title: Relaxin is a candidate drug for lung preservation: relaxin-induced protection of rat lungs from ischemia-reperfusion injury.
abstract: BACKGROUND
  Pulmonary injury leading to early allograft dysfunction is caused by ischemia-reperfusion injury (IR) and originates from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, and peroxidation of cell membrane lipids, followed by pulmonary cell alterations and edema. The potent vasoconstrictor and proinflammatory mediator endothelin (ET)-1 plays a major role in this cascade. This study was conducted to determine whether treatment with relaxin, an anti-inflammatory and vasoactive hormone, prevents IR.
  
  
  METHODS
  Isolated male Wistar rat lungs were perfused in a recirculatory model in the presence of 5-nmol/liter relaxin (n = 17) or vehicle alone (n = 14). After IR (60 minutes each) we determined wet-to-dry weight ratio, and levels of ET-1, neutrophil elastase (NE), myeloperoxidase (MPO), and malondialdehyde (MDA).
  
  
  RESULTS
  IR lungs displayed significantly elevated W/D ratios after IR compared with control lungs (p = 0.001). In the presence of relaxin, the values obtained under IR conditions were significantly reduced compared with those in the vehicle-treated IR group, but not significantly different from those obtained in the control + relaxin group (p = 0.079). The IR-stimulated increase in ET-1, NE, MPO, and MDA (3.6-, 8.4-, 6.0- and 3.0-fold over baseline, p < 0.001) was significantly reduced by relaxin (p < 0.007).
  
  
  CONCLUSIONS
  These results show that human relaxin exerts a protective effect in IR-induced lung injury, likely due to ET reduction, endothelial protection, decreased leukocyte recruitment, and hindrance of free radical-mediated tissue injury, which renders relaxin a candidate drug for lung preservation.
authors.affiliation: Department of Cardiac Surgery, University of Technology Dresden, Dresden, Germany. k_alexiou@yahoo.de <k_alexiou@yahoo.de>
authors.forename: Konstantin
authors.initials: K
authors.lastname: Alexiou
authors.forename: Klaus
authors.initials: K
authors.lastname: Matschke
authors.forename: Angelika
authors.initials: A
authors.lastname: Westphal
authors.forename: Karl
authors.initials: K
authors.lastname: Stangl
authors.forename: Thomas
authors.initials: T
authors.lastname: Dschietzig
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism; D004727:Endothelium / Q000473:pathology; D019272:Leukocyte Elastase / Q000378:metabolism; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D023421:Models, Animal; D009926:Organ Preservation / Q000379:methods*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012065:Relaxin / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D019332:Endothelin-1; D008315:Malondialdehyde; D012065:Relaxin; D009195:Peroxidase; D019272:Leukocyte Elastase