[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 Ca(2+)-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.


CONCLUSIONS
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.
Gerbershagen
M U
MU
Klinik und Poliklinik für Anästhesiologie Universitätsklinikum Hamburg-Eppendorf. gerbershagen@uke.uni-hamburg.de
Fiege
M
M
Weisshorn
R
R
Kolodzie
K
K
Wappler
F
F
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013552:Swine; D013806:Theophylline / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D013806:Theophylline; D002118:Calcium