ALTERATIONS OF INOSITOL POLYPHOSPHATES IN SKELETAL-MUSCLE DURING PORCINE MALIGNANT HYPERTHERMIA

Malignant hyperthermia (MH) may result from increased intracellular ca lcium concentrations. Increased 1,4,5-IP3 concentrations could mediate this increase in Ca2+. In this study we measured inositol polyphospha tes in selectively bred MH susceptible (MHS) and MH non-susceptible (M HN) swine. MH crisis was induced by halothane challenge, and dantrolen e was administered in order to measure inositol polyphosphates after M H reversal. Muscle biopsies of skeletal muscles of the hind limbs were obtained in random order and inositol polyphosphates determined by hi gh pressure liquid chromatography using a metal dye detection method. Inositol polyphosphates were determined in three groups: (1) MHS vs MH N basal, (2) during MH crisis induced by halothane and (3) following t reatment with dantrolene after halothane challenge. Clinical variables (P (v) over bar O-2, P (v) over bar CO2, PE'(CO2) and pH) indicated t hat MH was readily induced in MHS swine. Basal concentrations of all i nositol polyphosphates were higher in MHS swine compared with MHN swin e. After halothane challenge, 1,3,4-IP3, 1,3,4,6-IP4 and 1,3,4,5-IP4 c oncentrations increased in MHS animals compared with the respective ba seline values, whereas no changes in MHN animals could be detected. Da ntrolene administration decreased inositol polyphosphate concentration s in MHS swine. MHN swine showed no changes in inositol polyphosphates after dantrolene. These findings indicate that inositol polyphosphate s may be involved in metabolic changes after triggering and treatment of MH.