title: Plasmin administration during ex vivo lung perfusion ameliorates lung ischemia-reperfusion injury.
abstract: BACKGROUND
  Donor lung thrombus is considered a significant etiology for primary graft dysfunction (PGD). We hypothesized that thrombolysis in ex vivo lung perfusion (EVLP) before lung transplantation could alleviate ischemia-reperfusion injury (IRI), resulting in a decreased incidence of PGD.
  
  
  METHODS
  Rats were divided into control (n = 5), non-plasmin (n = 7) and plasmin (n = 7) groups. In the non-plasmin and plasmin groups, cardiac arrest was induced by withdrawal of ventilation without heparinization. After 120 minutes of warm ischemia, the lungs were ventilated and flushed. Hearts and both lungs were excised en bloc. The lungs were perfused and ventilated in the EVLP for 30 minutes, and plasmin or placebo was administered on EVLP initiation. The lungs were then stored at 4°C for 90 minutes and finally perfused with rat blood for 80 minutes. We assessed physiologic and histologic findings during reperfusion and the correlation between physiologic data during EVLP and after reperfusion.
  
  
  RESULTS
  Physiologic results were better in the plasmin group than in the non-plasmin group. The plasmin group lungs had fewer signs of histologic injury. Caspase-3 and -7 activity in the plasmin group was lower in the non-plasmin group. Pulmonary vascular resistance (PVR) during EVLP correlated with that at the end of reperfusion.
  
  
  CONCLUSIONS
  Plasmin administration during EVLP protected the donor lungs after reperfusion. We also found that several physiologic values in EVLP may be predictive markers of lung function after reperfusion.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Motoyama
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Fengshi
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hijiya
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohsumi
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Aoyama
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Bando
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: hdate@kuhp.kyoto-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D004195:Disease Models, Animal; D005341:Fibrinolysin / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D010477:Perfusion / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D015912:Thrombolytic Therapy / Q000379:methods*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D015415:Biomarkers; D005341:Fibrinolysin; D053148:Caspase 3; D053179:Caspase 7
keywords: ex vivo lung perfusion; fibrinolytic treatment; lung transplantation; marginal donor; plasmin