Heart rate responses to a muscarinic agonist in rats with experimentally induced acute and subacute chagasic myocarditis

Abstract

SUMMARYWe administered arecoline to rats, with experimentally induced chagasic myocarditis, in order to study the sinus node sensitivity to a muscarinic agonist. Sixteen month old rats were inoculated with 200,000 T. cruzi parasites ("Y" strain). Between days 18 and 21 (acute stage), 8 infected rats and 8 age-matched controls received intravenous arecoline as a bolus injection at the following doses: 5.0, 10.0, 20.0, 40.0, and 80.0 µg/kg. Heart rate was recorded before, during and after each dose of arecoline. The remaining 8 infected animals and 8 controls were subjected to the same experimental procedure during the subacute stage, i.e., days 60 to 70 after inoculation. The baseline heart rate, of the animals studied during the acute stage (349 ± 68 bpm, mean ± SD), was higher than that of the controls (250 ± 50 bpm, p < 0.005). The heart rate changes were expressed as percentage changes over baseline values. A doseresponse curve was constructed for each group of animals. Log scales were used to plot the systematically doubled doses of arecoline and the induced-heart rate changes. The slope of the regression line for the acutely infected animals (r = -0.99, b =1.78) was not different from that for the control animals (r = -0.97, b = 1.61). The infected animals studied during the subacute stage (r = -0.99, b = 1.81) were also not different from the age-matched controls (r = -0.99, b = 1.26, NS). Consequently, our results show no pharmacological evidence of postjunctional hypersensitivity to the muscarinic agonist arecoline. Therefore, these results indirectly suggest that the postganglionic parasympathetic innervation, of the sinus node of rats with autopsy proved chagasic myocarditis, is not irreversibly damaged by Trypanosoma cruzi.

Trypanosoma cruzi infection induces up-regulation of cardiac muscarinic acetylcholine receptors in vivo and in vitro

“…Our observations are consistent with Tanowitz and colleagues (22), who reported no significant changes in the number and kinetics properties (Kd and Bmax) of the mAChR 22 of chagasic mice on the acute phase of the disease. Similarly, Torres et al (21), working on chagasic Wistar rats in the acute or subacute phase of the disease, also failed to demonstrate any significant cardiac mAChR supersensitivity.…”

“…Even though there is strong evidence in favor of both neurogenic and immunogenic theories, some investigators have failed to demonstrate mAChR up-or down-regulation. Torres et al (21) observed that the mAChR function is neither depressed nor enhanced during the acute stage of Chagas disease in rats. Similarly, Tanowitz et al (22) did not observe changes in the mAChR number or function in the heart of T. cruzi-infected mice.…”

A Decreased Expression and Functionality of Muscarinic Cholinergic Receptor in Acute Chagas Myocarditis

“…Here in the presence of pirenzepine, the recovery from the bradycardia induced by phenylephrine was faster in T. cruzi infected rats. This could imply that acetylcholine reserves in synaptic terminals at sinoatrial nodes were lower as a consequences of vagal denervation caused by parasite invasion of the neurons, degeneration caused by periganglionic inflammation or antineuronal autoimmune reaction [29] or that, conversely, sympathetic tone is higher in chagasic rats [30].…”

Beta-adrenergic blockers in chronic systolic heart failure secondary to Chagas' disease

“…We, at the Institute of Cardiovascular Research of the University of Los Andes in Mérida, Venezuela, were puzzled by the heterogeneity of the results of the functional and morphological studies on the autonomic nervous system of chagasic patients [7]. Therefore, we began a series of experimental [8][9][10][11][12][13] and clinical studies [14][15][16] aimed at assessing the functional status of the autonomic nervous system, in acutely infected laboratory animals and in chagasic patients who were in the different stages of the natural history of the disease (acute, indeterminate and congestive stages). To this purpose, the presence and extent of myocardial damage was assessed by autopsy in the former and by left ventricular cine-angiography in the latter.…”

“…Left ventricular enddiastolic volume and ejection fraction). All of these studies consistently questioned the primary nature of the cardiac parasympathetic abnormalities [9][10][11][12][13][14][15][16]. It was now absolutely necessary to determine when, in the different stages of the natural history of Chagas' disease, the activation of the sympathetic nervous system occurred [17][18][19].…”