Preservation of ischemic myocardium by a new converting enzyme inhibitor, enalaprilic acid, in acute myocardial infarction.
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 less than 0.01). The percentage of LVFW spared was significantly (p less than 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 less than 0.05). This represents a significant increase in the percentage of LVFW spared, 65 +/- 5% vs 85 +/- 6% (p less than 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.
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D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D004151:Dipeptides / Q000627:therapeutic use*; D015773:Enalaprilat; D006352:Heart Ventricles / Q000201:enzymology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System
D004151:Dipeptides; D000804:Angiotensin II; D003402:Creatine Kinase; D015773:Enalaprilat