一氧化氮合酶抑制剂可降低缺血再灌注模型中冠状窦的自由基浓度，并改善心肌顿抑。

Nitric oxide synthase inhibitors decrease coronary sinus-free radical concentration and ameliorate myocardial stunning in an ischemia-reperfusion model.

作者信息

Zhang Y, Bissing J W, Xu L, Ryan A J, Martin S M, Miller F J, Kregel K C, Buettner G R, Kerber R E

机构信息

Cardiovascular Center, University of Iowa, Iowa City, USA.

出版信息

J Am Coll Cardiol. 2001 Aug;38(2):546-54. doi: 10.1016/s0735-1097(01)01400-0.

DOI:10.1016/s0735-1097(01)01400-0

PMID:11499751

Abstract

OBJECTIVES

Our objective was to determine the effect of a nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NNA) on free radical generation and myocardial contractility after ischemia-reperfusion.

BACKGROUND

Cardiotoxic free radicals are generated by ischemia-reperfusion sequences. Nitric oxide reacts with superoxide radical to form peroxynitrite, which generates additional free radicals. Our hypothesis was that by inhibiting NO production, free radical formation will be diminished, which should be cardioprotective.

METHODS

We studied 32 dogs. Coronary occlusion-reperfusion (20 min each) sequences were created by intracoronary balloon angioplasty inflation-deflation. Using electron paramagnetic resonance, we monitored the coronary sinus concentration of ascorbate free radical (Asc*-), a measure of total oxidative flux. The L-NNA (4.8 mg/kg total) was infused intravenously during occlusion-reperfusion; control dogs received saline. Immunohistochemical staining demonstrated the peroxynitration product nitrotyrosine.

RESULTS

In the control dogs Asc*- rose from 3.2 +/- SD 0.5 nmol/l to 4.8 +/- 1.1 nmol/l with reperfusion, a 50% rise. With L-NNA the Asc*- rose from 3.2 +/- 0.9 nmol/l to 4.0 +/- 1.2 nmol/l, a 25% rise (p < 0.01, L-NNA vs. control). Echocardiographic left ventricular fractional area shortening (FAS) in the control dogs declined from 38 +/- 19% (baseline) to 26 +/- 14% (ischemia), and to 22 +/- 11% with reperfusion (p < 0.01 vs. baseline). With L-NNA, FAS declined from 36 +/- 13% (baseline) to 27 +/- 12% (ischemia) but then rose to 33 +/- 14 with reperfusion (p = NS vs. baseline). Nitrotyrosine was present in the myocardium subjected to ischemia-reperfusion, but almost absent in dogs receiving L-NNA. Myocardial perfusion was not altered by L-NNA.

CONCLUSIONS

The NO synthase inhibitors decrease coronary sinus free radical concentration and ameliorate myocardial stunning after ischemia-reperfusion.

摘要

目的

我们的目的是确定一氧化氮合酶抑制剂NG-硝基-L-精氨酸（L-NNA）对缺血再灌注后自由基生成和心肌收缩力的影响。

背景

心脏毒性自由基由缺血再灌注过程产生。一氧化氮与超氧阴离子反应形成过氧亚硝酸盐，后者会产生更多自由基。我们的假设是，通过抑制一氧化氮的产生，自由基的形成将减少，这应该具有心脏保护作用。

方法

我们研究了32只狗。通过冠状动脉内球囊血管成形术的充气-放气来建立冠状动脉闭塞-再灌注（各20分钟）序列。使用电子顺磁共振，我们监测了冠状窦中抗坏血酸自由基（Asc* -）的浓度，这是总氧化通量的一个指标。在闭塞-再灌注期间静脉输注L-NNA（总量4.8mg/kg）；对照犬接受生理盐水。免疫组织化学染色显示过氧亚硝化产物硝基酪氨酸。

结果

在对照犬中，再灌注时Asc* -从3.2±标准差0.5nmol/l升至4.8±1.1nmol/l，升高了50%。使用L-NNA时，Asc* -从3.2±0.9nmol/l升至4.0±1.2nmol/l，升高了25%（p<0.01，L-NNA与对照相比）。对照犬的超声心动图左心室面积缩短分数（FAS）从38±19%（基线）降至26±14%（缺血），再灌注时降至22±11%（与基线相比p<0.01）。使用L-NNA时，FAS从36±13%（基线）降至27±12%（缺血），但再灌注时升至33±14%（与基线相比p=无显著性差异）。硝基酪氨酸存在于经历缺血再灌注的心肌中，但在接受L-NNA的犬中几乎不存在。L-NNA未改变心肌灌注。