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碱性成纤维细胞生长因子增强 CorMatrix-ECM 生物材料修复心外膜梗死可减轻缺血性心脏重构。

Epicardial infarct repair with basic fibroblast growth factor-enhanced CorMatrix-ECM biomaterial attenuates postischemic cardiac remodeling.

机构信息

Campbell Cardiovascular Translational Research Program, Division of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.

Campbell Cardiovascular Translational Research Program, Division of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.

出版信息

J Thorac Cardiovasc Surg. 2014 May;147(5):1650-9. doi: 10.1016/j.jtcvs.2013.08.005. Epub 2013 Sep 26.

Abstract

OBJECTIVES

Dysregulation of extracellular matrix (ECM) following myocardial infarction is a key contributor to myocardial fibrosis, chamber dilation, and progression to heart failure. Basic fibroblast growth factor is a potent inhibitor of fibrosis. We propose a novel surgical procedure leveraging a commercially available ECM biomaterial for the treatment of ischemic heart failure.

METHODS

Epicardial infarct repair using CorMatrix-ECM biomaterial patch (CorMatrix Cardiovascular Inc, Roswell, Ga) was compared with sham in a rat myocardial infarction model. Key indices of ischemic remodeling, including inflammation, fibrosis, and myocardial performance were evaluated 16 weeks post-treatment.

RESULTS

Histology and immunohistochemistry demonstrated comprehensive integration of CorMatrix-ECM biomaterial patch without evidence of immune reaction and an increase in basic fibroblast growth factor expression in treated animals. Functional analysis by serial echocardiography of normal (n = 13), sham (n = 15), nonenhanced CorMatrix-ECM patch (n = 18), and basic fibroblast growth factor-enhanced CorMatrix-ECM patch (n = 10) animals revealed an improvement in ejection fraction in basic fibroblast growth factor-enhanced CorMatrix-ECM patch animals compared with shams (55.3% ± 8.0% vs 35.1% ± 7.6%; P < .001). Prevention of left ventricle remodeling was also confirmed by pressure volume loop analysis, which demonstrated reduced left ventricular end diastolic volumes in basic fibroblast growth factor-enhanced CorMatrix-ECM patch animals (n = 5) compared with shams (n = 6) (208.0 ± 59.3 μL vs 363. 1 ± 108.7 μL; P < .01) and improved left ventricle contractility in nonenhanced CorMatrix-ECM patch (n = 7) and basic fibroblast growth factor-enhanced CorMatrix-ECM patch animals compared with shams (0.709 ± 0.306 and 0.609 ± 0.160 vs 0.437 ± 0.218; P < .05).

CONCLUSIONS

Epicardial infarct repair with basic growth factor-enhanced CorMatrix-ECM biomaterial patch attenuates myocardial remodeling and improves cardiac performance after subacute myocardial infarction in a rat coronary ligation model. These observations establish proof-of-concept for this novel surgical approach.

摘要

目的

心肌梗死后细胞外基质(ECM)的失调是心肌纤维化、心室扩张和心力衰竭进展的关键因素。碱性成纤维细胞生长因子是纤维化的有效抑制剂。我们提出了一种利用商业 ECM 生物材料治疗缺血性心力衰竭的新手术方法。

方法

在大鼠心肌梗死模型中,比较了经心外膜梗死修复使用 CorMatrix-ECM 生物材料补片(CorMatrix Cardiovascular Inc,Roswell,Ga)与假手术。治疗后 16 周评估缺血性重构的关键指标,包括炎症、纤维化和心肌功能。

结果

组织学和免疫组织化学显示 CorMatrix-ECM 生物材料补片的全面整合,没有免疫反应的证据,并且在治疗动物中碱性成纤维细胞生长因子的表达增加。通过对正常(n=13)、假手术(n=15)、未经增强的 CorMatrix-ECM 补片(n=18)和经碱性成纤维细胞生长因子增强的 CorMatrix-ECM 补片(n=10)动物的连续超声心动图进行功能分析,发现与假手术相比,碱性成纤维细胞生长因子增强的 CorMatrix-ECM 补片动物的射血分数有所改善(55.3%±8.0%vs35.1%±7.6%;P<0.001)。压力-容积环分析也证实了左心室重构的预防,结果显示碱性成纤维细胞生长因子增强的 CorMatrix-ECM 补片动物的左心室舒张末期容积减少(n=5)与假手术相比(n=6)(208.0±59.3μL vs 363.1±108.7μL;P<0.01),未经增强的 CorMatrix-ECM 补片(n=7)和碱性成纤维细胞生长因子增强的 CorMatrix-ECM 补片动物的左心室收缩力增强与假手术相比(0.709±0.306 和 0.609±0.160 vs 0.437±0.218;P<0.05)。

结论

在大鼠冠状动脉结扎模型中,用碱性成纤维细胞生长因子增强的 CorMatrix-ECM 生物材料补片进行心外膜梗死修复可减轻亚急性心肌梗死后的心肌重构,改善心脏功能。这些观察结果为这种新的手术方法提供了初步的证据。

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