EFFECTS OF SPIRAPRILAT, AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, ON ANESTHETIZED DOGS IN A NEW MODEL OF ACUTE LEFT-VENTRICULAR FAILURE

Spiraprilat, a new angiotensin-converting enzyme (ACE) inhibitor, was compared with enalaprilat for its ability to improve left ventricular (LV) function and metabolism in anesthetized open-chest dogs with a ne w model of acute LV failure (ALVF) induced by embolization of the left coronary artery with 50 mum plastic microspheres followed by intraven ous (i.v.) infusion of methoxamine. With this procedure, LV end-diasto lic pressure (LVEDP) increased from 4.2 +/- 0.7 to 12.8 +/- 1.3 mm Hg and remained at approximately 12 mm Hg throughout the experiment. Card iac output (CO) decreased from 1.25 +/- 0. 12 to 0.79 +/- 0.06 and 0.5 5 +/- 0.02 L/min at 30 and 90 min after methoxamine infusion, respecti vely. LV dP/dt(max) and dP/dt/P decreased, while total peripheral resi stance (TPR) increased. These hemodynamic changes indicated establishm ent of stable ALVF of a moderate degree. Moreover, decreases in myocar dial lactate consumption and contents of creatine phosphate in the myo cardium indicated the existence of moderate ischemia. The new ACE inhi bitor, spiraprilat, as well as enalaprilat (30 mug/kg i.v.) effectivel y decreased mean aortic pressure (30%), LVEDP (20%), and TPR (30%) and increased stroke volume (SV) CO, and dP/dt/P. Both agents decreased m yocardial oxygen consumption (20%) and caused a significant increase i n myocardial creatine phosphate contents. These data indicate that the beneficial effects of both inhibitors extended not only to LV functio n but also to myocardial energy metabolism in ALVF.