Preventive effect of inhaled anesthetics on muscle atrophy in sepsis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08922
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Kyoto University
• Principal Investigator: KAI SHINICHI 京都大学, 医学研究科, 講師 (30770177)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 筋萎縮 / 吸入麻酔 / 鎮静

Outline of Final Research Achievements

In this study, we investigated the effects of inhaled anesthetics on skeletal muscle. In vitro experiments using C2C12 cells showed that inhaled anesthetics, isoflurane and sevoflurane, reduced myotube diameter in a concentration-dependent manner. As a mechanism, we showed that Inhaled anesthetics reduced the Akt phosphorylation, increased two protein degradation pathways (ubiquitin proteasome pathway and autophagy lysosome pathway) and decreased protein synthesis.
Through in vivo experiments using mice, we found decreased Akt phosphorylation, increased protein degradation and decreased protein synthesis on the skeletal muscle in the isoflurane exposure group compared to the two immobilization models (the sciatic nerve denervation and the tail suspension). These results suggest that inhaled anesthetics may impact on the skeletal muscle regardless of immobilization.

Free Research Field

麻酔

Academic Significance and Societal Importance of the Research Achievements

本研究では、in vitro実験から吸入麻酔薬が直接作用し骨格筋を萎縮させること、in vivo実験から吸入麻酔薬暴露が不動化に比べ筋萎縮を助長させる可能性を示した。呼吸循環動態の安定化や人工呼吸管理のため重症患者に鎮静を必要とすることは多いが、吸入麻酔薬による鎮静は骨格筋萎縮を助長するかもしれない。
吸入麻酔薬には抗炎症作用を有するとの報告もあるため侵襲下における検討を重ねる必要はあるものの、吸入麻酔薬には鎮静による不動化だけでなく直接的に骨格筋に作用し骨格筋萎縮を助長する可能性がある。本研究の結果は、重症患者に対する鎮静を必要最小限に抑えるという現在の標準管理を支持するものかもしれない。