在缺血再灌注猪心脏中通过抑制Na(+)-H+交换实现心肌保护

Myocardial protection by Na(+)-H+ exchange inhibition in ischemic, reperfused porcine hearts.

作者信息

Klein H H, Pich S, Bohle R M, Wollenweber J, Nebendahl K

机构信息

Department of Cardiology, University of Marburg, Germany.

出版信息

Circulation. 1995 Aug 15;92(4):912-7. doi: 10.1161/01.cir.92.4.912.

DOI:10.1161/01.cir.92.4.912

PMID:7641374

Abstract

BACKGROUND

Studies in isolated myocytes and isolated heart preparations have suggested that Na(+)-H+ exchange is an important mechanism for myocardial ischemia-reperfusion injury. This study was undertaken to determine whether inhibition of Na(+)-H+ exchange limits infarct size and improves regional systolic shortening in regional ischemia and reperfusion in intact pigs.

METHODS AND RESULTS

The left anterior descending coronary artery was occluded in 18 anesthetized and thoracotomized pigs for 45 minutes and then reperfused for 24 hours. As main end points of this study, regional systolic shortening (sonomicrometry) and infarct size (percentage of infarcted to ischemic myocardium) were determined at the end of the experiments. Infarcted myocardium was assessed by histochemistry (tetrazolium stain) and by quantitative histology of one heart slice. The Na(+)-H+ exchange inhibitor Hoe 694 was administered intravenously at a dose of 3 mg/kg in 6 pigs each either 10 minutes before ischemia (group A) or 10 minutes before the onset of reperfusion (group B). Six pigs served as controls (group C). Treatment with Hoe 694 before ischemia decreased histochemical infarct size from 65 +/- 18% (control group) to 13 +/- 8% (P < .01) and histological infarct size from 49 +/- 20% (control group) to 14 +/- 4% (P < .01). Histochemical (55 +/- 19%) and histological (42 +/- 15%) infarct sizes of group B were insignificantly reduced by 15%. Myocardial protection in group A was associated with an attenuated contracture after 10 minutes of reperfusion and an improved regional systolic shortening after 24 hours of reperfusion (group A, 25 +/- 12%; control group, 6 +/- 5%; P = .01). These parameters remained unaffected in group B.

CONCLUSIONS

This study clearly demonstrates that Na(+)-H+ exchange is an important mechanism for cell death in myocardial ischemia and reperfusion in intact pigs; thus, inhibition of this exchange system may prove a promising new strategy in the clinical treatment of myocardial ischemia and reperfusion.

摘要

背景

对分离的心肌细胞和离体心脏标本的研究表明，钠氢交换是心肌缺血再灌注损伤的重要机制。本研究旨在确定抑制钠氢交换是否能限制梗死面积，并改善完整猪局部缺血和再灌注时的局部收缩期缩短。

方法与结果

18只麻醉开胸猪的左前降支冠状动脉闭塞45分钟，然后再灌注24小时。作为本研究的主要终点，在实验结束时测定局部收缩期缩短（超声微测法）和梗死面积（梗死心肌与缺血心肌的百分比）。通过组织化学（四氮唑染色）和对一片心脏切片进行定量组织学评估梗死心肌。6只猪在缺血前10分钟（A组）或再灌注开始前10分钟（B组）静脉注射3mg/kg剂量的钠氢交换抑制剂Hoe 694，每组6只猪。6只猪作为对照组（C组）。缺血前用Hoe 694治疗可使组织化学梗死面积从65±18%（对照组）降至13±8%（P<.01），组织学梗死面积从49±20%（对照组）降至14±4%（P<.01）。B组的组织化学梗死面积（55±19%）和组织学梗死面积（42±15%）仅减少15%，无显著差异。A组的心肌保护作用与再灌注10分钟后挛缩减轻以及再灌注24小时后局部收缩期缩短改善有关（A组，25±12%；对照组，6±5%；P=.01）。这些参数在B组中未受影响。