Effect of propranolol on ischemic myocardial damage and left ventricular hypertrophy following permanent coronary artery occlusion or occlusion followed by reperfusion.
This study was designed to assess the effect of propranolol for limiting myocardial damage and hypertrophy in rats with permanent coronary artery occlusion or occlusion followed by reperfusion. Rats were subjected to occlusion of the left main coronary artery for 48 h (MI) or 0.5 h of occlusion followed by reperfusion for 47.5 h (MI/R). Myocardial injury was determined by measuring the depletion of creatine phosphokinase (CK) levels from the left ventricular free wall. In comparison to sham-occluded animals, myocardial CK levels were significantly decreased by 40% in MI + vehicle animals and 30% in MI/R + vehicle animals. Propranolol (0.3 mg/kg 1 min before occlusion followed by 1 mg/kg at 4 and 24 h after occlusion) significantly reduced the loss of myocardial CK-specific activity in MI animals, but failed to prevent the loss of CK-specific activity in animals subjected to coronary artery reperfusion. Left ventricular hypertrophy developed to a similar extent in both vehicle-treated MI and MI/R groups. Propranolol had no effect on the myocardial hypertrophy in MI or MI/R animals. Likewise, in MI/R animals no diminution of polymorphonuclear leukocyte infiltration was seen with propranolol. These data indicate that propranolol had a significant cardioprotective effect in rats with permanent coronary artery occlusion but failed to salvage ischemic tissue, reduce myocardial hypertrophy or mitigate neutrophil infiltration in animals with early reperfusion of the ischemic myocardium. These results suggest that propranolol may afford a significant protection of the ischemic myocardium, but the combination of reperfusion and propranolol may not result in any greater reduction in infarct size than reperfusion alone.
Smith
E F
EF
Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, Pa.
Egan
J W
JW
Griswold
D E
DE
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003331:Coronary Vessels / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011433:Propranolol