Malignant hyperthermia: A runaway thermogenic futile cycle at the sodium channel level

• 作者: Charles H. Williams
• 来源期刊: 生命科学与技术进展(英文)
• 学科: 医学
• 关键词: MALIGNANT HYPERTHERMIA Thermogenic
• 年，卷（期）: smkxyjsjzyw_2014,（3）
• 页码范围: 197-200
• 页数: 4页
• 分类号: R73

摘要

Malignant Hyperthermia (“MH”)—the rapid onset of extremely high fever with muscle rigidity—is caused by a runaway heat production futile cycle mediated via the sodium channels at the myoneural receptor sites. MH is not triggered by non-depolarizing muscle relaxants;however, depolarizing muscle relaxants may trigger it [1]. Here we present a de novo hypothesis of how MH is triggered and develops. We believe that the acetylcholine receptor/sodium channels in the muscles of MH susceptible pigs initiate MH by allowing an increased flux of sodium ions when it is depolarized by acetylcholine or other depolarizing agents, such as succinylcholine and Halothane. Our theory is consistent with our observations of the effects of general anesthetics over twenty years. Succinylcholine is a depolarizing agent that is a potent MH trigger. Acetylcholine, the natural depolarizing muscle activator, may trigger MH if the susceptible patient or animal is exposed to sufficient stress, i.e., during strenuous activity, such as transport, fighting, breeding, etc. Halothane apparently destabilizes the myoneural sodium channels, which rapidly induces MH. The increased sodium channel activity releases heat with cascades that further releases of heat which results in the rapid onset of MH. MH susceptible pigs have increased action potential amplitudes at their myoneural junctions that are abnormally long in duration. This increased activity is thought to induce hypertrophy of muscle mass, increase metabolic rate, and cause other physical manifestations. When slaughtered, this increased metabolic activity causes the rapid post mortem release of heat in the muscles of MH susceptible pigs and, at the same time, the accumulation of low acidity, all of which denatures the muscle proteins to result in a pale, soft, exudative, pork meat considered to be of lesser quality for human consumption. The potency of inhalation anesthetics as a MH triggers varies widely. The inhalation anesthetic Halothane is a strong trigger of MH, causing MH withi