KEY POINTS

1. MH is an anesthetic-related disorder of increased metabolism of skeletal muscle. It is an inherited condition and occurs in swine and humans.
2. Skeletal muscle accounts for approximately 40% of body weight; its increased metabolism therefore has a profound effect on whole-body metabolism.
3. Signs of MH, including tachycardia, increased expired carbon dioxide, muscle rigidity, and increased temperature, are related to increased metabolism.
4. Function of the ryanodine receptor of skeletal muscle is abnormal in MH, causing barely controlled calcium concentration within the cell.
5. Added loss of control of intracellular calcium leads to marked metabolic stimulation within the cell to provide extra ATP to drive the calcium pumps that restore calcium to its reservoirs (e.g., SR, mitochondrion, extracellular fluid).
6. Dantrolene markedly attenuates loss of calcium from SR, restoring metabolism to normal, with reversal of the signs of metabolic stimulation.
7. MH is inherited; one mutation accounts for all porcine MH, and more than 30 mutations account for human MH.
8. Evaluation of persons susceptible to MH includes contracture of a skeletal muscle biopsy specimen with halothane or caffeine, estimation of muscle permeability by measurement of plasma CK level, and evaluation of DNA to identify mutations. Only DNA testing is needed to evaluate swine MH.
9. Future MH goals include advancement of genetic evaluations in North American and European medical programs and finances that are stronger for supporting genetic studies, identification of the mode of action of dantrolene, determination of the immediate cause of MH triggering, and development of effective, nondestructive tests for MH susceptibility.