SUMMARY

MH is a subclinical myopathy featuring an eerie and erratic metabolic mayhem that is unmasked on exposure to potent volatile anesthetics or succinylcholine. Skeletal muscle acutely and unexpectedly increases its oxygen consumption and lactate production, resulting in greater heat production, respiratory and metabolic acidosis, muscle rigidity, sympathetic stimulation, and increased cellular permeability. MH-susceptible skeletal muscle differs from normal muscle in that it is always closer to loss of control of Ca²⁺ concentration within the muscle fiber, and it can involve a generalized alteration in cellular or subcellular membrane permeability. This is an EC coupling defect resulting from an alteration in the receptor encoded by RYR1. It is a homozygous, single-point mutation of RYR1 in swine and a heterozygous disorder in humans, in whom there may also be a modification of RYR1 protein function by interacting structures, membranes, or enzymes; MH may occur as a final common path phenomenon. Diagnosis rests on extraordinary temperature, acid-base alterations, and muscle aberrations. Specific treatment is the action of dantrolene on muscle Ca²⁺ movements; symptomatic treatment is by reversal of acid-base and temperature changes. Evaluation of affected families is guided by measurements of circulating CK, analysis of drug-induced muscle contractures (by European IVCT and North American CHCT protocols), and genetic testing of DNA samples. General or regional anesthesia is safe for patients susceptible to MH, provided that care is taken to specially prepare the anesthesia machine and to avoid all potent volatile anesthetics and succinylcholine if a general technique is chosen.

Research on MH has yielded insights into the physiology of metabolism and into the molecular biology of genetic muscle disorders. Remaining challenges include identification of all genetic mutations responsible for human MH, elucidation of the mechanism that links exposure to the subsequent loss of Ca²⁺ control, development of noninvasive and nondestructive testing for susceptibility, and determination of the mode of action of dantrolene.