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）恶性高热是一种仅在麻醉期间观察到的罕见综合征，我们根据期刊、问卷调查和个人通讯等收集的病例进行了回顾性调查。由于麻醉医师对这种疾病有了更好的了解，恶性高热逐年减少。2) 对症状和体征的分析表明，一些因素导致了死亡率。平均年龄较高，危象期间的最高体温较低。死亡病例中出现体温升高前症状的低血压、心动过缓和心律失常的比例在统计学上较高，但死亡病例中咬肌痉挛的发生率较低。这是一种针对这种综合征的特别有效的药物，可降低死亡率。按性别、氯化琥珀胆碱的使用情况、心动过速和高血压的情况来看，死亡病例和存活病例之间没有统计学差异。在危机期间，发现肌红蛋白尿和除咬肌痉挛之外的一般肌肉强直。3) 由于这种综合征被认为是遗传性和遗传性的，因此高度期望通过 HLA（人类白细胞抗原）分型来检测这种综合征的携带者。已观察到 DR 基因座中 NJ28 的发生率较高，最近的分析表明，该抗原常见于患有该综合征的患者，而且也见于未接受过热治疗的肌红蛋白尿患者。因此，本研究进行了这项研究。应该扩展到包括恶性高热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。已对取自患者的红细胞膜的流动性异常的可能性进行了研究。该综合征是通过使用自旋标记方法测量的，在危机发生后两周内温度恢复正常。为了确认这种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，骨骼肌肌浆网钙诱导钙释放（CICR）速率的加速已在该综合征患者中得到证实。CICR 的增强已通过多种方法进行了研究。临床浓度的挥发性麻醉剂和使用豚鼠皮纤维的局部麻醉剂被证实在其他药剂中强烈增强 CICR。然而，临床浓度的局部麻醉剂没有影响。 CECR机制。通过使用这种剥皮纤维技术，据说与恶性高热有关的恶性综合征病例的肌肉CICR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。

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)

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。