並列タイトル等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
タイトル（掲載誌）The journal of physiological sciences
一般注記type:Thesis
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
identifier:The journal of physiological sciences Vol.63 No.2 p.113-123
identifier:18806546
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2702
identifier:The journal of physiological sciences, 63(2): 113-123
DOIinfo:doi/10.1007/s12576-012-0243-6
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