Du X J, Gao X M, Jennings G L, Dart A M, Woodcock E A
Baker Medical Research Institute and Alfred Heart Centre, Alfred Hospital, Melbourne 8008, Victoria, Australia.
Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2456-63. doi: 10.1152/ajpheart.2000.279.5.H2456.
Effects of cardiac specific overexpression of beta(2)-adrenergic receptors (beta(2)-AR) on the development of heart failure (HF) were studied in wild-type (WT) and transgenic (TG) mice following myocardial infarction (MI) by coronary artery occlusion. Animals were studied by echocardiography at weeks 7 to 8 and by catheterization at week 9 after surgery. Post-infarct mortality, due to HF or cardiac rupture, was not different among WT mice, and there was no difference in infarct size (IS). Compared with the sham-operated group (all P < 0.01), WT mice with moderate (<36%) and large (>36%) IS developed lung congestion, cardiac hypertrophy, left ventricular (LV) dilatation, elevated LV end-diastolic pressure (LVEDP), and suppressed maximal rate of increase of LV pressure (LV dP/dt(max)) and fractional shortening (FS). Whereas changes in organ weights and echo parameters were similar to those in infarcted WT groups, TG mice had significantly higher levels of LV contractility in both moderate (dP/dt(max) 4,862 +/- 133 vs. 3,694 +/- 191 mmHg/s) and large IS groups (dP/dt(max) 4,556 +/- 252 vs. 3,145 +/- 312 mmHg/s, both P < 0.01). Incidence of pleural effusion (36% vs. 85%, P < 0.05) and LVEDP levels (6 +/- 0.3 vs. 9 +/- 0.8 mmHg, P < 0.05) were also lower in TG than in WT mice with large IS. Thus beta(2)-AR overexpression preserved LV contractility following MI without adverse consequence.
通过冠状动脉闭塞诱导心肌梗死（MI）后，在野生型（WT）和转基因（TG）小鼠中研究了心脏特异性过表达β₂-肾上腺素能受体（β₂-AR）对心力衰竭（HF）发展的影响。术后第7至8周通过超声心动图对动物进行研究，第9周通过导管插入术进行研究。WT小鼠中因HF或心脏破裂导致的梗死后死亡率无差异，梗死面积（IS）也无差异。与假手术组相比（所有P<0.01），IS为中度（<36%）和重度（>36%）的WT小鼠出现肺充血、心脏肥大、左心室（LV）扩张、左心室舒张末期压力（LVEDP）升高、左心室压力最大上升速率（LV dP/dt(max)）和缩短分数（FS）降低。虽然器官重量和超声参数的变化与梗死的WT组相似，但TG小鼠在中度（dP/dt(max) 4,862±133 vs. 3,694±191 mmHg/s）和重度IS组（dP/dt(max) 4,556±252 vs. 3,145±312 mmHg/s，均P<0.01）中的LV收缩力水平显著更高。TG小鼠的胸腔积液发生率（36% vs. 85%，P<0.05）和LVEDP水平（6±0.3 vs. 9±0.8 mmHg，P<0.05）也低于重度IS的WT小鼠。因此，β₂-AR过表达在MI后保留了LV收缩力，且无不良后果。
