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The effects of chagasic sera containing an antibody (EVI antibody) on "non toxic" and "toxic" actions of ouabain on isolated rat atria suspended in different media, were explored. Ouabain failed to evoke any significantly positive contractile effect on atria beating in EVI Positive Human Sera (EVI(+)S), and only produced "toxic" actions (arrhythmias, contracture enhanced frequency, reduced inotropism). On the contrary, atria beating in Krebs-Ringer-Bicarbonate (KRB) or in Normal Human Sera (NHS) reacted to added ouabain with a classical dose-dependent positive inotropic effect. The threshold concentration of ouabain required to elicit the onset of "toxic" effects was higher in KRB than in EVI(+)S. Decreasing the extracellular Ca2+ concentration or treating the auricles with verapamil, facilitated positive inotropic influence of ouabain and attenuated the "toxic" effects observed on atria beating in EVI(+)S. In addition, the combination of (--)-propranolol plus verapamil enhanced the facilitatory influence of verapamil induced on the positive inotropic effect of ouabain and reduced the "toxic" influences evoked on atria exposed to EVI(+)S. These findings support the notion that the overall "toxic" responses to ouabain on cardiac tissue immersed in an EVI(+)S containing solution may be related to a combined effect of the EVI antibody activating beta-adrenoceptors as well as to a rise in the tissue Ca2+ content.

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, 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 beta-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.