尽管存在分子改变，但梗死后期重塑的大鼠心脏中的心肌细胞收缩功能仍保持完好。

Myocyte contractile function is intact in the post-infarct remodeled rat heart despite molecular alterations.

作者信息

Gupta S, Prahash A J, Anand I S

机构信息

Division of Cardiology, Department of Medicine, VA Medical Center 111C and University of Minnesota, 1 Veterans Drive, Minneapolis, MN 55417, USA.

出版信息

Cardiovasc Res. 2000 Oct;48(1):77-88. doi: 10.1016/s0008-6363(00)00160-7.

DOI:10.1016/s0008-6363(00)00160-7

PMID:11033110

Abstract

OBJECTIVE

To investigate the cellular mechanisms underlying global and regional LV dysfunction in the post-infarct (MI) remodeled rat hearts.

METHODS

LV remodeling and function were quantified by echocardiography, morphometry, in vivo hemodynamics, and isolated perfused heart studies in 6 weeks post-MI and sham-operated rats. LV myocytes from sham and MI hearts were used for morphometric and functional studies. Myocyte contractile function and intracellular calcium kinetics were measured at different stimulation frequencies (0.2-2 Hz), temperatures (30 and 37 degrees C), and external viscous load (1, 15, 200 and 300 centipoise). Myocyte apoptosis was measured by DNA laddering; BCL-2, BAX, Na(+)-Ca(2+) exchanger, and SERCA-2 proteins by western blot; and brain natriuretic peptide (BNP), SERCA-2 mRNA by RT-PCR.

RESULTS

MI hearts were remodeled (Echo LV diameter 7.3+/-0.38 vs. 5.9+/-0.16 mm, P<0.03), and showed global (Echo % fractional shortening 30+/-2.4 vs. 58+/-3, P<0.001), and regional contractile dysfunction of non-infarcted myocardium (Echo % systolic posterior wall thickening 36+/-2 vs. 57+/-1.7, P<0.001). In vivo hemodynamic and isolated heart function studies confirmed depressed LV systolic and diastolic function and increased volumes. Whereas, myocytes isolated from infarcted hearts were remodeled (40% longer and 10% wider), their contractile function and calcium kinetics under basal conditions and at high stimulation frequency, temperature and viscous load were similar to sham myocytes. The mRNA for BNP was increased whereas that for SERCA-2 decreased, but the SERCA-2 protein was normal. Despite myocyte hypertrophy, ventricular septal thickness was reduced in infarcted hearts (2.2+/-0.1 vs. 2. 6+/-0.07 mm, P<0.01), and showed increased apoptosis.

CONCLUSIONS

Myocytes from remote non-infarcted myocardium of the remodeled hearts have normal contractile function, despite structural remodeling and altered gene expression. Non-myocyte factors may be more important in genesis of contractile dysfunction in the remodeled heart, for up to 6 weeks after MI.

摘要

目的

研究心肌梗死后（MI）重构大鼠心脏整体及局部左心室功能障碍的细胞机制。

方法

通过超声心动图、形态学测量、体内血流动力学以及对梗死后6周的大鼠和假手术大鼠进行离体灌注心脏研究，对左心室重构和功能进行量化。采用假手术组和心肌梗死组心脏的左心室心肌细胞进行形态学和功能研究。在不同刺激频率（0.2 - 2Hz）、温度（30和37摄氏度）以及外部粘性负荷（1、15、200和300厘泊）条件下，测量心肌细胞的收缩功能和细胞内钙动力学。通过DNA梯状条带分析检测心肌细胞凋亡；采用蛋白质印迹法检测BCL-2、BAX、钠钙交换体和SERCA-2蛋白；采用逆转录聚合酶链反应（RT-PCR）检测脑钠肽（BNP）、SERCA-2 mRNA。

结果

心肌梗死组心脏发生重构（超声心动图测量左心室直径7.3±0.38 vs. 5.9±0.16mm，P<0.03），表现出整体收缩功能障碍（超声心动图测量左心室短轴缩短率30±2.4 vs. 58±3，P<0.001）以及梗死周边心肌局部收缩功能障碍（超声心动图测量后壁收缩期增厚率36±2 vs. 57±1.7，P<0.001）。体内血流动力学和离体心脏功能研究证实左心室收缩和舒张功能降低以及容积增加。然而，梗死心脏分离出的心肌细胞虽发生重构（长40%，宽10%），但其在基础条件下以及高刺激频率、温度和粘性负荷时的收缩功能和钙动力学与假手术组心肌细胞相似。BNP的mRNA增加而SERCA-2的mRNA减少，但SERCA-2蛋白正常。尽管心肌细胞肥大，但梗死心脏的室间隔厚度降低（2.2±0.1 vs. 2.6±0.07mm，P<0.01），且凋亡增加。