ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundMice in which the gene encoding NPR-A, a guanylyl cyclase-linked natriuretic peptide receptor, has been disrupted were used to examine the contribution of natriuretic peptides to maintaining pulmonary vascular homeostasis in normal- and low-oxygen environments.Methods and Results-Wild-type (+/+), heterozygous (+/-), and homozygous null mutants (-/-) were studied. The response of the pulmonary vasculature to atrial, B-type, and C-type natriuretic peptides (ANP, BNP, and CNP) during acute hypoxia was studied in isolated perfused lungs. Right ventricular systolic pressure (RVSP), RV weight, and pulmonary vascular remodeling were measured in each genotype exposed to normal air and after 7 and 21 days in a hypoxic atmosphere (10% O2). ANP and BNP (300 ng) reduced pulmonary artery pressure during acute hypoxiainduced pulmonary vasoconstriction in +/+ mice, but this effect was attenuated in +/- and absent in -/- mice. CNP (600 ng) had little effect in all 3 genotypes. RVSP and RV weight were similar in the 3 genotypes housed in a normal-O2environment. Seven and 21 days of hypoxia produced a pronounced and significantly greater increase in RVSP and RV weight in -/- mice compared with +/+ or +/- mice and more rapid muscularization of distal pulmonary arterioles.ConclusionsANP and BNP do not contribute to maintaining normal pulmonary artery pressure but play an important role in attenuating the pulmonary vascular response to hypoxia. NPR-A mediates the vasorelaxant effect of ANP in pulmonary vasculature. (Circulation. 1999;99:605-607.)

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundExperiments under controlled flow conditions indicate that the binding of von Willebrand factor (vWF) to platelet glycoprotein (GP) Ib alpha and integrin alphaIIbbeta3(GP IIb/IIIa complex) is crucial for aggregation at elevated shear rates. We have tested how the plasma of patients with acute myocardial infarction affects this process.Methods and Results-Citrated plasma was obtained from 18 patients with acute myocardial infarction within 6 hours from the onset of symptoms and from 26 control subjects with chest pain syndrome without evidence of ischemia. Aggregation of normal platelets at high shear rates was significantly greater in the presence of patient than control plasma and was inhibited by both anti-GP Ib alpha and anti-alphaIIbbeta3monoclonal antibodies. The observed values (mean +/- SD) were 47.6 +/- 17.8% versus 30.1 +/- 9.9% at 10 800 s-1(P<0.01) and 32.9 +/- 14.1% versus 17.5 +/- 9.5% at 7200 s-1(P<0.01), respectively, and were positively correlated with plasma vWF antigen levels and ristocetin cofactor activities. In contrast, at the lower shear rate of 1200 s-1, aggregation was similar in the presence of control or patient plasma and was not inhibited by the anti-GP Ib alpha antibody. Both vWF antigen and platelet aggregation decreased 2 weeks after the onset of myocardial infarction.ConclusionsShear-induced platelet aggregation is enhanced in plasma in the presence of acute myocardial infarction, apparently as a result of increased vWF concentration. This may contribute to the onset of acute coronary artery thrombosis and early reocclusion after reperfusion treatment. (Circulation. 1999;99:608-613.)

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe potential role of activated protein C (APC) resistance in arterial thrombosis and disease is a matter of ongoing controversy.Methods and Results-In the present population-based survey, a random sample of 826 men and women underwent high-resolution duplex ultrasound scanning of the carotid and femoral arteries. Response to APC was expressed in APC ratios. Subjects were tested for the factor V Leiden mutation. The risk of carotid stenosis increased gradually with decreasing response to APC (adjusted OR [95% CI] for a 1-U decrease of response to APC, 1.6 [1.2 to 2.2]), as did the risk of femoral artery stenosis (1.7 [1.3 to 2.3]) and prevalent cardiovascular disease (1.4 [1.1 to 2.0]). The association between low APC ratio and atherosclerotic vascular disease applied equally to subjects with the factor V Leiden mutation and those without. Our study identified various nongenetic determinants of poor response to APC in the general population, including behavioral, hormonal, and environmental factors.ConclusionsThe present study revealed an independent and gradual association between low response to APC and both advanced atherosclerosis (stenosis) and arterial disease. Resistance to APC due to factor V Leiden mutation was only one facet of this relationship. (Circulation. 1999;99:614-619.)

