Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine
Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine
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DOI：
10.1007/s00540-010-0948-8
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发表时间：
2010-08-01
影响因子：
2.8
通讯作者：
Sumikawa, Koji
中科院分区：
文献类型：
--
作者：
Akiyama, Daiji;Hara, Tetsuya;Sumikawa, Koji
中性粒细胞弹性蛋白酶抑制剂是否能有效减轻心肌缺血/再灌注损伤仍存在争议。因此，我们研究了中性粒细胞弹性蛋白酶抑制剂sivelestat对心肌顿抑的可能保护作用，即，实验分为对照组（C组）、西维来司他低剂量组（L组）和西维来司他高剂量组（H组），每组7只。结扎冠状动脉左前降支（LAD）造成心肌缺血12 min，再灌注90 min。L组和H组在再灌注期间分别以6和60 mg/ml的浓度冠状动脉内输注西维来司特，而C组则输注生理盐水。心率（HR）、左室发展压（LVdP）、LVdP最大速率（LVdP/dt（max））、LV舒张末期压（LVEDP）、节段缩短百分比（%SS，局部心肌收缩力指数），在缺血诱导前和再灌注过程中测定LAD灌注区冠状静脉血IL-6浓度，缺血/再灌注损伤对HR无明显影响，各组的LVdP、LVdP/dt（max）和LVEDP。C组LAD灌注区%SS明显降低，IL-6浓度明显升高。在L组和H组中，%SS和白细胞介素-6浓度的这些变化均大大减弱，但未被阻止。西维来司他可能通过抑制嗜中性粒细胞衍生的弹性蛋白酶，从而抑制活化的中性粒细胞中白细胞介素-6的产生，来减弱由于心肌顿抑引起的心肌收缩功能障碍。
It seems controversial whether or not neutrophil elastase inhibitors are effective in attenuating myocardial ischemia/reperfusion injury. We thus investigated possible protective effects of sivelestat, a neutrophil elastase inhibitor, against myocardial stunning i.e., prolonged myocardial dysfunction following a brief episode of ischemia.Swine were divided into control group (group C), low-dose sivelestat group (group L), and high-dose sivelestat group (group H) (n = 7 for each group). All the swine were subjected to myocardial ischemia through ligation of the left anterior descending (LAD) coronary artery for 12-min, followed by 90-min reperfusion. Sivelestat was infused intracoronally at concentrations of 6 and 60 mg/ml throughout the reperfusion period in groups L and H, respectively, while saline was infused in the group C. Heart rate (HR), left ventricular developed pressure (LVdP), maximum rate of LVdP (LVdP/dt (max)), LV end-diastolic pressure (LVEDP), percentage of segment shortening (%SS, an index of regional myocardial contractility), and coronary venous interleukin-6 concentration in the LAD perfusion area were measured before ischemic induction and during reperfusion.The ischemia/reperfusion insult did not cause any significant changes in HR, LVdP, LVdP/dt (max), and LVEDP in all groups. However, it significantly reduced %SS in the LAD perfusion area and increased the interleukin-6 concentration in group C. Those changes in %SS and the interleukin-6 concentration were both greatly attenuated, but not prevented, in groups L and H.Sivelestat presumably attenuates myocardial contractile dysfunction due to myocardial stunning by inhibiting neutrophil-derived elastase, thereby suppressing the production of interleukin-6 in activated neutrophils.