias/mortalidade , Doença das Coronárias/patologia , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
Although electrocardiographic (ECG) voltage can be used to estimate left ventricular mass, day-to-day variability of voltage combinations used for this purpose must be established before ECG changes are taken as evidence of progression or regression of hypertrophy. Accordingly, serial ECGs (mean 8 days apart), derived from 10 s samples digitized at 250 Hz, were examined in 78 patients with no intercurrent change in clinical status. The coefficient of variation was calculated as 1 SD of the difference between paired voltage measurements, divided by the average mean value. Coefficient of variation for single leads was 22.3% for SV1, 27.0% for RV5 or RV6, 27.1% for RaVL and 34.7% for SV3. Coefficient of variation was lower for voltage combinations than for individual lead measurements: 18.5% for Sokolow-Lyon voltage (SV1 + RV5 or RV6), 22.3% for Gubner-Ungerleider voltage (R1 + S3) and 24.8% for Cornell voltage (RaVL + SV3). Serial reclassification due to variation above and below standard criteria for left ventricular hypertrophy occurred in only 3% of patients for Sokolow-Lyon voltage and 4% of patients for Cornell voltage in this group. Minute to minute reproducibility of voltage was assessed with electrodes in place in a separate group of 26 patients, and the coefficient of variation was 2.6% for Sokolow-Lyon voltage, 5.9% for Gubner-Ungerleider voltage and 2.9% for Cornell voltage. These data indicate that serial variability of computer-measured ECG voltage combinations is high, due primarily to changes in lead placement and body position, but less than the variability of computer-measured voltage in individual leads.
Assuntos
Cardiomegalia/diagnóstico , Eletrocardiografia , Adulto , Cardiomegalia/fisiopatologia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por ComputadorRESUMO
This study was designed to assess the effects of blood-free reperfusion with oxygenated or unoxygenated intracoronary perfluorochemical (Fluosol-DA 20%) on myocardial perfusion and to determine its mechanism or mechanisms of limiting no reflow. Twenty-four dogs underwent 90 min of coronary occlusion followed by 210 min of reperfusion and were randomized to either: 1) blood-free reperfusion with intracoronary oxygenated perfluorochemical (20 ml/kg per min) for 20 min followed by blood reperfusion (n = 8); 2) intracoronary unoxygenated perfluorochemical administered as in those treated with oxygenated perfluorochemical (n = 8); and 3) blood reperfusion alone (control) (n = 8). Regional myocardial blood flow was serially determined and global myocardial perfusion was assessed by an intravenous injection of the fluorescent dye (thioflavin-S). Quantitative studies were performed to determine neutrophil infiltration and extent of endothelial injury. Hemodynamic variables were similar in all groups. The zone of impaired perfusion (thioflavin negative), expressed as a percent of the left ventricle, averaged 10 +/- 2%, 6 +/- 2% and 3 +/- 1%, in control and unoxygenated and oxygenated perfluorochemical groups, respectively (control versus oxygenated perfluorochemical p less than 0.004). The reduction in thioflavin-negative area with oxygenated perfluorochemical was associated with a notable recovery of endocardial blood flow (0.97 +/- 0.22 vs. control 0.39 +/- 0.08 ml/min per g; p less than 0.04) at 210 min of reperfusion. The number of capillaries plugged by neutrophils (per 200 capillaries) in thioflavin-negative areas was similar with both oxygenated (5.9 +/- 1.4) and unoxygenated perfluorochemical (5.4 +/- 0.8) treatment and was significantly less than that with the control group (18.9 +/- 3.2, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Substitutos Sanguíneos/uso terapêutico , Fluorocarbonos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Sangue , Circulação Coronária/fisiologia , Cães , Combinação de Medicamentos , Endotélio Vascular/patologia , Derivados de Hidroxietil Amido , Masculino , Microscopia Eletrônica , Reperfusão Miocárdica/métodos , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologiaRESUMO
Morphologic correlates of pathologic success or failure were studied at autopsy in 28 patients with 40 coronary arteries that had been subjected to balloon angioplasty. The presence of the following histologic features was evaluated: plaque concentricity or eccentricity, calcification, fibrous or fibropultaceous plaque, medial disruption, luminal thrombus and inflammation. Angioplasty was considered successful (residual cross-sectional luminal area greater than 25%) on pathologic examination in 14 arteries and unsuccessful in 26 arteries. Eccentric plaques were more likely to be successfully dilated than were concentric lesions (p less than 0.05). Six (50%) of 12 fibropultaceous plaques were successfully dilated compared with only 8 (29%) of 28 fibrous plaques. Moderate to severe calcification did not preclude morphologic success. Medial stretching or dissection, or both, was more often associated with a successful result. Thus, plaque morphology may be an important determinant of pathologic outcome after coronary angioplasty.
Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Vasos Coronários/patologia , Idoso , Doença da Artéria Coronariana/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
OBJECTIVES: This study assessed the relation between histologic acute and long-term lumen size after coronary angioplasty. BACKGROUND: Angiographic studies suggest that the creation of a larger acute lumen is associated with a reduced incidence of restenosis. Histologic evaluation of the influence of the acute lumen on late outcome has not been previously reported. METHODS: Detailed histologic examination and planimetry were performed in 28 postmortem coronary arteries subjected to angioplasty at an average of 71 weeks antemortem. The lumen area on each histologic segment was defined as the final lumen area. The lumen area immediately after angioplasty, the acute lumen area, was defined by the sum of the neointimal area plus final lumen. A final lumen area > or = 25% of the arterial area was considered a long-term success; a final lumen area < 25% was considered a long-term failure. RESULTS: Arterial size and neointimal area were similar in long-term successes and failures. In successes, the mean (+/- SD) acute lumen area was greater than in failures (4.1 +/- 1.9 vs. 2.7 +/- 1.4 mm2, respectively, p < 0.001). The acute lumen area as a percent of arterial area was 46 +/- 10% in successes versus 27 +/- 11% in failures (p < 0.0001). The corresponding estimated mean acute lumen diameter stenosis was 24 +/- 8% in successes versus 42 +/- 12% in failures (p < 0.0001). Plaque area was greater in failures (7.1 +/- 3.2 mm2) than in successes (4.8 +/- 2.4 mm2, p < 0.002). CONCLUSIONS: Neointimal proliferation after angioplasty occurs in all dilated coronary arteries, and the amount of neointimal growth is independent of vessel size. The creation of a larger lumen and a larger lumen as a percent of vessel size were associated with an improved long-term histologic patency.
Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/patologia , Doença das Coronárias/terapia , Vasos Coronários/patologia , Túnica Íntima/patologia , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Tempo , Grau de Desobstrução VascularRESUMO
OBJECTIVES: The goal of this study was to demonstrate myocardial infarct extension during reperfusion within the same animal. BACKGROUND: Whether myocardial reperfusion can result in the extension of myocardial necrosis remains controversial. The transformation of reversibly injured myocytes into irreversibly damaged cells after reperfusion has been difficult to demonstrate pathologically. METHODS: New Zealand White rabbits (Group I, n = 10) were subjected to 30 min of coronary artery occlusion and 180 min of reperfusion. Horseradish peroxidase, a tracer protein that permeates the sarcolemma of irreversibly injured myocytes, was used to quantitate myocyte necrosis at the beginning of reperfusion. Within the same heart, infarct size was measured after 180 min of reperfusion by triphenyltetrazolium chloride (TTC) staining. In separate experiments to demonstrate the validity of the model, rabbits were subjected to 30 min of coronary occlusion, followed by intravenous infusion of horseradish peroxidase and rapid induction of death (Group II) or 30 min of occlusion, 180 min of reperfusion with horseradish peroxidase administered after 180 min of reperfusion and TTC staining after induced death (Group III). RESULTS: In Group I, infarct size at the onset of reperfusion, delineated by horseradish peroxidase, measured 45.3 +/- 2.8% of the area of risk and was significantly less than TTC-delineated infarct size after 180 min of reperfusion (59.8 +/- 3.3%, p = 0.0002). By electron microscopy, border areas within the ischemic bed demonstrated irreversibly injured horseradish peroxidase-positive myocytes adjacent to irreversibly injured horseradish peroxidase-negative myocytes, suggesting that further cell death occurred during reperfusion. In Group II, infarcts delineated by horseradish peroxidase after 30 min of coronary occlusion were similar in size to infarcts measured by this tracer in Group I. In Group III, infarcts delineated by horseradish peroxidase at 180 min of reperfusion were similar in size to infarcts measured by TTC and similar to TTC-delineated infarcts measured at 180 min of reperfusion in Group I. CONCLUSIONS: These results provide evidence that there is a subset of myocytes in border areas within the ischemic region that are viable at the beginning of reperfusion but subsequently progress to irreversible injury during the reperfusion period.
