Furlani D, Klopsch C, Gäbel R, Ugurlucan M, Pittermann E, Klee D, Wagner K, Li W, Wang W, Ong L L, Nizze H, Titze U, Lützow K, Lendlein A, Steinhoff G, Ma N
Department of Cardiac Surgery, University of Rostock, Rostock, Germany.
Transplant Proc. 2008 May;40(4):962-6. doi: 10.1016/j.transproceed.2008.03.033.
Systemic administration of erythropoietin (Epo) protects the myocardium from an ischemic insult and promotes beneficial remodeling. We hypothesized that intracardiac injection of Epo may exhibit cardioprotective potential with reduced systemic toxicity. Following myocardial infarction (MI), Epo was injected directly into the border of the infarction. Six weeks after an MI, we evaluated infarction size, angiogenesis, and pathologic effects of the treatment. Myocardial performance was assessed with a Forced Swim Test adapted to the study. Anti-inflammatory and cellular proliferative effects of Epo were analyzed by measuring expression of integrin-beta and CdK4 by reverse transcriptase-polymerase chain reaction (RT-PCR). The findings indicated improved cardiac status with direct Epo administration. Exercise capacity detected by the Forced Swim Test was significantly increased. There was radical reduction of absolute infarction size, ventricular dilatation, and hypertrophy in the Epo group. Integrin-beta was down-regulated and CdK4 expression was increased significantly with Epo. In conclusion, the study demonstrated that intramyocardial Epo injection, following MI, reduced inflammation, enhanced angiogenesis and proliferation, improved myocardial functions, and did not lead to intramural thrombus formation.
全身性给予促红细胞生成素(Epo)可保护心肌免受缺血性损伤,并促进有益的重塑。我们推测心内注射Epo可能具有心脏保护潜力且全身毒性降低。心肌梗死(MI)后,将Epo直接注射到梗死边缘。MI六周后,我们评估了梗死面积、血管生成及治疗的病理效应。采用适合该研究的强迫游泳试验评估心肌性能。通过逆转录聚合酶链反应(RT-PCR)测量整合素β和细胞周期蛋白依赖性激酶4(CdK4)的表达,分析Epo的抗炎和细胞增殖作用。结果表明,直接给予Epo可改善心脏状态。强迫游泳试验检测到的运动能力显著提高。Epo组的绝对梗死面积、心室扩张和肥大明显减少。Epo可使整合素β下调,CdK4表达显著增加。总之,该研究表明,MI后心肌内注射Epo可减轻炎症、增强血管生成和增殖、改善心肌功能,且不会导致壁内血栓形成。