摘要:

Background Vasoconstrictor responses to serotonin are augmented in monkeys with diet-induced atherosclerosis and improve after 18 months of normal diet. We tested the hypothesis that functional improvement may occur early during regression, before evidence of structural improvement.Methods and Results Responses of the iliac artery to serotonin were measured by quantitative angiography and a Doppler flow probe in several groups of monkeys: (1) normal monkeys, (2) monkeys fed an atherogenic diet for 2 years (atherosclerotic), and (3) monkeys fed an atherogenic diet for 2 years (preregression) followed by a normal diet for 4, 8, or 12 months (regression). In normal monkeys, serotonin produced minimal constriction of the iliac artery, and blood flow to the legs increased. In atherosclerotic monkeys, there was pronounced constriction of the iliac artery, and blood flow to the legs decreased markedly. After 4 months of regression diet, four of eight monkeys demonstrated marked reduction in hyperresponsiveness to serotonin angiographically, and by 8 months, six of eight monkeys had significant improvement. After regression, serotonin produced minimal changes in flow. There was no reduction in intimal area (ie, atherosclerotic lesion) in iliac arteries from regression monkeys compared with atherosclerotic monkeys, but there was a marked reduction in cholesteryl ester in arteries from regression monkeys.Conclusions Abnormal vasoconstrictor responses to serotonin usually return to or toward normal within a few months during regression of atherosclerosis. Functional improvement occurs in conjunction with early resorption of lipid from the arterial wall and occurs before detectable changes in mass of the atherosclerotic lesion. (Circulation. 1994;89:1810-1818.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Cocaine use has been associated with cardiomyopathy and ischemic coronary syndromes. However, the pathophysiological mechanisms responsible for these syndromes are not clear and have been suggested to involve direct effects of cocaine on myocyte contractility and coronary resistance as well as indirect effects via altered autonomic tone, secondary mediators, and myocardial metabolism. We sought to distinguish direct from indirect effects of cocaine on ventricular function and coronary resistance by comparison of the administration of intracoronary cocaine (0.12 to 0.36 mg/min constant infusion) with intravenous cocaine (5 mg/kg bolus infusion) in an in vivo anesthetized pig preparation.Methods and Results To control for changes in coronary resistance secondary to autoregulation and myocardial metabolism, the left anterior descending coronary artery was perfused at constant coronary pressure and the interventricular vein was cannulated for coronary venous oxygen saturation measurement. Coronary blood flow, regional percent segment shortening, myocardial oxygen consumption, and serum cocaine concentrations were measured. Intracoronary cocaine produced a dose-dependent decrease in percent segment shortening in the absence of significant changes in coronary flow or systemic hemodynamics. In contrast, intravenous cocaine had mild biphasic effects on coronary resistance with an initial brief vasodilation (30.0+-5% increase in flow from control) followed by more prolonged vasoconstriction (17.0+-3.3% decrease in flow from control), which were independent of autoregulation or myocardial metabolism. In addition, intravenous cocaine caused an early 48% decrease in percent segment shortening, at which time the measured cocaine concentration was 20.1 micrograms/mL blood. This was comparable to the intracoronary cocaine concentration of 17.1 micrograms/mL blood, which produced a similar 48% decrease in percent segment shortening.Conclusions We conclude that the effects of acute cocaine exposure on ventricular function are predominantly direct but of brief duration and therefore probably not clinically relevant. The effects of cocaine on coronary tone are predominantly indirect and biphasic, with early vasodilation followed by mild and more prolonged vasoconstriction. In the absence of coronary stenosis or ventricular hypertrophy, this small amount of vasoconstriction is unlikely to cause ischemia. (Circulation. 1994;89:1819-1828.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Contractile function of the ex vivo, isolated left atrium (LA) has been described by a time-varying elastance, but this atrial chamber property has not been shown in vivo.Methods and Results Instantaneous LA pressure-volume (P-V) relations were studied in 12 anesthetized, autonomically blocked, atrially paced dogs. LA volume was calculated from orthogonal sonomicrometer pairs using a cast-validated formula. Data were collected during increases in LA pressure produced by a phenylephrine bolus (200 to 400 micrograms IV). Isochronal P-V points from 5 beats, representing a wide range of atrial pressures, were fitted by linear regression analysis (range of R2,.92 to.99). There were significant time-dependent increases in the slopes (E sub (t)) and small but statistically insignificant decreases in the volume axis intercepts (Vo sub (t)) of the instantaneous LA P-V relations during atrial contraction; maximal elastance (Emax) occurred 29+-16 milliseconds before atrial end systole (minimal LA volume). Emaxwas not significantly different than the slopes of either the nonisochronal end-systolic P-V relation (Ees) or the nonisochronal maximal P-to-V relation (EmaxPV): 5.5+-2.8, 4.3+-1.5, and 5.4+-4.2 mm Hg/mL, respectively. In 7 dogs, data were collected both before and after a rapid infusion of calcium gluconate (1 to 2 g IV). Emaxincreased significantly with a calcium-induced increase in inotropic state (4.5+-1.6 to 5.7+-1.8 mm Hg/mL, P<.01), but the volume axis intercept was unchanged (3.6+-0.7 versus 3.4+-1.9, P=NS). In 4 additional dogs with heart failure (mean LA pressure, 26+-6 mm Hg) produced by 3 weeks of rapid right ventricular pacing, LA stroke volume was significantly greater than and elastance determinations were similar to those of normal dogs. However, the effects of calcium infusion on LA function were attenuated in these animals.Conclusions We conclude that (1) in the intact heart, LA contraction may be approximated by time-varying elastance with time-dependent changes in E sub (t) and that (2) LA systolic P-V relations using either the nonisochronal maximum P-to-V ratio or end systole may be useful as an estimate of Emax, are highly linear and sensitive to calcium-induced changes in inotropic state, and may be useful in identifying LA chamber adaptation to chronic hemodynamic loads. (Circulation. 