5-HT2 receptor antagonist-mediated inhibition of halothane-induced contractures in skeletal muscle specimens from malignant hyperthermia susceptible patients

Administration of 5-HT2 receptor agonists induced malignant hyperthermia (M H) in susceptible pigs. Furthermore, the 5-HT2 receptor antagonist ritanser in pre vented 5-HT-induced porcine MH. It has been shown that 5-HT2 recepto r agonists induce marked contractures in skeletal muscle specimens from MH susceptible (MHS) but not in specimens from normal patients. The purpose of this study was to investigate the effects of ritanserin on halothane-induc ed contractures in muscle specimens from MHS patients. Twenty-five patients aged 8-56 years (29.5 +/- 13.6) classified as MHS by t he in vitro contracture test (IVCT) with halothane and caffeine according t o the protocol of the European MH Group participated in this study. Muscle specimens were pretreated with ritanserin 10 mu mol/l (n = 14), 20 mu mol/l (n = 14) and 100 mu mol/l (n = 12) for 10 min and subsequently halothane w as added incrementally (0.11-0.22-0.44 mmol/l) to the tissue bath as descri bed in the European MH protocol. The results of the halothane contracture t est were used as control. Following administration of halothane, muscle contractures reached a maximu m of 16.9 +/- 4.2 mN. Ritanserin led to a significant inhibition of halotha ne-induced contractures in MHS muscles. Following pretreatment with ritanse rin. halothane-induced contracture maximum was significantly smaller with 7 .5 +/- 3.1 mN after 10 mu mol/l ritanserin, 4.9 +/- 1.5 mN after 20 mu mol/ l ritanserin and 0.5 +/- 0.2 mN after 100 mu mol/l ritanserin than without pretreat ment. Administration of ritanserin induced at all concentrations a decrease in muscle twitch height. Increase in muscle twitch following halo thane was reduced in a concentration-dependent manner by ritanserin. The pr esented findings indicate that 5-HT might be involved in the mechanisms of halothane-induced MH in humans. Further studies have to determine the patho physiological role of the 5-HT system in MH, and whether ritanserin could b e an alternative for treatment or prevention of halothane-induced MH.