The proposed research continues to investigate the effects of anesthesia and surgery on metabolism, circulation and respiration in normal and abnormal states. Specifically we will investigate the mechanisms of malignant hyperthermia using an isolated hind limb preparation so as to study the responses of a large mass of muscle with constant adequate perfusion. We can then duplicate the events that lead to triggering in awake swine and, with allowances for species differences, gain further understanding of these responses in susceptible humans. The continued evaluation of muscle biopsy responses in normal and susceptible humans and swine will help to evaluate their efficacy in the accurate diagnosis of susceptibility to malignant hyperthermia. Further studies on relaxant induced hyperkalemia are for the determination of the duration of susceptibility and supersensitivity in rats with upper motor neuron lesions.