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It has been suggested that vasodilation distal to a stenosis may cause a profound decrease in perfusion pressure and adversely affect regional left ventricular function. This phenomenon could explain the clinical concept of reversal of regional dysfunction by coronary revascularization. To evaluate the hypothesis that regional myocardial function parallels regional coronary blood pressure in the absence of changes in coronary flow, dogs chronically instrumented with left circumflex coronary artery flow probes, cuff occluders, pressure catheters and segmental function sonomicrometers were studied. By decreasing regional coronary vascular resistance with selective intracoronary dipyridamole and controlling blood flow with a proximal coronary cuff occluder, the mean left circumflex artery pressure was reduced from 83 +/- 3 to 38 +/- 2 mm Hg while circumflex coronary blood flow was maintained constant. Regional contractile function as measured by circumflex sonomicrometers was unchanged at constant circumflex subendocardial blood flow as measured by radioactive microspheres. These findings suggest that regional contractile function is dependent on subendocardial blood flow and is independent of coronary perfusion pressure.

The mechanism of the increase in function in myocardial segments adjacent to those subjected to regional ischemia is not known. To investigate the hypothesis that changes in regional loading are an important causative factor of this phenomenon, 17 dogs were instrumented with segmental shortening sonomicrometers in the left anterior descending and circumflex artery distributions, circumflex coronary flow probes and cuff occluders, as well as circumflex coronary pressure catheters. Additionally, the animals had aortic pressure catheters and ventricular pressure micromanometers. This animal model allowed modulation of regional inotropic state with regional ischemia or isoproterenol administration. With circumflex coronary bed ischemia, segmental shortening in the circumflex distribution decreased from 11.9 to 6.3% (p = 0.001) whereas left anterior descending regional shortening increased from 11.6 to 13.4% (p less than 0.001). These reciprocal changes occurred in the absence of changes in global afterload or heart rate. Systemic beta-receptor blockade did not change this response, suggesting that it was not reflex- or catecholamine-mediated. Infusing isoproterenol into the circumflex coronary artery resulted in an increase in circumflex regional shortening from 12.5 to 17.4% (p less than 0.02) whereas left anterior descending regional shortening decreased from 13.5 to 8.3% (p less than 0.001), again without change in heart rate or left ventricular or aortic pressure. These data suggest that reciprocal functional interaction between adjacent myocardial segments is a result of changes in regional afterload for the most part, with changes in local preload and timing of ejection also contributing to the observed effect.

Depressed left ventricular function during the early part (first third) of both systole and diastole in the resting state have been reported to be sensitive indicators of coronary artery disease in patients with normal global function at rest. To evaluate the possible mechanisms of these findings, 11 dogs were chronically instrumented with segmental function sonomicrometers in the left circumflex and left anterior descending coronary artery distribution, circumflex coronary flow probes and cuff occluders, aortic flow probes and ventricular pressure transducers. Percent segmental function during the first third of systole and diastole was measured in the control state and with graded circumflex artery flow reductions. Significant decreases in early systolic function with ischemia in the circumflex artery distribution were partially offset by compensatory augmented shortening in the left anterior descending artery distribution. With ischemia in the circumflex distribution, there was prolonged contraction into diastole manifested as impaired relaxation. Simultaneously, in the left anterior descending artery distribution, there was minimal compensatory enhanced relaxation. These results suggest that early systolic dysfunction in ischemic segments may be offset by enhanced function in nonischemic segments, rendering minimal, if any, change in global systolic function. Early diastolic dysfunction in ischemic segments exceeds compensatory changes in nonischemic areas by two-to-four-fold. Hence, early diastolic functional indexes may be more sensitive indicators of ischemia at rest than early systolic functional indexes.

Currently there is no accepted method for measurement of myocardial infarct size in humans. Analysis of both global and regional left ventricular function provides an indirect indication of extent of myocardial necrosis. Acute coronary occlusion results in cessation of function and in some cases dilatation of the involved myocardial segment. Often there is reciprocal hyperfunction of the non-ischemic segments resulting in little impairment of global ventricular function. Average global left ventricular function does not change from hospital admission through hospital discharge in patients with acute myocardial infarction, treated conventionally. With successful coronary reperfusion, however, both regional and global ventricular function have been reported to improve over several weeks after the initial ischemic insult. Improvement in ventricular function is most likely to occur in patients with collaterals or some preservation of antegrade flow to the involved myocardial segment who successfully undergo reperfusion. Return of function occurs in 82% of patients successfully treated within two hours after onset of chest pain. Approximately 50% of patients successfully treated two to 18 hours after onset of chest pain have demonstrated significant improvement in function. Patients admitted with normal ventricular function are less likely to demonstrate improved global ventricular function than those admitted with ejection fractions less than 45%. Acute PTCA with or without thrombolysis may result in a greater return in function than thrombolysis alone. Delayed revascularization more than 48 hours after successful reperfusion does not appear to affect ventricular function a late follow-up but may improve probability of survival. Patients discharged with ejection fractions greater than 45% clearly have an improved prognosis compared to those with depressed ejection fractions post-myocardial infarction.

The Hemopump is a new 7-mm diameter left ventricular assist device that provides as much as 3.5 l/min of nonpulsatile cardiac output after fluoroscopic placement into the left ventricle through a femoral artery cutdown. The purpose of this study was to measure the effects of Hemopump assist on hemodynamics, left ventricular function, and perfusion in the presence and absence of ischemia. Eight dogs were instrumented under pentobarbital anesthesia with left ventricular, left atrial, and aortic catheters, a loose silk ligature around the midleft anterior descending coronary artery, and sonomicrometer crystals in midwall myocardium within the left anterior descending and circumflex perfusion territories. Hemodynamic variables, regional systolic fractional shortening, and myocardial perfusion after left atrial injection of 15-microns radiolabeled microspheres were measured in the presence and absence of Hemopump assist before and after left anterior descending artery occlusion. In the absence of ischemia, Hemopump left ventricular assist resulted in reduced left ventricular end-diastolic pressure while aortic mean pressure was maintained, and there was significant reduction in regional systolic fractional shortening (reflecting systolic unloading) that correlated with an 18% decline in regional myocardial perfusion. During left anterior descending artery occlusion, left ventricular systolic and diastolic pressures were reduced during Hemopump assist while aortic mean pressure was maintained. Perfusion rose in the ischemic territory (from 13.0 +/- 8.7% to 26.2 +/- 19.8% of nonischemic flow, p = 0.045). Reduced fractional shortening was again seen in nonischemic tissue with Hemopump assist during left anterior descending artery occlusion, and this was often correlated with reduced perfusion (r = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)