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.

Effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output and vascular resistance in acute heart failure in the anaesthetized rat

“…The mercury‐induced acute heart failure was associated with a significant decrease in blood pressure, cardiac output and left ventricular d P /dt, and a significant increase in left ventricular end‐diastolic pressure (Leddy et al ., 1983). The microsphere‐induced acute heart failure also caused a significant decrease in cardiac contractility, blood pressure and cardiac output, and an increase in left ventricular end‐diastolic pressure and right atrial pressure (Schölkens et al ., 1986; Gorodetskaya et al ., 1990).…”

Ramipril

“…This embolization produced stable left ventricular pump failure characterized by markedly increased left ventricular end-diastolic pressure and reductions in left ventricular dp/dt,,, and cardiac output. Blood pressure and heart rate were not changed in these animals, but total peripheral resistance was increased (35). After intravenous administration of ramipril, left ventricular end-diastolic pressure, mean pulmonary artery pressure, systemic blood pressure, and total peripheral resistance decreased, whereas left ventricular dp/dt,,,, heart rate, and cardiac output remained unchanged.…”

Hemodynamic Effects of Benazeprilat in the Anesthetized Dog with Acute Left Ventricular Failure.

“…Moreover, it was demonstrated that several ACE inhibitors were effective in ALVF induced in experimental animals by coronary embolization (4)(5)(6). Therefore, us ing a similar animal model of ALVF, we eval uated the action of benazeprilat, a new potent and long acting ACE inhibitor with no direct inotropic effect (7,11,16), on acute heart fail ure. ALVF was induced by injecting micro spheres into the left coronary artery of an anes thetized open chest dog.…”

“…An acute left ventricular failure (ALVF) in duced by repeated injections of plastic micro spheres into the coronary artery has been used for evaluating the effects of ACE inhibitors on heart failure (5-7). ACE inhibitors were found to produce a significant improvement of hemodynamic parameters, especially the left ventricular end-diastolic pressure (LVEDP) (5,7).…”