Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts.
Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts.
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DOI：
10.1186/cc6913
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Becker BF
中科院分区：
文献类型：
--
作者：
Bruegger D;Rehm M;Jacob M;Chappell D;Stoeckelhuber M;Welsch U;Conzen P;Becker BF
缺血后对冠状动脉血管内皮细胞的损伤，尤其是内皮细胞的糖基化反应，可能会引起液体外渗。在再灌流过程中遇到的氧化还原应激触发了糖萼的脱落，应通过自由基清除剂一氧化氮(NO)来缓解。本研究的目的是探讨再灌流期间外源性NO对冠脉内皮细胞和血管完整性的影响。豚鼠心脏热缺血15min，再灌流20min，对照组(对照组)和4-μ-M-NO组(NO组)。在进一步的实验中，用肝素酶降解内皮细胞，然后再灌注，不加(HEP组)和有NO(HEP+NO组)。缺血再灌流对血管内皮细胞的糖基化损伤严重。在NO存在的情况下，硫酸乙酰肝素的脱落和电子显微镜评估的损伤较少。与基线相比，对照组、HEP组和HEP+NO组缺血后冠脉液体外渗量增加，而NO组几乎没有变化。在这组患者中，组织水肿明显减轻。冠脉血管阻力在再灌流期间增加了25%至30%，但在应用NO时不会增加，无论糖基化状态如何。四组急性缺血后心肌乳酸释放量相似，而腺核苷酸分解代谢物释放量在NO组减少42%。冠状静脉血尿酸是一种有效的抗氧化剂和过氧亚硝酸盐的清除剂，在缺血后注入NO的过程中，尿酸的水平反而下降。NO在缺血再灌流中的心脏保护作用包括防止冠脉血管渗漏和间质水肿，以及阻止NO复流和血管内皮细胞的降解。
Postischemic injury to the coronary vascular endothelium, in particular to the endothelial glycocalyx, may provoke fluid extravasation. Shedding of the glycocalyx is triggered by redox stress encountered during reperfusion and should be alleviated by the radical scavenger nitric oxide (NO). The objective of this study was to investigate the effect of exogenous administration of NO during reperfusion on both coronary endothelial glycocalyx and vascular integrity. Isolated guinea pig hearts were subjected to 15 minutes of warm global ischemia followed by 20 minutes of reperfusion in the absence (Control group) and presence (NO group) of 4 μM NO. In further experiments, the endothelial glycocalyx was enzymatically degraded by means of heparinase followed by reperfusion without (HEP group) and with NO (HEP+NO group). Ischemia and reperfusion severely damaged the endothelial glycocalyx. Shedding of heparan sulfate and damage assessed by electron microscopy were less in the presence of NO. Compared with baseline, coronary fluid extravasation increased after ischemia in the Control, HEP, and HEP+NO groups but remained almost unchanged in the NO group. Tissue edema was significantly attenuated in this group. Coronary vascular resistance rose by 25% to 30% during reperfusion, but not when NO was applied, irrespective of the state of the glycocalyx. Acute postischemic myocardial release of lactate was comparable in the four groups, whereas release of adenine nucleotide catabolites was reduced 42% by NO. The coronary venous level of uric acid, a potent antioxidant and scavenger of peroxynitrite, paradoxically decreased during postischemic infusion of NO. The cardioprotective effect of NO in postischemic reperfusion includes prevention of coronary vascular leak and interstitial edema and a tendency to forestall both no-reflow and degradation of the endothelial glycocalyx.