Comparative Effects of Dobutamine and Corwin, a β1-Adrenergic Partial Agonist, in Experimental Left Ventricular Failure

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Abstract
Corwin is a long-acting .beta.1-adrenergic partial agonist for oral and i.v. use. The effects of corwin were compared with those of dobutamine in acute ischemic left ventricular failure in dogs. Failure was produced by embolization of the left main coronary artery with 50 .mu.m plastic microspheres. This induced severe depression in left ventricular function, as evidenced by a marked increase in left ventricular end-diastolic pressure, reduction in left ventricular dP/dtmax [maximal change in pressure/change in time] and cardiac output. After 45 min was allowed for stabilization, the 27 dogs were randomly assigned to 3 groups: control (n = 9), dobutamine-treated (5-10 .mu.g/kg min i.v., n = 9) and corwin-treated (0.025-0.10 mg/kg i.v., n = 9). The doses of dobutamine and corwin were adjusted to give an increase in left ventricular dP/dtmax of 50%. Both drugs similarly increased cardiac output (P < 0.01), lowered left ventricular end-diastolic pressure (P < 0.01) and total peripheral vascular resistance (P < 0.01), but did not affect the heart rate. Only dobutamine increased the mean arterial pressure (P < 0.01). Both drugs also increased the arterial concentrations and myocardial uptake of fatty acids (P < 0.05) but caused only a small and nonsignificant increase in myocardial O2 consumption. The hemodynamic and metabolic profiles of corwin and dobutamine are similar, and both drugs should be of special value in the treatment of congestive heart failure. Since corwin can be given orally and has a longer duration of action, it is potentially useful in the long-term treatment of heart failure.