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Vagal stimulation and heart rate slowing in acute experimental chagasic myocarditis
Journal of the Autonomic Nervous System, 25 (1988) 233-234 Elsevier
233
JAN 00891
Short Communication
Vagal stimulation and heart rate slowing in acute experimental chagasic myocarditis Diego F. Davila, Carlos F. Gottberg, Jose H. Donis, Argenis Torres, Abdel J. F u e n m a y o r and Osman Rossell Centro Cardiovascular and Departamento de Biologia, Unwersidad de Los Andes, Merida (Venezuela) (Received 22 March 1988) (Revised version received and accepted 18 October 1988)
Morphologic studies indicate that cardiac vagal postganglionic neurons may be destroyed by Trypanosoma cruzi-induced myocarditis [4,10]. This selective denervation should severely compromise the parasympathetic innervation of the sinus node [8]. In rats with acute chagasic myocarditis, we have studied the functional status of the efferent parasympathetic innervation of the sinus node, by examining the response of the heart rate to electrical stimulation of the cardiac vagus [6]. Fourteen rats were inoculated intraperitoneally with 200,000 parasites (Y strain of T. cruzi). Between days 18 and 21, after inoculation, the animals were anesthetized and secured supine on an animal board. They breathed spontaneously through tracheal cannulation. Eight age-matched, noninfected, animals were used as controls. The right vagus nerve was isolated, in the neck, and transected. Electrical stimulation was carried out through platinum electrodes by an isolated square wave stimulator (Grass-88, SIU-5). The stimuli were of supramaximal voltage (4.0 V) and duration (4.0 ms). The heart rate was recorded in a Grass 7 polygraph. Standard limb leads were used and the paper speed was 50 mm/s. All the animals were stimulated with frequencies ranging from 1-15 pulses per second (pps). At the end of
Correspondence: D.F. Davila, Apartado Postal 590, Merida, 5101, Venezuela.
the experiment, they were sacrificed for histological studies. The baseline heart rate of the infected animals was significantly higher than that of the controls. Electrical stimulation of the transected right vagus provoked a frequency-dependent decrease in heart rate. At the lower frequencies (1-4 pps), the control animals responded to a greater extent; at the higher frequencies, however, the negative chronotropic response was similar in both groups of animals. Plotting of these two variables showed that the initial portion of the curve of the infected animals was relatively flat, and regression analysis [2] demonstrated that they were linearly related. The slopes of these regression lines were not significantly different (Fig. 1). Histological section of the hearts of the infected animals revealed unequivocal evidence of acute chagasic myocarditis [9]. The normal responses of these animals to high frequency electrical stimulation [7] do not support the hypothesis of a selective parasympathetic denervation, in Trypanosoma cruzi-induced myocarditis. The abnormal responses to low frequency electrical stimulation are not necessarily due to a primary defect in the vagus nerve itself. They may represent a decreased excitability, and a higher stimulation threshold. These functional abnormalities are probably secondary to the acute inflammatory process, and to augmented background sympathetic tone [1,3,5,9]. In summary,
0165-1838/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)
234
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PULSES PER ~CONO
Fig. 1. Vagal stimulation and heart rate slowing in controls ( 0 ) and infected animals (O). The initial part of the curve of the infected animals is relatively fiat; and the negative chronotropic response is significantly diminished, at the lower frequencies. The chronotropic response, however, is similar in both groups of animals at the higher frequencies. The two variables are inversely and linearly related and the slopes of their regression lines are not significantly different. Values represent the mean response per unit of electrical stimulation. (Standard errors omitted for purposes of clarity in constructing the figure).
the very severe cardiac vagal abnormalities, described in most morphological studies concerning experimental chagasic myocarditis, are not matched by comparable degrees of dysfunction of the efferent parasympathetic innervation of the sinus node. We gratefully acknowledge Miss Irlanda Marquez for her valuable secretarial assistance. Supported by Grants M-201 and C-163. Consejo de DesarroUo Cientifico, Humanistico y Tecnologico (CDCI-IT) de la Universidad de Los Andes.
References 1 Chassaing, C.. Duchene-Marullaz. P. and Veyrac. M.J.. Effects of catecholarmnes on cardiac chronotropic responses to vagal stimulation in the dog, A m J. PhysioL. 245 (1983) H721-H724. 2 Godfrey, K., Simple linear regression in medical research. N. Eng. J. Meal, 313 (1985) 1629-1636. 3 Gottberg, C.F.. Donis. J.H.. Torres. A.. Fuenmayor. A.J. and Davila. D.F.. Heart rate changes in acute chagasic myocarditis. Trans. R. Soc. Trop. M e d Hyg., 82 (1988) in press. 4 Koberle. F., Chagas' heart disease. Pathol. Cardiology, 52 (1968) 81-100. 5 McGrattan. P.A.. Brown. J.H. and Brown. O.M., Parasympathetic effects on in vivo rat heart can be regulated through an alpha-adrenergic receptor. Circ. Res.. 60 f1987) 465-471. 6 Parker. P.. Celler. B.G.. Potter, E.K. and McCIoskley, D.I., Vagal stimulation and cardiac slowing, J. A UtO~L Nero. Syst., 11 (1984) 226-231 7 Randall. W.C. and Ardell. J.L., Selective parasympathectomy of the automatic and conduetile tissues in the canine heart, Am. d. Physiol., 248 (1985) H 6 t - H 6 8 . 8 Randall. W.C., Ardell. J.L, Wurster, R.D. and Milosavljevic, M.. Vagal postganglionic innervation of the canine sinoatrial node. J. Auton. Nero. Syst., 20 (1987) 13-23. 9 Scorza. C. and Scorza, J.V., Acute myocarditis m rats inoculated with Trypanosoma cruz,: study of animals sacrifized between the fourth and twenty-ninth day after infection, Reo. Inst. M e d Trop. Sao Paulo, 14 (1972) 171-177. 10 Tafuri. W.U. Pathogenesis of lesions of the autonomic nervous system of the mouse in experimental acute Chagas' disease. Am. J. Trop. Med. Hyg., 19 (1970~ 405-417.
233
JAN 00891
Short Communication
Vagal stimulation and heart rate slowing in acute experimental chagasic myocarditis Diego F. Davila, Carlos F. Gottberg, Jose H. Donis, Argenis Torres, Abdel J. F u e n m a y o r and Osman Rossell Centro Cardiovascular and Departamento de Biologia, Unwersidad de Los Andes, Merida (Venezuela) (Received 22 March 1988) (Revised version received and accepted 18 October 1988)
Morphologic studies indicate that cardiac vagal postganglionic neurons may be destroyed by Trypanosoma cruzi-induced myocarditis [4,10]. This selective denervation should severely compromise the parasympathetic innervation of the sinus node [8]. In rats with acute chagasic myocarditis, we have studied the functional status of the efferent parasympathetic innervation of the sinus node, by examining the response of the heart rate to electrical stimulation of the cardiac vagus [6]. Fourteen rats were inoculated intraperitoneally with 200,000 parasites (Y strain of T. cruzi). Between days 18 and 21, after inoculation, the animals were anesthetized and secured supine on an animal board. They breathed spontaneously through tracheal cannulation. Eight age-matched, noninfected, animals were used as controls. The right vagus nerve was isolated, in the neck, and transected. Electrical stimulation was carried out through platinum electrodes by an isolated square wave stimulator (Grass-88, SIU-5). The stimuli were of supramaximal voltage (4.0 V) and duration (4.0 ms). The heart rate was recorded in a Grass 7 polygraph. Standard limb leads were used and the paper speed was 50 mm/s. All the animals were stimulated with frequencies ranging from 1-15 pulses per second (pps). At the end of
Correspondence: D.F. Davila, Apartado Postal 590, Merida, 5101, Venezuela.
the experiment, they were sacrificed for histological studies. The baseline heart rate of the infected animals was significantly higher than that of the controls. Electrical stimulation of the transected right vagus provoked a frequency-dependent decrease in heart rate. At the lower frequencies (1-4 pps), the control animals responded to a greater extent; at the higher frequencies, however, the negative chronotropic response was similar in both groups of animals. Plotting of these two variables showed that the initial portion of the curve of the infected animals was relatively flat, and regression analysis [2] demonstrated that they were linearly related. The slopes of these regression lines were not significantly different (Fig. 1). Histological section of the hearts of the infected animals revealed unequivocal evidence of acute chagasic myocarditis [9]. The normal responses of these animals to high frequency electrical stimulation [7] do not support the hypothesis of a selective parasympathetic denervation, in Trypanosoma cruzi-induced myocarditis. The abnormal responses to low frequency electrical stimulation are not necessarily due to a primary defect in the vagus nerve itself. They may represent a decreased excitability, and a higher stimulation threshold. These functional abnormalities are probably secondary to the acute inflammatory process, and to augmented background sympathetic tone [1,3,5,9]. In summary,
0165-1838/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)
234
o
ts
-taO. -ZOOt
-t60
b ~ i
~ i
~ i
200
PULSES PER ~CONO
Fig. 1. Vagal stimulation and heart rate slowing in controls ( 0 ) and infected animals (O). The initial part of the curve of the infected animals is relatively fiat; and the negative chronotropic response is significantly diminished, at the lower frequencies. The chronotropic response, however, is similar in both groups of animals at the higher frequencies. The two variables are inversely and linearly related and the slopes of their regression lines are not significantly different. Values represent the mean response per unit of electrical stimulation. (Standard errors omitted for purposes of clarity in constructing the figure).
the very severe cardiac vagal abnormalities, described in most morphological studies concerning experimental chagasic myocarditis, are not matched by comparable degrees of dysfunction of the efferent parasympathetic innervation of the sinus node. We gratefully acknowledge Miss Irlanda Marquez for her valuable secretarial assistance. Supported by Grants M-201 and C-163. Consejo de DesarroUo Cientifico, Humanistico y Tecnologico (CDCI-IT) de la Universidad de Los Andes.
References 1 Chassaing, C.. Duchene-Marullaz. P. and Veyrac. M.J.. Effects of catecholarmnes on cardiac chronotropic responses to vagal stimulation in the dog, A m J. PhysioL. 245 (1983) H721-H724. 2 Godfrey, K., Simple linear regression in medical research. N. Eng. J. Meal, 313 (1985) 1629-1636. 3 Gottberg, C.F.. Donis. J.H.. Torres. A.. Fuenmayor. A.J. and Davila. D.F.. Heart rate changes in acute chagasic myocarditis. Trans. R. Soc. Trop. M e d Hyg., 82 (1988) in press. 4 Koberle. F., Chagas' heart disease. Pathol. Cardiology, 52 (1968) 81-100. 5 McGrattan. P.A.. Brown. J.H. and Brown. O.M., Parasympathetic effects on in vivo rat heart can be regulated through an alpha-adrenergic receptor. Circ. Res.. 60 f1987) 465-471. 6 Parker. P.. Celler. B.G.. Potter, E.K. and McCIoskley, D.I., Vagal stimulation and cardiac slowing, J. A UtO~L Nero. Syst., 11 (1984) 226-231 7 Randall. W.C. and Ardell. J.L., Selective parasympathectomy of the automatic and conduetile tissues in the canine heart, Am. d. Physiol., 248 (1985) H 6 t - H 6 8 . 8 Randall. W.C., Ardell. J.L, Wurster, R.D. and Milosavljevic, M.. Vagal postganglionic innervation of the canine sinoatrial node. J. Auton. Nero. Syst., 20 (1987) 13-23. 9 Scorza. C. and Scorza, J.V., Acute myocarditis m rats inoculated with Trypanosoma cruz,: study of animals sacrifized between the fourth and twenty-ninth day after infection, Reo. Inst. M e d Trop. Sao Paulo, 14 (1972) 171-177. 10 Tafuri. W.U. Pathogenesis of lesions of the autonomic nervous system of the mouse in experimental acute Chagas' disease. Am. J. Trop. Med. Hyg., 19 (1970~ 405-417.