Assuntos
Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Animais , Constrição , Vasos Coronários , Peroxidase do Rábano Silvestre , Masculino , Microscopia Eletrônica , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/citologia , Miocárdio/ultraestrutura , Necrose , Coelhos , Fatores de TempoRESUMO
OBJECTIVES: The aim of this study was to assess whether hyperoxic reperfusion contributes to the efficacy of Fluosol 20% or poloxamer 188 for infarct size reduction and whether suppression of polymorphonuclear leukocyte function is responsible for cardioprotection. BACKGROUND: The perfluorochemical Fluosol and its detergent component poloxamer 188 limit myocardial reperfusion-induced injury; however, the underlying mechanism(s) are uncertain. METHODS: A series of in vivo and ex vivo studies were performed in a 30-min temporary coronary occlusion rabbit model. Before reperfusion, rabbits received a 25-ml/kg infusion of 1) Fluosol; 2) poloxamer 188 (equivalent % w/v to Fluosol, 675 mg/kg body weight); or 3) 5% dextrose (control). In protocol A, animals were subjected to either normoxic or hyperoxic reperfusion; in protocols B and C, hyperoxic reperfusion was studied. In protocol B, myocardial blood flow was assessed. In protocol C, polymorphonuclear leukocyte function and myocardial myeloperoxidase were determined. RESULTS: In rabbits subjected to normoxic reperfusion, infarct size (normalized to risk region weight) was not significantly different among groups. In rabbits subjected to hyperoxic reperfusion, infarcts were significantly reduced with both poloxamer 188 and Fluosol treatment compared with control animals (p = 0.05 and p = 0.0004, respectively). Blood flow at 3 h of reperfusion within the ischemic endocardium was greater in the Fluosol and poloxamer 188 groups than in the control group (p = 0.001 and p = 0.08, respectively). Myeloperoxidase activity was not affected by treatment, nor was there suppression of polymorphonuclear leukocyte function. CONCLUSIONS: Fluosol and poloxamer 188 reduce infarct size in rabbits subjected to hyperoxic reperfusion. Suppression of polymorphonuclear leukocyte function was not demonstrated, suggesting a greater role for increased arterial oxygen delivery in salvaging ischemic myocardium.
