Comparison of effects of dobutamine and ouabain on left ventricular contraction and relaxation in closed-chest dogs

Abstract

Because catecholamines and digitalis have different effects on the time course of myocardial intracellular calcium concentration, their effects on the time course of left ventricular contraction and relaxation may also be different. To study this question, dogs were instrumented to measure left ventricular pressure and determine left ventricular volume from three ultrasonic dimensions. After full recovery from the instrumentation, the effects of dobutamine (2-10 micrograms/kg), ouabain (0.5 mg i.v.) alone, and ouabain given after propranolol (2 mg/kg i.v.), or phentolamine (5 mg i.v.) and incremental doses of ouabain (0.25-0.75 mg i.v.) were assessed on different days. Left ventricular pressure and volume were varied by caval occlusions. Dobutamine significantly increased the slope of the left ventricular end-systolic pressure-volume relation (Emax) and the slope of the dP/dtmax-end-diastolic volume relation (dE/dtmax), while significantly decreasing the time from end-diastole to end-systole (tmax) and the time constant (T) of the isovolumic fall in left ventricular pressure. Ouabain also increased Emax and dE/dtmax but did not alter tmax or T. Dobutamine produced a greater increase in dE/dtmax than in Emax, whereas ouabain produced similar increases in both. These effects of ouabain were not altered by pretreatment with propranolol or phentolamine. We conclude that although dobutamine and ouabain are both positive inotropes that increase Emax, dobutamine speeds the rate of left ventricular contraction (tmax) and relaxation (T), whereas ouabain does not. These effects of ouabain and dobutamine on global parameters of left ventricular chamber performance mirror their influence on intracellular calcium availability. Furthermore, these observations are consistent with the predictions of the time-varying elastance model of the left ventricle and support its usefulness as a conceptual framework to understand and link events occurring during isovolumic contraction, end-systole, and isovolumic relaxation.