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Diltiazem and nifedipine reduce thein vitro contracture response to halothane in malignant hyperthermia-susceptible muscle

Abstract

The effects of diltiazem (1 μM) and nifedipine (I μM) were examined separately on the in vitrohalothane tests for malignant hyperthermia (MH) susceptibility. Eighteen patients with MH susceptibility were diagnosed as MH-susceptible (MHS) according to the protocol of the European MH Group. In addition, halothane tests were carried out in the presence of either diltiazem (ten patients) or nifedipine (eight patients). These two calcium channel blockers significantly reduced the halothane contracture. Furthermore, in five of the ten MHS patients tested in the presence of diltiazem as well as in five of the eight MHS patients tested in the presence of nifedipine the halothane contracture test could be classified as negative. It is concluded that the presence of clinical concentrations of either diltiazem or nifedipine in the muscle bath affects the in vitrodiscrimination for MH susceptibility to halothane.

Résumé

Les effets du diltiazem (1 μM) et de la nifedipine (1 μM) ont été étudiés separement sur le test halothane in vitrode depistage de l’hyperthermie maligne (HM). Des lambeaux musculaires provenant de dix huit patients sensibles à l’HM ont été testes suivant le protocole del’« European MH Group ». Le test à l’halothane à été realise seul, puis en présence de diltiazem (dix patients) ou de nifédipine (huit patients). Le pretraitement des lambeaux musculaires au diltiazem classe cinq des dix sujets susceptibles comme negatif à l’halothane. De meme cinq des huit lambeaux musculaires pretraités à la nifedipine classe ces sujets suceptibles comme negatif au test à i halothane. Il semble done que la présence de concentrations cliniques de diltiazem ou de nifedipine dans le liquide de perfusion affecte les resultats du test à l’halothane.

References

  1. Britt BA, Kalow W, Gordon A, Humphrey JG, Rewcastle NB. Malignant hyperthermia: an investigation of five patients. Can Anacsth Soc J 1973; 20: 431–67.

    CAS  Google Scholar 

  2. Kalow W, Britt BA, Richter A. The caffeine test of isolated human muscle in relation to malignant hyperthermia. Can Anaesth Soc J 1977; 24: 678–94.

    PubMed  CAS  Google Scholar 

  3. Britt BA, Endrenyi L, Frodis W, Scott E, Kalow W. Comparison of effects of several inhalation anaesthetics on caffeine-induced contractures of normal and malignant hyperthermic skeletal muscle. Can Anaesth Soc J 1980; 27: 12–5.

    PubMed  Article  CAS  Google Scholar 

  4. The European Malignant Hypcrpyrexia group. A protocol for the investigation of malignant hypcrpyrexia susceptibility. BrJ Anaesth, 1984; 56: 1267–9.

    Article  Google Scholar 

  5. Moulds RFW, Denborough MA. A study of the action of caffeine, halothane, potassium chloride and procaine on normal human skeletal muscle. Clin Exp Pharmacol Physiol 1974; 1: 197–209.

    PubMed  Article  CAS  Google Scholar 

  6. Britt BA, Scott E, Frodis W, Clements MJ, Endrenyi L. Dantrolene-in vitro studies in malignant hyperthermia susceptible (MHS) and normal skeletal muscle. Can Anaesth Soc J 1984; 31: 130–54.

    PubMed  CAS  Article  Google Scholar 

  7. Ording H. Influence of propanolol on the in vitro muscle response to caffeine and halothane in malignant hyperthermia. Acta Anaesthesiol Scand 1987; 31 (Suppl 86): A 230.

    Google Scholar 

  8. Braunwald E. Mechanism of action of calcium-channelblocking agents. N Engl J Med 1982; 307: 1618–27.

    PubMed  CAS  Google Scholar 

  9. Ilias WK, Williams CH, Fulfer RT, Dozier SE. Diltiazem inhibits halothane-induced contractions in malignant hyperthermia-susceptible muscles in vitro. Br J Anacsth 1985; 57: 994–6.

    Article  CAS  Google Scholar 

  10. Foster PS, Denborough MA. Effect of diltiazem and dantrolene on the contractility of isolated malignant hyperpyrcxia-susceptible porcine skeletal muscle. Br J Anaesth 1989; 62: 566–72.

    PubMed  Article  CAS  Google Scholar 

  11. Iwatsuki N, Koga Y, Amaha K. Calcium channel blocker for treatment of malignant hyperthermia. Ancsth Analg 1983; 62: 861–2.

    Article  CAS  Google Scholar 

  12. Kinney EL, Moskowitz RM, Zelis R. The pharmacokinetics and pharmacology of oral diltiazem in normal volunteers. J Clin Pharmacol 1981; 21: 337–42.

    PubMed  CAS  Google Scholar 

  13. Rouei V, Gomeni R, Mitchard M et al. Pharmacokinetics and metabolism of diltiazem in man. Acta Cardiol 1980; 35: 35–45.

    Google Scholar 

  14. Gallant EM, Goettl VM. Effects of calcium antagonists on mechanical responses of mammalian skeletal muscles. Eur J Pharmacol 1985; 117: 259–65.

    PubMed  Article  CAS  Google Scholar 

  15. Myers MG, Raemsch KD. Comparative pharmacokinetics and antihypertensive effects of the nifedipine tablet and capsule. J Cardiovasc Pharmacol 1987; Suppl 10: 76–8.

  16. Sperelakis N. Electrophysiology of calcium antagonists. J Mol Cell Cardiol 1987; 19 (Suppl. 11): 19–47.

    PubMed  Article  CAS  Google Scholar 

  17. Deuster PA, Bockman EL, Biscardi H, Muldoon SM. Verapamil and zero Ca 2+ alter responses of cat muscle to halothane and caffeine. J Appl Physiol 1986; 60: 935–41.

    PubMed  Article  CAS  Google Scholar 

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Supported by l’Association Françhise des Myopathcs.

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Adnet, P.J., Krivosic-Horber, R.M., Haudecoeur, G. et al. Diltiazem and nifedipine reduce thein vitro contracture response to halothane in malignant hyperthermia-susceptible muscle. Can J Anaesth 37, 556 (1990). https://doi.org/10.1007/BF03006325

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  • DOI: https://doi.org/10.1007/BF03006325

Key words

  • anaesthetics, volatile: halothane
  • hyperthermia: malignant
  • pharmacology: calcium channel blockers, diltiazem, nifedipine