Cardiovascular Effects of the Converting Enzyme Inhibitor Ramipril (HOE 498) In Anesthetized Dogs with Acute Ischemic Left Ventricular Failure

Abstract

The non-sulfhydryl converting enzyme inhibitor Ramipril (HOE 498) is characterized by long lasting antihypertensive activity in man. To examine its cardiovascular potential in heart failure, ramipril was administered during acute ischemic left ventricular failure in pentobarbital anesthetized dogs, induced by repeated injections of plastic microspheres into the left main coronary artery. Repeated embolizations produced stable left ventricular (LV) pump failure characterized by LV enddiastolic pressure of 22 mmHg, reductions in LV dp/dt max and cardiac output. Blood pressure and heart rate were not changed while total peripheral resistance increased. After a stabilization period ramipril was administered in two doses at 30 or 100 micrograms/kg as an intravenous bolus followed by continuous infusion of 3 or 10 micrograms/kg/min for 150 min. Ramipril in the lower dose decreased LV enddiastolic pressure by 8 mmHg, mean pulmonary artery pressure by 4 mmHg, systemic blood pressure by 40 mmHg and total peripheral resistance by 1280 dyn x sec x cm-5. LV dp/dt max, heart rate and cardiac output remained unchanged during ramipril administration. More pronounced effects were obtained with the higher dose. In conclusion, the improvements of hemodynamics produced by ramipril during acute ischemic left ventricular failure in anesthetized dogs are best explained by a reduction in both preload and afterload.