Theophylline induces contractures in porcine skeletal muscle preparations with the disposition to malignant hyperthermia

Objective: Theophylline, a methylxanthine, leads to an increase of the cytoplasmic Ca2+-concentration in the muscle cell. Since the in-vitro contracture test (IVCT) with halothane and caffeine does not distinguish a 100% between malignant hyperthermia susceptible (MHS) and non-susceptible (MHN), we examined the in-vitro effects of theophylline in porcine skeletal muscle preparations. Methods: After approval by the local animal care committee ten MHS- and nine MHN-swine were anaesthetized and muscle biopsies taken. For IVCT, muscle specimens were exposed to bolus administrations of theophylline in concentrations of 3.0 respectively 5.0 mmol/l. Muscle contracture development and twitch amplitudes were recorded over a period of 30 minutes. Data are expressed as medians and ranges. Results: After both theophylline bolus administrations MHS-muscles developed significantly higher contractures compared to the MHN-specimens. The MHS-muscles reached a maximum contracture of 17.0 mN (7.2-59.6 mN) after administration of 3.0 mmol/l theophylline. In comparison, two MHN-specimens showed weak contractures with a maximum of 1.4 mN. The 5.0 mmol/l theophylline IVCT resulted in maximum contractures of 19.1 mN (2.1-39.2 mN) for the MHS-preparations. just in three MHN-muscles weak contractures of 0.0 mN (0.0-0.8 mN) were recorded. Thus, a significant difference without overlap was revealed for the maximum contracture. Conclusion: Theophylline in concentrations of 3.0 and 5.0 mmol/l revealed a clear difference between MHS- and MHN-porcine muscle preparations. Further examinations on human skeletal muscles are needed to demonstrate the value of theophylline in the IVCT MH-diagnosis.