RELATIONSHIPS BETWEEN MYOCARDIAL BIOENERGETIC AND LEFT-VENTRICULAR FUNCTION IN HEARTS WITH VOLUME-OVERLOAD HYPERTROPHY

Background Left ventricular (LV) hypertrophy secondary to volume overl oad can result in alterations in myocardial bioenergetics and LV dysfu nction. This study examined whether bioenergetic abnormalities contrib ute to the pump dysfunction. Methods and Results Severe mitral regurgi tation (MR) was produced in 10 dogs by disruption of the chordal appar atus. Hemodynamics and ventricular function were examined 11.7 months later under baseline conditions and during treadmill exercise. Myocard ial high-energy phosphates were measured by using magnetic resonance s pectroscopy at rest, during coronary vasodilation with adenosine. and during oxidative stress induced by rapid pacing and dobutamine. Chroni c MR caused a 30% increase in LV mass and a 65% increase in LV volume. In MR animals. the hemodynamic and LV function were normal at rest, b ut abnormalities developed during beta-blockade and exercise. Myocardi al creatine phosphate-to-ATP ratios were significantly lower in each l ayer across the LV wall in MR hearts than normal hearts. Myocardial bl ood how and coronary reserve were normal in MR hearts, Moreover, hyper perfusion did not correct the abnormal bioenergetics. Despite altered bioenergetics at rest, the MR hearts tolerated rapid pacing and dobuta mine infusion well. Conclusions In volume-overloaded LV hypertrophied hearts, alterations in myocardial high-energy phosphate levels do not induce abnormal mechanical performance at rest but may be related to a decreased contractile reserve during exercise.