Assuntos
Circulação Coronária , Fluorocarbonos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Reperfusão Miocárdica , Neutrófilos/fisiologia , Oxigênio/administração & dosagem , Poloxaleno/uso terapêutico , Animais , Circulação Colateral , Detergentes , Combinação de Medicamentos , Fluorocarbonos/administração & dosagem , Derivados de Hidroxietil Amido , Infusões Intravenosas , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Reperfusão Miocárdica/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/enzimologia , Neutrófilos/efeitos dos fármacos , Peroxidase/metabolismo , CoelhosRESUMO
OBJECTIVES: This study was performed to define the evolution of lesion morphology and its relation to thrombus formation and smooth muscle cell proliferation after experimental coronary stent placement. BACKGROUND: Restenosis after percutaneous revascularization may develop because of thrombus accumulation and smooth muscle cell proliferation. In animal models of restenosis, thrombus may assume a significant role in neointimal formation by providing an absorbable matrix into which smooth muscle cells proliferate. METHODS: Twenty-eight oversized stents were placed in the coronary arteries of 23 juvenile domestic pigs. The histologic degree of vessel injury, lesion morphometry and smooth muscle cell proliferation measured by immunolocalization with a monoclonal antibody to proliferating cell nuclear antigen (PCNA) were assessed at 24 h and 7, 14 and 28 days after stent placement. RESULTS: The area of thrombus was minimal at 24 h ([mean +/- SE] 0.44 +/- 0.12 mm2). Neointimal area at 7 days (0.72 +/- 0.20 mm2) was similar to the area of thrombus, followed by a significant increase at 14 days (3.15 +/- 0.39 mm2) and 28 days (3.30 +/- 0.28 mm2) (p < 0.0036, 24 h and 7 days vs. 14 and 28 days). At 14 and 28 days, neointimal thickness correlated with the histologic degree of vessel injury (p < 0.003). In arteries with severe injury, the increase in neointimal thickness is accounted for by replacement of the damaged media. The smooth muscle cell proliferation index was 18.6 +/- 3.5% at 7 days compared with 9.6 +/- 1.3% by 14 days (p = 0.0247) and declined to 1.1 +/- 0.97% by 28 days (p < 0.008, 7 and 14 days vs. 28 days). CONCLUSIONS: Early thrombus formation is minimal, and thrombus accounts for a small portion of subsequent neointimal formation. Smooth muscle cell proliferation and matrix formation are the major factors relating to neointimal formation in this proliferative model of restenosis. The evolution of neointimal formation after coronary stenting shows maximal smooth muscle cell proliferation at 7 days, with a decline to low levels by 28 days. Therefore, these data may be useful for developing effective therapies for restenosis.
Assuntos
Doença das Coronárias/patologia , Trombose Coronária/patologia , Vasos Coronários/lesões , Músculo Liso Vascular/patologia , Stents , Animais , Divisão Celular/fisiologia , Vasos Coronários/patologia , Antígeno Nuclear de Célula em Proliferação/análise , Recidiva , Suínos , Fatores de Tempo , Túnica Íntima/patologia , Túnica Média/patologiaRESUMO
OBJECTIVES: We sought to evaluate the plaque and patient variables related to arterial remodeling responses of early, de novo atherosclerotic lesions involving the left coronary artery. BACKGROUND: Coronary artery remodeling is a lesion-specific process involving either enlargement or shrinkage of atherosclerotic coronary arteries. There are little histologic data available correlating plaque morphologic and patient clinical characteristics with the degree and type of arterial remodeling in early atherosclerosis. METHODS: We studied 736 serial arterial sections from the left coronary system of 97 autopsy cases (mean age 33 +/- 11 years) by correlating the arterial remodeling response to plaque with demographic, serologic and histologic variables. Using the most proximal section as a reference, and considering the expected degree of internal elastic lamina tapering, remodeling was classified as positive (including neutral remodeling or compensatory enlargement) or negative. RESULTS: Remodeling was classified as positive in 84.3% (compensatory in 30.6%) and negative in 15.7% of sections with an overall mean luminal stenosis of 10.4 +/- 9.9%. In the lesions with the greatest arterial cross-sectional narrowing from each case, compensatory enlargement was associated with higher high-density lipoprotein (HDL) cholesterol (59.4 +/- 27.2 mg/dl) compared with either neutral (49.3 +/- 15.5 mg/dl) or negative remodeling (30.4 +/- 5.2 mg/dl; p = 0.019). In subjects with advanced atherosclerosis (maximum American Heart Association histologic grade 5 atherosclerosis), there was a modest linear relationship between higher HDL cholesterol and the propensity for positive remodeling (r2 = 0.37; p = 0.025). On multivariate analysis, only HDL cholesterol was related to the arterial remodeling response. CONCLUSIONS: Negative arterial remodeling occurs in early atherosclerosis. Higher HDL cholesterol may favor positive remodeling.
