摘要:

BackgroundThe participation of the renin-angiotensin system in the control of blood pressure in normal, sodium-replete subjects is not clear. The use of a specific inhibitor of human renin should allow a better delineation of the importance of this system.Methods and ResultsBlood pressure responses were measured 1 hour after randomized, double-blind administration of the renin inhibitor Ro 42-5892 (600 mg p.o.) or the angiotensin converting enzyme inhibitor captopril (50 mg p.o.) in 20 healthy men on an ad libitum sodium diet. Effective inhibition of the renin-angiotensin system by either compound was indicated by increases of immunoreactive renin associated with an increase of angiotensin I production rate of 67.8±33.6% after captopril and a decrease of 79.5±16.4% after Ro 42-5892. Furthermore, Ro 42-5892 decreased plasma renin activity by 64%. Whereas intra-arterial diastolic (60±5.1 to 51.4±7.2 mm Hg,p< 0.01) and mean arterial (77.7±6.0 to 71.4±8.5 mm Hg,p< 0.001) pressures decreased after captopril, they remained unchanged after Ro 42-5892. Captopril, but not Ro 42-5892, increased forearm blood flow (2.4±0.8 versus 1.9±0.8 ml/min/100 ml,p< 0.01) and significantly enhanced the increase of forearm blood flow to brachial artery infusions of bradykinin (0.15, 1.5, 5, 15, and 50 ng/min/100 ml; 5 minutes each) from 744±632% to 1,383±514% (p< 0.01). Furthermore, repeat bradykinin infusions resulted in further decreases of blood pressure (from mean pressure of 71.4±8.5 to 63.2±7.6 mm Hg,p< 0.01) only after captopril. Changes of blood pressure after captopril were unrelated to baseline plasma renin activity but correlated with captopril-induced enhancement of vasodilation to bradykinin (r= 0.68,p< 0.05)ConclusionsThe lack of blood pressure effects of renin inhibition in contrast to angiotensin converting enzyme inhibition suggests that the renin-angiotensin system does not contribute significantly to blood pressure control in normotensive, sodium-replete subjects. The hypotensive activity of angiotensin converting enzyme inhibitors may result from additional hormonal effects, for example, inhibition of bradykinin degradation and/or subsequent increases of vasodilating prostaglandins or endothelium-derived relaxing factor(s).

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundEnhanced uptake of the glucose analogue18F-fluorodeoxyglucose (FDG) in relation to flow has been proposed as an accurate method of identifying viable myocardium. The evaluation of myocardial oxidative metabolism could be an alternate way to identify reversible injury. The aim of the present study was to investigate in patients with reperfused anterior infarction whether differences in regional oxidative metabolism exist among regions with and without flow-metabolism mismatch.Methods and Resuts.Fifteen patients with reperfused anterior myocardial infarction were studied between 2 weeks and 3 months after the acute event. Regional myocardial blood flow (13N-ammonia; three-compartment model), oxidative metabolism (11C-acetate; monoexponential clearance), and glucose uptake (FDG, linear graphic analysis) were evaluated with dynamic positron emission tomography. Flow-metabolism patterns were used to differentiate reversibly (FDG/flow >1.2) from irreversibly injured myocardium (FDG/flow < 1.2) using circumferential profile technique. Relative13N-ammonia uptake was reduced in 71 of 90 anterior and/or septal segments, including 24 with (seven patients) and 38 without (eight patients) flow-metabolism mismatch. Acetate clearance (k), reflecting oxidative metabolism, was reduced by 51% in the center of the infarct area versus remote segments (27±12 versus 55±13 min−1.10−3,p< 0.001). Compared with infarct segments without flow-metabolism mismatch, segments exhibiting increased glucose uptake relative to flow had faster acetate clearance (35±14 versus 23±9 min−1.10−3,p< 0.01). Similarly, myocardial blood flow was better preserved in segments with flow-metabolism mismatch (54±13 versus 45±8 ml/min/100 g,p< 0.0l) compared with segments without mismatch. However, at similar levels of hypoperfusion, there was no significant difference in acetate clearance among segments with and those without flow-metabolism mismatch: 37±14 versus 41±15 min−1.10−3, respectively. A positive correlation (r= 0.89,p< 0.001) was found between absolute myocardial blood flow and acetate clearance, regardless of the flow-metabolism pattern.ConclusionsIn patients with reperfused myocardial infarction studied between 2 weeks and 3 months after the acute event, regional oxidative metabolism is reduced in proportion to residual myocardial blood flow and does not differ significantly among similarly hypoperfused segments with and without flow-metabolism mismatch.