Muscarinic antibodies and heart rate responses to dynamic exercise and to the Valsalva maneuver in chronic chagasic patients

Abstract

SUMMARYWe have studied the cardiac chronotropic responses to the Valsalva maneuver and to dynamic exercise of twenty chronic chagasic patients with normal left ventricular function and no segmental wall abnormalities by two-dimensional echocardiogram. The absolute increase in heart rate of the patients (∆ = 21.5 ± 10 bpm, M±SD) during the maneuver was significantly diminished when compared to controls (∆ = 31.30 ± 70, M±SD, p = 0.03). The minimum heart rate (58.24 ± 8.90 vs. 62.80 ± 10, p = 0.68) and the absolute decrease in heart rate at the end of the maneuver (∆ = 38.30 ± 13 vs. ∆ = 31.47 ± 17, p = 0.10) were not different from controls. The initial heart rate acceleration during dynamic exercise (∆ = 12 ± 7.55 vs. ∆ = 19 ± 7.27, M±SD, p = 0.01) was also diminished, but the heart rate recovery during the first ten seconds was more prominent in the sero-positive patients (Median: 14, Interquartile range: (9.75-17.50 vs. 5(0-8.75, p = 0.001). The serum levels of muscarinic cardiac auto-antibodies were significantly higher in the chagasic patients (Median: 34.58, Interquartile Range: 17-46.5, Optical Density) than in controls (Median: 0, Interquartile Range: 0-22.25, p = 0.001) and correlated significantly and directly (r = 0.68, p = 0.002) with early heart rate recovery during dynamic exercise. The results of this investigation indirectly suggest that, the cardiac muscarinic auto-antibodies may have positive agonist effects on parasympathetic heart rate control of chagasic patients.

Efeitos do exercí­cio fí­sico em indiví­duos com cardiomiopatia chagásica

“…Coadunando com este pensamento Neves et al verificaram que indivíduos com Doença de Chagas independente de serem sintomáticos ou assintomáticos apresentam exacerbação da resposta parassimpática quando comparados a indivíduos sadios, ou seja, apresentam menor aumento da frequência cardíaca, durante o exercício, que pode provocar diminuição da manutenção do esforço físico e menor capacidade funcional que indivíduos sadios [16]. Talvez, por isso esses indivíduos tolerem melhor os exercícios resistidos com pesos que exercícios aeróbicos não resistidos, já que os mesmos são menos dependentes da resposta cronotrópica.…”

Association of Anti-β1 and Anti-M2 Antibodies with Autonomic Nervous System Modulation in Patients with Chronic Chagas Cardiomyopathy

“…Both anti-β1 and anti-M2 antibodies modulate the cascade of adaptive ANS responses during exercise. 41,42 Considering the findings of previous studies on autoantibodies, 37 at least three distinct effects of these antibodies on their respective receptors must be considered: they modulate binding of true ligands; they activate various effector pathways; and they modulate the disposition of the receptor and simultaneous binding to the receptor. However, how autoantibodies cause changes in receptor activity and how this relates to the pathogenesis and severity of CCC remains unclear.…”

Cardiac Autonomic Control Mechanisms in the Pathogenesis of Chagas' Heart Disease

“…Therefore, adjustments of heart rate in response parasympathetic efferent activity are expected to be apparently “impaired” [ 62 ]. Consequently, we have studied the cardiac chronotropic responses to the Valsalva maneuver and to dynamic exercise and correlated them with the serum levels of cardiac muscarinic autoantibodies, of Chagasic patients who were in the chronic phase of the disease [ 12 ]. Our clinical investigation included asymptomatic Chagasic patients, who were in the indeterminate and cardiac forms of the disease and had normal two-dimensional echocardiograms.…”

“…Therefore, the more prominent heart rate recovery of the Chagasic patients could be an expression of a positive allosteric effect of the muscarinic autoantibodies on the membrane muscarinic receptor. Alternatively, these results could be due to a direct agonist effect of the autoantibodies on the muscarinic receptor and thereby potentiate early heart recovery [ 12 ]. The results of this investigation provide a plausible explanation for the heterogeneity of heart rate responses to conventional cardiac autonomic tests [ 55 – 60 , 67 ].…”

“…Recent investigations have shown, on the contrary, that these autonomic abnormalities are indeed secondary and characterized by an impairment of cardiac parasympathetic control and activation of the sympathetic nervous system [ 2 , 10 ]. Moreover, muscarinic cardiac autoantibodies appear to enhance parasympathetic control of heart rate and therapeutic strategies, which antagonize the cardiotoxic effects of catecholamines, increase quality of life and survival of these patients [ 11 , 12 ]. Therefore, the main purpose of this paper is to analyze how knowledge on Chagas disease evolved from being initially considered as a primary cardioneuromyopathy to the current status of a congestive cardiomyopathy of parasitic origin.…”