title: Effect of a vascular endothelial cadherin antagonist in a rat lung transplant model.
abstract: BACKGROUND
  Adherens junctions are critically important in control of endothelial cell permeability. Bβ15-42 is a peptide product of fibrin degradation that binds to vascular endothelial cadherin, the major component of endothelial adherens junctions. We tested the hypothesis that Bβ15-42 improves lung function in our rat lung transplant model.
  
  
  METHODS
  Bβ15-42 was administered to donors before lung retrieval and to recipients by continuous intravenous infusion, or just to recipients, or neither. Recipients were monitored, anesthetized and ventilated, for 6 hours. Outcome measures were indices of lung function (edema [wet-to-dry weight ratio], oxygenation, dynamic compliance) and bronchoalveolar fluid measures of inflammation (protein, cell count, differential, and cytokines).
  
  
  RESULTS
  Bβ15-42 therapy was associated with improved graft lung function, including less edema, and improved oxygenation and airway pressure, particularly if Bβ15-42 was administered to both the donor and recipient. However, Bβ15-42 had little or no effect on bronchoalveolar fluid measures of inflammation. Analysis of bronchoalveolar fluid protein concentration showed Bβ15-42 may enhance alveolar fluid clearance.
  
  
  CONCLUSIONS
  Bβ15-42 may be a useful therapy to reduce edema and improve graft function after lung transplant, alone or as an adjunct to other therapies.
authors: Division of Cardiothoracic Surgery, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7065, USA.
authors: Zhigang
authors: Z
authors: Tian
authors: Boming
authors: B
authors: Dong
authors: John W
authors: JW
authors: Blackwell
authors: Paul W
authors: PW
authors: Stewart
authors: Thomas M
authors: TM
authors: Egan
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D015820:Cadherins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005338:Fibrin Fibrinogen Degradation Products / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006084:Graft Rejection / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007262:Infusions, Intravenous; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D016040:Lung Transplantation; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D000099152:Cadherin 5; C033786:fibrinogen Bbeta (15-42)