A new calpain inhibitor protects left ventricular dysfunction induced by mild ischemia-reperfusion in in situ rat hearts.

We have previously indicated that a new soluble calpain inhibitor, SNJ-1945 (SNJ), attenuates cardiac dysfunction after cardioplegia arrest-reperfusion by inhibiting the proteolysis of α-fodrin in in vitro study. Nevertheless, the in vivo study design is indispensable to explore realistic therapeutic approaches for clinical use. The aim of the present in situ study was to investigate whether SNJ attenuated left ventricular (LV) dysfunction (stunning) after mild ischemic-reperfusion (mI-R) in rat hearts. SNJ (60 μmol/l, 5 ml i.p.) was injected 30 min before gradual and partial coronary occlusion at proximal left anterior descending artery. To investigate LV function, we obtained curvilinear end-systolic pressure–volume relationship by increasing afterload 60 min after reperfusion. In the mI-R group, specific LV functional indices at midrange LV volume (mLVV), end-systolic pressure (ESPmLVV), and pressure–volume area (PVAmLVV: a total mechanical energy per beat, linearly related to oxygen consumption) significantly decreased, but SNJ reversed these decreases to time control level. Furthermore, SNJ prevented the α-fodrin degradation and attenuated degradation of Ca2+ handling proteins after mI-R. Our results indicate that improvements in LV function following mI-R injury are associated with inhibition of the proteolysis of α-fodrin in in situ rat hearts. In conclusion, SNJ should be a promising tool to protect the heart from the stunning.;博士(医学)・甲617号・平成26年3月17日;開始ページ : 113;終了ページ : 123;PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/23242912

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書名 A new calpain inhibitor protects left ventricular dysfunction induced by mild ischemia-reperfusion in in situ rat hearts.
著作者等 日本生理学会
Ito Haruo
Mitsuyama Shinichi
Obata Koji
Takaki Miyako
Tanaka Midori
Taniguchi Shigeki
Yoshikawa Yoshirou
Zhang Guo-Xing
Takeshita Daisuke
書名別名 新しいカルパイン阻害剤はラット生体位心における緩和な虚血再灌流による左心室機能障害を保護する
出版元 Springer Japan / Physiological Society of Japan
刊行年月 2006-
ページ数 v.
大きさ 30 cm
ISSN 18806546
NCID AA12129145
※クリックでCiNii Booksを表示
全国書誌番号
01012049
※クリックで国立国会図書館サーチを表示
言語 英語
出版国 日本
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