Abstract 650: Cardiac Metabolic Manipulation Improves Left Ventricular Performance under Dobutamine Stress
Background: Current pharmacological and interventional treatments for cardiac ischemia work by either increasing myocardial oxygen supply or reducing demand. Manipulation of cardiac metabolism to increase glucose oxidization in place of free fatty acids (FFA) generates more ATP per molecule of O2 consumed and may improve myocardial efficiency. We hypothesized that hyperinsulinemia would suppress FFA oxidation and as a result improve cardiac performance in subjects with coronary artery disease (CAD) undergoing dobutamine stress echocardiography (DSE).
Methods: Twenty subjects (240 myocardial segments) with significant CAD awaiting revascularization and normal resting LV function underwent 2 standard DSEs. Hyperinsulinemic, euglycemic clamping (HEC) was perfomed prior to one of the DSEs. Insulin (rate 43MU.m−2.min−1) was co-administered with an infusion of 20% dextrose at variable rates to maintain euglycemia. Digital ultrasound images of the LV were acquired with tissue Doppler at each stage and analyzed off-line. Measurements of the peak systolic (Vs) velocities of 12 non-apical segments and the long axis function at the mitral annulus were recorded, as well as LV ejection fraction (EF) calculated using Simpson’s Biplane method. Segmental wall motion scoring index (WMSI) was performed offline by a cardiologist experienced in DSE, blinded to the treatment.
Results: HEC significantly altered the metabolic environment, suppressing FFAs whilst maintaining euglycaemia. Significant improvements in LV performance at peak stress, measured by EF and peak Vs were observed in HEC DSEs (see table 1⇓).
Conclusion: Suppression of FFA metabolism by hyperinsulinemia, whilst maintaining euglycaemia, improves LV perfomance during peak stress in subjects with CAD. Metabolic manipulation appears to be a promising target for future therapy.