title: Reduction of post-ischemic lung reperfusion injury by fibrinolytic activity suppression.
abstract: BACKGROUND
  Although extensive studies on the detailed mechanisms of ischemia-reperfusion injury have been conducted, the implication of the fibrinolytic system has not been known. To determine the role of the fibrinolytic system in ischemia-reperfusion injury, we used tranexamic acid, a synthetic specific plasmin and tissue-type plasminogen activator inhibitor, to suppress fibrinolytic activity in a rabbit lung ischemia-reperfusion model.
  
  
  METHODS
  New Zealand White rabbits were randomly divided into two groups: a simple ischemia group and a group injected with tranexamic acid before left hilar occlusion. After 2 hours of warm ischemia, plasma was collected from pulmonary vessels. Fibrin zymography was used to ascertain fibrinolytic activity, and enzyme-linked immunosorbent assay was used to determine soluble thrombomodulin levels as a marker for endothelial cells damage. Changes in left pulmonary function including arterial oxygen tension, peak airway pressure, and pulmonary vascular resistance were recorded during reperfusion after the 2 hours of warm ischemia.
  
  
  RESULTS
  Fibrinolytic activity and soluble thrombomodulin levels increased in the vessels of the ischemic lung, indicating endothelial cell injury. The increased fibrinolytic activity and the rise in soluble thrombomodulin were suppressed by the preadministration of tranexamic acid, resulting in remarkably improved pulmonary function during reperfusion. After 2 hours of reperfusion, the wet-to-dry weight ratios and histological studies showed reduced pulmonary edema in the group that had received tranexamic acid.
  
  
  CONCLUSIONS
  These findings suggest that the fibrinolytic system is involved in the onset mechanism of ischemia-reperfusion injury through induced endothelial cell damage and increased vascular permeability.
authors.affiliation: Second Department of Surgery, Miyazaki Medical College, Kiyotake, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Edagawa
authors.forename: E
authors.initials: E
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: K
authors.initials: K
authors.lastname: Shibuya
authors.forename: K
authors.initials: K
authors.lastname: Shibata
authors.forename: T
authors.initials: T
authors.lastname: Onitsuka
authors.forename: M
authors.initials: M
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D005342:Fibrinolysis / Q000187:drug effects*; D007511:Ischemia / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011652:Pulmonary Circulation / Q000502:physiology*; D011654:Pulmonary Edema / Q000517:prevention & control; D011817:Rabbits; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D012129:Respiratory Function Tests; D018180:Thrombomodulin / Q000097:blood; D014148:Tranexamic Acid / Q000627:therapeutic use*
chemical_list: D000933:Antifibrinolytic Agents; D018180:Thrombomodulin; D014148:Tranexamic Acid