Krause Korff T, Jaquet Kai, Geidel Stephan, Schneider Carsten, Mandel Christina, Stoll Hans-Peter, Hertting Klaus, Harle Tobias, Kuck Karl-Heinz
Cardiology, St. Georg Hospital, Hamburg, Germany.
Eur J Heart Fail. 2006 Aug;8(5):443-50. doi: 10.1016/j.ejheart.2005.10.017. Epub 2006 Feb 7.
Apart from its well-known stimulation of erythropoiesis, erythropoietin (EPO) exhibits angiogenic and anti-apoptotic effects. These cellular protective effects have also been described in experimental acute myocardial infarction models. We investigated the effects of EPO in a porcine model of chronic progressive myocardial ischaemia.
At weeks 2 and 6 after implantation of a circumflex ameroid constrictor, endocardial electromechanical NOGA system (Biosense Webster, Inc., California, USA) mapping of the left ventricle, coronary and ventricular angiography, as well as echocardiography were performed. Two weeks after ameroid placement, 13 pigs were randomized with 7 pigs receiving 10.000 U EPO and 6 pigs receiving placebo into the ischaemic region using a NOGA guided percutaneous transendocardial injection catheter, MYOSTAR. After 6 weeks, histology (Masson's Trichrome) was analyzed.
Endocardial electromechanical mapping showed an increase of mean unipolar voltage (UV) amplitude in the ischaemic myocardial segments in the EPO-treated animals (8.5 mV pre and 10.6 mV post treatment) and a significantly reduced ischaemic surface area compared to the control group (19% vs. 41%) suggesting a decline in ischaemic injury. Echocardiography revealed 2,2 hypokinetic segments of the lateral wall in the EPO group vs. 3,3 in the control groups. The mean ejection fraction was 64% in the EPO group and 55% in the placebo group. Quantitative histological analysis of the ischaemic regions revealed a reduction of myocardial fibrosis (8% vs. 28%) in the EPO group.
Endocardial EPO injection may induce cardioprotective effects in hibernating myocardium and may attenuate the progression of ischaemic tissue damage.
除了其众所周知的对红细胞生成的刺激作用外，促红细胞生成素（EPO）还具有血管生成和抗凋亡作用。这些细胞保护作用在实验性急性心肌梗死模型中也有描述。我们研究了EPO在猪慢性进行性心肌缺血模型中的作用。
在植入回旋支类淀粉样变缩窄器后第2周和第6周，使用心内膜机电NOGA系统（美国加利福尼亚州Biosense Webster公司）对左心室进行标测、冠状动脉和心室血管造影以及超声心动图检查。在放置类淀粉样变缩窄器两周后，13头猪被随机分组，7头猪接受10000 U EPO，6头猪接受安慰剂，通过NOGA引导的经皮心内膜注射导管MYOSTAR将药物注射到缺血区域。6周后，进行组织学（Masson三色染色法）分析。
心内膜机电标测显示，EPO治疗组动物缺血心肌节段的平均单极电压（UV）幅度增加（治疗前为8.5 mV，治疗后为10.6 mV），与对照组相比，缺血表面积显著减小（19%对41%），提示缺血损伤减轻。超声心动图显示，EPO组侧壁有2.2个运动减弱节段，而对照组有3.3个。EPO组的平均射血分数为64%，安慰剂组为55%。对缺血区域的定量组织学分析显示，EPO组心肌纤维化减少（8%对28%）。
心内膜注射EPO可能对冬眠心肌产生心脏保护作用，并可能减轻缺血组织损伤的进展。
