COMPARISON OF NORMAL, HYPODYNAMIC, AND HYPERDYNAMIC MOUSE HEARTS USING ISOLATED WORK-PERFORMING HEART PREPARATIONS

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.