Epinephrine induced myocardial necrosis: effects of aminophylline and adrenergic blockade.
The pathogenesis of myocardial necrosis produced in the albino rat by a single large dose of the potent alpha and beta adrenergic agonist epinephrine was investigated. In confirmation and extension of earlier observations with the alpha adrenergic antagonist tolazoline, it was found that alpha adrenergic blockade with phenoxybenzamine or beta adrenergic blockade with propranolol only partially attenuated the cardiotoxic effect of epinephrine while complete prevention of myocardial injury was achieved with the combined use of the two antagonists. In the presence of alpha adrenergic blockade alone, phosphodiesterase inhibition (aminophylline) caused a dramatic increase of epinephrine cardiotoxicity, demonstrating the importance of unopposed beta adrenergic activation. These results are consistent with the assumption that, in the rat, a cardiotoxic dose of epinephrine produces powerful alpha adrenergic activation which overshadows the effects of the beta adrenergic component of this catecholamine. It is concluded that in epinephrine induced myocardial necrosis, excessive alpha-adrenergic receptor activation in the cardiovascular system is clearly dominant in the initial phases. However, the contribution of the beta-adrenergic component of this catecholamine is of considerable importance for the eventual full development of the injury.
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013565:Sympatholytics / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013565:Sympatholytics; D000628:Aminophylline; D004837:Epinephrine