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This Article Full Text Full Text (PDF) Buy All Versions of this Article: 298/2/H643    most recent 00849.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yoshikawa, Y. Articles by Takaki, M. PubMed PubMed Citation Articles by Yoshikawa, Y. Articles by Takaki, M.

Cardioprotective effects of a novel calpain inhibitor SNJ-1945 for reperfusion injury after cardioplegic cardiac arrest

Departments of ¹Physiology II and ²Thoracic-Cardiovascular Surgery, Nara Medical University School of Medicine, Kashihara, Nara, Japan

Submitted September 8, 2009 ; accepted in final form November 25, 2009

We have previously indicated that calpain inhibitor-1 prevents the heart from ischemia- reperfusion injury associated with the impairment of total Ca²⁺ handling by inhibiting the proteolysis of -fodrin. However, this inhibitor is insoluble with water and inappropriate for clinical application. The aim of the present study was to investigate the protective effect of a newly developed calpain inhibitor, SNJ-1945 (SNJ), with good aqueous solubility on left ventricular (LV) mechanical work and energetics in the cross-circulated rat hearts. SNJ (150 µM) was added to KCl (30 meq) cardioplegia (CP). Mean end-systolic pressure at midrange LV volume (ESP_mLVV) and systolic pressure-volume area (PVA) at mLVV (PVA_mLVV; a total mechanical energy per beat) were hardly changed after CP plus SNJ arrest-reperfusion (post-CP + SNJ), whereas ESP_mLVV and PVA_mLVV in post-CP group were significantly (P < 0.01) decreased. Mean myocardial oxygen consumption for the total Ca²⁺ handling in excitation-contraction coupling did not significantly decrease in post-CP + SNJ group, whereas it was significantly (P < 0.01) decreased in post-CP group. The mean amounts of 145- and 150-kDa fragments of -fodrin in the post-CP group were significantly larger than those in normal and post-CP + SNJ groups. In contrast, the mean amounts of L-type Ca²⁺ channel and sarcoplasmic reticulum Ca²⁺-ATPase were not significantly different among normal, post-CP, and post-CP + SNJ groups. Our results indicate that soluble SNJ attenuates cardiac dysfunction due to CP arrest-reperfusion injury associated with the impairment of the total Ca²⁺ handling in excitation-contraction coupling by inhibiting the proteolysis of -fodrin.

cardiac function; systolic pressure-volume area; oxygen consumption; -fodrin