The performance of the cardiovascular system depends on the interaction of its components. We propose to investigate the coupling of the left ventricle (LV) and arterial systems in conscious animals with intact reflexes at rest, during exercise, and with depressed LV performance. The analysis of LV and arterial pressure (P)-volume (V) relations to be used in these studies is based on previous observations in the isolated LV ejecting into a model of the arterial system. These concepts have not been evaluated in the circulation of intact, conscious animals and the effects of exercise and clinically important disease processes have not been previously investigated. The following specific hypotheses will be evaluated. Hypothesis 1: The stroke volume (SV) and the LV end-systolic P (PES) are linearly related over the physiologically relevant range. The slope of this relation, EA, is the effective elastance of the arterial system, and is primarily determined under most circumstances by the heart rate and total peripheral vascular resistance. Hypothesis 2: LV stroke work is maximal when end-systolic elastance of the LV (EES) is equal to EA, while mechanical efficiency (the ratio of arterial stroke work to total pressure-volume area, SW/PVA) is maximum when EES is greater than EA. Hypothesis 3: The normal cardiovascular system operates at rest with EES slightly greater than EA, intermediate between points for maximum SW and mechanical efficiency. Hypothesis 4: During exercise, the LV and arterial system function closer to the point of maximum mechanical efficiency with EES > EA; similar increases in heart rate produced by pacing at rest result in suboptimal matching with EES < EA, Hypotheses 5 and 6: When LV function is depressed by rapid pacing induced heart failure or coronary occlusion, the coupling of the LV and arterial system is not optimal, as EA > EES, but can be returned toward optimal by decreasing EA using vasodilators. Hypothesis 1 will be evaluated both in an anesthetized, open-chest preparation in which stroke volume can be precisely controlled by right heart bypass in conscious dogs. The other hypotheses will be evaluated by studying conscious dogs previously instrumented to measure LV pressure and volume. EES will be determined as the slope of the LV end- systolic pressure-volume relation produced by varying LV P and V by transient caval occlusions. EA will be determined as PES/SV. These studies will supply important new information on the coupling of the LV and arterial system of the conscious animal with intact reflexes at rest, during exercise, and following depression of LV performance. These studies may lead to rational interventions to improve pump function in patients with common cardiovascular diseases.
Showing the most recent 10 out of 20 publications
