实验性心肌梗死后再灌注立即给予内皮素A受体拮抗剂对犬的瘢痕愈合无影响。

Endothelin A-receptor antagonist administration immediately after experimental myocardial infarction with reperfusion does not affect scar healing in dogs.

作者信息

Basso Cristina, Thiene Gaetano, Della Barbera Mila, Angelini Annalisa, Kirchengast Michael, Iliceto Sabino

机构信息

Institute of Pathological Anatomy, University of Padua Medical School, Via A. Gabelli 61, 35121 Padova, Italy.

出版信息

Cardiovasc Res. 2002 Jul;55(1):113-21. doi: 10.1016/s0008-6363(02)00340-1.

DOI:10.1016/s0008-6363(02)00340-1

PMID:12062714

Abstract

OBJECTIVE

Endothelin (ET) receptor antagonists have been reported to reduce both infarct size and no-reflow phenomenon; however, in rat models their effect on the healing process after myocardial infarction (MI) is controversial. The study aimed to evaluate the effect of early administration of the ET(A) receptor antagonist darusentan on scar healing in an ischemia-reperfusion model in dogs.

METHODS

Thirty male mongrel dogs surviving 180 min left anterior descending coronary artery balloon occlusion were randomised to: darusentan i.v. bolus-5 mg/kg 5 min before reperfusion-(group I); darusentan i.v. bolus+chronic oral-10 mg/kg/day-(group II); saline (group III). Five age-matched dogs served as controls (group IV). At 6 weeks weight, volume, mass/volume, wall thickness, thinning ratio and expansion index were assessed in the explanted hearts. Infarct size and scar area tissue composition were evaluated by computerized histomorphometry. Cellularity, vessels and TGFbeta in the scar area were scored by immunohistochemistry.

RESULTS

24 dogs (80%; 7 group I, 8 group II, 9 group III) developed an anterior MI, transmural in 15 and subendocardial in 9, mean size 11.5+/-4% of left ventricular area and 37+/-9% of left ventricular endocardial circumference. MIs were homogeneously distributed among the three groups regarding either infarct size or transmural extent. No differences were found in the three MI groups regarding thinning ratio, expansion index and scar area tissue characterization. Percent scar collagen content (37+/-17 vs. 53+/-20 vs. 46+/-14), myofibroblasts (1.2 vs. 1.3 vs. 1.4), macrophages (1.2+/-0.5 vs. 1.3+/-0.5 vs. 1.4+/-0.5), neovessels (2.8+/-0.4 vs. 2.6+/-0.5 vs. 2.9+/-0.3) and TGFbeta score (2 vs. 2.25 vs. 2.11) were not significantly different.

CONCLUSIONS

Early administration of the ET(A) receptor antagonist darusentan does not affect the scar healing process at 6 weeks after experimental MI with reperfusion in dogs.

摘要

目的

据报道，内皮素（ET）受体拮抗剂可减小梗死面积并减轻无复流现象；然而，在大鼠模型中，其对心肌梗死（MI）后愈合过程的影响存在争议。本研究旨在评估早期给予ET（A）受体拮抗剂达卢生坦对犬缺血再灌注模型瘢痕愈合的影响。

方法

30只在左冠状动脉前降支球囊闭塞180分钟后存活的雄性杂种犬被随机分为：再灌注前5分钟静脉推注5mg/kg达卢生坦（I组）；静脉推注达卢生坦+每日口服10mg/kg（II组）；生理盐水（III组）。5只年龄匹配的犬作为对照（IV组）。6周时，评估取出心脏的重量、体积、质量/体积、壁厚、变薄率和扩张指数。通过计算机组织形态计量学评估梗死面积和瘢痕区域组织组成。通过免疫组织化学对瘢痕区域的细胞性、血管和转化生长因子β进行评分。

结果

24只犬（80%；I组7只，II组8只，III组9只）发生前壁心肌梗死，其中透壁性梗死15只，心内膜下梗死9只，平均面积为左心室面积的11.5±4%和左心室心内膜周长的37±9%。在梗死面积或透壁程度方面，心肌梗死在三组中分布均匀。在三组心肌梗死组中，变薄率、扩张指数和瘢痕区域组织特征方面未发现差异。瘢痕胶原含量百分比（37±17对53±20对46±14）、肌成纤维细胞（1.2对1.3对1.4）、巨噬细胞（1.2±0.5对1.3±0.5对1.4±0.5）、新生血管（2.8±0.4对2.6±0.5对2.9±0.3）和转化生长因子β评分（2对2.25对2.11）无显著差异。