Vagal dysfunction and the pathogenesis of chronic Chagas disease

Abstract

Vagal dysfunction is thought to be an early, primary and specific abnormality of chronic Chagas disease. However, chagasic patients with unequivocal evidence of heart disease, can have normal or abnormal vagal control of heart rate. A common explanation for these apparently discordant and contradictory results is proposed. D

Early occurrence of anti-muscarinic autoantibodies and abnormal vagal modulation in Chagas disease

“…Moreover, levels of anti-M 2 cholinergic autoantibodies detected by ELISA were significantly elevated in Chagas disease independently of the presence of LV dysfunction, suggesting also that this immune reaction could not be ascribed to a non-specific LV deterioration, challenging the argument that both vagal dysfunction and anti-muscarinic antibodies occur lately in Chagas disease [18]. Indeed, our data confirm previous results of our group (unpublished data) in which antimuscarinic autoantibodies were observed in all stages of Chagas disease and could not be related to the deterioration of LV function that characterizes the advanced cardiac form.…”

“…The low-to-high frequency component ratio (LF/HF) was also calculated [18,19]. In order to minimize non-stationary oscillations of heart rate variability, spectral analysis was performed during sleep, in a 5-min segment of good quality and without ectopic beats, close to the lowest heart rate.…”

“…Circulating autoantibodies with partial muscarinic cholinergic agonistic activity have been found in dysautonomic asymptomatic Chagas disease patients with normal ECG and chest X-ray, suggesting that they can have a causal role in the observed dysautonomia [15]. Nonetheless, the role of these autoantibodies in the genesis of autonomic dysfunction remains a matter of controversy, since patients with advanced non-chagasic cardiac disease also have cardiac autoantibodies with muscarinic and adrenergic activities [16][17][18]. Indeed, Davila and coauthors recently [18] stated that emergence of both vagal dysfunction and of these autoantibodies are late and nonspecific consequences of the syndrome of left ventricular (LV) dysfunction.…”

Anti-muscarinic autoantibodies and vagal modulation in Chagas disease: Positive allosteric modulators vs desensitization and downregulation of M2 cardiac acetylcholine receptors

“…Therefore, the opposite findings of these clinical investigations should be taken into consideration when analyzing Ribeiro's [7] results and conclusions [18,19]. Further research is urgently needed to clarify this very important and controversial issue [20,21].…”

Autonomic nervous system and preventive treatment of ventricular arrhythmias in chagasic disease

“…Even though benefit of neurohumoral blockade with enalapril and betablockers has been shown [8], we still do not know if other preventive interventions on the autonomic system can be advantageous. The combination of sympathectomy and implantation of a cardiodefibrillator sounds attractive for patients with high probability of arrhythmic death, even without advanced myocardial dysfunction.…”