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 (M/V ratio) and increased dependence 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 early in the progression of hypertrophy and associated with the onset of ventricular dilatation.

METHODS AND RESULTS

Ten-day-old rabbits underwent banding of the descending aorta. Development of hypertrophy was followed by transthoracic echocardiography to measure left ventricular M/V ratio. Glucose uptake rate, as determined by (31)P-nuclear magnetic resonance spectroscopy measuring 2-deoxyglucose conversion to 2-deoxyglucose-6-phosphate, was measured in isolated perfused hearts obtained from banded rabbits when M/V ratio had increased by 15% from baseline (compensated hypertrophy) and by 30% from baseline (early-decompensated hypertrophy). In age-matched control animals, the rate of glucose uptake was 0.61+/-0.08 micromol x g of wet weight(-1) x 30 min(-1) (mean+/-SEM). With a 15% M/V ratio increase, glucose uptake rate remained at control levels (0.6+/-0.05 micromol x g of wet weight(-1) x 30 min(-1)), compared with hearts with 30% increased M/V ratios, where glucose uptake was significantly lower (0.42+/-0.05 micromol x g of wet weight(-1) x 30 min(-1); P</=0.05). Glucose transporter protein expression was the same in all groups.

CONCLUSIONS

Glucose uptake rate is maintained during compensated hypertrophy. However, coinciding with severe hypertrophy, preceding ventricular dilatation, and glucose transporter protein downregulation, glucose uptake is significantly decreased. Because of the increased dependence of the hypertrophied hearts on glucose use, we speculate that this impairment may be a contributing factor in the progression to failure.