Background : Mice with combined LDL-Receptor and leptin deficiency develop several features of the metabolic syndrome. However, it is unknown whether the observed obesity, insulin resistance, hyperlipidemia and atherosclerosis are associated with cardiac dysfunction, as seen in humans. The aim of this study was to determine cardiac contractility in these mice.
Methods : Double mutant LDLR-/-;ob/ob (DM, n=7) or C57BL/6 (co, n=7) mice of 24 weeks were anesthetized (1200 mg/kg urethane - 50 mg/kg -chloralose IP), tracheotomized and ventilated with room air. A microtip-pressure-conductance catheter was introduced in the left ventricle through the right carotid artery, and connected to an ARIA-1 system (Millar, Houston, TX) to study pressure-volume relationships in vivo. After stable baseline measurements the inferior vena cava was transiently occluded to reduce preload.
Results : At baseline, heart rate was comparable in both groups (544±17 in DM vs. 564±62 bpm in co). End-systolic pressure was significantly lower in DM than in co (75.3±8.6 vs. 87.3±9.3 mmHg, p=0.03), with a concomitant increase in end-diastolic pressure (5.7±2.1 vs.0.9±1.3 mmHg, p<0.01) and a comparable stroke volume (2.21±0.67 vs. 2.47±0.77 RVU), indicating systolic dysfunction. Also relaxation seems to be impaired (Tau 6.3±0.6 vs. 5.4±0.8 ms, p=0.04). Preload recruitable stroke work is a load-independent parameter of contractility and is worse in DM than in co (42.9±8.8 vs. 75.1±27.2 mmHg, p=0.01).
Conclusion : Cardiac function is impaired in LDRL-/-;ob/ob mice. These mice may serve as a model to study the development and pathophysiology of heart failure associated with the metabolic syndrome.