Preservation of ischemic myocardium by a new converting enzyme inhibitor, enalaprilic acid, in acute myocardial infarction

• Published in: The American heart journal Vol. 109; no. 2; pp. 222 - 228
• Main Authors: Hock, Carl E, Ribeiro, Lair G.T, Lefer, Allan M
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.1985; Elsevier
• Subjects: Angiotensin II - metabolism; Animals; Antianginal agents. Coronary vasodilator agents; Biological and medical sciences; Cardiovascular system; Coronary Circulation; Creatine Kinase - metabolism; Dipeptides - therapeutic use; Enalaprilat; Heart Ventricles - enzymology; Male; Medical sciences; Myocardial Infarction - drug therapy; Myocardial Infarction - enzymology; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Infarct; Rat; Acute; Rodentia; Enzyme inhibitor; Cardiovascular disease; Coronary heart disease; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Animal; Angiotensin converting enzyme; Myocardium
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/0002-8703(85)90587-3

Enalaprilic acid (MK-422), the biologically active diacid of the converting enzyme inhibitor enalapril, was studied in myocardial ischemia (MI). Acute left coronary artery ligation was produced in 62 male Sprague-Dawley rats, and infarct size was determined by left ventricular free wall (LVFW) creatine kinase (CK) activity. Administration of enalaprilic acid (2 mg/kg) 2 minutes and 24 hours after MI significantly blunted the reduction in LVFW CK activity at 48 hours after ligation, when compared to the MI rats given vehicle (6.4 ± 0.5 vs 4.7 ± 0.2 IU/mg protein, respectively; p < 0.01). The percentage of LVFW spared was significantly ( p < 0.01) increased from 28 ± 2% to 45 ± 5% by MK-422. MK-422 also significantly blunted the loss of LVFW CK activity 48 hours after a coronary ligation (10 minutes) followed by reperfusion, when compared to vehicle (10.1 ± 0.6 vs 8.3 ± 0.6 IU/mg protein, respectively; p < 0.05). This represents a significant increase in the percentage of LVFW spared, 65 ± 5% vs 85 ± 6% ( p < 0.05). These data indicate a significant protective action afforded by MK-422 in two different protocols of ischemic damage to the myocardium and suggest a role for the renin-angiotensin system in the extension of ischemic damage.