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

Davila, Diego F.; Gotterberg, Carlos F.; Torres, Argenis; Holzhaker, Geza; Barrios, Richard; Ramoni, Paolo; Donis, José H.

doi:10.1590/S0036-46651995000200011

Abstracts

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.

Myocarditis; Chagas disease; Cardiac Autonomic System; Atropine; Beta-Blockers

Com a finalidade de pesquisar o mecanismo responsável pela taquicardia sinusal transitória que ocorre nas ratas com miocardite chagásica aguda, foi estudado o balanço autonômico cardíaco em 16 ratas inoculadas com Trypanosoma cruzi por via intraperitoneal. Oito animais foram estudados aos 18 e 21 dias após-inoculação (Estádio agudo); os oito animais restantes foram estudados entre os dias 60 a 70 após inoculação (Estádio sub-agudo). Todos os animais em estudo bem como os controles receberam atenolol e atropina. No estádio agudo, a frequência cardíaca basal dos animais infectados foi significativamente maior que a dos controles. A resposta cronotrópica negativa pela administração de atenolol foi quatro vezes maior nos animais infectados. No estádio sub-agudo, a frequência cardíaca basal e a resposta cronotrópica ao atenolol e atropina foi similar nos dois grupos do estudo. Os nossos resultados sugerem que no estádio agudo da miocardite chagásica experimental, a atividade simpática encontra-se periodicamente aumentada.

TRYPANOSOMIASIS

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

O balanço autonômico cardíaco nas ratas com miocardite chagásica aguda experimental

Diego F. Davila; Carlos F. Gotterberg; Argenis Torres; Geza Holzhaker; Richard Barrios; Paolo Ramoni; José H. Donis

Centro Cardiovascular. Departamento de Biología, Departamento de Fisiopatología, Laboratorio de Procesamiento de Señales. Universidad de Los Andes, Mérida, 5101, Venezuela

SUMMARY

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.

Keywords: Myocarditis; Chagas disease; Cardiac Autonomic System; Atropine; Beta-Blockers.

RESUMO

Com a finalidade de pesquisar o mecanismo responsável pela taquicardia sinusal transitória que ocorre nas ratas com miocardite chagásica aguda, foi estudado o balanço autonômico cardíaco em 16 ratas inoculadas com Trypanosoma cruzi por via intraperitoneal. Oito animais foram estudados aos 18 e 21 dias após-inoculação (Estádio agudo); os oito animais restantes foram estudados entre os dias 60 a 70 após inoculação (Estádio sub-agudo). Todos os animais em estudo bem como os controles receberam atenolol e atropina. No estádio agudo, a frequência cardíaca basal dos animais infectados foi significativamente maior que a dos controles. A resposta cronotrópica negativa pela administração de atenolol foi quatro vezes maior nos animais infectados. No estádio sub-agudo, a frequência cardíaca basal e a resposta cronotrópica ao atenolol e atropina foi similar nos dois grupos do estudo. Os nossos resultados sugerem que no estádio agudo da miocardite chagásica experimental, a atividade simpática encontra-se periodicamente aumentada.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Recebido para publicação em 07/07/1994.

Aceito para publicação em 15/12/1994.

Supported in part by grants M-354-90 and C-534-91 (CDCHT-ULA).

1. BESTETTI, R.B.; SOARES, E. & SALES-NETO, V.N. et al. - The resting EKG of Trypanosoma cruzi infected rats. Rev. Inst. Med. trop. S. Paulo, 29: 224-229, 1987.
2. BESTETTI, R.B.; BAZOLDI, G. & SALES-NETO, V.N. - The usefulness of the resting EKG for characterizing acute Chagas' heart disease in the rat. Int. J. Cardiol., 18: 305-315, 1988.
3. BRENER, Z. - Contribuiçăo ao estudo da terapęutica experimental da doença de Chagas. Belo Horizonte, 1961 (Tese de Docęncia - Livre - Fac. de Odontologia e Farmácia da Universidade de Minas Gerais).
4. CAMARGOS, E.R.S. & MACHADO, C.R.S. - Morphometric and histological analysis of the superior cervical ganglion in experimental Chagas' disease in rats. Amer. J. trop. Med. Hyg., 39: 456-461, 1988.
5. CHAPADEIRO, E.; FLORENCIO, R.F.C.; AFONSO, P.C. et al. - Neuronal counting and parasympathetic dysfunction in the hearts of chronically Trypanosoma cruzi-infected rats. Rev. Inst. Med. trop. S. Paulo, 33: 337-341, 1991.
6. DAVILA, D.F.; GOTTBERG, C.F.; DONIS, J.H. et al. - Vagal stimulation and cardiac slowing in acute chagasic myocarditis. J. Autonomic nerv. Syst., 25: 233-234, 1988.
7. DAVILA, D.F.; ROSSELL, O. & DONIS, J.H. - Cardiac parasympathetic abnormalities. Cause or consequence of Chagas' heart disease?. Parasit. today, 5: 327-329, 1989.
8. DAVILA, D.F.; DONIS, J.H.; TORRES, A. et al. - Cardiac parasympathetic innervation in Chagas' heart disease. Med. Hypothesis, 35: 80-84, 1991.
9. DAVILA, D.F.; DONIS, J.H. & TORRES, A. - Chagas' heart disease and neuropathy. Amer. Heart J., 124: 1665-1666, 1992.
10. DAVILA, D.F.; BELLARBA, G.; DONIS, J.H. et al. - Cardiac autonomic control mechanisms in Chagas' heart disease. Therapeutic implications. Med. Hypothesis, 40: 33-37, 1993.
11. DAVILA, D.F.; DONIS, J.H.; TORRES, A. et al. - Apical left ventricular aneurysms and cardiac parasympathetic innervation in Chagas' heart disease. Med. Hypothesis, 42: 53-56, 1994.
12. DUNLAP, E.D.; SAMOLS, E.; WAITE, L.C. et al. - Development of a method to determine autonomic nervous function in the rat. Metabolism, 36: 193-197, 1987.
13. GODFREY, K. - Simple linear regression analysis in medical research. New Engl. J. Med., 313: 842-849, 1985.
14. GOTTBERG, C.F.; DONIS, J.H.; TORRES, A. et al. - Heart rate changes in rats with acute chagasic myocarditis. Trans. roy. Soc. trop. Med. Hyg., 82: 851-852, 1988.
15. GUS, I.; MOLAN, M.E. & BUENO, A.P. - Chagas' disease. Acute Chagas' myocarditis 8 cases simultaneous review - 25 years later. Arq. bras. Cardiol., 60: 99-101, 1993.
16. HIGGINS, C.B.; VATNER, S.F. & BRAUNWALD, E. - Parasympathetic control of the heart. Pharmacol. Rev., 25: 119-155, 1973.
17. HUDSON, L. - Immunopathogenesis of experimental Chagas' disease in mice: damage to the autonomic nervous system. In: Cytopathology of Parasitic Disease. London, Pitman Books, 1983. p.234-251. (Ciba Foundation Symposium, 99).
18. KOBERLE, F. - Cardiopathia ParasympathicoPriva. Munch. Med. Wochenschr., 101: 1308-1310, 1959.
19. MATHEW, N.L. - Sympathetic parasympathetic interactions in the heart. In: KULBERTUS, H.E. & FRANK, G., ed. Neurocardiology. New York, Futura Publ., 1988. p. 85-98.
20. MATHEW, N.L. - Parasympathetic control of the heart. In: RANDALL, W.C., ed. Neural control of the heart. New York, Oxford Univ. Press, 1977. p. 95-129.
21. PEREIRA, F.E. & PIRE, J.G. - Chronotropic responses to acetylcholine in atria of mice chronically infected with "Y" and "CL" strains of Trypanosoma cruzi. Braz. J. med. biol. Res., 21: 1019-1021, 1988.
22. RANDALL, W.C. - Sympathetic control of the heart. In: RANDALL, W.G., ed. - Neural control of the heart. New York, Oxford Univ. Press, 1977. p. 43-94.
23. RANDALL, D.G.; RANDALL, W.C; BROWN, D.R. et al. - Heart rate control in awake dogs after selective sa-nodal parasympathec-tomy. Amer. J. Physiol., 262: H1128-H1135, 1992.
24. RIGEL, D.F.; LIPSON, D. & KATONA, P.G. - Excess tachycardia: heart rate after muscarinic agents in dogs. Amer. J. Physiol., 246: H168-H173, 1984.
25. SCORZA, C. & SCORZA, J.V. - Acute myocarditis in rats inocculated with Trypanosoma cruzi: study of animals sacrificed between the fourth and twenty-ninth days after infection. Rev. Inst. Med. trop. S. Paulo, 14: 171-177, 1972.
26. STILES, G.L.; GARON, M.G. & LEFKOWITZ, R.J. - Beta-adrenergic receptors: biochemical mechanisms of physiological regulation. Physiol. Rev., 66: 661-743, 1987.
27. TAFURI, W.L. - Pathogenesis of lesions of the autonomic nervous system of the mouse with experimental acute chagasic myocarditis. Amer. J. trop. Med. Hyg., 19: 405-417, 1970.
28. TANOWITZ, H.B.; DAVIES, P. & WITTNER, M. - Alterations in acetylcholine receptors in experimental Chagas' disease. J. infect. Dis., 147: 460-466, 1989.
29. WONG, W.C.; TAN, C.K.; SINGH, M. & YICK, T.Y. - Ultrastructure of murine cardiac ganglia in experimental Chagas' disease. Histol. Histopathol., 7: 371-378, 1992.

Publication Dates

Publication in this collection
22 Feb 2007
Date of issue
Apr 1995

History

Accepted
15 Dec 1994
Received
07 July 1994

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. BESTETTI, R.B.; SOARES, E. & SALES-NETO, V.N. et al. - The resting EKG of Trypanosoma cruzi infected rats. Rev. Inst. Med. trop. S. Paulo, 29: 224-229, 1987.

[2] 2. BESTETTI, R.B.; BAZOLDI, G. & SALES-NETO, V.N. - The usefulness of the resting EKG for characterizing acute Chagas' heart disease in the rat. Int. J. Cardiol., 18: 305-315, 1988.

[3] 3. BRENER, Z. - Contribuiçăo ao estudo da terapęutica experimental da doença de Chagas. Belo Horizonte, 1961 (Tese de Docęncia - Livre - Fac. de Odontologia e Farmácia da Universidade de Minas Gerais).

[4] 4. CAMARGOS, E.R.S. & MACHADO, C.R.S. - Morphometric and histological analysis of the superior cervical ganglion in experimental Chagas' disease in rats. Amer. J. trop. Med. Hyg., 39: 456-461, 1988.

[5] 5. CHAPADEIRO, E.; FLORENCIO, R.F.C.; AFONSO, P.C. et al. - Neuronal counting and parasympathetic dysfunction in the hearts of chronically Trypanosoma cruzi-infected rats. Rev. Inst. Med. trop. S. Paulo, 33: 337-341, 1991.

[6] 6. DAVILA, D.F.; GOTTBERG, C.F.; DONIS, J.H. et al. - Vagal stimulation and cardiac slowing in acute chagasic myocarditis. J. Autonomic nerv. Syst., 25: 233-234, 1988.

[7] 7. DAVILA, D.F.; ROSSELL, O. & DONIS, J.H. - Cardiac parasympathetic abnormalities. Cause or consequence of Chagas' heart disease?. Parasit. today, 5: 327-329, 1989.

[8] 8. DAVILA, D.F.; DONIS, J.H.; TORRES, A. et al. - Cardiac parasympathetic innervation in Chagas' heart disease. Med. Hypothesis, 35: 80-84, 1991.

[9] 9. DAVILA, D.F.; DONIS, J.H. & TORRES, A. - Chagas' heart disease and neuropathy. Amer. Heart J., 124: 1665-1666, 1992.

[10] 10. DAVILA, D.F.; BELLARBA, G.; DONIS, J.H. et al. - Cardiac autonomic control mechanisms in Chagas' heart disease. Therapeutic implications. Med. Hypothesis, 40: 33-37, 1993.

[11] 11. DAVILA, D.F.; DONIS, J.H.; TORRES, A. et al. - Apical left ventricular aneurysms and cardiac parasympathetic innervation in Chagas' heart disease. Med. Hypothesis, 42: 53-56, 1994.

[12] 12. DUNLAP, E.D.; SAMOLS, E.; WAITE, L.C. et al. - Development of a method to determine autonomic nervous function in the rat. Metabolism, 36: 193-197, 1987.

[13] 13. GODFREY, K. - Simple linear regression analysis in medical research. New Engl. J. Med., 313: 842-849, 1985.

[14] 14. GOTTBERG, C.F.; DONIS, J.H.; TORRES, A. et al. - Heart rate changes in rats with acute chagasic myocarditis. Trans. roy. Soc. trop. Med. Hyg., 82: 851-852, 1988.

[15] 15. GUS, I.; MOLAN, M.E. & BUENO, A.P. - Chagas' disease. Acute Chagas' myocarditis 8 cases simultaneous review - 25 years later. Arq. bras. Cardiol., 60: 99-101, 1993.

[16] 16. HIGGINS, C.B.; VATNER, S.F. & BRAUNWALD, E. - Parasympathetic control of the heart. Pharmacol. Rev., 25: 119-155, 1973.

[17] 17. HUDSON, L. - Immunopathogenesis of experimental Chagas' disease in mice: damage to the autonomic nervous system. In: Cytopathology of Parasitic Disease. London, Pitman Books, 1983. p.234-251. (Ciba Foundation Symposium, 99).

[18] 18. KOBERLE, F. - Cardiopathia ParasympathicoPriva. Munch. Med. Wochenschr., 101: 1308-1310, 1959.

[19] 19. MATHEW, N.L. - Sympathetic parasympathetic interactions in the heart. In: KULBERTUS, H.E. & FRANK, G., ed. Neurocardiology. New York, Futura Publ., 1988. p. 85-98.

[20] 20. MATHEW, N.L. - Parasympathetic control of the heart. In: RANDALL, W.C., ed. Neural control of the heart. New York, Oxford Univ. Press, 1977. p. 95-129.

[21] 21. PEREIRA, F.E. & PIRE, J.G. - Chronotropic responses to acetylcholine in atria of mice chronically infected with "Y" and "CL" strains of Trypanosoma cruzi. Braz. J. med. biol. Res., 21: 1019-1021, 1988.

[22] 22. RANDALL, W.C. - Sympathetic control of the heart. In: RANDALL, W.G., ed. - Neural control of the heart. New York, Oxford Univ. Press, 1977. p. 43-94.

[23] 23. RANDALL, D.G.; RANDALL, W.C; BROWN, D.R. et al. - Heart rate control in awake dogs after selective sa-nodal parasympathec-tomy. Amer. J. Physiol., 262: H1128-H1135, 1992.

[24] 24. RIGEL, D.F.; LIPSON, D. & KATONA, P.G. - Excess tachycardia: heart rate after muscarinic agents in dogs. Amer. J. Physiol., 246: H168-H173, 1984.

[25] 25. SCORZA, C. & SCORZA, J.V. - Acute myocarditis in rats inocculated with Trypanosoma cruzi: study of animals sacrificed between the fourth and twenty-ninth days after infection. Rev. Inst. Med. trop. S. Paulo, 14: 171-177, 1972.

[26] 26. STILES, G.L.; GARON, M.G. & LEFKOWITZ, R.J. - Beta-adrenergic receptors: biochemical mechanisms of physiological regulation. Physiol. Rev., 66: 661-743, 1987.

[27] 27. TAFURI, W.L. - Pathogenesis of lesions of the autonomic nervous system of the mouse with experimental acute chagasic myocarditis. Amer. J. trop. Med. Hyg., 19: 405-417, 1970.

[28] 28. TANOWITZ, H.B.; DAVIES, P. & WITTNER, M. - Alterations in acetylcholine receptors in experimental Chagas' disease. J. infect. Dis., 147: 460-466, 1989.

[29] 29. WONG, W.C.; TAN, C.K.; SINGH, M. & YICK, T.Y. - Ultrastructure of murine cardiac ganglia in experimental Chagas' disease. Histol. Histopathol., 7: 371-378, 1992.

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

O balanço autonômico cardíaco nas ratas com miocardite chagásica aguda experimental

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