ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background The relative absence of coronary atherosclerosis in premenopausal women has been established. Estrogen is presumed to play a role in the protection of coronary arteries from atherosclerosis, and part of this protective effect appears to be mediated by amelioration of serum lipid profiles. However, all of the atheroprotective effect of estrogen is not explained by alteration of serum lipids. In this study, we attempt to identify evidence of estrogen receptors in coronary artery specimens of female patients and in human vascular smooth muscle cells.Methods and Results Postmortem coronary artery specimens were obtained from premenopausal (n=18) and postmenopausal (n=22) women who died with significant coronary artery disease (n=19) and from noncardiac causes with normal coronary arteries (n=21). Sections were examined for evidence of estrogen receptor expression using a monoclonal antibody stain. Radioligand binding assays for estrogen receptors were performed on human vascular smooth muscle cells in culture, and gel retardation assays were performed to confirm the presence of functional estrogen receptors. Estrogen receptor expression was identified by immunostaining in a total of 21 coronary arteries, with the majority of normal arteries (15 positive of 21 total, P=.0117) demonstrating evidence of estrogen receptor expression. Conversely, a minority (6 of 19, P=NS) of atherosclerotic arteries were positive for estrogen receptor expression. Furthermore, the relation between estrogen receptor expression and absence of coronary atherosclerosis was most evident in premenopausal subjects, with 10 of 12 normal arteries in this group demonstrating evidence of estrogen receptors, whereas only 1 of 6 atherosclerotic coronary arteries was positive (P=.0062). Radioligand binding assays confirmed the presence of estrogen receptors at significant concentrations in intact human vascular smooth muscle cells. Gel retardation assays also documented the presence of functional estrogen receptors in extracts from human vascular smooth muscle cells.Conclusions This investigation provides evidence of estrogen receptors in smooth muscle cells from human coronary arteries. The demonstrated relation between the presence of the receptors and the absence of atherosclerosis in premenopausal women suggests that these receptors may play a functional role in coronary atheroprotection. (Circulation. 1994;89:1501-1510.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In this study, we demonstrate, for the first time, the localization of insulin-like growth factor I (IGF-I) in de novo and restenotic human coronary atherectomy plaques by using immunocytochemical techniques. Smooth muscle cells (SMCs) exhibiting the synthetic phenotype contained a statistically significant higher concentration of IGF-I than SMCs of the contractile phenotype or SMCs from normal coronary arteries. In addition, we provide data to suggest that the long-acting somatostatin analogues octreotide and angiopeptin inhibit IGF-I- and basic fibroblast growth factor (b-FGF)-induced human coronary artery SMC proliferation. Platelet-derived growth factor (PDGF)-stimulated cultures were minimally affected by the addition of octreotide but were significantly inhibited by angiopeptin. All three growth factors stimulated SMC migration in a dose-dependent manner. The somatostatin analogues tested had no effect on growth factor-stimulated SMC migration. Our data suggest that by reducing SMC proliferation, somatostatin analogues may have clinical usefulness in reducing the high incidence of restenosis observed after percutaneous transluminal coronary artery interventions. (Circulation. 1994;89:1511-1517.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Catheter-based systems are being developed to deliver drugs directly into the vessel wall. Pressure-mediated trauma and lack of homogeneous delivery are key limitations of these approaches.Methods and Results We studied a new catheter-based delivery system that uses electrical current to force the drug into the vessel wall. The in vivo feasibility of this approach has been assessed by delivering Iodine-125-hirudin into porcine carotid arteries. Vascular levels of hirudin after active iontophoresis (4 mA/cm2, 5 minutes) were 80-fold greater than those achieved by passive diffusion (without electricity). Tissue hirudin levels declined over time; by 1 hour after delivery, 80% of the drug had left the vessel wall, and by 3 hours later, the levels of hirudin within the wall were similar to those achieved by passive diffusion. Autoradiography revealed distribution of the drug throughout the entire circumference of the arterial wall within the intima, media, and adventitia. Iontophoresis-mediated vessel wall trauma was minimal (less than 10% endothelial denudation and medial smooth muscle cell damage). Balloon injury after local delivery changed neither kinetics nor distribution of the drug into the arterial wall.Conclusions (1) High local concentrations of hirudin in the arterial wall may be achieved with the iontophoretic balloon catheter. (2) The drug is distributed throughout the entire vessel wall without significant damage. (3) The retention of hirudin in the arterial wall is time dependent. (4) This technique might be useful to deliver therapeutic agents before or after percutaneous vascular interventions. (Circulation. 