Assuntos
HDL-Colesterol/sangue , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Adolescente , Adulto , Idoso , Análise de Variância , Autopsia/métodos , Autopsia/estatística & dados numéricos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/classificação , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: This study evaluated the delivery characteristics and vascular response to placement of a novel balloon-expandable stent in swine with experimentally induced atherosclerosis. BACKGROUND: The Multi-Link stent is a balloon-expandable stainless steel stent with an interconnected ring structure designed to provide a high degree of compressive resistance while preserving longitudinal flexibility. The placement characteristics and vascular response to this stent in atherosclerotic coronary arteries have not been characterized. METHODS: We tested the delivery characteristics and vascular response to the Multi-Link stent in 19 miniature swine with experimentally induced coronary atherosclerosis created in 37 coronary artery segments by overstretch balloon injury and high cholesterol diet. Quantitative coronary angiography was used to define stent performance characteristics, such as lesion dilation and compressive resistance. Pathologic assessment of the stented arteries was used to evaluate the immediate and long-term vascular response to stent placement. RESULTS: Nineteen (95%) of 20 stents were successfully implanted in the left anterior descending (n = 11), left circumflex (n = 7) or right (n = 1) coronary artery. The baseline angiographic minimal lumen diameter of the stented coronary segment was 2.48 +/- 0.09 mm (reference diameter 2.87 +/- 0.06 mm, mean +/- SE) and increased to 2.82 +/- 0.05 mm (p < 0.001) after stent placement. The balloon-inflated stent diameter was 2.98 +/- 0.06 mm with minimal recoil to a final minimal lumen diameter of 2.82 +/- 0.06 mm at 15 min after implantation (p = 0.001). Angiographic and histologic follow-up at 72 h (n = 7), 14 days (n = 4) and 56 days (n = 8) demonstrated that all stents were patent, without evidence of migration, intraluminal filling defects or side branch occlusion. At 56 days, mean neointimal thickness was significantly greater at the stent wire sites in the region of the plaque where the media was absent than the stent wire sites, where the internal elastic lamina was intact with underlying normal media (0.48 +/- 0.01 vs. 0.27 +/- 0.02 mm, p < 0.0001). Compared with the nonstented atherosclerotic lesions, after 56 days the stented vessels had a mildly reduced lumen area when normalized to the proximal reference vessel (2.81 +/- 0.27 vs. 2.68 +/- 0.30 mm2, p = 0.07). The mean change in the area within the external elastic lamina relative to a normal proximal reference segment was significantly greater in stented vessels (1.45 +/- 0.34 mm2) than nonstented atherosclerotic vessels (0.44 +/- 0.28 mm2, p = 0.033). CONCLUSIONS: Morphologic data confirm that the principal beneficial effect of stent placement is vessel expansion and attenuation of constrictive remodeling. In vessels with eccentric atherosclerotic fibrocellular plaques, the presence of normal media underlying the stent determines the degree of neointimal formation. These data may be useful in understanding the mechanism of stent restenosis in patients with prior percutaneous transluminal coronary angioplasty.
