Cardiac autonomic dysfunction and neuroganglionitis in a rat model of chronic Chagas' disease

Cardiovasc Res. 1992 Apr;26(4):324-9. doi: 10.1093/cvr/26.4.324.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Blood Pressure / drug effects
  • Bradycardia / chemically induced
  • Chagas Disease / pathology
  • Chagas Disease / physiopathology*
  • Disease Models, Animal
  • Ganglia, Autonomic / pathology
  • Ganglia, Autonomic / physiopathology*
  • Heart Rate / drug effects
  • Male
  • Myocardium / pathology
  • Parasympathetic Nervous System / physiopathology*
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Inbred Strains

Substances

  • Phenylephrine
  • Atropine