1994;89:1518-1522.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Platelets contain several factors that inhibit heparin. This study was designed to assess the heparin-neutralizing activity present in acute, platelet-rich arterial thrombi formed at sites of arterial injury in animals.Methods and Results Platelet-rich thrombi (n=3) were induced in pig coronary arteries by balloon catheter-mediated arterial injury. Soluble extracts were prepared from each thrombus and assayed for the capacity to inhibit heparin in an in vitro clotting assay (activated partial thromboplastin time). Mean heparin-neutralizing activity was 28 U of heparin neutralized per milliliter of thrombus, indicating that 1 vol of coronary thrombus completely inhibited the heparin present in 140 vols of therapeutically anticoagulated (0.2 U heparin/mL) plasma. In contrast, thrombus extracts had no effect on the anticoagulant activity of hirudin, a direct-acting thrombin inhibitor. The heparin-neutralizing activity present in coronary thrombi bound to heparin-agarose and was eluted from it by 1.4 mol/L NaCl, suggesting that platelet factor 4 mediated the antiheparin effect of thrombi. Consistent with this hypothesis, a murine monoclonal antibody to rabbit platelet factor 4 nearly completely inhibited the heparin-neutralizing activity present in rabbit thrombi (n=3) generated by carotid artery injury.Conclusions Extracts prepared from platelet-rich arterial thrombi significantly inhibit the in vitro anticoagulant potency of heparin but not of hirudin. This antiheparin effect appears to be mediated by platelet factor 4. These results are consistent with the hypothesis that localized inhibition of heparin at sites of platelet activation may reduce its antithrombotic efficacy. In addition, they suggest an additional mechanism for the apparent superiority of hirudin over heparin as a thrombin inhibitor at sites of arterial injury. (Circulation. 1994;89:1523-1529.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Cholesterol lowering over 1- to 3-year trials is associated with modest regression or no progression of focal coronary artery stenoses compared with progression in controls, a decrease in cardiac events proportionately more than the modest improvement in percent stenosis, and in experimental animals improved endothelial-mediated coronary vasodilation.Methods and Results Accordingly, we hypothesized that there would be improvement in size and severity of perfusion abnormalities by rest-dipyridamole positron emission tomography (PET) imaging in a randomized intensive cholesterol-lowering trial with each patient studied after a baseline control period, a 90-day intensive cholesterol-lowering treatment, and a final control period off cholesterol-lowering regimens. Completely automated, objective measures of size and severity of perfusion abnormalities on rest-dipyridamole PET images were made by computer algorithm in 12 patients with coronary artery disease. There were statistically significant decreases (improvement) in size and severity of perfusion abnormalities by rest-dipyridamole PET on comparison of baseline control with perfusion abnormalities after intensive 90-day cholesterol lowering and significant increases (worsening) in size and severity after the final control period, respectively, as follows. (1) The percent of left ventricle outside 2.5 SD of normal values on the dipyridamole-to-rest ratio image of normalized counts was 22+-20% after the initial control period, 13+-14% after the treatment period, and 26+-22% after the final control period with a significant decrease (improvement) occurring between the initial control and treatment periods (P=.02) and an increase (worsening) occurring between the treatment and final control periods (P=.009). (2) The percent of left ventricle with a ratio of <=0.66 in the dipyridamole-to-rest ratio image of normalized counts was 11+-13% after the initial control period, 5.8+-10% after the treatment period, and 14+-19% after the final control period with a significant decrease (improvement) occurring between the initial control and treatment periods (P=.04) and an increase (worsening) occurring between the treatment and final control periods (P=.02). (3) The myocardial quadrant on the polar display with the lowest average activity expressed as a percent of maximal activity was 0.81+-0.18 after the initial control period, 0.87+-0.014 after the treatment period, and 0.77+-0.23 after the final control period with significant improvement occurring between the initial control and treatment periods (P=.05) and worsening occurring between the treatment and final control periods (P=.05).Conclusions These results suggest that relatively short-term, intensive cholesterol lowering over 90 days improves myocardial perfusion capacity before anatomic regression of stenoses occurs and that such improvement, or deterioration after withdrawal of lipid-lowering treatment, can be followed noninvasively by dipyridamole PET, reflecting the integrated flow capacity of the entire coronary arterial/arteriolar vascular system affected by diffuse atherosclerosis. (Circulation. 