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundA large and consistent body of evidence supports the judgment that elevation of total plasma blood cholesterol is a cause of myocardial infarction (MI) and that high levels of low density lipoprotein (LDL) cholesterol have a positive relation and high levels of high density lipoprotein (HDL) cholesterol an inverse relation with MI. At present, however, the roles, if any, of the major subfractions of HDL, namely, HDL2and HDL3, have not been clarified. In addition, the relation of plasma apolipoprotein concentrations to MI and whether they provide predictive information over and above their lipoprotein cholesterol associations is unknown.Methods and ResultsWe evaluated these questions in a case-control study of patients hospitalized with a first MI and neighborhood controls of the same age and sex. Cases had significantly lower levels of total HDL (p< 0.0001) as well as HDL2(p< 0.0001) and HDL3(p< 0.000l) cholesterol. These differences persisted after controlling for a large number of demographic, medical history, and behavioral risk factors and levels of other lipids. There were significant (p< 0.0001) inverse dose-response relations with odds ratios for those in the highest quartile relative to those in the lowest of 0.15 for total HDL, 0.17 for HDL2, and 0.29 for HDL3cholesterol levels. Levels of LDL and very low density lipoprotein cholesterol and triglycerides were also higher among cases than controls, but only for triglycerides was the difference statistically significant after adjustment for coronary risk factors and other lipids (p= 0.044). Apolipoproteins A-I and A-II were both significantly (p< 0.0001) lower in cases, and differences remained even after adjustment for coronary risk factors and lipids. There were significant dose-response relations for both apolipoprotein A-I (p= 0.026) and A-II (p= 0.002). Neither apolipoprotein B nor E was significantly related to MI after adjustment for lipids and other coronary risk factors. When all four apolipoproteins were taken together, there was an increased level of prediction of MI over the information provided by the lipids and other coronary risk factors (p= 0.003), but this appeared present only for the individual apolipoproteins A-I (p= 0.027) and A-II (p= 0.011)ConclusionsThese data indicate that both HDL2and HDL3cholesterol levels are significantly associated with MI. They also raise the possibility that apolipoprotein levels, especially A-I and A-II, may add importantly relevant information to determination of risk of MI.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundThe role of lipoprotein disturbances in the development of peripheral vascular disease (PVD) has not been sufficiently clarified.Methods and ResultsThe relations among concentrations of intermediate density lipoproteins (IDL), apoprotein (apo) B, apo E, and other lipoproteins were studied in 102 men with PVD and 100 healthy men who formed the control group. Patients with PVD had significantly higher levels of serum triglycerides, very low density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL proteins, IDL cholesterol, and IDL triglycerides and lower levels of high density lipoproteins (HDL) than controls. Serum cholesterol and triglycerides were normal in 30 patients (cholesterol, < 5.2 mmol/l; triglycerides, < 2.3 mmol/1), who had significant increases in IDL triglycerides and significant decreases in HDL cholesterol compared with the 47 controls, who had normal cholesterol and triglyceride levels. Patients with more severe distal involvement showed higher cholesterol and triglycerides carried by IDL and a greater reduction in HDL cholesterol. Smoking patients with PVD showed increased VLDL cholesterol and VLDL triglycerides and lower HDL concentrations. Apo E polymorphism in our study population does not differ from that reported for other European populations. Alleles ∈2 and ∈4 had a major impact on serum triglycerides and VLDL lipids in our patients with PVDConclusionsLipoprotein disturbances are a major risk factor for PVD. IDL abnormalities play an important role in the development and severity of PVD and should also be considered a vascular risk factor in normocholesterolemic and normotriglyceridemic patients.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundWe studied the joint effect of baseline triglyceride and lipoprotein cholesterol levels on the incidence of cardiac end points in the trial group (n= 4,081) of the Helsinki Heart Study, a 5-year randomized coronary primary prevention trial among dyslipidemic middle-aged men. The relative risks (RR) were calculated using Cox proportional hazards models with a dummy variable technique that allows simultaneous study of subgroup combinations from the placebo and treatment groups.Methods and ResultsIn the placebo group (n= 2,045), the low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio was the best single predictor of cardiac events. This ratio in combination with the serum triglyceride level revealed a high-risk subgroup: subjects with LDL-C/HDL-C ratio >5 and triglycerides >2.3 mmol/1 had a RR of 3.8 (95% CI, 2.2-6.6) compared with those with LDL-C/HI)L-C ratio ≤5 and triglyceride concentration ≤2.3 mmol/1. In subjects with triglyceride concentration >2.3 mmol/l and LDL-C/H1)L-C ratio ≤5, RR was close to unity (1.1), whereas in those with triglyceride level ≤2.3 mmoVIl and LDL-C/HDL-C ratio >5, RR was 1.2. The high-risk group with LDL-C/HDL-C ratio >5 and triglyceride level >2.3 mmol/1 profited most from treatment with gemfibrozil, with a 71% lower incidence of coronary heart disease events than the corresponding placebo subgroup. In all other subgroups, the reduction in CHD incidence was substantially smallerConclusionsSerum triglyceride concentration has prognostic value, both for assessing coronary heart disease risk and in predicting the effect of gemfibrozil treatment, especially when used in combination with HDL-C and LDL-C.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundMyocardial adrenergic neurotransmitters and β-adrenergic receptor levels were measured in left and right ventricular myocardial specimens obtained from 30 patients with biventricular failure resulting from idiopathic dilated cardiomyopathy.Methods and ResultsNonfailing myocardium obtained from 12 organ donors provided control data. Norepinephrine, dopamine, and neuropeptide Y concentrations were significantly decreased in failing compared with nonfailing control hearts. The mean ratio of dopamine to norepinephrine and of dopamine to neuropeptide Y in failing hearts was also significantly decreased compared with nonfailing control hearts. Compared with nonfailing control hearts, Bmaxand β-receptor density were significantly decreased in failing hearts and there were weak but significantly positive correlations of Bmaxand β-adrenergic receptors with norepinephrine, dopamine, and neuropeptide YConclusionsNorepinephrine and its cotransmitter neuropeptide Y are depleted in failing human ventricular myocardium. Decreased norepinephrine stores correlate weakly with β-adrenergic receptor downregulation consistent with the hypothesis that norepinephrine depletion occurs in response to increased adrenergic drive. Decreased dopamine relative to norepinephrine implies that an abnormality of dopamine conversion to norepinephrine is not present in failing human heart.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundThe vasodilatory response to local specific type III phosphodiesterase inhibition with amrinone was evaluated before and immediately after local administration of digoxin in 14 patients with severe congestive heart failure (CHF).Methods and ResultsA 3F polyethylene catheter was inserted into the common femoral artery for drug administration and pressure monitoring. Mean blood flow velocity (MBFV) was continuously determined in the superficial femoral artery by transcutaneous Doppler ultrasonography. After intra-arterial administration of 10 mg amrinone, group MBFV increased from 7.7±1.4 to 16.0±2.1 cm/sec (p< 0.05,n= 10). Local administration of 20 μg digoxin, which was infused over 20 minutes, did not alter group MBFV (i.e., 8.2±1.6 versus 7.6±1.5 cm/sec;p= NS,n=10). The second administration of 10 mg amrinone, which immediately followed completion of local digoxin infulsion, increased group MBFV but to a lesser extent than that produced by the first amrinone administration (i.e., 11.9±1.9 versus 16.0±2.1 cm/sec;p< 0.05,n= 10). When placebo was administered instead of digoxin, group MBFV was similar after the first and second administrations of amrinone (i.e., 15.3±3.3 versus 15.6±3.8 cm/sec;p= NS,n= 4)ConclusionsAlthough local administration of digoxin did not significantly alter baseline vascular tone in patients with CHF, it substantially decreased the direct vasodilatory effect induced by specific type III phosphodiesterase with amrinone.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundDetection and treatment for rejection after transplantation are based on the identification of myocyte damage upon endomyocardial biopsy. Noninvasive detection of such damage is possible with111In-labeled monoclonal antimyosin antibodies (MAA). Although the presence and degree of MAA uptake parallels the rejection activity detected by biopsy, the relation between the degree of uptake and the occurrence of severe rejection-related complications has not been previously assessed.Methods and ResultsTwo hundred forty-seven MAA studies were performed coinciding with biopsies in 52 patients 1-71 months after transplantation. A heart-to-lung ratio (HLR) was used as a measure of relative MAA uptake, with an HLR of 1.55 discriminating normal from abnormal studies. Of the 247 antimyosin studies, 149 coincided with absent, 38 with mild, and 60 with moderate rejection at biopsy. HLR was 1.68±0.27, 1.79±0.22, and 1.91±0.33 in the three biopsy groups, respectively (p< 0.0001). Two hundred thirty-eight of 247 antimyosin studies coexisted with absent rejection-related complications; in nine of 247 patients, such complications were detected (five congestive heart failure episodes due to rejection and four episodes of vascular occlusion, which resulted in five deaths), and mean HLR was 1.74±0.3 and 2.1±0.16 in the two groups, respectively (p< 0.0001). No complications were noted in 193 studies of patients with HLR of less than 2.00, whereas in nine of 45 with HRL of 2.00 or greater, complications occurred (p< 0.0001). None of the 23 patients prospectively followed since surgery who had a gradual decrease in MAA uptake during the first 3 months showed rejection-related complications, whereas persistent uptake was associated with complications in five of nine patients (p< 0.001)ConclusionsNo rejection-related complications are seen coinciding with HLR of less than 2.00, whereas patients who have complications have an HLR of more than 2.00. The early 3-month pattern of decreasing MAA uptake is associated with a clinical course free of rejection-related complications, whereas a persistent pattern is a signal of the possibility of such complications.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundCoronary artery vasomotion is altered after cardiac transplantation. The impact of accelerated transplant coronary atherosclerosis and myocardial rejection on vasomotion is not well understood. Intravascular ultrasound is a new imaging method with the ability to study real-time changes in coronary artery dimensions.Methods and ResultsEpicardial coronary artery response to nitroglycerin was studied in 32 cardiac transplant recipients (age, 47±11 years) 3 weeks to 10 years after transplantation with intracoronary ultrasound. Cross-sectional luminal area and diameter were measured at a fixed position in the left anterior descending artery immediately before and every 30 seconds for 5 minutes after 0.4 mg of sublingual nitroglycerin. Cross-sectional area increased from a baseline of 13.1±3.9 mm2to 15.8±3.9 mm2at maximal vasodilation; luminal diameter increased from 4.0±0.6 mm to 4.5±0.6 mm. This increase reached statistical significance (p< 0.001) at 1.5 minutes after administration of nitroglycerin; mean maximum increase occurred at 4.5 minutes (24% for cross-sectional area and 11% for luminal diameter). Patients with biopsy-proven mild or moderate concurrent rejection had a significantly blunted vasodilatory response versus the nonrejection group (9% versus 27% for cross-sectional area,p< 0.04), although a vasodilatory effect was still present. Nitroglycerin response was well preserved in patients up to 10 years after transplantation; however, there was a trend toward a decreased response in patients studied immediately after transplantation (21% versus 29%,p= 0.37). Coronary intimal thickness, as measured by ultrasound, had no impact on the vasodilatory response (R= 0.23,p= 0.34)ConclusionsVasodilatory response to nitroglycerin in cardiac transplant recipients is attenuated during episodes of cardiac rejection. This response is preserved in long-term survivors and is independent of the degree of intimal thickening. Intravascular ultrasound provides a new method to document real-time epicardial coronary vasomotion.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundCoronary angiography in acute myocardial infarction has revealed complicated atherosclerotic plaque and a high rate of thrombotic occlusion. However, the characteristics of lesions at high risk of subsequent occlusion are not well known.Methods and ResultsIn the present study, the qualitative and quantitative angiographic features of 38 coronary artery lesions that occluded within 3 years to cause an acute myocardial infarction were compared with 64 control segments from the same patients that did not occlude. Compared with control lesions, the lesions that occluded were more likely to have a division branch originating within the stenosis (76% versus 52%,p< 0.05). The percent lumen diameter reduction was more severe (47.5±17.8% versus 41±12.5%,p< 0.05) and the inflow (21±10° versus 16±7°,p< 0.05) and outflow (20±10° versus 16±8°,p< 0.05) angles of the stenosis were steeper. Time to myocardial infarction after the angiogram interacted with the importance of these features (p< 0.02). Thus, paired analysis of the lesions that occluded within 3 months and of the most severe control lesion from each patient showed percent lumen diameter reduction of 62.1±11.5% and 46.4±11.4%, respectively (p< 0.001). The length of the stenosis, its asymmetry, and the irregularity of the contours did not help differentiate occlusive from control segments.ConclusionsCoronary artery lesions at high risk of thrombotic occlusion share common characteristics that favor higher shear stress and flow separation.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID