Studies on the Diagnosis and the Treatment of Malignant Hyperthermia

恶性高热的诊治研究

• 批准号: 60480347
• 负责人: FUJIOKA Yasuhiro
• 金额: $ 3.58万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480347/
• 关键词: Malignant Hyperthermia; Statistical Analysis; HLA typing; Membrane Fluidity; Skinned Fiber Test; Ca-induced Ca release(CICR); 吸入麻酔薬; 麻酔合併症

1) Malignant hyperthermia is a kind of rare syndrome only observed during anesthesia. As a retrospective survey of this syndrome, a statistical analysis was made on the basis of cases which we collected through journals, questionnaire surveys, and personal communications. The mortality rate of malignant hyperthermia has declined year by year partly because of the better understanding of this desease by anesthesiologist.2) Analysis of the signs and symptoms has revealed that some factors contribute to mortality. The mean age was higher and the maximum body temperature during the crisis was higher in the deceased cases than in the surviving cases. Hypotension, Bradycardia and arrhtyhmia as signs before elevation of body temperature were observed in deceased cases in a statistically higher rate. However, the incidence of masseter spasm was lower in deceased cases. Administration of dantrolene which is a specifically effective agent for this syndrome reduced the mortality. There was no sta … More tistical difference between the deceased and survived cases by sex, usage of succinylcholine chloride, tachycardia and hypertension during the crisis, finding of myoglobinuria, and general muscle rigidity other than masseter spasm.3) Since this syndrome is thought to be hereditary and genetic, typing of HLA( Human Leukocyte Antigen ) is highly expected to detect carriers of this syndrome. Although a higher incidence of NJ28 in DR locus has been observed, recent analysis has shown that this antigen is frequently found in patients with this syndrome but also in patient myoglobinuria without hyperthermia. Therefore, this study should be extended to cover a broader range of muscle diseases including malignant hyperthermia.4) the mechanism of this syndrome has not yet been well elucidated. The possibility of abnormal function of the memberane has been studied. The fluidity of erythrocyte membrane taken from patients of this syndrome was measured by using the spin-labeled method. Shift of fluidity be temperature was restored to normal in two weeks after the crisis. To confirm this change as a general character of this syndrome, more samples of this syndrome should be analysis.5) As a diagnosis test and triggering mechanism of this syndrome, acceleration of the rate of calcium-induced calcium release (CICR) from the sarcoplasmic reticulum of the skeletal muscle has been confirmed in patients with this syndrome. Potentiation of CICR was studied with a variety of volatile anesthetic agents and local anesthetic agents using the skinned fiber of the guinea pig. Halothane in clinical concentration was confirmed to potentiate strongly CICR among the other agents. However, local anesthetics in clinical concentration did not affect CECR mechanism. By using this skinned fiber technique, CICR of muscle of cases with malignant syndrome which is said to be related to malignant hyperthermia was found to be intact. Less

1）恶性高温是一种仅在麻醉期间观察到的罕见综合征。作为对该综合征的回顾性调查，根据我们通过期刊，问卷调查和个人通讯收集的案件进行了统计分析。由于麻醉师对这种解剖学的了解更好地理解了这种解次，但对符号和符号的分析表明，某些因素会导致死亡率。在死者病例中，危机期间的最高体温高于生存情况。低血压，心动过缓和Arrhtyhmia作为在死者病例中观察到体温升高之前的迹象，其统计学率更高。但是，在死者病例中，蜂蜜痉挛的事件较低。丹托烯的给药是为此特别有效的药物……死者和生存的案例之间通过性别，在危险期间使用琥珀酰胆碱，氯化琥珀酰胆碱的用法，心动过速和高血压，肌红素尿尿，肌红素尿素的发现，肌肉spasm.3的肌肉和人类的一般肌肉施加，以及范围内的人类疾病（任何人）。尽管已经观察到抗原）高度期望检测到这种载体的载体，尽管已经观察到NJ28在基因座DR中的较高事件，但最近的分析表明，该抗原经常在该综合征患者中，但在患者肌性尿性尿液中经常发现。因此，应扩展这项研究以涵盖包括恶性高温在内的更广泛的肌肉疾病。4）该综合征的机制尚未得到很好的阐明。构件异常功能的可能性已经研究了。通过使用自旋标记的方法测量了从该综合征患者中获得的红细胞膜的流动性。危机后两周内，流动性BE温度的变化恢复到正常。为了确认这一变化是该综合征的一般特征，应分析该综合征的更多样本。5）作为该综合征的诊断测试和触发机制，钙诱导的钙释放率（CICR）的加速度从骨骼肌的肌胞膜骨骼释放（CICR）的加速度证实，已证实在该综合征患者中。 CICR的增强是使用多种挥发性麻醉剂和局部麻醉剂使用豚鼠的皮肤纤维进行了研究的。在其他药物中，证实了临床浓度的氟烷在强烈的CICR中得到证实。但是，临床浓度的局部麻醉药不会影响CECR机制。通过使用这种皮肤纤维技术，发现与恶性高温有关的恶性综合征病例的CICR被发现完好无损。

项目成果

Kikuchi,H.,Morio,M.,Fujii,K.,Yuge,O.: "Malignant Hyperthermia and Its Therapy by Dantrolene" Proceedings of the 3rd Western Pacific Association of Critcal Care Medicine Congress. 169-170 (1985)

Kikuchi,H.、Morio,M.、Fujii,K.、Yuge,O.：“恶性高热及其丹曲林治疗”第三届西太平洋重症监护医学协会大会论文集。

Kawamot,M.,Fujii,K.,Kikuchi,H.,Morio M.: "Increased Membrane Fluidity of Erythrocytes in a Case with Malignant Hyperthermia" J. Anesthesia. 1. 88-92 (1987)

Kawamot，M.，Fujii，K.，Kikuchi，H.，Morio M.：“恶性高热病例中红细胞膜流动性增加”J.麻醉。

Kikichi, M;Morip, M;Fujii, K;Yuge, O: Prociedings of 3rd Western Pacific Association of Critical Care Meaicine Congress. 169-170 (1985)

Kikichi, M;Morip, M;Fujii, K;Yuge, O：第三届西太平洋重症监护医学协会大会论文集。

Matsui,K.,Kikuchi,H.,Fujii,K.,Fujioka,Y.,Morio,M.: "The Effect of Inhalational Anesthetics on Ca++ Uptake by the Sarcoplasmic Reticulum in the Skinned Skeletal Muscle Fibers" Hiroshima Journal of Anesthesia (Sapplement). 23. 13-18 (1987)

Matsui,K.、Kikuchi,H.、Fujii,K.、Fujioka,Y.、Morio,M.：“吸入麻醉药对皮肤骨骼肌纤维中肌浆网 Ca 摄取的影响”广岛麻醉杂志（

菊地博達,盛生倫夫,藤井宏融,弓削孟文,石原晋,河内正治,山野上敬夫,平良裕子,井上徹英,向田圭子: 悪性高熱研究の進歩【X】 麻酔と蘇生. 22(別15). 91-94 (1986)

Hirotatsu Kikuchi、Michio Morio、Hirotoshi Fujii、Mengfumi Yuge、Susumu Ishihara、Masaharu Kawachi、Takao Yamanoue、Yuko Taira、Tetsuhide Inoue、Keiko Mukoda：恶性高热研究进展 [X] 麻醉和复苏 22（第 15 部分）。 94 (1986)