López J R, Allen P D, Alamo L, Jones D, Sreter F A
Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela.
Muscle Nerve. 1988 Jan;11(1):82-8. doi: 10.1002/mus.880110113.
Malignant hyperthermia (MH) is a genetic syndrome usually initiated by exposure to volatile anesthetic agents or depolarizing neuromuscular blocking agents. We have used Ca2+-selective microelectrodes to measure in vivo the intracellular ionized calcium ([Ca2+]i) in skeletal muscle fibers of MH-susceptible swines before and during hyperthermic episodes and also after dantrolene administration. The animals were anesthetized with thiopental and fentanyl and maintained with a mixture of nitrous oxide (66%) and oxygen (34%). The malignant hyperthermic episode was triggered by exposure to halothane. Determinations of [Ca2+]i during the episode show an increase from 0.44 +/- 0.01 microM +/- SEM, n = 20) to 8.44 +/- 0.68 microM (mean +/- SEM, n = 10). Administration of dantrolene (2 mg/kg) during the hyperthermic episode reduces [Ca2+]i to 0.17 + 0.01 microM (mean +/- SEM, n = 10) and reverses the clinical symptoms. These results show that the MH episode is associated with an increase in the myoplasmic free Ca2+ concentration and that the therapeutic effect of dantrolene is related to a decrease in [Ca2+]i.
恶性高热（MH）是一种遗传性综合征，通常由接触挥发性麻醉剂或去极化神经肌肉阻滞剂引发。我们使用钙离子选择性微电极在体内测量了易患恶性高热的猪骨骼肌纤维在高热发作前、发作期间以及丹曲林给药后的细胞内游离钙离子浓度（[Ca2+]i）。动物用硫喷妥钠和芬太尼麻醉，并用一氧化二氮（66%）和氧气（34%）的混合气体维持麻醉状态。通过接触氟烷引发恶性高热发作。发作期间[Ca2+]i的测定结果显示，其浓度从0.44±0.01微摩尔/升（±标准误，n = 20）增加到8.44±0.68微摩尔/升（平均值±标准误，n = 10）。在高热发作期间给予丹曲林（2毫克/千克）可使[Ca2+]i降至0.17±0.01微摩尔/升（平均值±标准误，n = 10），并逆转临床症状。这些结果表明，恶性高热发作与肌浆游离钙离子浓度升高有关，且丹曲林的治疗效果与[Ca2+]i降低有关。