1994;89: 1530-1538.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Recent research indicates that levels of conventional coronary heart disease risk factors in children are related to the premature development of atheroma. It is therefore important to determine how risk factors might be modified on a population scale in children.Methods and Results In 1985, the Australian Schools Health and Fitness Survey was conducted on a representative sample of Australian schoolchildren aged 7 to 15 years. In children aged 9, 12, and 15, data on plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were obtained along with measurements of blood pressure, fitness, and body fatness. From an original sample of 2400 in these three age categories 1919 underwent the full set of measurements. Univariate analysis of these data revealed a strong association between body fatness and plasma lipids. There was no significant association between fitness (measured as physical work capacity at a heart rate of 170 beats per minute per kilogram of lean body mass) and plasma lipids, but a significant negative association was found for fitness and systolic blood pressure (r=-.12, P<.001). Multiple regression analysis revealed that the association of fitness with systolic blood pressure was only partly accounted for by the confounding effect of lower body fatness in fitter children.Conclusions These data collected on a representative sample of children under standardized conditions confirm a previous finding of a link between fitness and blood pressure in schoolchildren and also support a growing consensus that fitness is only weakly linked to plasma lipids and lipoproteins in children and adolescents. (Circulation. 1994;89:1539-1544.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Although coronary thrombosis plays a critical role in the pathogenesis of unstable angina and non-Q-wave myocardial infarction (NQMI), the effects of thrombolytic therapy in these disorders is not clear. Also, the role of routine early coronary arteriography followed by revascularization has not been established.Methods and Results Patients (n=1473) seen within 24 hours of ischemic chest discomfort at rest, considered to represent unstable angina or NQMI, were randomized using a 2 x 2 factorial design to compare (1) TPA versus placebo as initial therapy and (2) an early invasive strategy (early coronary arteriography followed by revascularization when the anatomy was suitable) versus an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients were treated with bed rest, anti-ischemic medications, aspirin, and heparin. The primary end point for the TPA-placebo comparison (death, myocardial infarction, or failure of initial therapy at 6 weeks) occurred in 54.2% of the TPA-treated patients and 55.5% of the placebo-treated patients (P=NS). Fatal and nonfatal myocardial infarction after randomization (reinfarction in NQMI patients) occurred more frequently in TPA-treated patients (7.4%) than in placebo-treated patients (4.9%, P=.04, Kaplan-Meier estimate). Four intracranial hemorrhages occurred in the TPA-treated group versus none in the placebo-treated group (P=.06). The end point for the comparison of the two strategies (death, myocardial infarction, or an unsatisfactory symptom-limited exercise stress test at 6 weeks) occurred in 18.1% of patients assigned to the early conservative strategy and 16.2% of patients assigned to the early invasive strategy (P=NS). In the latter, the average length of initial hospitalization, incidence of rehospitalization within 6 weeks, and days of rehospitalization all were significantly lower.Conclusions In the overall trial, patients with unstable angina and NQMI were managed with low rates of mortality (2.4%) and myocardial infarction or reinfarction (6.3%) at the time of the 6-week visit. These results can be achieved using either an early conservative or early invasive strategy, the latter resulting in a reduced incidence of days of hospitalization and of rehospitalization and in the use of antianginal drugs. The addition of a thrombolytic agent is not beneficial and may be harmful. (Circulation. 1994;89:1545-1556.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID