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Ventricular dysfunction and necrosis produced by adrenochrome metabolite of epinephrine: Relation to pathogenesis of catecholamine cardiomyopathy

1981; Elsevier BV; Volume: 102; Issue: 2 Linguagem: Inglês

10.1016/s0002-8703(81)80012-9

1097-6744

John C. Yates, Robert E. Beamish, Naranjan S. Dhalla,

Ion channel regulation and function

We have examined the effects of adrenochrome and other metabolites of epinephrine on the ultrastructure and contractile activity of isolated rat hearts perfused under conditions in which the heart rate and coronary flow were controlled. Perfusion of hearts with epinephrine or metanephrine significantly increased contractile force; vanillyimandelic acid and dihydroxymandelic acid did not alter contractile force development, whereas adrenochrome (50 mg/L) declined contractile force with complete disappearance of contractile activity by 30 minutes. Increased contractile force with epinephrine (50 mg/L) was associated with increased resting tension and maximum rates of force development and relaxation, and decreased time for peak tension development and ½ relaxation. On the other hand, hearts perfused with adrenochrome showed early decline followed by steady increase in resting tension; maximum rates of force development and relaxation were reduced and times for peak tension development and ½ relaxation were increased. Hearts perfused for 10 minutes or more with adrenochrome (50 mg/L), but not epinephrine, metanephrine, dihydroxymandelic acid or vanillylmandelic acid, showed ultrastructural damage. Adrenochrome concentrations of 10 or 25 mg/L altered the appearance of mitochondria after 30 minutes of perfusion. Infusion of epinephrine (1 mg/L) during perfusion with adrenochrome partially maintained contractile force during the first 15 minutes of perfusion but did not alter the severity of ultrastructural changes due to adrenochrome. These results are consistent with the concept that oxidation products of catecholamines such as adrenochrome are partly responsible for inducing myocardial necrosis and failure following massive catecholamine injections in intact animals.