Prunier F, Pottier P, Clairand R, Mercier A, Hajjar R J, Planchon B, Furber A
Protection et remodelage du myocarde, UPRES EA 3860, Faculté de Médecine et Centre Hospitalier Universitaire, rue Haute de Reculée, Angers Cedex 1, France.
Cardiology. 2009;112(2):129-34. doi: 10.1159/000142723. Epub 2008 Jul 3.
Whereas administration of erythropoietin (EPO) acutely after myocardial infarction (MI) reduces infarct size and chronic EPO therapy attenuates post-MI remodeling, the safety of chronic EPO therapy following MI is unknown. Therefore, we examined the thrombogenic effects of a chronic EPO therapy after MI.
Rats underwent coronary occlusion followed by reperfusion. They were assigned to one of the following groups: EPO-A, single injection of EPO 5,000 U/kg at the time of reperfusion; EPO-C, injection of EPO 5,000 U/kg at the time of reperfusion followed by 300 U/kg/week; PBS-C, injection of vehicle only. After eight weeks of treatment they were exposed to a validated prethrombotic test based on partial stenosis of the inferior vena cava.
As compared to the rats receiving vehicle only, the rats treated with EPO exhibited a significant reduction in MI size (28.7 +/- 2.1% and 25.8 +/- 1.9 vs. 39.8 +/- 3.0% in EPO-A, EPO-C and PBS-C, respectively; p < 0.05). Whereas the hematocrit was significantly increased in EPO-C (59.7 +/- 2.0% vs. 44.7 +/- 0.9% in EPO-A, p < 0.001), the proportion of rats in which a thrombus occurred was similar in all groups (p = 0.52).
Chronic EPO therapy added to the single high dose of EPO injected acutely did not induce venous pro-thrombotic effect in rats.
心肌梗死(MI)后急性给予促红细胞生成素(EPO)可减小梗死面积,而慢性EPO治疗可减轻MI后的重塑,但MI后慢性EPO治疗的安全性尚不清楚。因此,我们研究了MI后慢性EPO治疗的血栓形成作用。
对大鼠进行冠状动脉闭塞并再灌注。将它们分为以下几组:EPO-A组,再灌注时单次注射5000 U/kg EPO;EPO-C组,再灌注时注射5000 U/kg EPO,随后每周注射300 U/kg;PBS-C组,仅注射赋形剂。治疗八周后,对它们进行基于下腔静脉部分狭窄的有效血栓前测试。
与仅接受赋形剂的大鼠相比,接受EPO治疗的大鼠梗死面积显著减小(EPO-A组为28.7±2.1%,EPO-C组为25.8±1.9%,PBS-C组为39.8±3.0%;p<0.05)。虽然EPO-C组的血细胞比容显著升高(59.7±2.0%,而EPO-A组为44.7±0.9%,p<0.001),但所有组中出现血栓的大鼠比例相似(p = 0.52)。
在急性单次注射高剂量EPO的基础上增加慢性EPO治疗,不会在大鼠中诱导静脉血栓前效应。