METABOLIC RESPONSE TO HALOTHANE IN PIGLETS SUSCEPTIBLE TO MALIGNANT HYPERTHERMIA - AN IN-VIVO P-31-NMR STUDY

Using in vivo P-31-nuclear magnetic resonance spectroscopy, we studied the skeletal muscle metabolism of 17 anesthetized malignant hyperther mia-susceptible piglets and 25 control piglets during and after a halo thane stress test. At rest, the phosphocreatine- (PCr) to-ATP ratio wa s 12% higher in the anesthetized piglets than in the control piglets, which may reflect a higher proportion of fast glycolytic fibers in the former. About 15 min of halothane administration sufficed to provoke onset of a reaction, which was characterized by a reciprocal drop in P Cr and an increase in P(i) with commencing intracellular acidosis. Hal othane was withdrawn after a 20% drop in PCr. Within the next few minu tes, intracellular pH dropped sharply and phosphomonoesters (PME) accu mulated excessively. ATP was observed to decrease in 8 of the 17 anima ls. Halothane inhalation provoked a switch of metabolism toward glycol ysis. Accumulation of PME suggests a mismatch between glycogenolysis a nd glycolysis. Despite severe acidification, glycolysis was not comple tely halted. Recovery of PCr and P(i) started approximately 5 min afte r halothane withdrawal, with a longer time constant for recovery of th e former. PME and intracellular pH aberrations lingered and started to recover later. Lost ATP was never restored within the observed recove ry period of approximately 20 min.