硫化氢疗法可减轻猪心肌缺血/再灌注损伤模型中的炎症反应。
Hydrogen sulfide therapy attenuates the inflammatory response in a porcine model of myocardial ischemia/reperfusion injury.
作者信息
Sodha Neel R, Clements Richard T, Feng Jun, Liu Yuhong, Bianchi Cesario, Horvath Eszter M, Szabo Csaba, Stahl Gregory L, Sellke Frank W
机构信息
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass., USA.
出版信息
J Thorac Cardiovasc Surg. 2009 Oct;138(4):977-84. doi: 10.1016/j.jtcvs.2008.08.074. Epub 2009 Jun 13.
INTRODUCTION
Hydrogen sulfide is produced endogenously in response to myocardial ischemia and thought to be cardioprotective. The mechanism underlying this protection has yet to be fully elucidated, but it may be related to sulfide's ability to limit inflammation. This study investigates the cardioprotection provided by exogenous hydrogen sulfide and its potential anti-inflammatory mechanism of action.
METHODS
The mid left anterior descending coronary artery in 14 Yorkshire swine was acutely occluded for 60 minutes, followed by reperfusion for 120 minutes. Controls (n = 7) received placebo, and treatment animals (n = 7) received sulfide 10 minutes before and throughout reperfusion. Hemodynamic and functional measurements were obtained. Evans blue and triphenyl tetrazolium chloride staining identified the area at risk and infarction. Coronary microvascular reactivity was assessed. Tissue was assayed for myeloperoxidase activity and proinflammatory cytokines.
RESULTS
Pre-ischemia/reperfusion hemodynamics were similar between groups, whereas post-ischemia/reperfusion mean arterial pressure was reduced by 28.7 +/- 5.0 mm Hg in controls versus 6.7 +/- 6.2 mm Hg in treatment animals (P = .03). Positive first derivative of left ventricular pressure over time was reduced by 1325 +/- 455 mm Hg/s in controls versys 416 +/- 207 mm Hg/s in treatment animals (P = .002). Segmental shortening in the area at risk was better in treatment animals. Infarct size (percent of area at risk) in controls was 41.0% +/- 7.8% versus 21.2% +/- 2.5% in the treated group (P = .036). Tissue levels of interleukin 6, interleukin 8, tumor necrosis factor-alpha, and myeloperoxidase activity decreased in the treatment group. Treated animals demonstrated improved microvascular reactivity.
CONCLUSIONS
Therapeutic sulfide provides protection in response to ischemia/reperfusion injury, improving myocardial function, reducing infarct size, and improving coronary microvascular reactivity, potentially through its anti-inflammatory properties. Exogenous sulfide may have therapeutic utility in clinical settings in which ischemia/reperfusion injury is encountered.
引言
硫化氢是心肌缺血时内源性产生的，被认为具有心脏保护作用。这种保护作用的潜在机制尚未完全阐明，但可能与硫化物限制炎症的能力有关。本研究探讨外源性硫化氢提供的心脏保护作用及其潜在的抗炎作用机制。
方法
对14只约克夏猪的左冠状动脉前降支中段进行急性闭塞60分钟，随后再灌注120分钟。对照组（n = 7）接受安慰剂，治疗组动物（n = 7）在再灌注前10分钟及整个再灌注过程中接受硫化物。进行血流动力学和功能测量。伊文思蓝和氯化三苯基四氮唑染色确定危险区域和梗死面积。评估冠状动脉微血管反应性。检测组织中的髓过氧化物酶活性和促炎细胞因子。
结果
缺血/再灌注前血流动力学在两组间相似，而缺血/再灌注后对照组平均动脉压降低28.7±5.0 mmHg，治疗组动物为6.7±6.2 mmHg（P = 0.03）。对照组左心室压力随时间的一阶导数降低1325±455 mmHg/s，治疗组动物为416±207 mmHg/s（P = 0.002）。治疗组动物危险区域的节段缩短情况更好。对照组梗死面积（危险区域的百分比）为41.0%±7.8%，治疗组为21.2%±2.5%（P = 0.036）。治疗组组织中白细胞介素6、白细胞介素8、肿瘤坏死因子-α水平及髓过氧化物酶活性降低。治疗组动物的微血管反应性得到改善。
结论
治疗性硫化物对缺血/再灌注损伤具有保护作用，可改善心肌功能，减小梗死面积，改善冠状动脉微血管反应性，可能是通过其抗炎特性实现的。外源性硫化物在遭遇缺血/再灌注损伤的临床环境中可能具有治疗作用。
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