1993 Fiscal Year Final Research Report Summary
Research on generation mechanism and in vitro diagnosis of malignant hyperthermia
| Project/Area Number |
04454396
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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 | Toho University |
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Principal Investigator |
KIKUCHI Hirosato Toho University School of Medicine, Professor, 医学部, 教授 (40034029)
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| Co-Investigator(Kenkyū-buntansha) |
SATA Ken Toho University School of Medicine, Assistant, 医学部, 助手 (00235300)
MAEDA Noriko Toho University School of Medicine, Assistant, 医学部, 助手 (30173355)
SHINODA Takahide Toho University School of Medicine, Assistant, 医学部, 助手 (50175387)
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| Project Period (FY) |
1992 – 1993
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| Keywords | malignant hyperthermia / skinned fiber technique / intramuscular calcium ion(Ca^<2+>) metabolism / Ca^<2+>-induced Ca^<2+>-release(CICR) / in vitro diagnosis / neuromuscular diseases / denervated skeletal muscle / Ca^<2+> channel blockers |
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| Research Abstract |
It is generally accepted that malignant hyperthermia, one of the serious complications of general anesthesia, results from abnormality of calcium ion(Ca^<2+>) metabolism in skeletal muscle. The skinned fiber technique which is essentially taken as an experimental method for this study can independently examine the components of Ca^<2+> metabolim in skeletal muscle (1.Ca^<2+>-induced Ca^<2+> release rate from sarcoplasmic reticulum, CICR rate. 2.Ca^<2+> uptake by sarcoplasmic reticulum. 3.Ca^<2+> sensitivity of contractile system proteins), and is applied to in vitro diagnosis of malignant hyperthermia. In the present study, we have accumulated the data of human skeletal muscles biopsied from the patients who were clinically suspected of the above disease, their family members and the patients who clinically presented malignant hyperthermia-like manifestations (myogloblinuria, hyper creatininekinasemia, etc) and tried to answer some of clinical questions. Also intra-muscular Ca^<2+> metabolism in some of neuro-muscular diseases was examined using the skinned fiber method, and one specific abnormality in one certain disease was identified. With animal specimens (guinea pig), denervated muscle presented lowered sensitivity of contraction to certain drugs (caffeine, one of xanthine delivertives and halothane, one of volatile anesthetics) based on the change in intramuscular Ca^<2+> metabolism, and this result may explain uncertainty of the caffeine, halothane contracture test which is used in North American and European countries for in vitro diagnosis of malignant hyperthermia. Again with animal skinned fibers the effect of some of the clinically used drugs (Ca^<2+> channel blockers, etc) on intramuscular Ca^<2+> metabolism were examined and their clinical safety was discussed.
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