naa a22 4500 510805965 CHVBK 20180411083418.0 cr unu---uuuuu 180411e20130301xx s 000 0 eng 10.1007/s12576-012-0243-6 doi (NATIONALLICENCE)springer-10.1007/s12576-012-0243-6 A new calpain inhibitor protects left ventricular dysfunction induced by mild ischemia-reperfusion in in situ rat hearts [Elektronische Daten] [D. Takeshita, M. Tanaka, S. Mitsuyama, Y. Yoshikawa, G. Zhang, K. Obata, H. Ito, S. Taniguchi, Miyako Takaki] 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 (60μmol/l, 5ml i.p.) was injected 30min 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 60min 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. The Physiological Society of Japan and Springer Japan, 2012 Mild ischemic-reperfusion injury nationallicence Cardioprotection nationallicence α-Fodrin nationallicence SNJ-1945 nationallicence BW : Body weight nationallicence Ea : Arterial effective elastance nationallicence E-C : Excitation-contraction nationallicence EDV : End-diastolic volume nationallicence EF : Ejection fraction nationallicence ESP : End-systolic pressure nationallicence ESPESV : End-systolic pressure at end-systolic volume nationallicence ESPmLVV : End-systolic pressure at mLVV nationallicence ESPVR : End-systolic pressure-volume relationship nationallicence ESV : End-systolic volume nationallicence HR : Heart rate nationallicence I-R : Ischemic-reperfusion nationallicence LTCC : L-type Ca2+ channel nationallicence LV : Left ventricular nationallicence LVP : Left ventricular pressure nationallicence LVV : Left ventricular volume nationallicence LVW : LV weight nationallicence mI-R : Mild ischemic-reperfusion nationallicence mLVV : Midrange LVV nationallicence NCX : Na+-Ca2+ exchanger nationallicence P-V : Pressure-volume nationallicence PVAmLVV : Systolic pressure-volume area at mLVV nationallicence SERCA2a : Sarcoplasmic reticulum Ca2+ ATPase nationallicence SV : Stroke volume nationallicence Takeshita D. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut Tanaka M. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut Mitsuyama S. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut Yoshikawa Y. Department of Thoracic and Cardiovascular Surgery, Nara Medical University, Nara, Japan aut Zhang G. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut Obata K. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut Ito H. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut Taniguchi S. Department of Thoracic and Cardiovascular Surgery, Nara Medical University, Nara, Japan aut Takaki Miyako Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut The Journal of Physiological Sciences Springer Japan 63/2(2013-03-01), 113-123 1880-6546 63:2<113 2013 63 12576 https://doi.org/10.1007/s12576-012-0243-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12576-012-0243-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takeshita D. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut NATIONALLICENCE 700 1- Tanaka M. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut NATIONALLICENCE 700 1- Mitsuyama S. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut NATIONALLICENCE 700 1- Yoshikawa Y. Department of Thoracic and Cardiovascular Surgery, Nara Medical University, Nara, Japan aut NATIONALLICENCE 700 1- Zhang G. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut NATIONALLICENCE 700 1- Obata K. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut NATIONALLICENCE 700 1- Ito H. Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut NATIONALLICENCE 700 1- Taniguchi S. Department of Thoracic and Cardiovascular Surgery, Nara Medical University, Nara, Japan aut NATIONALLICENCE 700 1- Takaki Miyako Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan aut NATIONALLICENCE 773 0- The Journal of Physiological Sciences Springer Japan 63/2(2013-03-01), 113-123 1880-6546 63:2<113 2013 63 12576 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer