1987 Fiscal Year Final Research Report Summary
Studies on the Diagnosis and the Treatment of Malignant Hyperthermia
| Project/Area Number |
60480347
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
麻酔学
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
FUJIOKA Yasuhiro Hiroshima University, School of Medicine, 医学部附属病院, 助手 (00192310)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Keiko Hiroshima University, School of Medicine, 医学部, 助手 (30167978)
KIKUCHI Hirosato Tohhou University, School of Medicine, 医学部, 助教授 (40034029)
FUKUDA Yasuhiko Hiroshima University, School of Medicine, 医学部, 講師 (40093801)
FUJII Kohyu Hiroshima University, School of Medicine, 医学部, 講師 (60034021)
MORIO Michio Hiroshima University, School of Medicine, 医学部, 教授 (80033950)
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| Project Period (FY) |
1985 – 1987
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| Keywords | Malignant Hyperthermia / Statistical Analysis / HLA typing / Membrane Fluidity / Skinned Fiber Test / Ca-induced Ca release(CICR) / 吸入麻酔薬 |
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| Research Abstract |
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
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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
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