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe platelet glycoprotein (GP) IIb/IIIa receptor is important in mediating platelet thrombus formation, and the GP IIb/IIIa antagonist abciximab (c7E3 Fab; ReoPro) is effective in preventing thrombotic ischemic cardiovascular complications of unstable angina and percutaneous coronary interventions. Small-molecule antagonists of GP IIb/IIIa based on the Arg-Gly-Asp (RGD) sequence show similar benefit, and some of these agents are orally active. However, there may be significant interindividual variation in response to such antagonists, especially with chronic oral therapy. It will be essential to balance the beneficial antithrombotic effect of these drugs with their potential for causing bleeding. In response to this need, we have developed a rapid platelet-function assay (RPFA), a point-of-care system that provides a quantitative measure of the competence of the GP IIb/IIIa receptor as reflected in the ability of platelets to agglutinate fibrinogen-coated beads.Methods and Results-Polystyrene beads were coated with fibrinogen and placed in a cartridge along with a lyophilized peptide that activates the thrombin receptor. Anticoagulated whole blood was added to the cartridge, and then a microprocessor-controlled operation mixed the reagents and detected agglutination between platelets and coated beads. Quantitative digital results were displayed within 3 minutes. Because there is no dilution of the blood, the assay can be used to measure platelet activity in samples that have been treated with GP IIb/IIIa antagonists with high dissociation rates. RPFA results of whole-blood samples treated with different GP IIb/IIIa antagonists correlated well with both conventional turbidimetric platelet aggregation (r2=0.95) and the percentage of free GP IIb/IIIa molecules in the sample (r2=0.96). The mean difference in measurements between RPFA and aggregometry was -4% (+/- 4% SD), and the mean difference in measurements between RPFA and free GP IIb/IIIa receptors was -2% (+/- 6% SD).ConclusionsThe RPFA provides rapid information on platelet function that mirrors turbidimetric platelet aggregation and reflects GP IIb/IIIa receptor blockade. (Circulation. 1999;99:620-625.)

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundEpicardial and resistance vessel function in the transplanted heart has been evaluated primarily in regions supplied by a single vessel. Heterogeneity of flow among multiple perfusion fields as a marker of early endothelial dysfunction in the microcirculation has not been evaluated previously. This study tested the hypothesis that increased variability of coronary flow reserve (CFR) among multiple vascular regions would be associated with allograft coronary vasculopathy.or=to50% coronary stenosis.ConclusionsThese data demonstrate that increased variability of CFR is associated with discernible allograft coronary arteriopathy and is predictive of outcome in patients after heart transplantation. (Circulation. 1999;99:626-632.)

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundPatients with treated diabetes in the randomized-trial segment of the Bypass Angioplasty Revascularization Investigation (BARI) who were randomized to initial revascularization with PTCA had significantly worse 5-year survival than patients assigned to CABG. This treatment difference was not seen among diabetic patients eligible for BARI who opted to select their mode of revascularization. We hypothesized that differences in patient characteristics, assessed and unmeasured, together with the treatment selection in the registry, at least partially account for this discrepancy.Methods and Results-Among diabetics taking insulin or oral hypoglycemic drugs at entry, angiographic and clinical presentations were comparable between randomized and registry patients. However, more registry patients were white, and registry diabetics tended to be more educated and more physically active and to report better quality of life. Procedural characteristics and in-hospital complications were comparable. The 5-year all-cause mortality rate was 34.5% in randomized diabetic patients assigned to PTCA versus 19.4% in CABG patients (P=0.0024; relative risk [RR]=1.87); corresponding cardiac mortality rates were 23.4% and 8.2%, respectively (P=0.0002; RR=3.10). The CABG benefit was more apparent among patients requiring insulin. In the registry, all-cause mortality was 14.4% for PTCA versus 14.9% for CABG (P=0.86, RR=1.10), with corresponding cardiac mortality rates of 7.5% and 6.0%, respectively (P=0.73; RR=1.07). These RRs in the registry increased to 1.29 and 1.41, respectively, after adjustment for all known differences between treatment groups.ConclusionsBARI registry results are not inconsistent with the finding in the randomized trial that initial CABG is associated with better long-term survival than PTCA in treated diabetic patients with multivessel coronary disease suitable for either surgical or catheter-based revascularization. (Circulation. 1999;99:633-640.)

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundIn the failing human heart, sarcoplasmic reticulum (SR) calcium handling is impaired, and therefore, calcium elimination and diastolic function may depend on the expression of sarcolemmal Na+-Ca2+exchanger.Methods and Results-Force-frequency relations were studied in ventricular muscle strip preparations from failing human hearts (n=29). Protein levels of Na+-Ca(2+) exchanger and SR Ca2+-ATPasewere measured in the same hearts. Hearts were divided into 3 groups by discriminant analysis according to the behavior of diastolic function when stimulation rate of muscle strips was increased from 30 to 180 min-1. At 180 compared with 30 min-1, diastolic force was increased by 160%, maximum rate of force decline was decreased by 46%, and relaxation time was unchanged in group III. In contrast, in group I, diastolic force and maximum rate of force decline did not change, and relaxation time decreased by 20%. Na+-Ca2+exchanger was 66% higher in group I than in group III. Na+-Ca2+exchanger was inversely correlated with the frequency-dependent rise of diastolic force when stimulation rate was increased (r=-0.74; P<0.001). Compared with nonfailing human hearts (n=6), SR Ca2+-ATPasewas decreased and Na+-Ca2+exchanger unchanged in group III, whereas Na+-Ca2+exchanger was increased and SR Ca2+-ATPaseunchanged in group I. Results with group II hearts were between those of group I and group III hearts.ConclusionsBy discriminating failing human hearts according to their diastolic function, we identified different phenotypes. Disturbed diastolic function occurs in hearts with decreased SR Ca2+-ATPaseand unchanged Na+-Ca2+exchanger, whereas increased expression of the Na+-Ca2+exchanger is associated with preserved diastolic function. (Circulation. 1999;99:641-648.)

ISSN:0009-7322    

出版商:OVID    

年代:1999

数据来源: OVID