Assuntos
Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/terapia , Stents , Túnica Íntima/patologia , Angioplastia Coronária com Balão/efeitos adversos , Animais , Doença da Artéria Coronariana/patologia , Hiperplasia , SuínosAssuntos
Stents Farmacológicos , Doença das Coronárias/mortalidade , Doença das Coronárias/terapia , Reestenose Coronária/prevenção & controle , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Stents Farmacológicos/efeitos adversos , Stents Farmacológicos/economia , Stents Farmacológicos/normas , Métodos Epidemiológicos , França , Humanos , Infarto do Miocárdio/mortalidade , Revascularização Miocárdica/efeitos adversos , Revascularização Miocárdica/normasRESUMO
AIM: sudden coronary death (SCD) in older individuals is generally associated with extensive coronary atherosclerosis, although it may be the first manifestation of ischaemic heart disease. In younger age-groups, SCD may occur in the presence of less severe disease. We sought to (1) examine the extent of coronary atherosclerosis in young victims of SCD compared with age- and sex-matched controls, (2) analyse the composition of atherosclerotic plaques in these patients, (3) identify the predominant mechanism of SCD, and (4) evaluate the possibility of detecting this mechanism on the basis of morphologic plaque features, in particular presence and amount of lipid accumulation and calcific deposits. METHODS AND RESULTS: coronary arteries were obtained at autopsy from 28 victims of SCD under age 50 with no prior clinical manifestation of ischaemic heart disease (IHD) and no myocardial scar formation and from 16 age- and sex-matched subjects dying of noncardiac causes out of hospital. Sections of all available major coronary arteries were cut in 5-mm intervals to yield a total of 1357 histologic sections, which were analysed using digitised planimetry. Victims of SCD had significantly more major coronary arteries per subject with luminal area narrowing > or = 75% than controls (on average, 2.1 vs. 0.2). Plaque area per histologic section was 5.1 +/- 2.1 mm(2) in SCD cases and 2.0 +/- 0.9 mm(2) in controls (P < 0.001). The major constituent of all plaques was fibrous tissue. Lipid core area per section was 0.49 +/- 0.59 mm(2) in SCD cases and 0.004 +/- 0.01 mm(2) in controls (P < 0.001), and calcified plaque area was 0.18 +/- 0.19 mm(2) in SCD cases and 0.02 +/- 0.05 mm(2) in controls (P < 0.001), both defining significant differences between SCD cases and controls. Arterial thrombosis, most often with underlying plaque rupture was the mechanism of SCD in > 80% of the cases. Considering histologic sections with > or = 50 and with > or = 75% area stenosis, plaque rupture was independently predicted by lipid core area. Calcific deposits were a frequent feature of plaque rupture but were only associated with it in univariate analysis. CONCLUSIONS: the extent and severity of coronary atherosclerosis in young victims of SCD as the first manifestation of IHD was substantially greater than in age-and sex-matched controls and comparable with that previously reported in SCD cases with a broader age range. Lipid core and calcified plaque areas provided for excellent separation between the two groups, which may have implications for identifying persons at increased risk for SCD by non invasive visualisation and assessment of the coronary arteries.
Assuntos
Doença da Artéria Coronariana/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Adulto , Índice de Massa Corporal , Calcinose/epidemiologia , Calcinose/patologia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/patologia , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Vasos Coronários/química , Vasos Coronários/patologia , Feminino , Fibrose , Humanos , Hiperplasia , Lipídeos/análise , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ruptura EspontâneaRESUMO
Compensatory arterial enlargement in response to atherosclerosis has been demonstrated for the left main coronary artery. Only limited data is available on the interaction of patient characteristics and atherosclerosis with coronary artery dimensions. The purpose of the present study was to evaluate the influence of age, race, body habitus, heart weight and atherosclerosis on coronary artery dimensions of young males. Hearts from 137 young men (age 32 +/- 8 years; 78 black, 59 white) with unnatural deaths (homicide, suicide, accident, drug overdose) were perfusion-fixed, and histologic sections were obtained from the left main, proximal left anterior descending and left circumflex coronary arteries. Computerized planimetry was performed on Movat stained sections. Multiple regression analysis was used to evaluate the relative contribution of plaque size, age, race, heart weight and body surface area on coronary dimensions and compensatory enlargement in response to atherosclerosis. In the left anterior descending and left main coronary arteries, black race, body surface area and age were independent predictors of increased lumen area. In the left circumflex, age was a predictor of lumen area. Plaque area, black race and body surface area independently predicted increased area enclosed by the internal elastic lamina area. There was compensatory enlargement of internal elastic lamina with increasing plaque size in both races in the three arteries, but the percent luminal stenosis was greater in whites due to smaller artery size. Luminal narrowing did not develop until plaques occupied 30% of internal elastic lamina area. Among a population of young men with non-cardiac deaths, blacks have larger lumen and area enclosed by internal elastic lamina than whites. Age and body surface area are major determinants of lumen areas, and compensatory arterial enlargement was seen in all examined arteries in the present study.
Assuntos
Antropometria , Arteriosclerose/patologia , Vasos Coronários/patologia , Adolescente , Adulto , Fatores Etários , Superfície Corporal , Feminino , Coração/anatomia & histologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Tamanho do Órgão , Grupos RaciaisRESUMO
PURPOSE: Studies have shown a potential benefit of brachytherapy in preventing restenosis. However, the effects of intravascular radiation on arterial healing have not been well-established. The purpose of this study was to explore the histologic changes following placement of beta-emitting radioactive stents in arteries focusing on intimal responses and endothelialization. METHODS AND MATERIALS: 3.0-mm beta-emitting (32)P stents (6-microCi and 24-microCi) were placed in rabbit iliac arteries with nonradioactive stents serving as controls. Animals were euthanized at 3 months and histologic assessment, morphometry, and analysis of endothelialization were performed. RESULTS: The lumen areas of 24-microCi stents (4.24 +/- 0.22 mm(2), p < 0.0007) and 6-microCi stents (4.23 +/- 0.49 mm(2), p < 0.01) were larger than control stents (3.64 +/- 0.44 mm(2)). The mean lumen percent stenosis was 11. 4 +/- 3.0% in the 24-microCi stents (p < 0.007 vs. 6-microCi stents and p < 0.0001 vs. control stents), 18.7 +/- 6.4% in the 6-microCi stents (p < 0.02 vs. control stents), and 25.0 +/- 4.9% in control stents. Neointimal area was least in the 24-microCi stent (54.2% smaller than controls and 42.7% smaller than 6-microCi); the neointimal area of the 6-microCi stents was 20.0% less than controls. The control stent neointima consisted of smooth muscle cells in a proteoglycan and collagen matrix. In contrast, the intima of radioactive stents showed persistent fibrin thrombus with nonconfluent areas of matrix. Actin-positive intimal cell density was reduced with radioactive stenting, but intimal cell proliferation was increased. Evans blue staining, an indicator of increased endothelial permeability, was present on 86 +/- 9% of the stented segment of 6-microCi stents vs. 10 +/- 11% in controls (p < 0.0001). Scanning electron microscopy demonstrated endothelialization of 97 +/- 8% of the intimal surface of control stents; in contrast, the midportion of the 6-microCi stents remained nonendothelialized, and only 33 +/- 15% (p < 0.0001) of the entire stent surface was endothelialized. CONCLUSIONS: (32)P beta-emitting stents reduce neointimal growth, but healing is incomplete with poor endothelialization at 3 months. Longer-term studies with complete arterial healing are needed to determine whether there is sustained neointimal inhibition by stent-delivered brachytherapy.
Assuntos
Radioisótopos de Fósforo/uso terapêutico , Lesões Experimentais por Radiação/fisiopatologia , Stents , Túnica Íntima/efeitos da radiação , Cicatrização/efeitos da radiação , Animais , Divisão Celular/efeitos da radiação , Endotélio Vascular/fisiologia , Endotélio Vascular/efeitos da radiação , Artéria Ilíaca/fisiologia , Artéria Ilíaca/efeitos da radiação , Masculino , Microscopia Eletrônica de Varredura , Coelhos , Radiobiologia , Dosagem Radioterapêutica , Túnica Íntima/fisiologia , Cicatrização/fisiologiaRESUMO
PURPOSE: Long-term preclinical studies using continuous, low-dose-rate vascular brachytherapy with (32)P beta-emitting stents have yielded largely disappointing results. In contrast, a shorter half-life, higher dose-rate (90)Y beta-emitting stent more closely mimics the delivery dose rate characteristics of clinically effective beta- and gamma-wire and balloon brachytherapy devices. We evaluated the dose response characteristics of a (90)Y beta-emitting stent in the canine coronary injury model and hypothesized that this device would reduce neointimal formation. METHODS: Seventy-seven (90)Y beta-emitting coronary stents (15 mm BXTM, 3.0- and 3.5-mm diameter) were implanted in 26 normal dogs (20-25 kg) using a randomized, blinded study design. Stent activity included nonradioactive controls (n = 24), 4.5 microCi (n = 15), 8 microCi (n = 12), 16 microCi (n = 18), and 32 microCi (n = 8). Histologic endpoints were assessed at 3 months. RESULTS: Luminal stenosis and neointimal area were similar in control stents and low-activity (4.5 and 8 microCi) (90)Y stents. Higher activity stents (16 and 32 microCi) were associated with significant adverse effects. Frequent total occlusions (5 of 18 stents, 28%; p = 0.008) and a 40% increase in neointimal area (p = 0.024 vs. control) occurred in the 16 microCi group. Incomplete neointimal healing and a trend for reduced neointimal cell density were evident only in the 16- and 32-microCi group. CONCLUSION: Despite unique characteristics (2.7 day half-life and a higher dose rate) of (90)Y beta-emitting coronary stents, they have an adverse effect on neointimal formation, including frequent total occlusions at high activity levels. Incomplete healing, present 90 days (33 half-lives) after stent placement, indicates prolonged recovery from radiation injury.
Assuntos
Braquiterapia/métodos , Vasos Coronários/efeitos da radiação , Stents , Túnica Íntima/efeitos da radiação , Radioisótopos de Ítrio/uso terapêutico , Animais , Braquiterapia/instrumentação , Vasos Coronários/lesões , Cães , Relação Dose-Resposta à Radiação , Método Duplo-Cego , Meia-Vida , Radioisótopos de Fósforo/uso terapêutico , Distribuição Aleatória , Stents/efeitos adversos , Túnica Íntima/lesõesRESUMO
There are multiple substrates for coronary thrombosis overlying an atherosclerotic plaque. The most common, plaque rupture, consists of an interruption of a thin fibrous cap overlying a lipid rich core. Plaque rupture is a result of macrophage infiltration and matrix degradation, is often seen in calcified plaques, and is highly associated with hypercholesterolemia. A less common substrate, plaque erosion, is not associated with elevated cholesterol and is the prime cause of coronary thrombosis in premenopausal women. The characteristic histologic features are abundant surface smooth muscle cells and proteoglycans, and a small or absent lipid rich core. The mechanisms of plaque erosion are unclear, and there are no consistent risk factors, although patients are often smokers.
Assuntos
Doença da Artéria Coronariana/patologia , Trombose Coronária/patologia , Adulto , Vasos Coronários/lesões , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ruptura , Fatores SexuaisRESUMO
Sudden death occurs in a small but important subset of patients with mitral valve prolapse (MVP). Clinical criteria for identifying patients at risk for sudden death have been elusive. To determine if certain morphologic characteristics were present in hearts from patients with sudden cardiac death and MVP, autopsy hearts from persons with sudden death and isolated MVP who were previously asymptomatic or had a history of cardiac arrhythmias (n = 27) were compared with (1) hearts from patients with congestive heart failure (CHF) and mitral regurgitation (MR) secondary to MVP (n = 14), and (2) hearts from persons dying from non-cardiac causes in which MVP was an incidental finding (n = 19). Patients who died suddenly were younger than both patients with MR/CHF and incidental cases (37 +/- 10 vs 65 +/- 16 and 58 +/- 21 years, respectively, p less than 0.001). Mitral valve annular circumference, anterior and posterior mitral valve leaflet lengths, posterior mitral valve thickness, and presence and extent of endocardial plaque were greater in hearts from patients with sudden death than hearts from those with incidental MVP. Hearts from patients with MR/CHF weighed significantly more, had greater left and right atrial cavity sizes and left ventricular cavity diameter than hearts from both sudden death and incidental cases.