Chagasic sera alter the effects of ouabain on isolated rat atria. Participation of adrenergic mechanisms

Abstract

The effects of chagasic sera, containing an antibody (EVI antibody) which reacts with the plasma membrane of working myocardial cells, on ‘toxic’ and ‘non-toxic’ actions of ouabain upon isolated self beating or paced rat atria suspended in different media, were explored. Although ouabain produced a dose-dependent positive inotropic influence on atria suspended in Krebs-Ringer-bicarbonate (KRB) and in KRB plus normal human serum (KRB + NHS) it did not elicit any significant positive inotropic effect on atria beating in KRB plus EVI positive human chagasic serum (EVI(+)S). Additionally, in EVI(+)S dose-response curves of classical signs of digitalis cardiac toxicity shifted to the left. The threshold concentration of ouabain required to elicit the onset of ‘toxic’ effects was higher in control preparations (kept in KRB or KRB + NHS) than in EVI(+)S exposed preparations. (−)-Propranolol attenuated the overall toxic action of ouabain in EVI(+)S and facilitated its positive inotropic influence. In control media, the β-adrenoceptor blocker failed to modify either the ‘non-toxic’ or the ‘toxic’ effect of ouabain. On the other hand, with control atria, subthreshold exogenous norepinephrine inhibited the positive inotropism of ouabain. The data suggest that an adrenergic mechanism is involved in the action of ouabain on cardiac tissue immersed in an EVI(+)S-containing solution. The foregoing results may explain the severe ‘toxic’ effects observed with cardioactive glycosides when they are used in patients with Chagas' heart disease, even at low doses.