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

We 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 microg/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 dose-response 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.

Serial heart rate changes in rats inoculated by conjunctival instillation of Trypanosoma cruzi obtained from bug faeces.

UNLABELLED: The cardiac effects of experimentally induced myocarditis, when the parasite is obtained from mouse blood, are well known. However, the consequences of the infection when the parasites are obtained from bug faeces are less well defined. In the present investigation, we have used the "Y" strain of Trypanosoma cruzi, which was maintained in Rhodnius prolixus by repeated passages in mice. The faeces of 30 infected bugs were collected, the number of parasites counted and 4,000 parasites inoculated by the conjunctival route in 60 rats. Twenty-nine other rats received faeces from noninfected bugs (sham-inoculated controls) and 40 were used as normal controls. The heart rate of the three groups of animals was recorded under general anesthesia with ether. The heart rate, at day 0 pre-inoculation, was similar in the three groups of animals ( CONTROLS: 379 +/- 27 beats/min Mean +/- SD; Sham-inoculated: 366 +/- 31; Infected: 351 +/- 29) (p> 0.05). In the infected animals, the mean heart rate began to increase significantly by day 12 following infection (375 +/- 31), reaching the highest values between days 18 (390 +/- 33) and 21 (403 +/- 33) and returned to baseline by day 30 (359 +/- 28) (p< 0.05). The heart rate changes were statistically different from those observed in the sham-inoculated controls and in the control animals. Therefore, these heart rate changes were provoked by the Trypanosoma cruzi-induced infection. Thus, it appears that irrespective of the source of the parasite and route of inoculation, Trypanosoma cruziacute infection provokes a transient sinus tachycardia.

Heart rate responses to intravenous serotonin in rats with acute chagasic myocarditis.

We administered serotonin to rats with experimentally induced chagasic myocarditis in order to study the Bezold-Jarisch reflex. Sixteen 4-month old Wistar 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 serotonin as a bolus injection at the following doses: 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0, 12.0, and 14.0 micrograms/kg. Heart rate was recorded before, during and after each dose of serotonin. 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 infected animals studied during the acute stage (327 +/- 62 beats/min, mean +/- SD) was higher than that of the controls (248 +/- 52, P < 0.01). The heart rate changes were expressed as percent changes to correct for the higher baseline heart rate of the infected animals. A dose-response curve was constructed for each group of animals. The slope for the acutely infected animals (r = -0.95, b = -3.98) was not different from that for the control animals (r = -0.92, b = -3.50). The infected animals studied during the subacute stage (r = -0.92, b = -4.33) were not different from the age-matched controls (r = -0.87, b = -4.03). These results suggest that the afferent and efferent pathways which mediate the Bezold-Jarisch reflex are functionally preserved in rats with histologically proved chagasic myocarditis.

Heart rate responses to intravenous serotinin in rats with acute chagasic myocarditis

We administered serotonin to rats with experimentally induced chagasic myocarditis in order to study the Bezold-Jarisch reflex. Sixteen 4-month old Wistar 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 serotonin as a bolus injection at the following doses: 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0, 12,0, and 14.0 mug/kg. Heart rate was recorded before, during and after each dose of serotonin. 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 infected animals studied during the acute stage (327 + 62 beats/min, mean + SD) was higher than that of the controls (248 + 52, P<0.01). The heart rate changes were expressed as percent changes to correct for the higher baseline heart rate of the infected animals. A dose-response curve was constructed for each group of animals. The slope for the acutely infected animals (r = -0.95, b = -3.98) was not different from that for the control animals (r = -0,92, b = -3.50). The infected animals studied during the subacute stage (r = -0.92, b = -4.33) were not different from the age-matched controls (r = -0.87, b = -4.03). These results suggest that the afferent and efferent pathways which mediate the Bezold-Jarisch reflex are functionally preserved in rats with histologically proved chagasic myocarditis.

Cardiac sympathetic-parasympathetic balance in rats with experimentally-induced acute chagasic myocarditis.

