2020 Fiscal Year Final Research Report

A novel adhesion prevention strategy using PAI-1 inhibitor

Research Project

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Project/Area Number	18K08724
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55030:Cardiovascular surgery-related
Research Institution	Tohoku University
Principal Investigator	Kawatsu Satoshi 東北大学, 医学系研究科, 大学院非常勤講師 (80633685)
Co-Investigator(Kenkyū-buntansha)	齋木佳克東北大学, 医学系研究科, 教授 (50372298) 安達理東北大学, 医学系研究科, 大学院非常勤講師 (30375092) 秋山正年東北大学, 医学系研究科, 准教授 (80526450)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	PAI-1 / TM5441 / 癒着 / 心臓血管外科 / 再手術 / プラスミン
Outline of Final Research Achievements	A postsurgical adhesion reduction strategy remains unestablished. One of the mechanisms of intrapericardial adhesion formation is fibrin accumulation on damaged pericardial layers. Plasminogen activator inhibitor-1(PAI-1), a serine protease inhibitor, is involved in numerous process including fibrin accumulation and fibrosis. In this study we aimed to prove adhesion reduction effect of PAI-1 inhibition using rabbit pericardial adhesion model. PAI-1 antagonist TM5441 was administered to rabbit pericardial adhesion models and adhesions were evaluated four weeks after surgery.TM5441 attenuates adhesions in the inner part of the pericardial sacs in rabbit models. Anterior mediastinum adhesion was not improved by TM5441. There were no adverse events. Combining trans-amino-methyl-cyclohexane-carboxylic acid and TM5441 reduces the adhesion reduction effect of TM5441. This shows plasminogen activation inhibition by tranexamic acid blocks plasminogen activation by t-PA activated by TM5441.
Free Research Field	心臓血管外科学
Academic Significance and Societal Importance of the Research Achievements	現在心臓血管外科手術後の再手術は増加している。再手術の際には心臓周囲の癒着剥離操作が必要となり、大血管や心臓損傷のリスクが上昇する。しかし未だ確立された癒着予防法は存在しない。現在は心臓損傷予防のためシート状の代用心膜を留置する手法が中心であるが、かえって癒着を増強させるリスクや感染の問題がある。そこで本研究では癒着の形成過程を阻害する薬剤の全身投与という、これまでになかった形での癒着の改善を目指し、動物実験でその効果を示し、今後臨床応用に向けてさらに研究を進めていく予定である。