Diagnosis of malignant hyperthermia susceptibility : by measuring change in myoplasmic calcium concentration in cultured human skeletal muscle cells and genetic analysis

我们测量了65名有麻醉相关恶性高热（MH）史、MH家族史或MH相关疾病的患者的CICR（钙诱导的钙释放）率。CICR率增高者18例，正常者47例。我们成功地从41条肌条中培养出成肌细胞。本文研究了咖啡因对4例加速CICR患者和6例正常CICR患者的骨骼肌细胞组成的肌管中钙离子浓度的影响。咖啡因引起的CICR加速组钙浓度升高明显高于CICR正常组。本文研究了氟烷对2例加速CICR患者和4例正常CICR患者的骨骼肌细胞组成的肌管中钙离子浓度的影响。氟烷引起的钙升高在两组之间没有显著性差异，因为我们猜测6名受试者是如此之少。我们对8例患者的Ryanodine受体（RYR1）的6个突变进行了遗传学分析，但未发现RYR1的突变。由于RYR1由5000个氨基酸组成，而RYTR1上与A7H相关的突变已报道近40个，因此寻找RYR1的MH连锁突变需要大量的时间和成本。

We measured the rate of CICR (Ca-induced Ca release) in 65 patients who had anesthesia-related malignant hyperthermia(MH) history, MH family history or diseases associated with MH. There were 18 patients with accelerated CICR rate and 47 patients with normal CICR rate. We succeeded to culture myoblast from 41 muscle strips. We studied the effect of caffeine on the calcium concentration in human myotubes made up of cultured skeletal muscle cells from 4 patients of accelerated CICR rate and 6 patients of normal CICR rate. The caffeine induced increase in calcium concentration of accelerated CICR rate group was significantly higher than normal CICR rate group. We studied the effect of halothane on the calcium concentration in human myotubes made up of cultured skeletal muscle cells from 2 patients of accelerated CICR rate and 4 patients of normal CICR rate. There was no significant difference of halothane-induced calcium increase between these two groups, because we guessed that 6 subjects was so few. We made genetic analysis of six mutations of the ryanodine receptor (RYR1) in 8 patients, but we didn't find out any mutations of the RYR1. We need much time and cost to search MH-linked mutations of RYR1, because RYR1 consists of 5000 amino acids and A7H related mutations on RYTR1 were reported almost 40 points.