促红细胞生成素和粒细胞集落刺激因子联合治疗在猪急性心肌梗死模型中的作用。

Cytokine combination therapy with erythropoietin and granulocyte colony stimulating factor in a porcine model of acute myocardial infarction.

机构信息

Division of Cardiology, Department of Medicine, University of California, 505 Parnassus Avenue, L-523, Box 0103, San Francisco, CA 94143-0103, USA.

出版信息

Cardiovasc Drugs Ther. 2010 Dec;24(5-6):409-20. doi: 10.1007/s10557-010-6263-7.

DOI:10.1007/s10557-010-6263-7

PMID:20809214

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3051072/

Abstract

PURPOSE

Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.

METHODS

MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI.

RESULTS

At week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41 ± 1% vs. 33 ± 1%, p < 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.

CONCLUSION

Our findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF.

摘要

目的

促红细胞生成素（EPO）和粒细胞集落刺激因子（GCSF）作为心肌梗死后的新型治疗方法引起了关注，但它们在大型动物模型中的联合治疗效果尚未得到研究。我们在猪模型中研究了 EPO 和 GCSF 联合治疗对心肌梗死后心功能、梗死面积和血管密度的影响。

方法

通过左前降支冠状动脉 90 分钟球囊阻塞诱导猪发生心肌梗死。16 只动物接受 EPO+GCSF 治疗或生理盐水（对照组）治疗。在心肌梗死后 1、6 周通过超声心动图和压力-容积测量评估心功能。在心肌梗死后 6 周进行组织病理学检查。

结果

在第 6 周，EPO+GCSF 治疗稳定了左心室射血分数（41±1%比 33±1%，p<0.01），并改善了舒张功能。与对照组相比，EPO+GCSF 治疗组可见更多的存活心肌和血管密度。尽管有这些令人鼓舞的结果，但在一项将联合治疗与 EPO 或 GCSF 单药治疗进行比较的历史分析中，联合治疗在 LVEF 和容积随时间的变化方面并没有显著的附加益处。