title: Glucose transporter upregulation improves ischemic tolerance in hypertrophied failing heart.
abstract: BACKGROUND
  Achieving successful myocardial preservation of hypertrophied hearts remains a difficult problem. Despite reportedly higher glycolytic potential, we have achieved limited benefit in hypertrophied hearts with strategies that successfully promote anaerobic glycolysis and long-term ischemic preservation in nonhypertrophied models. We therefore tested the hypotheses that (l) glucose transport into myocytes is a critical limiting factor in hypertrophied heart and (2) stimulation of glucose transport with vanadyl sulfate would improve postischemic recovery.
  
  
  RESULTS
  Left ventricular hypertrophy in rabbits was created by aortic banding of 7- to 10-day-old rabbits. At 4 weeks of age, 1 group of animals received oral vanadyl sulfate for 3 to 4 weeks. Glucose transport (measured by the conversion of 2-deoxyglucose to 2-deoxyglucose-6-phosphate; 31P-nuclear magnetic resonance), myocardial glucose transporter content (GLUT-1 and GLUT-4 by immunoblotting), and functional recovery from ischemia-reperfusion (isolated perfused Langendorff model) were measured. Myocardial glucose transport rate was significantly reduced in hypertrophied hearts without significant reductions in glucose transporter content; these hearts were significantly less tolerant of ischemia-reperfusion than age-matched controls. Vanadyl sulfate normalized glucose transport rate and improved tolerance to ischemia-reperfusion so that postischemic function equaled that seen in controls. Lactate production during ischemia, an indication of anaerobic glycolysis, was significantly higher in hearts from vanadate-treated animals.
  
  
  CONCLUSIONS
  Despite reportedly higher glycolytic enzyme activities, maximal glucose transport appears to be reduced and is rate limiting in hypertrophied heart. Stimulation of membrane glucose transport with vanadyl sulfate significantly improved glycolytic flux and ischemic preservation in hypertrophied hearts.
authors.affiliation: Department of Cardiac Surgery, Children's Hospital, Boston, MA 02115, USA.
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: F X
authors.initials: FX
authors.lastname: McGowan
authors.forename: P
authors.initials: P
authors.lastname: Glynn
authors.forename: A M
authors.initials: AM
authors.lastname: Moran
authors.forename: C M
authors.initials: CM
authors.lastname: Rader
authors.forename: H
authors.initials: H
authors.lastname: Cao-Danh
authors.forename: P J
authors.initials: PJ
authors.lastname: del Nido
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002303:Cardiac Output, Low / Q000503:physiopathology*; D006332:Cardiomegaly / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits
chemical_list: D009004:Monosaccharide Transport Proteins; D005947:Glucose