To clarify the mechanism responsible for the transient sinus tachycardia in rats with acute chagasic myocarditis, we have examined the cardiac sympathetic-parasympathetic balance of 29 rats inoculated with 200,000 parasites (Trypanosoma cruzi). Sixteen infected animals and 8 controls were studied between days 18 and 21 after inoculation (acute stage). The remaining 13 infected animals and 9 controls were studied between days 60 and 70 after inoculation (sub-acute stage). Under anesthesia (urethane 1.25 g/kg), all animals received intravenous atenolol (5 mg/kg) and atropine (10 mg/kg). Acute stage: The baseline heart rate of the infected animals was significantly higher than that of the controls (P < 0.0001). The magnitude of the negative chronotropic response to atenolol was 4 times that of the controls (P < 0.00001). This response correlated with the baseline heart rate (r = -0.72, P < 0.001). The heart rate responses to the beta-blocker and to atropine, of the infected animals studied during the sub-acute stage, were not different from controls. These findings suggest that cardiac sympathetic activity is transiently enhanced and cardiac parasympathetic activity is not impaired, in rats with acute chagasic myocarditis. The transient predominance of cardiac sympathetic activity could explain, in part, the sinus tachycardia observed in the acute stage of experimentally-induced chagasic myocarditis.

Apical left ventricular aneurysms and cardiac parasympathetic innervation in Chagas' heart disease.

Left ventricular apical aneurysms are present in Chagasic patients who have normal cardiac parasympathetic innervation. Cardiac parasympathetic abnormalities are found, in later stages of the disease, when diffuse myocardial damage and ventricular dilatation are already present. The apical region of the left ventricle is also affected in several acute and chronic non-Chagasic cardiac diseases. Therefore, thinning of the left ventricular apex, with aneurysm formation, may be a non-specific myocardial sequelae, secondary to myocardial damage.

Cardiac parasympathetic innervation in Chagas' heart disease.

Trypanosoma cruzi is thought to selectively destroy the postganglionic cardiac vagal neurons of chagasic cardiac patients. This theory is based on morphologic and functional evidences obtained from chagasic individuals who were in very advanced stages of the disease. We have studied chagasic patients who were in both the early and late stages of the disease. Our findings and the review of the available literature suggest that myocardial damage and mild left ventricular dilatation precede the cardiac parasympathetic abnormalities. Furthermore, we have found a strong correlation between the degree of left ventricular dilatation and the extent of cardiac parasympathetic impairment. Consequently, we propose that the cardiac parasympathetic abnormalities arise as a compensating mechanism for the progressive left ventricular dilatation.

Electrocardiographic abnormalities and left ventricular systolic function in Chagas' heart disease.

In chagasic patients, the electrocardiogram becomes abnormal very late in the course of the disease. Most clinical studies concerning cardiac autonomic function of chagasic patients have been carried out in this very late stage of the disease. The purpose of this study was to assess accurately the left ventricular systolic function of chagasic patients with abnormal electrocardiograms. We performed left ventricular contrast cineangiography in 44 patients with positive complement fixation test for Chagas' disease and abnormal electrocardiograms. On the basis of the electrocardiographic abnormalities found in the electrocardiogram taken the night before the hemodynamic procedure, we divided our patients into three subgroups; those with rhythm disturbances, those with ventricular conduction abnormalities, and those with rhythm disturbances plus ventricular conduction abnormalities. The chagasic patients with only cardiac rhythm disturbances, had left ventricular volumes and ejection fractions which were similar to those of controls. On the other hand, the left ventricular volumes of the chagasic patients with ventricular conduction defects, although slightly larger, were still not different from those of controls. Finally, the chagasic patients, with cardiac rhythm disturbances and left ventricular conduction defects, had the largest left ventricular volumes (P less than 0.05), and the lowest ejection fractions (P less than 0.001) of all three subgroups. These findings clearly indicate that chagasic patients, in this very late stage of the disease, have a very variable degree of left ventricular systolic dysfunction. Furthermore, our results show a distinct tendency for the left ventricular volumes to increase, and for the ejection fraction to decrease; when the electrocardiogram becomes progressively more abnormal, and "mixed" electrocardiographic abnormalities appear.(ABSTRACT TRUNCATED AT 250 WORDS)