Impaired glucose transporter activity in pressure-overload hypertrophy is an early indicator of progression to failure

Background-Severe hypertrophy and heart failure are important risk factors in cardiac surgery. Early adaptive changes in hypertrophy include increased ventricular mass-to-cavity volume ratio (MN ratio) and increased dependenc e on glucose for energy metabolism. However, glucose uptake is decreased in the late stages of hypertrophy when ventricular dilatation and failure are present. We hypothesized that impaired glucose uptake would be evident ear ly in the progression of hypertrophy and associated with the onset of ventr icular dilatation, Methods and Results-Ten-day-old rabbits underwent banding of the descending aorta. Development of hypertrophy was followed by transthoracic echocardio graphy to measure left ventricular MN ratio. Glucose uptake rate, as determ ined by P-31-nuclear magnetic resonance spectroscopy measuring 2-deoxygluco se conversion to 2-deoxyglucose-6-phosphate, was measured in isolated perfu sed hearts obtained from banded rabbits when MN ratio had increased by 15% from baseline (compensated hypertrophy) and by 30% from baseline (early-dec ompensated hypertrophy). In age-matched control animals, the rate of glucos e uptake was 0.61+/-0.08 mu mol . g of wet weight(-1) 30 min(-1) (mean+/-SE M), With a 15% M/V ratio increase, glucose uptake rate remained at control levels (0.6+/-0.05 mu mol . g of wet weight(-1). 30 min(-1)), compared with hearts with 30% increased MN ratios, where glucose uptake was significantl y lower (0.42+/-0.05 mu mol g of wet weight(-1) 30 min(-1) ; P less than or equal to 0.05). Glucose transporter protein expression was the same in all groups. Conclusions-Glucose uptake rate is maintained during compensated hypertroph y. However, coinciding with severe hypertrophy, preceding ventricular dilat ation, and glucose transporter protein downregulation, glucose uptake is si gnificantly decreased. Because of the increased dependence of the hypertrop hied hearts on glucose use, we speculate that this impairment may be a cont ributing factor in the progression to failure.