Sera from chronic chagasic patients depress cardiac electrogenesis and conduction

Abstract

We report results obtained with sera from 58 chronic chagasic patients that were evaluated for effects on heart rate and atrioventricular (AV) conduction in isolated rabbit hearts and screened for the presence of muscarinic and beta-adrenergic activity. We show that sera from 26 patients decreased heart rate, while 10 increased it and 22 had no effect. Additionally, sera from 20 of the 58 patients blocked AV conduction. Muscarinic activation seems to be involved in both effects, but is not the only mechanism, since atropine did not antagonize the decrease in heart rate in 23% of sera or AV block in 40%. Sera from patients with complex arrhythmias were significantly more effective in depressing both heart rate and AV conduction. Sera that induce increases in heart rate seem to operate exclusively through beta-adrenergic activation. Two of these sera, evaluated with respect to intercellular communication in primary cultures of embryonic cardiomyocytes were able to block gap junction conductance evaluated by a dye injection technique after 24-h exposure. The mechanisms underlying this uncoupling effect are currently being investigated.

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

“…The production of autoantibodies against beta1 and beta2-adrenoreceptors correlated with primary electrical cardiac abnormalities (Chiale et al 1995). It was also demonstrated that sera from chronic chagasic individuals interfere with electric and mechanical activities of embryonic myocardial cells in vitro (Costa et al 2000, Kaplan et al 1997 and affect cardiac electrogenesis and conduction when perfused in the rabbit heart (de Oliveira et al 1997). These alterations in heart-cell function seem to result from the binding of antibodies to β-adrenergic and M2-cholinergic receptors on the myocardial cell surface (Costa et al 2000, de Oliveira et al 1997, Kaplan et al 1997.…”

“…It was also demonstrated that sera from chronic chagasic individuals interfere with electric and mechanical activities of embryonic myocardial cells in vitro (Costa et al 2000, Kaplan et al 1997 and affect cardiac electrogenesis and conduction when perfused in the rabbit heart (de Oliveira et al 1997). These alterations in heart-cell function seem to result from the binding of antibodies to β-adrenergic and M2-cholinergic receptors on the myocardial cell surface (Costa et al 2000, de Oliveira et al 1997, Kaplan et al 1997. Thus, by stimulating the production of autoantibodies against certain self-antigens, T. cruzi infection may cause disturbances in heart cell functions, which may lead to complications associated with CChC.…”

Noninvasive prognostic markers for cardiac death and ventricular arrhythmia in long-term follow-up of subjects with chronic Chagas' disease

“…Palpitations have been considered a harbinger of adverse outcome (26). On the other hand, conduction delay, reported in 5.8 to 20.2% of subjects with chronic Chagas' cardiomyopathy (27,28), is a muscarinic-like immunoglobulin G-mediated disturbance considered to be a key point in the physiopathogenesis of intraventricular electrical abnormalities in Chagas' disease (29)(30)(31)(32). The exclusion of subjects with atrioventricular delay at enrollment eliminated those at a higher risk for adverse events (11).…”

The presence of antiautonomic membrane receptor antibodies do not correlate with brain lesions in Chagas' disease

“…The method for eCG recording from isolated rabbit hearts has been described in detail 7 . In brief, young rabbits weighing 1.5 to 2.0 kg were killed by cervical dislocation, and their hearts were rapidly removed and cannulated through the aorta for continuous perfusion of the coronary circulation with Tyrode solution (mmol/l): NaCl, 127; KCl, 2.7; NahCo3, 12; MgCl2, 0.5; glucose, 10; and CaCl2, 2.7; ph 7.2 at 36 o C±0.2 o C. The hearts were immersed in warmed Tyrode solution in a water-jacketed glass flask; three glass electrodes filled with 1 mol/l NaCl were positioned inside the flask to obtain optimal eCG recordings.…”

“…Considering that the pathogenesis of the autonomic nervous system dysfunction has an autoimmune basis 5 , it would be fair to postulate that autonomic dysfunction such as observed even in the early phase of Chagas' disease might be consequent to autoreactive antibodies. These antiautonomic membrane receptor antibodies are able to activate, either, beta adrenergic-(Ab-β) 6 , muscarinic (Ab-M) or both, muscarinic and beta adrenergic (Ab-Mβ) autonomic receptors 7 . In addition, Ribeiro et al has shown strong correlation between the presence of Ab-M and abnormal vagal modulation in chronic chagasic patients 8 .…”