DOBUTAMINE INCREASES CARDIAC-OUTPUT OF THE TOTAL ARTIFICIAL-HEART - IMPLICATIONS FOR VASCULAR CONTRIBUTION OF INOTROPIC AGENTS TO AUGMENTED VENTRICULAR-FUNCTION

Background. The synthetic catecholamine dobutamine increases stroke volume in normal subjects and in patients with congestive heart failure. In addition to its direct influence on myocardial contractility, dobutamine may significantly modulate vascular tone because of its alpha-and beta-adrenergic agonist activity. Methods and Results. To test the hypothesis that such vasoactive properties significantly contribute to the improved ventricular performance noted with this agent, hemodynamic parameters were measured during stepped ascension infusion of dobutamine in a model that is insensitive to positive inotropic stimulation. Administration of dobutamine in nine calves that underwent replacement of the native right and left ventricles with pneumatically driven total artificial hearts resulted in a significant (p = 0.0001) increase in cardiac output from 7.0 +/- 1.8 to 8.2 +/- 1.8 l/min and a significant (p = 0.0001) decrease in total peripheral vascular resistance from 1,224 +/- 559 to 745 +/- 317 dyne.sec/cm5. A less marked influence was noted on the pulmonary vasculature, with pulmonary vascular resistance exhibiting a significant (p < 0.05) decrease from its baseline value only at the peak infusion. Consistent with an increase in venous return, both left and right atrial pressures increased significantly (p < 0.005) with dobutamine administration. Conclusions. These data demonstrate that the vasoactive properties of dobutamine significantly contribute to improved ventricular performance independent of direct myocardial stimulation. This effect appears to result in part from a direct modulation of arterial and venous tones rather than from a reflex response to primary changes in contractility.