Iwase M, Uechi M, Vatner D E, Asai K, Shannon R P, Kudej R K, Wagner T E, Wight D C, Patrick T A, Ishikawa Y, Homcy C J, Vatner S F
Department of Medicine, Harvard Medical School, Massachusetts, USA.
Am J Physiol. 1997 Jan;272(1 Pt 2):H585-9. doi: 10.1152/ajpheart.1997.272.1.H585.
The goal of this study was to determine whether chronic endogenous sympathetic stimulation resulting from the overexpression of cardiac stimulatory G protein alpha subunit (Gs alpha) in transgenic mice (15.3 +/- 0.1 mo old) resulted in a clinical picture of cardiomyopathy. The left ventricular ejection fraction, measured by echocardiography, was reduced in older mice with Gs alpha overexpression (50.4 +/- 5.4%) compared with age-matched control mice (70.9 +/- 1.6%; P < 0.05). When ejection fractions were compared at similar heart rates, the Gs alpha mice exhibited a greater left ventricular end-diastolic dimension than control mice (4.3 +/- 0.2 vs. 3.7 +/- 0.1 mm; P < 0.05). Baseline heart rates were elevated in conscious Gs alpha mice (722 +/- 27 beats/min; n = 5) compared with control mice (656 +/- 28 beats/min; n = 5). Moreover, electrocardiographic monitoring demonstrated a high incidence of arrhythmias. Increased mortality compared with control mice (31.6 vs. 3.0%; P < 0.01) was also observed. Thus older mice with Gs alpha overexpression exhibit many of the features of dilated cardiomyopathy. This study supports the concept that chronic sympathetic stimulation over an extended period of time, i.e., over the life of an animal, is deleterious and actually may result in cardiomyopathy.
本研究的目的是确定转基因小鼠（15.3±0.1月龄）心脏刺激型G蛋白α亚基（Gsα）过表达所导致的慢性内源性交感神经刺激是否会引发心肌病的临床表现。通过超声心动图测量，与年龄匹配的对照小鼠（70.9±1.6%）相比，Gsα过表达的老年小鼠左心室射血分数降低（50.4±5.4%；P<0.05）。当在相似心率下比较射血分数时，Gsα小鼠的左心室舒张末期内径大于对照小鼠（4.3±0.2对3.7±0.1mm；P<0.05）。清醒的Gsα小鼠的基础心率高于对照小鼠（722±27次/分钟；n=5）（656±28次/分钟；n=5）。此外，心电图监测显示心律失常发生率很高。与对照小鼠相比，死亡率也增加（31.6对3.0%；P<0.01）。因此，Gsα过表达的老年小鼠表现出许多扩张型心肌病的特征。本研究支持这样一种观点，即长时间的慢性交感神经刺激，即在动物的整个生命过程中，是有害的，实际上可能导致心肌病。
