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小鼠心肌梗死与重塑:再灌注的影响

Myocardial infarction and remodeling in mice: effect of reperfusion.

作者信息

Michael L H, Ballantyne C M, Zachariah J P, Gould K E, Pocius J S, Taffet G E, Hartley C J, Pham T T, Daniel S L, Funk E, Entman M L

机构信息

DeBakey Heart Center and Department of Medicine, Baylor College of Medicine, Houston, Texas 77030-3498, USA.

出版信息

Am J Physiol. 1999 Aug;277(2 Pt 2):H660-8. doi: 10.1152/ajpheart.1999.277.2.H660.

DOI:10.1152/ajpheart.1999.277.2.H660
PMID:10444492
Abstract

Anatomic and functional changes after either a permanent left anterior descending coronary artery occlusion (PO) or 2 h of occlusion followed by reperfusion (OR) in C57BL/6 mice were examined and compared with those in sham-operated mice. Both interventions generated infarcts comprising 30% of the left ventricle (LV) measured at 24 h and equivalent suppression of LV ejection velocity and filling velocity measured by Doppler ultrasound at 1 wk. Serial follow-up revealed that the ventricular ejection velocity and filling velocity returned to the levels of the sham-operated controls in the OR group at 2 wk and remained there; in contrast, PO animals continued to display suppression of both systolic and diastolic function. In contrast, ejection fractions of PO and OR animals were depressed equivalently (50% from sham-operated controls). Anatomic reconstruction of serial cross sections revealed that the percentage of the LV endocardial area overlying the ventricular scar (expansion ratio) was significantly larger in the PO group vs. the OR group (18 +/- 1.7% vs. 12 +/- 0.9%, P < 0.05). The septum that was never involved in the infarction had a significantly (P < 0.002) increased mass in PO animals (22.5 +/- 1.08 mg) vs. OR (17.8 +/- 1.10 mg) or sham control (14.8 +/- 0.99 mg) animals. Regression analysis demonstrated that the extent of septal hypertrophy correlated with LV expansion ratio. Thus late reperfusion appears to reduce the degree of infarct expansion even under circumstances in which it no longer can alter infarct size. We suggest that reperfusion promoted more effective ventricular repair, less infarct expansion, and significant recovery or preservation of ventricular function.

摘要

研究并比较了C57BL/6小鼠永久性左前降支冠状动脉闭塞(PO)或闭塞2小时后再灌注(OR)后的解剖学和功能变化,并与假手术小鼠进行对比。两种干预措施均导致梗死面积在24小时时占左心室(LV)的30%,且在1周时通过多普勒超声测量发现左心室射血速度和充盈速度受到同等程度的抑制。连续随访显示,OR组在2周时心室射血速度和充盈速度恢复到假手术对照组的水平并维持不变;相比之下,PO组动物的收缩和舒张功能持续受到抑制。相反,PO组和OR组动物的射血分数同等程度降低(较假手术对照组降低50%)。连续横断面的解剖重建显示,PO组左心室覆盖心室瘢痕的心内膜面积百分比(扩张率)显著大于OR组(18±1.7%对12±0.9%,P<0.05)。未发生梗死的室间隔质量在PO组动物(22.5±1.08mg)中显著高于OR组(17.8±1.10mg)或假手术对照组(14.8±0.99mg)动物(P<0.002)。回归分析表明,室间隔肥厚程度与左心室扩张率相关。因此,即使在再灌注不再能改变梗死面积的情况下,晚期再灌注似乎也能减少梗死扩展程度。我们认为,再灌注促进了更有效的心室修复、减少了梗死扩展,并显著恢复或保留了心室功能。

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