促红细胞生成素通过信号转导保护大鼠线粒体生物能量功能促进室颤复律。
Erythropoietin facilitates resuscitation from ventricular fibrillation by signaling protection of mitochondrial bioenergetic function in rats.
机构信息
Department of Medicine and Resuscitation Institute at Rosalind Franklin University of Medicine and Science 3333 Green Bay Road, North Chicago, Illinois 60064, USA.
出版信息
Am J Transl Res. 2013 Apr 19;5(3):316-26. Print 2013.
OBJECTIVE
We previously reported beneficial myocardial effects during chest compression after administration of high-dose erythropoietin. We hypothesized that erythropoietin also elicits post-resuscitation myocardial benefits partly linked to protection of mitochondrial bioenergetic function.
METHODS
Two series of 10 rats each underwent ventricular fibrillation for 10 minutes (series-1) and 8 minutes (series-2) and were randomized to erythropoietin (5,000 U/kg) or 0.9% NaCl before chest compression. Dobutamine was infused post-resuscitation in series-2 harvesting their hearts at 120 minutes.
RESULTS
During chest compression, a statistically insignificant trend showing progressively higher coronary perfusion pressure in the erythropoietin group was observed consistent with previously reported preservation of left ventricular distensibility. Post-resuscitation, in the absence of dobutamine (series-1) erythropoietin failed to improve post-resuscitation myocardial function or survival; in the presence of dobutamine (series-2) all rats survived and those treated with erythropoietin reversed post-resuscitation myocardial dysfunction yielding higher cardiac work index (CWI; 39±3 vs 25±10 mmHg·ml/kg, p<0.01) and higher mean aortic pressure (MAP; 99±4 vs 83±16, p<0.01) at 120 minutes post-resuscitation. Better myocardial function was associated with lesser increases in plasma cytochrome c, attaining levels which inversely correlated with CWI (p=0.026) and MAP (p=0.025). Hearts from erythropoietin-treated rats had higher phosphorylation levels of cytosolic Akt and higher phosphorylation levels of cytosolic and mitochondrial PKCε and maintained cytochrome c oxidase activity.
CONCLUSION
Erythropoietin activated mitochondrial protective mechanisms that helped maintain bioenergetic function enabling reversal of post-resuscitation myocardial dysfunction in the presence of dobutamine.
目的
我们之前报道了在给予大剂量促红细胞生成素后进行胸部按压时有益的心肌效应。我们假设促红细胞生成素还会引起复苏后心肌获益，部分与保护线粒体生物能功能有关。
方法
两系列各 10 只大鼠均经历心室颤动 10 分钟（系列 1）和 8 分钟（系列 2），并在胸部按压前随机分为促红细胞生成素（5000 U/kg）或 0.9%生理盐水组。在系列 2 中，在复苏后给予多巴酚丁胺，并在 120 分钟时收获心脏。
结果
在胸部按压期间，观察到促红细胞生成素组的冠状动脉灌注压呈统计学上的显著升高趋势，这与先前报道的左心室伸展性保存一致。在没有多巴酚丁胺的情况下（系列 1），复苏后，促红细胞生成素未能改善复苏后的心肌功能或存活率；在存在多巴酚丁胺的情况下（系列 2），所有大鼠均存活，且接受促红细胞生成素治疗的大鼠逆转了复苏后的心肌功能障碍，产生更高的心脏做功指数（CWI；39±3 对 25±10 mmHg·ml/kg，p<0.01）和更高的平均主动脉压（MAP；99±4 对 83±16，p<0.01）在复苏后 120 分钟时。更好的心肌功能与血浆细胞色素 c 的增加幅度较小有关，达到了与 CWI（p=0.026）和 MAP（p=0.025）呈反比的水平。接受促红细胞生成素治疗的大鼠心脏具有更高的细胞质 Akt 磷酸化水平，以及更高的细胞质和线粒体 PKCε 磷酸化水平，并维持细胞色素 c 氧化酶活性。
结论
促红细胞生成素激活了线粒体保护机制，有助于在存在多巴酚丁胺的情况下维持生物能功能，从而逆转复苏后的心肌功能障碍。
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