title: Vascular endothelial growth factor attenuates myocardial ischemia-reperfusion injury.
abstract: BACKGROUND
  Hypoxic endothelial cell activation plays a key role in the myocardial dysfunction resulting from ischemia-reperfusion injury. Recent evidence suggests that vascular endothelial growth factor (VEGF) may, in addition to promoting angiogenesis, modulate various aspects of endothelial function and repair. We examined whether administration of VEGF in the cardioplegic solution might have a beneficial effect on myocardial ischemia-reperfusion injury in an isolated rat heart model.
  
  
  METHODS
  Hearts from Sprague-Dawley rats were perfused with Krebs-Henseleit solution in a modified Langendorff apparatus. Percent recovery of cardiac output, coronary flow, stroke work, and percent increase in coronary vascular resistance were measured after 2 hours of global ischemia and 40 minutes of reperfusion. Coronary effluent was collected after ischemia and reperfusion for measurement of creatine kinase.
  
  
  RESULTS
  Hearts receiving cardioplegia solution containing 125 microg VEGF showed significantly improved recovery of cardiac output, coronary flow, and stroke work, and significantly reduced coronary vascular resistance compared with hearts receiving hyperkalemic cardioplegia only (p < 0.05). Coadministration of a nitric oxide synthase inhibitor attenuated the VEGF-induced cardiprotective effects. Hearts treated with VEGF released significantly less creatine kinase compared with control hearts.
  
  
  CONCLUSIONS
  Addition of VEGF to hyperkalemic cardioplegia protects against myocardial ischemia-reperfusion injury in the isolated rat heart.
authors.affiliation: Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135-2997, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Luo
authors.forename: M
authors.initials: M
authors.lastname: Diaco
authors.forename: T
authors.initials: T
authors.lastname: Murohara
authors.forename: N
authors.initials: N
authors.lastname: Ferrara
authors.forename: J M
authors.initials: JM
authors.lastname: Isner
authors.forename: J F
authors.initials: JF
authors.lastname: Symes
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002314:Cardioplegic Solutions; D003402:Creatine Kinase / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008222:Lymphokines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014325:Tromethamine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D002314:Cardioplegic Solutions; D016228:Endothelial Growth Factors; C074097:Krebs-Henseleit solution; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014325:Tromethamine; D019001:Nitric Oxide Synthase; D003402:Creatine Kinase; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester