Alterações funcionais da junção neuromuscular provocadas em ratos pela administração diária e prolongada de um agente curarizante

Zanini, Antonio Carlos

doi:10.1590/S0004-282X1967000200004

Resumos

A ratos adultos, machos, foi administrado durante 8 semanas, uma vez ao dia, o iodeto do dimetiléter da d-tubocurarina (DMT), pela via intraperitoneal. Os animais foram distribuídos em 3 lotes: os do 1.°, receberam 5,5 gama de DMT/kg/dia; os do 2.°, 16,6 gama/kg/dia; os do 3.° (controle), 1 ml da solução isotônica de cloreto de sódio. A força muscular dos animais foi avaliada uma vez por semana, de acordo com o método descrito no texto, antes e após a injeção intraperitoneal da referida substância. Com o decorrer da experimentação, observou-se que: a) houve diminuição significativa da força muscular dos animais, avaliada após esvaecimento da atividade curarizante do DMT; b) a determinação da força muscular, feita logo após a injeção, mostrou que a dose de 5,5 gama/kg/dia provoca um aumento da suscetibilidade dos animais à ação curarizante do DMT; c) o efeito inibidor provocado pela dose de 16,6 gama/kg/dia de DMT aumentou no início mas diminuiu significantemente após a 5ª semana, muito embora houvesse uma progressiva diminuição da força muscular, sugerindo independência entre os dois efeitos. Com base nesses resultados, são discutidos alguns fenômenos que podem ocorrer na instalação e tratamento da miastenia grave.

Dimethylether of d-tubocurarine iodide (DMT) was administered daily, by intraperitoneal route, to adult male rats during 8 weeks. The animals were divided in three groups: the animals of the first group were given 5.5 gama/kg/day of DMT; those of the second group were given 16.6 gama/ kg/day; the rats of the 3rd (the control group), received 1 cm³ of isotonic saline solution. The animals muscular force was evaluated once a week right before and after intraperitoneal injection of the drug. During the course of the trial, it was noted: a)a significant reduction of the animals muscular force, evaluated after disappearance of the DMT curarizing effect; b)measurements of muscular force, performed straight after the injection, showed that a 5.5 gama/kg/daily dose induced an increase of the animals susceptibility to the blocking action of DMT; c) the inhibitory effect induced by DMT 16.6 gama/kg daily dose increased at the beginning but decreased significantly after the 5th week of the trial, despite a progressive decrease in muscular force suggest independence of the two effects. Based on these results, some of the phenomena that may occur at the heginning and during treatment of myasthenia gravis are discussed.

Alterações funcionais da junção neuromuscular provocadas em ratos pela administração diária e prolongada de um agente curarizante

Functional changes of the neuromuscular junction induced in rats by a daily and prolonged ministration of a curare agent

Antonio Carlos Zanini

Departamento de Farmacologia da Faculdade de Medicina da Universidade de São Paulo (Prof. Charles E. Corbett): Professor Assistente

RESUMO

A ratos adultos, machos, foi administrado durante 8 semanas, uma vez ao dia, o iodeto do dimetiléter da d-tubocurarina (DMT), pela via intraperitoneal. Os animais foram distribuídos em 3 lotes: os do 1.°, receberam 5,5 gama de DMT/kg/dia; os do 2.°, 16,6 gama/kg/dia; os do 3.° (controle), 1 ml da solução isotônica de cloreto de sódio. A força muscular dos animais foi avaliada uma vez por semana, de acordo com o método descrito no texto, antes e após a injeção intraperitoneal da referida substância.

Com o decorrer da experimentação, observou-se que: a) houve diminuição significativa da força muscular dos animais, avaliada após esvaecimento da atividade curarizante do DMT; b) a determinação da força muscular, feita logo após a injeção, mostrou que a dose de 5,5 gama/kg/dia provoca um aumento da suscetibilidade dos animais à ação curarizante do DMT; c) o efeito inibidor provocado pela dose de 16,6 gama/kg/dia de DMT aumentou no início mas diminuiu significantemente após a 5ª semana, muito embora houvesse uma progressiva diminuição da força muscular, sugerindo independência entre os dois efeitos. Com base nesses resultados, são discutidos alguns fenômenos que podem ocorrer na instalação e tratamento da miastenia grave.

SUMMARY

Dimethylether of d-tubocurarine iodide (DMT) was administered daily, by intraperitoneal route, to adult male rats during 8 weeks. The animals were divided in three groups: the animals of the first group were given 5.5 gama/kg/day of DMT; those of the second group were given 16.6 gama/ kg/day; the rats of the 3rd (the control group), received 1 cm³ of isotonic saline solution. The animals muscular force was evaluated once a week right before and after intraperitoneal injection of the drug.

During the course of the trial, it was noted: a)a significant reduction of the animals muscular force, evaluated after disappearance of the DMT curarizing effect; b)measurements of muscular force, performed straight after the injection, showed that a 5.5 gama/kg/daily dose induced an increase of the animals susceptibility to the blocking action of DMT; c) the inhibitory effect induced by DMT 16.6 gama/kg daily dose increased at the beginning but decreased significantly after the 5th week of the trial, despite a progressive decrease in muscular force suggest independence of the two effects. Based on these results, some of the phenomena that may occur at the heginning and during treatment of myasthenia gravis are discussed.

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Departamento de Farmacologia Faculdade de Medicina da USP Caixa Postal 2921 São Paulo, SP Brasil.

Nota do autor Agradecemos o auxilio prestado pela técnica Maria José Costa.

