Mechanism of isoproterenol induced myocardial damage.
To study the harmful effects of isoproterenol on myocardium rats were injected with isoproterenol 10 or 0.1 mg.kg-1 or with isoproterenol 10 mg.kg-1 after an injection of propranolol 20 mg.kg-1. Endogenous phospholipase activity in heart homogenate and tissue adenosine triphosphate concentrations were determined 1, 7, and 15 h after isoproterenol injection. The activities of three segments (NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase) of the electron transport chain in heart mitochondria were also measured in the same manner. In the group given isoproterenol 0.1 mg.kg-1 the tissue adenosine triphosphate concentration was decreased after 1 h but returned to control value after 15 h. No significant change in phospholipase activity or in the activities of the three segments in mitochondria was observed throughout the study. In the group given isoproterenol 10 mg.kg-1 the tissue adenosine triphosphate concentration was significantly decreased after 1 h and did not return to control values after 15 h. Phospholipase activity was increased and the activities of NADH-cytochrome c reductase and cytochrome c oxidase were significantly decreased after 15 h. The activity of succinate-cytochrome c reductase was not affected. In the propranolol group, pretreatment with propranolol protected against a reduction in adenosine triphosphate after isoproterenol 10 mg.kg-1. Propranolol also prevented activation of phospholipase and maintained the activities of the three segments of mitochondria throughout the study. In an in vitro study mitochondria prepared from intact rat hearts were incubated with 0.1 unit phospholipase A2.(ABSTRACT TRUNCATED AT 250 WORDS)
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000255:Adenosine Triphosphate; D009245:NADH Dehydrogenase; D010740:Phospholipases; D007545:Isoproterenol