RITANSERIN ATTENUATES THE IN-VITRO EFFECTS OF THE 5-HT2 RECEPTOR AGONIST DOI ON SKELETAL-MUSCLES FROM MALIGNANT HYPERTHERMIA-SUSCEPTIBLE PATIENTS

Study Objectives: To study the in vitro effects of the serotonin(2) (5 -HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ( DOI) in skeletal muscle specimens from malignant hyperthermia-suscepti ble (MHS) and normal (MHN) patients following pretreatment with the 5- HT2 receptor antagonist ritanserin. Design: Prospective study. Setting : Malignant hyperthermia (MH) laboratory at a university hospital. Pat ients: 41 patients undergoing in vitro contracture test for diagnosis of MH susceptibility. Interventions: Skeletal muscle biopsies in adult patients were performed with a 3-in-1 nerve block with 40 ml prilocai ne 1%. In children, general anesthesia was induced with 50 mu g/kg alf entanil intravenously (IV) and 2 to 2.5 mg/kg propofol IV and maintain ed with a continuous infusion of propofol (less than or equal to 150 m u g/kg/min) and nitrous oxide (66%) in oxygen. Measurements and Main R esults: Patients were first classified as MHS or MHN by, the in vitro contracture test according to the European MH protocol. Surplus muscle specimens of 21 MHS and 20 MHN patients were used in this study. At f irst, DOI was added to the organ bath at a concentration of 0.02 mM. I n the second part of the study, muscle specimens were preincubated wit h ritanserin 0.01 mM for 10 minutes before DOI 0.02 mM was added to th e bath. Muscle specimens from all patients developed contractures afte r administration of DOI. The onset of contractures was significantly f aster in MHS muscles, and the magnitude of contracture was significant ly greater than in MHN The muscle twitch decreased significantly in bo th groups after DOI. After treatment with ritanserin, start of contrac ture was significantly delayed in MHS muscles. MHN muscles failed to d evelop contractures. The maximum level of contracture was significantl y reduced in MHS. Muscle twitch decreased also in both MHS and MHN gro ups. Conclusions: The findings may indicate that stimulation of 5-HT2 receptors is involved in MH induction. Furthermore, 5 = HT2 receptor a ntagonists could possible be effective in preventing MH. Additional st udies are required to determine if administration of 5-HT2 receptor an tagonists could be of additional value in the treatment or prevention of anesthetic-induced MH. (C) 1997 by Elsevier Science Inc.