1. ASSIS, L. M. & SARAIVA, P. A. P. Miastenia grave. Tratamento das crises pelo repouso da placa motora. Trabalho apresentado na Academia Brasileira de Neurologia, julho de 1966. Resultados năo publicados.
2. BOTELHO, S. Y. Comparison of simultaneously recorded electrical and mechanical activity in Myasthenia gravis patients and in partially curarized normal humans. Amer. J. Med. 19:693, 696, 1955.
3. CANNON, W. B. & ROSEMBLUETH, A. The supersensitivity of denervated structures. Macmillan Co., New York, 1949.
4. CHURCHILL-DAVIDSON, H. C. Discussion on myasthenia. Proc. roy. Soc. Med. 49:793-795, 1956.
5. CHURCHILL-DAVIDSON, H. C. Myasthenic crisis. Therapeutic use of d-tubocurarine. Lancet 273:1221-1224, 1957.
6. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. The action of decamethonium iodide in myasthenia gravis. J. Neurol. Neurosurg. Psychiat. 15: 129-133, 1952.
7. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. Neuromuscular transmission in myasthenia gravis. J. Physiol. Lond. 122:252-263, 1953.
8. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. Neuromuscular transmission in myasthenia gravis. Amer. J. Med. 19:691-692, 1955.
9. DAHLBACK, O.; ELMQVIST, D.; JOHNS, T. R.; RADNER, S. & THERSLEFF, S. An electrophysiologic study of the neuromuscular junction in myasthenia gravis. J. Physiol. (London) 156:336-340, 1961.
10. EMMELIN, N. Supersensitivity following "pharmacological denervation". Pharmacological Rev. 13:17-37, 1961.
11. FENICHEL, G. M. Muscle lesions in myasthenia gravis. Ann. N.Y. Acad. Sci. 135:35-59, 1966.
12. GROB, D.; JOHN, R. J. & HARVEY, A. M. Alteration in neuromuscular transmission in myasthenia gravis as determined by studies of drug action. Amer. J. Med. 19:684-690, 1955.
13. GROB, D.; NAMBA, T. & FELDMAN, O. S. Alterations in reactivity to acetylcholine in myasthenia gravis and carcinomatous myopathy. Ann. N.Y. Acad. Sci. 135:247-275, 1966.
14. HOSEIN, B. A.; OTTOLENGHI, B. & DROFMAN, S. Myasthenia gravis. Second International Symposium. ApudGROB, D. Neuromuscular pharmacology. Ann. Rev. Pharmacol. 1:250, 1961.
15. KALOW, W. The distribution and elimination of muscle relaxants. InSymposium on Muscle Relaxants. Anesthesiology 20:505-518, 1959.
16. NASTUK, W. L. Fundamental aspects of neuromuscular transmission. Ann. N.Y. Acad. Sci. 135:110-135, 1966.
17. NASTUK, W. L. & PLESCIA, O. J. Current status of research on myasthenia gravis. Ann. N.Y. Acad. Sci. 135:664-677, 1966.
18. NOWELL, P. T. & WILSON, A. Myasthenia gravis. Second International Symposium. ApudGROB, D. Neuromuscular pharmacology. Ann. Rev. Pharmac. 1:250, 1961.
19. OSSERMAN, K. E. Studies in myasthenia gravis: reduction in mortality rate alter crisis. J. Amer. med. Ass. 183:97-101, 1963.
20. PARKES, J. D. & McKINNA, J. A. Neuromuscular blocking activity in the blood of patients with myasthenia gravis. Lancet (1):388-391, 1966.
21. RAMOS, A. O. Açăo curarizante do plasma e do extrato de timo de paciente portador de miastenia grave. Rev. Bras. Biol. 18:93-100, 1958.
22. SHARPLESS, S. K. Reorganization of function in the nervous system: use and disuse. Ann. Rev. Physiol. 26:357-388, 1964.
23. THESLEFF, S. Acetylcholine utilization in myasthenia gravis. Ann. N.Y. Acad. Sci. 135:195-206, 1966.
24. TUKEY, J. W. The problem of multiple comparisons. Princeton University, 1953. InSTEEL, R. G. D. & TORRIE, J. H. Principles and Procedures in Statistics. McGraw-Hill, New York, 1960, págs. 109-110.
25. WILSON, A. & STONER, H. B. Myasthenia gravis: a consideration of its causation in a study of fourteen cases. Quart. J. Med. 13:1-18, 1944.
26. WOLFE, S. M.; SIMONS, R. L. .& NASTUK, W. L. Effect of age and sex on sensitivity to d-tubocurarine in rat. Proc. Soc. Exper. Biol. N.Y. 117:1-3, 1964.
27. ZACKS, S. I. The Motor Endplate. W. B. Saunders Co., Philadelphia, 1964.

Datas de Publicação

Publicação nesta coleção
23 Maio 2013
Data do Fascículo
Jun 1967

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

[1] 1. ASSIS, L. M. & SARAIVA, P. A. P. Miastenia grave. Tratamento das crises pelo repouso da placa motora. Trabalho apresentado na Academia Brasileira de Neurologia, julho de 1966. Resultados năo publicados.

[2] 2. BOTELHO, S. Y. Comparison of simultaneously recorded electrical and mechanical activity in Myasthenia gravis patients and in partially curarized normal humans. Amer. J. Med. 19:693, 696, 1955.

[3] 3. CANNON, W. B. & ROSEMBLUETH, A. The supersensitivity of denervated structures. Macmillan Co., New York, 1949.

[4] 4. CHURCHILL-DAVIDSON, H. C. Discussion on myasthenia. Proc. roy. Soc. Med. 49:793-795, 1956.

[5] 5. CHURCHILL-DAVIDSON, H. C. Myasthenic crisis. Therapeutic use of d-tubocurarine. Lancet 273:1221-1224, 1957.

[6] 6. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. The action of decamethonium iodide in myasthenia gravis. J. Neurol. Neurosurg. Psychiat. 15: 129-133, 1952.

[7] 7. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. Neuromuscular transmission in myasthenia gravis. J. Physiol. Lond. 122:252-263, 1953.

[8] 8. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. Neuromuscular transmission in myasthenia gravis. Amer. J. Med. 19:691-692, 1955.

[9] 9. DAHLBACK, O.; ELMQVIST, D.; JOHNS, T. R.; RADNER, S. & THERSLEFF, S. An electrophysiologic study of the neuromuscular junction in myasthenia gravis. J. Physiol. (London) 156:336-340, 1961.

[10] 10. EMMELIN, N. Supersensitivity following "pharmacological denervation". Pharmacological Rev. 13:17-37, 1961.

[11] 11. FENICHEL, G. M. Muscle lesions in myasthenia gravis. Ann. N.Y. Acad. Sci. 135:35-59, 1966.

[12] 12. GROB, D.; JOHN, R. J. & HARVEY, A. M. Alteration in neuromuscular transmission in myasthenia gravis as determined by studies of drug action. Amer. J. Med. 19:684-690, 1955.

[13] 13. GROB, D.; NAMBA, T. & FELDMAN, O. S. Alterations in reactivity to acetylcholine in myasthenia gravis and carcinomatous myopathy. Ann. N.Y. Acad. Sci. 135:247-275, 1966.

[14] 14. HOSEIN, B. A.; OTTOLENGHI, B. & DROFMAN, S. Myasthenia gravis. Second International Symposium. ApudGROB, D. Neuromuscular pharmacology. Ann. Rev. Pharmacol. 1:250, 1961.

[15] 15. KALOW, W. The distribution and elimination of muscle relaxants. InSymposium on Muscle Relaxants. Anesthesiology 20:505-518, 1959.

[16] 16. NASTUK, W. L. Fundamental aspects of neuromuscular transmission. Ann. N.Y. Acad. Sci. 135:110-135, 1966.

[17] 17. NASTUK, W. L. & PLESCIA, O. J. Current status of research on myasthenia gravis. Ann. N.Y. Acad. Sci. 135:664-677, 1966.

[18] 18. NOWELL, P. T. & WILSON, A. Myasthenia gravis. Second International Symposium. ApudGROB, D. Neuromuscular pharmacology. Ann. Rev. Pharmac. 1:250, 1961.

[19] 19. OSSERMAN, K. E. Studies in myasthenia gravis: reduction in mortality rate alter crisis. J. Amer. med. Ass. 183:97-101, 1963.

[20] 20. PARKES, J. D. & McKINNA, J. A. Neuromuscular blocking activity in the blood of patients with myasthenia gravis. Lancet (1):388-391, 1966.

[21] 21. RAMOS, A. O. Açăo curarizante do plasma e do extrato de timo de paciente portador de miastenia grave. Rev. Bras. Biol. 18:93-100, 1958.

[22] 22. SHARPLESS, S. K. Reorganization of function in the nervous system: use and disuse. Ann. Rev. Physiol. 26:357-388, 1964.

[23] 23. THESLEFF, S. Acetylcholine utilization in myasthenia gravis. Ann. N.Y. Acad. Sci. 135:195-206, 1966.

[24] 24. TUKEY, J. W. The problem of multiple comparisons. Princeton University, 1953. InSTEEL, R. G. D. & TORRIE, J. H. Principles and Procedures in Statistics. McGraw-Hill, New York, 1960, págs. 109-110.

[25] 25. WILSON, A. & STONER, H. B. Myasthenia gravis: a consideration of its causation in a study of fourteen cases. Quart. J. Med. 13:1-18, 1944.

[26] 26. WOLFE, S. M.; SIMONS, R. L. .& NASTUK, W. L. Effect of age and sex on sensitivity to d-tubocurarine in rat. Proc. Soc. Exper. Biol. N.Y. 117:1-3, 1964.

[27] 27. ZACKS, S. I. The Motor Endplate. W. B. Saunders Co., Philadelphia, 1964.