title: Protective effect of plasmin in marginal donor lungs in an ex vivo lung perfusion model.
abstract: BACKGROUND
  Donor lung thrombi are considered an important etiology for primary graft dysfunction in lung transplantation. We hypothesized that thrombolysis before lung transplantation could alleviate ischemia-reperfusion injury. This study was designed to evaluate the effect of the fibrinolytic agent plasmin on lungs damaged by thrombi in an ex vivo lung perfusion (EVLP) system.
  
  
  METHODS
  Rats were divided into control, non-plasmin, and plasmin groups (n = 7 each). In the control and plasmin groups, cardiac arrest was induced by withdrawal of mechanical ventilation without heparinization. Ventilation was restarted 150 minutes after cardiac arrest. The lungs were flushed, and the heart and lungs were excised en bloc. The lungs were perfused in the EVLP system for 60 minutes, and plasmin or placebo was administered upon EVLP initiation.
  
  
  RESULTS
  Fibrin/fibrinogen degradation products in the perfusate were significantly higher in the plasmin group than in the control and non-control groups (p < 0.001 for both). Plasmin administration significantly decreased pulmonary vascular resistance (plasmin vs non-plasmin, p = 0.011) and inhibited the exacerbation of dynamic compliance (plasmin vs non-plasmin, p = 0.003). Lung weight gain was less in the plasmin group than in the non-plasmin group (p = 0.04).
  
  
  CONCLUSIONS
  Our results confirmed that plasmin administration in an EVLP model dissolved thrombi in the lungs, resulting in reconditioning of the lungs as assessed by various physiologic parameters.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Motoyama
authors.forename: Fengshi
authors.initials: F
authors.lastname: Chen
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohsumi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hijiya
authors.forename: Kenji
authors.initials: K
authors.lastname: Okita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakajima
authors.forename: Jin
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yamada
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.forename: Akihiro
authors.initials: A
authors.lastname: Aoyama
authors.forename: Toru
authors.initials: T
authors.lastname: Bando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000494:pharmacology / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D010477:Perfusion / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D005343:Fibrinolytic Agents; D005337:Fibrin; D005340:Fibrinogen; D005341:Fibrinolysin