Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs
Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs
复制标题
DOI：
10.1016/j.jacc.2006.04.008
复制
发表时间：
2006-07-04
影响因子：
24
通讯作者：
Hori, Masatsugu
中科院分区：
文献类型：
--
作者：
Hirata, Akio;Minammo, Tetsuo;Hori, Masatsugu
目的 我们研究促红细胞生成素 (EPO) 对心肌梗死 (MI) 后新生血管和心功能的影响。 背景 促红细胞生成素发挥抗凋亡作用并动员内皮祖细胞 (EPC)。 方法 我们静脉注射 EPO (1,000 IU/kg) 立即[EPO(0)组]、6 h[EPO(6h)组]、或狗冠状动脉永久结扎后1周[EPO(1wk)组]。对照动物在结扎后立即接受生理盐水。 结果 MI后6小时，EPO(0)组的梗塞面积明显小于对照组(61.5+/-6.0%对22.9+/-2.2%)。 MT后1周，EPO(0)组和EPO(6h)组循环CD34阳性单核细胞数均显着高于对照组。在缺血区，MI后4周EPO(0)组和EPO(6h)组的毛细血管密度和心肌血流量均显着高于对照组。 MI后4周，EPO(6h)组左心室(LV)射血分数(48.6+/-1.9%)显着高于对照组(41.9+/-0.9%)或EPO(1wk)(42.6+/-1.2%)组，但显着低于EPO(0)组(56.1+/-2.3%)。 MI后4周，EPO(0)组和EPO(6h)组的左室舒张末压均显着低于对照组或EPO(1wk)组。血液学参数在各组之间没有差异。 结论 除了其急性梗塞面积限制作用外，EPO 可能通过 EPC 动员增强新血管形成，并改善慢性期的心功能障碍，尽管它有时间窗限制。
OBJECTIVES We investigated the effects of erythropoietin (EPO) on neovascularization and cardiac function after myocardial infarction (MI).BACKGROUND Erythropoietin exerts antiapoptotic effects and mobilizes endothelial progenitor cells (EPCs).METHODS We intravenously administered EPO (1,000 IU/kg) immediately [EPO(0) group], 6 h [EPO(6h) group], or 1 week [EPO(1wk) group] after the permanent ligation of the coronary artery in dogs. Control animals received saline immediately after the ligation.RESULTS The infarct size 6 h after MI was significantly smaller in the EPO(0) group than in the control group (61.5 +/- 6.0% vs. 22.9 +/- 2.2%). One week after MT, the circulating CD34-positive mononuclear cell numbers in both the EPO(0) and the EPO(6h) groups were significantly higher than in the control group. In the ischemic region, the capillary density and myocardial blood flow 4 weeks after MI was significantly higher in both the EPO(0) and the EPO(6h) groups than in the control group. Four weeks after MI, left ventricular (LV) ejection fraction in the EPO(6h) (48.6 +/- 1.9%) group was significantly higher than that in either the control (41.9 +/- 0.9%) or the EPO(1wk) (42.6 +/- 1.2%) group but significantly lower than that in the EPO(0) group (56.1 +/- 2.3%). The LV end-diastolic pressure 4 weeks after MI in both the EPO(0) and the EPO(6h) groups was significantly lower than either the control or the EPO(1wk) group. Hematologic parameters did not differ among the groups.CONCLUSIONS In addition to its acute infarct size-limiting effect, EPO enhances neovascularization, likely via EPC mobilization, and improves cardiac dysfunction in the chronic phase, although it has time-window limitations.