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新型钠/钙交换体抑制剂KB-R7943对麻醉犬顿抑心肌的心脏保护作用

Cardioprotective effects of KB-R7943, a novel inhibitor of Na+/Ca2+ exchanger, on stunned myocardium in anesthetized dogs.

作者信息

Yoshitomi Osamu, Akiyama Daiji, Hara Tetsuya, Cho Sungsam, Tomiyasu Shiro, Sumikawa Koji

机构信息

Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

出版信息

J Anesth. 2005;19(2):124-30. doi: 10.1007/s00540-004-0290-0.

DOI:10.1007/s00540-004-0290-0
PMID:15875129
Abstract

PURPOSE

The present study was carried out to determine the cardioprotective effects of KB-R7943 (KBR), a selective inhibitor of the reverse mode of Na+/Ca2+ exchanger (NCX), on stunned myocardium in anesthetized dogs.

METHODS

The dogs were allocated to one of three groups (n = 7 for each group), and received drug vehicle (group C), low-dose KBR (5 mg x kg(-1) i.v.) (group L) or high-dose KBR (10 mg x kg(-1) i.v.) (group H) at 15 min before left anterior descending coronary artery (LAD) occlusion. Stunned myocardium was produced by 15-min occlusion of LAD and 90-min reperfusion in all dogs. Regional myocardial contractility was evaluated with segment shortening (%SS).

RESULTS

Recovery of %SS at 90 min after reperfusion was significantly improved in group H (70.8% +/- 3.9% of baseline), whereas the recovery was poor in groups C and L (34.3% +/- 2.8% and 36.4% +/- 5.4% of baseline, respectively). Regional myocardial blood flow showed no significant difference among groups. KBR had no effect on coronary or systemic hemodynamics.

CONCLUSION

The results show that preischemic administration of high-dose KBR markedly improves myocardial contractile dysfunction after ischemia-reperfusion in anesthetized dogs, indicating that KBR protects myocardium against the ischemia-reperfusion injury in vivo.

摘要

目的

本研究旨在确定钠/钙交换体(NCX)反向模式的选择性抑制剂KB-R7943(KBR)对麻醉犬顿抑心肌的心脏保护作用。

方法

将犬分为三组(每组n = 7),在左前降支冠状动脉(LAD)闭塞前15分钟,分别给予药物载体(C组)、低剂量KBR(5 mg·kg⁻¹静脉注射)(L组)或高剂量KBR(10 mg·kg⁻¹静脉注射)(H组)。所有犬均通过LAD闭塞15分钟和再灌注90分钟来制备顿抑心肌。用节段缩短率(%SS)评估局部心肌收缩力。

结果

再灌注90分钟时,H组的%SS恢复情况显著改善(为基线的70.8%±3.9%),而C组和L组的恢复情况较差(分别为基线的34.3%±2.8%和36.4%±5.4%)。各组局部心肌血流量无显著差异。KBR对冠状动脉或全身血流动力学无影响。

结论

结果表明,缺血前给予高剂量KBR可显著改善麻醉犬缺血再灌注后的心肌收缩功能障碍,表明KBR在体内可保护心肌免受缺血再灌注损伤。

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