ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

BackgroundVascular smooth muscle cell proliferation is the key event of coronary artery disease. Mechanical forces, in particular, pulsatile stretch and platelet-derived growth factor, may play an important role.Methods and Results.Vascular smooth muscle cells were cultured from the media of human left descending coronary arteries obtained from organ donors using the explant method. To study effects of pulsatile stretch on vascular smooth muscle cell proliferation, a computer-controlled in vitro pulsatile stretch device was used. Cells were seeded onto Flex I culture plates with deformable membranes and exposed to pulsatile stretch (60 cycles per minute) and/or growth factors. Proliferation of smooth muscle cells was determined by Hydrogen-3-thymidine incorporation. Pulsatile stretch markedly stimulated Hydrogen-3-thymidine incorporation of coronary smooth muscle cells (180+-15 to 432+-27 cpm/105cells; P<.05) after 24 hours and increased cell number after 6 days (10.3+-0.7 x 104/mL to 11.7+-0.5 x 104/mL; P<.05). Platelet-derived growth factor-AB (0.01 to 10 ng/mL) concentration-dependently stimulated Hydrogen-3-thymidine incorporation in coronary smooth muscle cells (EC50, 0.1 ng/mL) and had additive effects with pulsatile stretch. The Ca2+ antagonist verapamil (10 sup -7 to 10 sup -5 M) concentration-dependently inhibited proliferation stimulated by platelet-derived growth factor back to control levels (P<.05 to.01) but not that induced by pulsatile stretch.ConclusionsPulsatile stretch and platelet-derived growth factor are potent stimuli for proliferation of coronary smooth muscle cells. The selective inhibitory effect of a Ca2+ antagonist on smooth muscle cell proliferation stimulated by platelet-derived growth factor but not by pulsatile stretch may explain why the drugs have only modest antiatherogenic effects in patients with coronary artery disease. (Circulation. 1993;88:832-836.)

ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

BackgroundPeripheral arterial disease measured noninvasively by the ankle-arm index (AAI) is common in older adults, largely asymptomatic, and associated with clinically manifest cardiovascular disease (CVD). The criteria for an abnormal AAI have varied in previous studies. To determine whether there is an inverse dose-response relation between the AAI and clinical CVD, subclinical disease, and risk factors, we examined the relation of the AAI to cardiovascular risk factors, other noninvasive measures of subclinical atherosclerosis using carotid ultrasound, echocardiography and electrocardiography, and clinical CVD.=65 years old at the baseline examination of the Cardiovascular Health Study. All subjects had detailed assessment of prevalent CVD, measures of cardiovascular risk factors, and noninvasive measures of disease. Participants were stratified by baseline clinical CVD status and AAI (=0.8 to =0.9 to =1.0 to <1.5). Analyses tested for a dose-response relation of the AAI with clinical CVD, risk factors, and subclinical disease. The cumulative frequency of a low AAI was 7.4% of participants <0.8, 12.4% <0.9, and 23.6% <1.0. Participants with an AAI <0.8 were more than twice as likely as those with an AAI of 1.0 to 1.5 to have a history of myocardial infarction, angina, congestive heart failure, stroke, or transient ischemic attack (all P<.01). In participants free of clinical CVD at baseline, the AAI was inversely related to history of hypertension, history of diabetes, and smoking, as well as systolic blood pressure, serum creatinine, fasting glucose, fasting insulin, measures of pulmonary function, and fibrinogen level (all P<.01). Risk factor associations with the AAI were similar in men and women free of CVD except for serum total and low-density lipoprotein cholesterol, which were inversely associated with AAI level only in women. Risk factors associated with an AAI of <1.0 in multivariate analysis included smoking (odds ratio (OR), 2.55), history of diabetes (OR, 3.84), increasing age (OR, 1.54), and nonwhite race (OR, 2.36). In the 3372 participants free of clinical CVD, other noninvasive measures of subclinical CVD, including carotid stenosis by duplex scanning, segmental wall motion abnormalities by echocardiogram, and major ECG abnormalities were inversely related to the AAI (all P<.01).ConclusionsThere was an inverse dose-response relation of the AAI with CVD risk factors and subclinical and clinical CVD among older adults. The lower the AAI, the greater the increase in CVD risk; however, even those with modest, asymptomatic reductions in the AAI (0.8 to 1.0) appear to be at increased risk of CVD. (Circulation. 1993;88:837-845.)

ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

BackgroundA continuously increasing risk of coronary heart disease with increasing levels of cholesterol has been reported by many observational and experimental studies. However, this type of association has not been observed in studies in the Russian Lipid Research Clinics.Methods and Results.Twelve-year coronary heart disease mortality among 40- to 59-year-old men was analyzed in the Moscow and St Petersburg examinees in the Russian Lipid Research Clinics Program. The baseline survey examined 6431 men fasting and free of prevalent coronary heart disease. Lipids and lipoproteins, blood pressure, body mass, education level, alcohol intake, and smoking history were obtained. Mortality follow-up was based on contacts with participants or their relatives or neighbors. Coronary heart disease mortality was analyzed based on risk factor levels and was further divided into rapid and nonrapid deaths. A J-shaped cholesterol-coronary heart disease risk function was present for both total and low-density lipoprotein cholesterol. Further examination showed hypocholesterolemic men to have lower low-density and higher high-density lipoprotein cholesterol, higher alcohol consumption, leaner body mass, and less education than men with normal or high cholesterol levels. When education level was considered, the J-shaped risk function was present only among men with less than a high school education. When deaths were classified into rapid (less than 24 hours after onset of symptoms) and nonrapid, the J-shaped risk function was restricted to rapid deaths.ConclusionsThe results disclose a sizeable subset of hypocholesterolemics in this population at increased risk of cardiac death associated with lifestyle characteristics. (Circulation. 1993;88:846-853.)

ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

BackgroundBoth beta1- and beta2-adrenoceptors (beta1AR and beta2AR) are present in human ventricle. This study was designed to determine whether the two subtypes contribute to contraction in single myocytes from human heart.Methods and Results.(-)-Epinephrine increased the contraction amplitude and velocity of single myocytes isolated from the ventricles of failing and nonfailing human hearts. Concentration-response curves to (-)-epinephrine were constructed in the presence and absence of selective antagonists for beta1AR (CGP 20712A) and beta2AR (ICI 118,551). Responses to (-)-epinephrine were antagonized to a variable degree by the blockers, suggesting heterogeneous contribution of beta1AR and beta sub 2 AR among cells. The most common response in single myocytes was that ICI 118,551 (50 nmol/L) shifted the concentration-response curve less than 10-fold: this was lower than the 100-fold shift expected for a pure beta2AR effect. Inclusion of CGP 20712A (300 nmol/L) with ICI 118,551 shifted the (-)-epinephrine curve still further. These observations suggest that both beta1AR and beta2AR contribute to the increase in contraction amplitude with (-)-epinephrine in this group of myocytes. When 300 nmol/L CGP 20712A was present as the sole antagonist, only a marginal shift of the concentration-response curve for (-)-epinephrine was usually observed, indicating that beta1AR were not mediating the effect of these low concentrations of (-)-epinephrine. Both beta1AR and beta2AR mediated a considerable abbreviation of the time to peak contraction and time to 50% relaxation in the single cells.Conclusionsbeta1AR and beta2AR coexist and function on human ventricular myocytes. At low (-)-epinephrine concentrations, contractile responses are predominantly mediated by beta2AR rather than beta1AR in myocytes from failing hearts. (Circulation. 1993;88:854-863.)

ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

BackgroundGap junctions are a determinant of myocardial conduction. Disturbances of gap-junctional content may account for abnormalities of impulse propagation, contributing to the arrhythmic tendency and mechanical inefficiency of ischemic and hypertrophied myocardium. The aim of this study was to characterize gap junction organization in normal human ventricular myocardium and to establish whether abnormalities exist in myocardium of chronically ischemic and hypertrophied hearts.Methods and Results.Cardiac gap-junctional connexin43 antibodies and confocal microscopy were used in a quantitative immunohistochemical study of surgical myocardial samples to explore the structural basis of electromechanical ventricular dysfunction in chronic ischemic and hypertrophic heart diseases. Normal adult human left ventricular myocardium had a gap-junctional surface area of 0.0051 microns2/microns3myocyte volume; gap junctions were confined to intercalated disks, of which there was a mean of 11.6 per cell. The right ventricle showed similar gap junction surface area. Left ventricular myocardium from ischemic hearts (distant from any fibrotic scarring), despite normal numbers of intercalated disks per cell, had a reduced gap junction surface area (0.0027 microns2/microns3; P=.02), as did hypertrophied myocardium (0.0031 microns2/microns3; P=.05). The cardiac myocytes in the pathological tissues were larger than normal, and estimated gap-junctional content per cell was reduced in ischemic ventricle (P=.02) compared with normal.ConclusionsGap junctions in normal adult human working ventricular myocardium occupy an area of 0.0051 microns2/microns3myocyte volume. This surface area is reduced in ventricular myocardium from hearts subject to chronic hypertrophy and ischemia, despite a normal number of intercellular abutments, and this alteration may contribute to abnormal impulse propagation in these hearts. (Circulation. 1993;88:864-875.)

ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

BackgroundCocaine ingestion has been associated with thrombosis of coronary as well as peripheral arteries, but the mechanism by which cocaine promotes thrombus formation is unknown. Accordingly, we determined whether cocaine activates human platelets by flow cytometric analysis of whole blood to which cocaine was added.Methods and Results.Activated platelets were detected by "two-color" flow cytometric analysis of the binding of fluorescently labeled antibodies directed against either platelet-associated fibrinogen or P-selectin, which are found on the surface of platelets only after stimulation. Platelets were distinguished from other constituents of whole blood by their ability to bind an anti-glycoprotein Ib antibody bound to both activated and resting platelets. Incubation of whole blood with cocaine, in concentrations of 10 micromolars to 13 mM, induced significant increases in both platelet-associated fibrinogen (range of increase, 45+-12% to 125+-40%) and P-selectin expression (36+-15% to 112+-24%). In platelets suspended in either buffer or plasma, however, P-selectin expression was detected only at the highest cocaine concentration (85+-13% increase in plasma and 59+-7% in buffer). Neither aspirin nor the ADP scavenger apyrase inhibited cocaine-induced P-selectin expression. Cocaine inhibited the uptake of Carbon-14-radiolabeled serotonin by platelets (IC50, 8.7 micromolars). P-selectin expression and fibrinogen binding were found after the addition of cocaine alone to blood taken from some but not all donors; however, platelet activation in response to submaximal concentrations of the agonists ADP or epinephrine was enhanced by a low concentration of cocaine added to blood from every donor.ConclusionsCocaine, in concentrations similar to those found clinically, induces activation of individual platelets studied in whole blood from some but not all donors, and platelet response to physiological agonists is enhanced by cocaine. Thus, cocaine-induced platelet activation may contribute to thrombosis following cocaine ingestion. (Circulation. 1993;88:876-883.)

ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

BackgroundMetabolic imaging with positron emission tomography (PET) can detect tissue viability in clinical infarct regions. With appropriate tracer kinetic models and serial PET imaging, regional myocardial blood flow and rates of metabolism can now be quantified in patients with recent myocardial infarctions.Methods and Results.Serial PET imaging with (Nitrogen-13)ammonia, (Carbon-11)acetate, and Fluorine-18-deoxyglucose was performed in 22 patients with recent infarctions to measure regional blood flow (in milliliters per gram per minute), glucose metabolism (in micromoles per gram per minute), and oxidative metabolism (in clearance rate per minute). Hypoperfused clinical infarct regions were classified as "PET mismatch" if Fluorine-18 was increased relative to Nitrogen-13 activity or "PET match" if Nitrogen-13 and Fluorine-18 activities were reduced concordantly. Blood flows differed significantly between normal, mismatch, and match segments (0.83+-0.20, 0.57+-0.20, and 0.32+-0.12 mL x g sup -1 x min sup -1, respectively). The relation between oxidative metabolism and blood flow was piecewise linear and differed significantly between PET mismatch and PET match. Oxidative metabolism was less severely reduced than blood flow in mismatch regions but reduced in proportion to blood flow in match regions. There was considerable overlap of blood flows between both types of PET segments.ConclusionsQuantification of regional blood flow and substrate metabolism in postinfarction patients revealed alterations in the relation between substrate delivery and consumption demonstrated previously only in invasive animal experiments. The preserved oxidative metabolism in myocardium with PET mismatches may be ascribed to a regional increase in oxygen extraction. Such increase together with preserved glucose utilization may be the prerequisite for survival of ischemically injured myocardium. (Circulation. 1993;88:884-895.)

ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

BackgroundThe ECG recognition of diffuse pericarditis following acute myocardial infarction has been based on changes of the ST segment and, to a lesser extent, alterations of the PQ segment. No ECG criteria exist for the diagnosis of postinfarction regional pericarditis. Recently, it was observed that the T wave evolution follows an atypical pattern before fatal free wall rupture and that this pattern is due to the associated pericarditis. Therefore, this study was conducted on 200 patients with acute myocardial infarction to further elucidate the sensitivity and specificity of the atypical T wave changes in patients with regional postinfarction pericarditis without rupture and to assess the affect of lytic treatment on the rapidity and amplitude of postinfarction T wave evolution.Methods and Results.An analysis of the clinical courses and serial ECGs of 200 consecutive patients with acute myocardial infarction was performed. Among 43 patients with postinfarction pericarditis, the pattern of T wave evolution consistently differed from the customary postinfarction pattern of T wave evolution. This unusual evolutionary course was expressed as either persistently positive T waves 48 or more hours after infarction (67%) or premature, gradual reversal of inverted T waves to positive deflections (33%). The sensitivity and specificity of these T wave alterations were 100% and 77%, respectively. The only other processes identified that caused this type of postinfarction T wave evolution were cardiopulmonary resuscitation, reinfarction, and very small infarcts. Both reperfusion, as judged by the creatine kinase-MB curve, and patency, as assessed by the angiogram, were correlated with the rapidity and depth of T wave inversion. Ninety percent of patients with reperfusion attained a maximum T wave negativity of 3 mm or more within 48 hours after the onset of chest pain in the lead that initially displayed the greatest ST segment elevation. Seventy-six percent of patients without reperfusion attained a maximum negativity of 2 mm or less within 72 hours. Thus, like the ST segment, accelerated evolution and deepening of the T wave may be noninvasive markers of reperfusion.ConclusionsFirst, premature reconcordancy of the ST segment and T wave after acute myocardial infarction is a sensitive, reasonably specific, and easily recognizable ECG manifestation of postinfarction regional pericarditis. Second, reperfusion is associated with accelerated evolution and deepening of the T waves following acute myocardial infarction. (Circulation. 1993;88:896-904.)

ISSN:0009-7322    

出版商:OVID    

年代:1993

数据来源: OVID