Effects of a 5HT2 receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia

The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT2A) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in body temperature, hyperventilation and acidosis in conscious MH-susceptible (MHS) pigs. Whether these symptoms are directly generated in skeletal muscle, result from central serotonergic overstimulation or from a porcine stress syndrome remains unresolved. In this study the in vivo effects of DOI on anaesthetized (and thus stress-protected) MHS and MH-normal (MHN) pigs were investigated. DOI 1 mg kg−1 was administered three times at 40-min intervals to five MHS and five MHN anaesthetized pigs. Body temperature, heart rate, muscle tone, arterial carbon dioxide pressure (PaCO2), pH and creatine kinase concentrations were measured. The clinical occurrence of MH was defined by PaCO2 above 70 mm Hg and an increase in body temperature of more than 2 °C. Intragroup differences were analysed with the Friedman test as an overall non-parametric anova and, in case of significance, with the Wilcoxon test. Intergroup comparisons were performed with the Mann–Whitney U-test (statistical significance P