title: Systemic pretreatment with dimethyloxalylglycine increases myocardial HIF-1α and VEGF production and improves functional recovery after acute ischemia/reperfusion.
abstract: BACKGROUND
  Stem cells protect the heart from ischemic damage in part by the release of cytoprotective growth factors, particularly vascular endothelial growth factor (VEGF). Production of VEGF is regulated in part by levels of the transcription factor hypoxia inducible factor 1-α (HIF-1α). Dimethyloxalylglycine (DMOG) prevents the deactivation of HIF-1α and increases VEGF production. However, the effects of systemic DMOG treatment on myocardial tolerance for ischemia are unknown. We hypothesized that systemic pretreatment with DMOG would improve myocardial ischemic tolerance.
  
  
  METHODS
  To study this hypothesis, adult male rats were randomly given an intraperitoneal injection of DMOG (40 mg/kg in 1 mL saline, n = 5) or saline (1 mL, n = 6) 24 h before cardiectomy and isolated heart perfusion. All hearts were subjected to 15 min equilibration, 25 min ischemia and 40 min reperfusion. Myocardial function was continuously monitored. Following reperfusion, myocardial homogenates were analyzed for HIF-1α and VEGF production.
  
  
  RESULTS
  We observed that hearts in the DMOG group exhibited greater recovery of left ventricular developed pressure LVDP, +dP/dt and -dP/dt. Myocardial HIF-1α and VEGF levels were increased by DMOG therapy.
  
  
  CONCLUSIONS
  In conclusion, systemic pretreatment with DMOG augments post-ischemic myocardial functional recovery through increased HIF-1α levels and greater VEGF production.
authors.affiliation: Cardiovascular Surgery, Methodist Hospital, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Poynter
authors.forename: Mariuxi C
authors.initials: MC
authors.lastname: Manukyan
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Brewster
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Herrmann
authors.forename: Brent R
authors.initials: BR
authors.lastname: Weil
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Abarbanell
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000600:Amino Acids, Dicarboxylic; D004791:Enzyme Inhibitors; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; C040947:oxalylglycine