mr-1452 and Myocardial-Infarction

The intravenous infusion of naloxone (Nal) (0.17 mg/kg/min) and of the selective kappa antagonist MR 1452 MS (0.07 mg/kg/min) on rats with left coronary artery occlusion was studied. The results demonstrated significant improvement of cardio-circulatory parameters, i.e., mean arterial pressure (MAP), heart rate (HR) and cardiac output (CO). The action of Nal is peripheral and central with prevalence of central effect, since its hypertensive effect is due to a rise in total peripheral resistance (TPR) (by 12%), rather than to an increase of CO (by 3% compared to saline-treated rats 20 min postinfarction). The effect of MR 1452 MS is mainly peripheral, since MAP increased due to increased CO (by 5% and by 8% compared to saline-treated animals 20 min and 2 h postinfarction). As a result of increased MAP and CO a reduction of myocardial oxygen deficiency was evident, and the development of cardiogenic shock in Nal- and MR 1452 MS-treated animals decreased by 7% and by 17% 2 and 24 h postinfarction. Reduction of the incidence of early arrhythmias (20 min-2 h postinfarction) by 25% and 16%, respectively, was found. Mortality was significantly reduced in both groups by 8% 2 h postinfarction and by 17% 24 h postinfarction, which suggested a comparable effect of both drugs in cardiogenic shock.

Topics: Acid-Base Equilibrium; Animals; Benzomorphans; Blood Pressure; Electrocardiography; Heart Rate; L-Lactate Dehydrogenase; Male; Morphinans; Myocardial Infarction; Naloxone; Narcotic Antagonists; Rats; Rats, Inbred Strains; Respiration