1994; 89:1829-1838.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Elevated intracellular calcium activity is thought to play an important role in arrhythmia induction, particularly during ischemia and reperfusion. Delayed afterdepolarization-induced triggered activity and intracellular communication problems are thought to be responsible.Methods and Results Increased extracellular calcium levels and rapid pacing are interventions known to elevate intracellular calcium activity. The present study, conducted using standard microelectrode techniques, was designed to compare the effects of increased (Ca2+)o(1.8 to 5.4 mmol/L) in isolated canine ventricular epicardial and endocardial tissues and to test the hypothesis that elevated intracellular calcium activity contributes to arrhythmogenesis in working ventricular myocardial tissues by promoting electrical heterogeneity. High (Ca2+)ocaused a slight abbreviation of action potential duration (APD90) in endocardium but more dramatic rate-dependent and dynamic changes in epicardium. Under steady-state conditions, epicardium displayed a marked abbreviation of APD sub 90 at fast rates but no significant changes at slow rates. A significant augmentation of phase 1 was evident at the faster stimulation rates. Vmaxand conduction velocity were only slightly reduced. The marked abbreviation of the epicardial response at the faster rates was due to loss of the action potential dome. Recovery of the dome after deceleration was not synchronous throughout the preparation. As a consequence, a sudden slowing of rate caused marked dispersion of repolarization among neighboring epicardial sites, giving rise to ectopic activity via a phase 2 reentry mechanism. These effects of high (Ca2+)owere mimicked by exposure of the preparations to low (Na sup +)o. Electrical homogeneity was restored and arrhythmias were abolished after addition of the Itoblocker 4-aminopyridine 1 mmol/L. 4-Aminopyridine also eliminated the differential response of epicardium and endocardium to high (Ca2+)o.Conclusions Our data demonstrate the induction of marked electrical heterogeneity and reentrant activity by high (Ca sup 2+) sub o and rapid stimulation, conditions known to elevate (Ca sup 2+) sub i. The results suggest that increased intracellular calcium activity, as occurs during ischemia and reperfusion, may contribute to the development of electrical inhomogeneity in the ventricle and thus to the genesis of ventricular arrhythmias through a mechanism other than triggered activity, namely, phase 2 reentry. Our data point to an increase in net outward current as the underlying mechanism for the calcium-induced changes. Our results also suggest that the presence of a prominent transient outward current (Ito) in epicardium sensitizes that tissue to the effects of high calcium. Finally, the results suggest that Itoblockers can reverse high calcium-induced electrical heterogeneity and thus can exert antiarrhythmic actions. (Circulation. 1994;89:1839-1850.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The automatic implantable cardioverter-defibrillator (ICD) is highly effective in reducing sudden death rates in patients with life-threatening ventricular tachyarrhythmias. However, the magnitude of the ability of the ICD to improve overall survival is less certain. Data supporting the contention that the ICD prolongs survival are reviewed. It is evident that the mortality benefit consequent to the marked reduction in sudden death varies widely across subpopulations in a predictable manner. This observation reflects the powerful influence of other clinical factors that constrain survival in typical ICD patients. The implications for future studies on the ICD are discussed. (Circulation. 1994;89:1851-1858.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Coronary stenting appears to provide more predictable immediate results and lower rates of restenosis than conventional balloon angioplasty for selected lesion types, but its hospital costs are significantly higher. This study was designed to evaluate the potential cost-effectiveness of Palmaz-Schatz coronary stenting relative to conventional balloon angioplasty for the treatment of patients with symptomatic, single-vessel coronary disease.23%, the angioplasty restenosis rate was <34%, or the cost of stenting (including vascular complications) exceeded that of conventional angioplasty by more than $3000. The alternative strategy of secondary stenting (initial angioplasty followed by stenting only for symptomatic restenosis) was estimated to be both less effective and less cost-effective than primary stenting over a wide range of plausible assumptions and thus does not appear to be cost-effective when primary stenting is also an option.Conclusions Decision-analytic modeling can be used to evaluate the potential cost-effectiveness of new coronary interventions. Our analysis suggests that despite its higher cost, elective coronary stenting may be a reasonably cost-effective treatment for selected patients with single-vessel coronary disease. Primary stenting is unlikely to be cost-effective for lesions with a low probability of restenosis (eg, <30%) or for patients for whom the cost of stenting is expected to be much higher than usual (eg, because of a high risk of vascular complications). Given the sensitivity of the cost-effectiveness ratios to even modest variations in the relative restenosis rates and cost estimates, future studies will be necessary to determine more precisely the cost-effectiveness of coronary stenting for specific patient and lesion subsets. (Circulation. 1994;89:1859-1874.)

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

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