Abstract
Background. Theophylline was shown to induce contracture development in porcine malignant hyperthermia (MH) susceptible (MHS) skeletal muscles in vitro. The purpose of the current study was to investigate the in vivo effects of theophylline in MHS and MH normal (MHN) swine. Methods. MH-trigger-free general anesthesia was performed in MHS and MHN swine. Theophylline was administered intravenously in cumulative doses up to 93.5 mg·kg−1. The clinical occurrence of MH was defined by changes of central-venous pCO2, central-venous pH, and body core temperature. Results. Theophylline induced comparable clinical alterations in the anesthetized MHS and MHN swine, especially in regard to hemodynamic data. No pig developed hypermetabolism and/or MH according to defined criteria. All animals died with tachycardia followed by ventricular fibrillation. Conclusions. The cumulative theophylline doses used in this study were much higher than doses used therapeutically in humans, as demonstrated by measured blood concentrations. Theophylline is thus not a trigger of MH in genetically determined swine.
Highlights
Malignant hyperthermia (MH) is an autosomally inherited, potentially lethal myopathy with a heterogeneous etiology that is usually triggered by volatile anesthetics and depolarizing muscle relaxants [1]
malignant hyperthermia (MH)-trigger-free general anesthesia was performed in MHS and MH normal (MHN) swine
Alterations in some second-messenger systems have been found to be associated with MH [2, 3]; the cyclic AMP system seems to be affected in MH
Summary
Malignant hyperthermia (MH) is an autosomally inherited, potentially lethal myopathy with a heterogeneous etiology that is usually triggered by volatile anesthetics and depolarizing muscle relaxants [1]. Ca2+ homeostasis in skeletal muscle is regulated by a variety of intracellular second-messenger systems. In skeletal-muscle cells from MH-susceptible (MHS) patients and animals, higher cAMP levels were measured compared to normal (MHN) subjects [4,5,6,7]. Theophylline was shown to induce contracture development in porcine malignant hyperthermia (MH) susceptible (MHS) skeletal muscles in vitro. The purpose of the current study was to investigate the in vivo effects of theophylline in MHS and MH normal (MHN) swine. MH-trigger-free general anesthesia was performed in MHS and MHN swine. Theophylline induced comparable clinical alterations in the anesthetized MHS and MHN swine, especially in regard to hemodynamic data. The cumulative theophylline doses used in this study were much higher than doses used therapeutically in humans, as demonstrated by measured blood concentrations. Theophylline is not a trigger of MH in genetically determined swine
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