title: Impaired glucose transporter activity in pressure-overload hypertrophy is an early indicator of progression to failure.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiac Surgery, The Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: I
authors.initials: I
authors.lastname: Friehs
authors.forename: A M
authors.initials: AM
authors.lastname: Moran
authors.forename: C
authors.initials: C
authors.lastname: Stamm
authors.forename: S D
authors.initials: SD
authors.lastname: Colan
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: H
authors.initials: H
authors.lastname: Cao-Danh
authors.forename: C M
authors.initials: CM
authors.lastname: Rader
authors.forename: F X
authors.initials: FX
authors.lastname: McGowan
authors.forename: P J
authors.initials: PJ
authors.lastname: del Nido
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism; D004106:Dilatation; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D011379:Prognosis; D011817:Rabbits; D016277:Ventricular Function, Left
chemical_list: D009004:Monosaccharide Transport Proteins