Ventricular dysfunction and necrosis produced by adrenochrome metabolite of epinephrine: relation to pathogenesis of catecholamine cardiomyopathy.
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; vanillylmandelic acid and dihydroxymandelic acid did not alter contractile force development, whereas adrenochrome (50 mg/L) declined 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 1/2 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 1/2 relaxation were increased. Hearts perfused or 10 minutes or more with adrenochrome (50 mg/L), but not epinephrine, metanephrine, dihydroxymandelic acid or vanillylmandelic aicd, 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.
D000323:Adrenochrome / Q000009:adverse effects*; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004837:Epinephrine / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects; D009200:Myocardial Contraction; D009206:Myocardium / Q000648:ultrastructure*; D051381:Rats; D013997:Time Factors
D000323:Adrenochrome; D004837:Epinephrine