Elsevier

American Heart Journal

Volume 102, Issue 2, August 1981, Pages 210-221
American Heart Journal

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

https://doi.org/10.1016/S0002-8703(81)80012-9Get rights and content

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.

References (63)

  • FleckensteinA et al.

    Myocardial fiber necrosis due to intracellular Ca-overload. A new principle in cardiac pathophysiology

  • KischB

    Die Autokatalyse der Adrenalinoxydation

    Biochem Z

    (1930)
  • TaamGML et al.

    Alterations in adrenochrome induced myocardial cell damage and contractile failure by cations

  • PearceRM

    Experimental myocarditis; a study of the histological changes following intravenous injections of adrenalin

    J Exp Med

    (1906)
  • SzakacsJE et al.

    1-norepinephrine myocarditis

    Am J Clin Pathol

    (1958)
  • RonaG et al.

    An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat

    Arch Pathol

    (1959)
  • BoutetM et al.

    Aspect microcirculatoire des lesions myocardiques provoquees par l'infusion de catecholamines. Etude ultrastructural a l'aide de traceurs de diffusion. I. Isoproterenol

    Pathol Biol (Paris)

    (1973)
  • BoutetM et al.

    Aspect microcirculatoire des lesions myocardiques provoquees par l'infusion de catecholamines. Etude ultrastructural a l'aide de traceurs de diffusion. II. Norepinephrine

    Pathol Biol (Paris)

    (1974)
  • HandforthCP

    Isoproterenol-induced myocardial infarction in animals

    Arch Pathol

    (1962)
  • HandforthCP

    Myocardial infarction and necrotizing arteritis in hamsters, produced by isoproterenol (Isoprel)

    Med Serv J Can

    (1962)
  • RonaG et al.

    Pathogenesis of isoproterenol induced myocardial alterations: Functional and morphological correlates

  • RonaG et al.

    Studies on infarct-like myocardial necrosis produced by isoproterenol: A review

    Rev Can Biol

    (1963)
  • MaruffoCA

    Fine structural study of myocardial changes induced by isoproterenol in Rhesus monkeys (macaca mulatta)

    Am J Pathol

    (1967)
  • ReganTJ et al.

    Myocardial ion and lipid exchange during ischemia and catecholamine induced necrosis: Relation to regional blood flow

  • RaabW

    Pathogenic significance of adrenalin and related substances in heart muscle

    Exp Med Surg

    (1943)
  • SobelB et al.

    Effect of catecholamines and adrenergic blocking agents on oxidative phosphorylation in rat heart mitochondria

    Circ Res

    (1966)
  • SeverinE et al.

    Direct toxic effects of isoproterenol on cultured cardiac muscle cells

    Experientia

    (1977)
  • MosingerB et al.

    Myocardial lesions induced by natural catecholamines in vitro

    Europ J Cardiol

    (1978)
  • BloomS et al.

    Myocytolysis and mitochondrial calcification in rat myocardium after low doses of isoproterenol

    Am J Pathol

    (1969)
  • CsapaZ et al.

    Early alterations of cardiac muscle cells in isoproterenol induced necrosis

    Arch Pathol

    (1972)
  • KutsunaF

    Electron microscopic studies on isoproterenol-induced myocardial lesions in rats

    Jpn Heart J

    (1972)
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    This study was supported by grants from The Great West Life Assurance Company, Winnipeg.

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