Investigation of malignant hyperthermia susceptibility in Denmark

摘要

Malignant hyperthermia (MH) is a genetic disease of humans (Den-boroughetal 1960), pigs (Ludvigsen 1954, Harrison etal 1969),dogs (Short et al 1973), and other animals. The underlying pathophysio-logy of MH is a defect in the control of the intracellular free, ionized calcium concentration in skeletal muscle (Louis et al 1992). In MH muscle, the release of calcium from the sarcoplasmic reticulum (SR) is augmented by anaesthetic agents which trigger MH, apparently due to a defect in the closing mechanism of the calcium channel (Louis et al 1992). Calcium itself stimulates calcium release, leading to a vicious cycle with ever increasing calcium concentrations. In muscle, calcium stimulates glucose metabolism with formation of increased amounts of carbon dioxide and heat. In addition, calcium above the mechanical threshold of 1x10~(-5) molxlitre~(-1) induces a contracture. Calcium also activates membrane-bound phospholipases with ensuing breakdown of the cell membrane, causing loss into the extracellular space of potassium, phosphate, myoglobin and creatine kinase (CK). With higher calcium concentrations, the mitochondria take up calcium at the expense of oxidative metabolism, thereby shifting metabolism to anaerobic pathways with formation of lactic acid and H~+. This in turn leads to sympathetic stimulation. The increase in plasma potassium may lead to arrhythmia and cardiac arrest. If the patient survives long enough renal insufficiency and bleeding because of myoglobinuria and disseminated intravascular coagulation are likely to occur.