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), São 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 micrograms). 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 less than 0.05) in the Y [-0.52(SD 0.19)%], São 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, São 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 less than 0.01) in the index was observed in all groups [-84(28)% to -95(17)%]; however, rats with depressed bradycardia showed a smaller (p less than 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 less than 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.

Neuronal counting and parasympathetic dysfunction in the hearts of chronically Trypanosoma cruzi infected rats

Dez ratos machos Wistar cronicamente infectados pelas cepas Colombiana, Sao Felipe (12SF), e Y do Trypanosoma cruzi, foram submetidos, apos 8 meses de infeccao, juntamente com dez animais controles, ao teste da resposta bradicardica barorreflexa pela injecao endovenosa de fenilefrina. Seis ratos chagasicos exibiram disfuncao cardiaca parassimpatica, caracterizada pela depressao do indice da resposta bradicardica barorreflexa. Embora o estudo histologico dos coracoes chagasicos mostrasse lesoes dos ganglios atriais, a contagem dos neuronios em cortes seriados, nao apresentou reducao numerica significativa dos mesmos.

Neuronal counting and parasympathetic dysfunction in the hearts of chronically Trypanosoma cruzi-infected rats.

Ten male Wistar rats, chronically infected with Colombian, São Felipe (12SF) and Y strains of Trypanosoma cruzi and ten non-infected control animals were submitted to the bradycardia responsiveness test, an assessment of heart parasympathetic function, after phenylephrine injection. Six chagasic animals showed heart parasympathetic dysfunction characterized by reduction in the index of bradycardia baroreflex responsiveness, as compared with the control group. Microscopic examination of the atrial heart ganglia of chagasic rats showed ganglionitis, but no statistically significant reduction in the number of neurons.

Lesöes cardíacas em ratos Wistar inoculados com diferentes cepas do Trypanosoma cruzi / Cardiac lesions in Wistar rats infected with different strains of Trypanosoma cruzi

Ratos albinos Wistar infectados com diferentes inóculos das cepas Y, Colombiana (COL) e Säo Felipe (12SF) do Trypanosoma cruzi desenvolveram parasitemia elevada entre 14 e 21 dias, a qual tornou-se desprezível ou desapareceu completamente ao final da 4ª semana. As lesöes do coraçäo foram avaliadas, semiquantitativamente, pelo sistema de "scores", conforme a intensidade e a extensäo da inflamaçäo, nas diferentes estruturas do órgäo, tendo sido observado que: a) na fase inicial (aguda) da infecçäo, os animais mortos espontaneamente ou em conseqüência do acidente anestésico apresentaram cardite de intensidade moderada a acentuada, näo havendo diferença em relaçäo as cepas utilizadas; as diferentes estruturas do coraçäo estavam uniformemente comprometidas; b) na fase crônica da infecçäo observou-se cardite de grau leve a moderado e as lesöes foram mais freqüentes e intensas quanto maior o inóculo empregado; no entanto, inóculos baixos só produziram lesöes quando a cepa utilizada foi a Colombiana. Trombose mural nos átrios e dilataçäo da ponta do ventrículo esquerdo foram observadas em 20% dos animais, independetemente da cepa. Na fase crônica 15% dos animais apresentaram miocardite crônica com fibrose, associada a hipertrofia das miocélulas. Os AA confirmam ser o rato albino suscetível a infeccäo chagásica e, portanto, um modelo útil no estudo das manifestaçöes cardíacas da Doença de Chagas