Treatment of porcine malignant hyperthermia: lactate gradient from muscle to blood.

Treatment of MH was studied in 21 pigs, using an isolated perfused caudal body preparation (L1 transection). Halothane one per cent triggered MH; data included oxygen consumption, blood/muscle lactate levels, plasma potassium, acid-base balance. Three treatment protocols had two phases each: A-1, discontinue halothane, inject dantrolene 7.5 mg X kg-1; A-2, inject HCO3- (113 +/- 6 mEq). B-1, Discontinue halothane, inject HCO3- (118 +/- 13 mEq); B-2, inject dantrolene 7.5 mg X kg-1; X C-1, Continue halothane, inject dantrolene 7.5 mg X kg-1; C-2, discontinue halothane, inject HCO3- (101 +/- 8 mEq). Dantrolene and HCO3- acted separately and differently: dantrolene reversed the hypermetabolism, both aerobic and anerobic, and HCO3- reversed the extracellular metabolic acidosis. Semitendinosus muscle biopsies demonstrated that both red and white muscle are involved in MH, that muscle lactate (to 35 mumol X g-1) consistently exceeded blood lactate (to 22 mumol X ml-1), and that blood lactate levels were slow to diminish following treatment. One could expect continued release of muscle lactate into blood, despite adequate therapy of MH; this might suggest a recurrence even when such is not the case.

Effect of CO2, calcium, digoxin, and potassium on cardiac and skeletal muscle metabolism in malignant hyperthermia susceptible swine.

The effects on whole body or cardiac metabolism of carbon dioxide, calcium, potassium, or digoxin were studied in 16 normal swine and 31 swine susceptible to malignant hyperthermia (MHS). Malignant hyperthermia (MH) was defined as an increase in metabolism that occurred in MHS but not in normal pigs. Whole body response: despite a sustained PaCO2 greater than 130 mmHg, MH did not develop in four intact MHS swine during thiopental-N2O anesthesia and controlled ventilation. Drugs given during total cardiopulmonary bypass: MH did not develop in five MHS pigs with blood ionized calcium to 15 mEq/l, in four MHS pigs with digoxin levels to 60 ng/ml, or in four normal pigs with potassium to 10 mEq/l. In six MHS pigs, oxygen consumption increased from 6.5 to 11.6 ml O2 X min-1 X kg-1 when potassium exceeded 6 mEq/l; lactate did not increase. Cardiac response (during extracorporeal right heart bypass): eight pigs (four normal, four MHS) with blood ionized calcium to 5 mEq/l and eight pigs (four normal, four MHS) with digoxin levels above 7.5 ng/ml had increased myocardial oxygen consumption. Cardiac potassium efflux or lactate production did not occur in normal or MHS pigs. Increased arterial potassium (7.4-8.5 mEq/l) did not alter myocardial oxygen consumption or lactate production in four MHS or four normal pigs. MH responses were initiated only by potassium and only in regard to whole body metabolism. Cardiac metabolism increased as a result of specific drugs (calcium, digoxin), unrelated to MH phenomena. Porcine inbreeding resulting in MH susceptibility of skeletal muscle does not imply abnormality in other tissues.

Electrical stimulation triggers porcine malignant hyperthermia.

Metabolic, haemodynamic and neuroendocrine responses to electrical neuromuscular stimulation were measured in five normal and five malignant hyperthermia-susceptible pigs. Normal animals recovered after stimulation but susceptible pigs showed malignant hyperthermia-like responses. Catecholamine levels were higher in malignant hyperthermia-sensitive than in normal pigs at all sampling times.

Malignant hyperthermia: responses of skeletal muscles to general anesthetics.

Anesthetic-induced malignant hyperthermia (MH) originally attracted scientific interest because of the associated high fatality rate. Recently, the introduction of treatment with the muscle relaxant dantrolene sodium has dramatically reduced the frequency of death from MH. Nonetheless, diagnosing MH susceptibility remains a problem because it necessitates a muscle biopsy specimen that must be tested in a specially equipped laboratory. Thus, diagnosis is both expensive and invasive. Development of simpler and less invasive methods would be aided by identification of the primary defect underlying initiation of MH. Our understanding of whole-body responses during MH episodes and the development of treatment with dantrolene sodium have both resulted from studies of porcine MH, which is similar to the syndrome in humans. Investigations of porcine MH have demonstrated that the defect responsible for initiation of MH must be located in skeletal muscle. Many abnormal responses of MH muscle have been identified after exposure to triggering agents. These defects contribute to the maintenance and amplification of the MH episode once it has been initiated. The primary defect responsible for triggering this complex chain of events, however, has thus far eluded definition.