Lipsic Erik, Westenbrink B Daan, van der Meer Peter, van der Harst Pim, Voors Adriaan A, van Veldhuisen Dirk J, Schoemaker Regien G, van Gilst Wiek H
Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
Eur J Heart Fail. 2008 Jan;10(1):22-9. doi: 10.1016/j.ejheart.2007.10.008.
Erythropoietin (EPO) may improve cardiac function and induce neovascularisation in experimental models of chronic heart failure (CHF). However, the increased haematocrit associated with EPO treatment might exert concomitant deleterious effects.
To investigate the haematocrit independent effects of EPO on cardiac function.
Rats underwent permanent coronary artery ligation to induce myocardial infarction (MI) or sham surgery. Three weeks after MI, rats were randomly allocated to treatment with vehicle (MI) or the long-acting EPO analogue darbepoetin alfa administered in a high (40 microg/kg/3 weeks, MI-EPO-high) or a low-dose (0.4 microg/kg/3 weeks, MI-EPO-low). After 9 weeks, haemodynamic parameters, myocardial histology and Myosin Heavy Chain (MHC) isoforms were determined. High-dose EPO resulted in a significant increase in haematocrit (p<0.01) while low-dose EPO had no effect on haematocrit levels. EPO significantly improved cardiac function in both EPO groups, reflected by increased left ventricular (LV)-developed pressure and improved contractility (dP/dt(max)) and relaxation (dP/dt(min)) indices of the LV at 9-weeks (all p<0.05 compared to MI). The improved cardiac function was associated with increased capillary growth (38% in MI-EPO-high (p<0.01) and 27% in MI-EPO-low (p<0.05)) and an attenuated switch to slow beta-MHC isoforms in both EPO groups.
EPO improves cardiac function and induces neovascularisation at a dose that does not increase haematocrit, thereby circumventing the possible deleterious effects of increased erythropoiesis.
在慢性心力衰竭（CHF）实验模型中，促红细胞生成素（EPO）可能改善心脏功能并诱导新血管形成。然而，与EPO治疗相关的血细胞比容升高可能会产生伴随的有害影响。
研究EPO对心脏功能的血细胞比容独立效应。
大鼠接受永久性冠状动脉结扎以诱导心肌梗死（MI）或假手术。MI后3周，将大鼠随机分配接受载体治疗（MI组）或长效EPO类似物达贝泊汀α高剂量（40μg/kg/3周，MI-EPO-high）或低剂量（0.4μg/kg/3周，MI-EPO-low）治疗。9周后，测定血流动力学参数、心肌组织学和肌球蛋白重链（MHC）亚型。高剂量EPO导致血细胞比容显著升高（p<0.01），而低剂量EPO对血细胞比容水平无影响。EPO在两个EPO组中均显著改善心脏功能，表现为左心室（LV）舒张末压升高，9周时LV的收缩性（dP/dt(max)）和舒张性（dP/dt(min)）指标改善（与MI组相比，所有p<0.05）。心脏功能的改善与毛细血管生长增加相关（MI-EPO-high组增加38%（p<0.01），MI-EPO-low组增加27%（p<0.05）），并且两个EPO组中向慢β-MHC亚型的转换减弱。
EPO以不增加血细胞比容的剂量改善心脏功能并诱导新血管形成，从而规避了红细胞生成增加可能产生的有害影响。
