Grupp I L, Subramaniam A, Hewett T E, Robbins J, Grupp G
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0575.
Am J Physiol. 1993 Oct;265(4 Pt 2):H1401-10. doi: 10.1152/ajpheart.1993.265.4.H1401.
It is now possible to manipulate the murine genome and produce transgenic mice in which genes encoding myocardial proteins have been ablated, resulting in an altered myocardial performance. In this study, we quantitate myocardial performance in work-performing mouse heart preparations from euthyroid, hypothyroid, and hyperthyroid mice. Our results show that time to peak pressure (TPP) and time to half-relaxation (RT1/2), together with first derivatives of intraventricular pressure (+/- dP/dt), are significant indicators of the quality and quantity of systolic contraction and relaxation. We compared the normal control indicators of contraction and relaxation of three different mouse strains at minimum afterloads (approximately 50 mmHg) and preloads (approximately 5 ml/min) and found them identical in range. All indicators of myocardial performance were significantly higher in the hyperthyroid and lower in the hypothyroid compared with normal mice. The cardiac myosin heavy chain isoform transcript shift (alpha-->beta) associated with hypothyroidism was observed. Because sympathetic activity is greatly enhanced with hyperthyroidism, we studied the effects of isoproterenol and the beta-blocker sotalol on cardiac contractility. Only approximately 50% of the myocardial hyperactivity displayed by hyperthyroid mice could be attributed to beta-adrenergic activity.
现在已经能够操纵小鼠基因组并培育出转基因小鼠，在这些小鼠中，编码心肌蛋白的基因已被剔除，从而导致心肌性能发生改变。在本研究中，我们对来自甲状腺功能正常、甲状腺功能减退和甲状腺功能亢进小鼠的做功小鼠心脏标本的心肌性能进行了定量分析。我们的结果表明，达到峰值压力的时间（TPP）和达到半松弛的时间（RT1/2），以及心室内压的一阶导数（±dP/dt），是收缩和舒张的质量和数量的重要指标。我们比较了三种不同小鼠品系在最小后负荷（约50 mmHg）和前负荷（约5 ml/min）下收缩和舒张的正常对照指标，发现它们的范围相同。与正常小鼠相比，甲状腺功能亢进小鼠的所有心肌性能指标均显著升高，而甲状腺功能减退小鼠的则降低。观察到与甲状腺功能减退相关的心肌肌球蛋白重链同工型转录本转换（α→β）。由于甲状腺功能亢进时交感神经活动大大增强，我们研究了异丙肾上腺素和β受体阻滞剂索他洛尔对心脏收缩力的影响。甲状腺功能亢进小鼠表现出的心肌活动亢进中，只有约50%可归因于β-肾上腺素能活动。
