Myocardial injury following endogenous catecholamine release in rabbits.
Catecholamines (CAT) given in large doses produce cardiomyopathic changes in several animal species. This study was designed to determine if endogenous release can also induce cardiac injury. Rabbits were infused with doses of tyramine (TYR), ranging from 200 to 500 micrograms/min/kg, i.v. for 90 min. Arterial pressure and heart rate were measured, as were total CAT concentrations, blood gases, pH and glucose. Two days later the animals were killed and cardiac injury assessed using a histological scoring system. All data were compared with controls given saline. Initial CAT averaged 452 pg/ml, rose to 2890 pg/ml after starting TYR, 500 micrograms/min/kg, and remained elevated for the duration of infusion. Circulating CAT levels were a function of TYR dose, and bore a linear relationship to the histological score (P less than 0.001). Development of lesions was unaltered by beta 1 blockade with practolol, but sharply reduced by alpha blockade with phentolamine (P less than 0.01). Pretreatment with insulin also reduced lesion formation, but diabetic (alloxan) rabbits showed no greater CAT injury. It is concluded that endogenous release of CAT induces myocardial injury in the rabbit in a dose-dependent manner. This is unrelated to myocardial O2 demand, and microvascular pathology was absent. Activation of alpha adrenergic pathways is likely the dominant or exclusive mechanism.
Downing
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Chen
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D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology* / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013565:Sympatholytics / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D002395:Catecholamines; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D013565:Sympatholytics; D014439:Tyramine