A cardioprotective agent of a novel calpain inhibitor,SNJ- 1945 exerts beta1-actions on left ventricular mechanical work and energetics.
A cardioprotective agent of a novel calpain inhibitor,SNJ- 1945 exerts beta1-actions on left ventricular mechanical work and energetics.
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SNJ-1945 是一种新型钙蛋白酶抑制剂的心脏保护剂，对左心室机械功和能量发挥 β1 作用。
DOI：
10.1152/ajpheart.00153.2010
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
他
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文献类型：
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作者：
Yoshikawa Y;Obata K;Asada K;Takaki M;他
我们以前已经证明，一种新开发的钙蛋白酶抑制剂，SNJ-1945（SNJ），具有良好的水溶性，防止心脏从氯化钾停搏-再灌注损伤与损害的总钙处理通过抑制α-胞衬蛋白作为心脏停搏液的蛋白水解。本研究的目的是研究钙蛋白酶抑制剂SNJ对交叉循环离体大鼠心脏进行40 μM SNJ血液灌注的左心室（LV）机械功和能量学的某些作用。SNJ灌注可显著增加中等LV容积的平均收缩末期压和mLVV（总机械能/搏动）的收缩压-容积面积（PVA）（P< 0.01）。心肌每搏平均耗氧量（V ~ o ~ 2）与PVA线性关系的截距（V ~ o ~ 2代表兴奋-收缩偶联和基础代谢中总Ca ~（2+）处理）显著增加（P< 0.01），而V ~ o ~ 2与PVA线性关系的平均斜率不变。用选择性β1受体阻滞剂兰地洛尔（10 μM）预处理可阻断SNJ灌注的这些效应。正常组、40 μM SNJ组和10 μM兰地洛尔+ 40 μM SNJ组之间的平均基础代谢耗氧量无显著差异。我们的结果表明，水溶性SNJ通过β1-肾上腺素能受体介导的机械功和能量学发挥积极作用，与兴奋-收缩偶联中总Ca 2+处理的增强和收缩效率不变有关。在临床环境中，SNJ的这种药理作用作为心脏停搏液的添加剂是有益的。
We have previously shown that a newly developed calpain inhibitor, SNJ-1945 (SNJ), with good aqueous solubility prevents the heart from KCl arrest-reperfusion injury associated with the impairment of total Ca2+handling by inhibiting the proteolysis of α-fodrin as a cardioplegia. The aim of the present study was to investigate certain actions of this calpain inhibitor, SNJ, on left ventricular (LV) mechanical work and energetics in cross-circulated excised rat hearts undergoing blood perfusion with 40 μM SNJ. Mean end-systolic pressure at midrange LV volume and systolic pressure-volume area (PVA) at mLVV (a total mechanical energy/beat) were significantly increased by SNJ perfusion (P< 0.01). Mean myocardial oxygen consumption per beat (V̇o2) intercepts (V̇o2for the total Ca2+handling in excitation-contraction coupling and basal metabolism) of V̇o2-PVA linear relations were significantly increased (P< 0.01) with unchanged mean slopes of V̇o2-PVA linear relations. Pretreatment with the selective β1-blocker landiolol (10 μM) blocked these effects of SNJ perfusion. There were no significant differences in mean basal metabolic oxygen consumption among normal, 40 μM SNJ, and 10 μM landiolol + 40 μM SNJ groups. Our results indicate that water-soluble SNJ exerted positive actions on mechanical work and energetics mediated via β1-adrenergic receptors associated with the enhancement of total Ca2+handling in excitation-contraction coupling and with unchanged contractile efficiency. In clinical settings, this pharmacological action of SNJ is beneficial as an additive agent for cardioplegia.