CARDIAC AUTONOMIC DYSFUNCTION AND NEUROGANGLIONITIS IN A RAT MODEL OF CHRONIC CHAGAS-DISEASE

Objective: The aim was to evaluate whether the cardiac parasympathetic function in a rat model of chronic Chagas' disease is impaired as in the human disease, and to correlate the functional state to histopathology of the intrinsic autonomic innervation of heart. Methods: 70 male Wistar rats 8 months infected with strains Y (n = 22), Sao Felipe (n = 18), and Colombia (n = 30) of Trypanosoma cruzi, were compared with 20 age and sex matched non-infected controls. Baroreflex bradycardia was quantified after multiple bolus injections of phenylephrine (3 to 12-mu-g). For each rat studied a mean was obtained of the absolute and relative (delta %) ratio (index) between the maximum heart rate decrease and the maximum systolic blood pressure increase. Results: For the relative index the means were smaller (p < 0.05) in the Y [-0.52(SD 0.19)%], SaoBAR Felipe [-0.45(0.28)%], and Colombia [-0.53(0.21%)] subgroups, as well as in the pooled chagasic group [-0.51(0.22)%], than in the control group [-0.64(0.13)%]. In 32% (7/22), 33%(6/18), and 20% (6/30) of rats infected with Y, SaoBAR Felipe, and Colombia strains, respectively, and in 27% (19/70) of the pooled group rats, the index exceeded the control group mean by -2 SD. After atropinisation, a similar pronounced reduction (p < 0.01) in the index was observed in all groups [-84(28)% to -95(17)%]; however, rats with depressed bradycardia showed a smaller (p < 0.05) reduction in the relative index than control rats, at -70(34) v -92(16)%. Inflammatory and degenerative lesions of the intrinsic cardiac innervation were observed in 87% of the rats with autonomic dysfunction. Rats with the lesions showed a mean relative index that was smaller than those without lesions, at -0.44(0.23) v -0.64(0.20)% (p < 0.01), and also smaller than in the controls. Conclusions: Cardiac autonomic dysfunction expressed by reduced baroreflex bradycardia was detected in rats chronically infected with T cruzi, as in human Chagas' disease. The disturbance, shown for the first time in an animal model of chagasic infection, resulted primarily from impaired efferent parasympathetic activity caused by intrinsic neuroganglionar lesions.