Plasmin administration during ex vivo lung perfusion ameliorates lung ischemia-reperfusion injury

Hideki Motoyama, Fengshi Chen, Kyoko Hijiya, Takeshi Kondo, Akihiro Ohsumi, Tetsu Yamada, Masaaki Sato, Akihiro Aoyama, Toru Bando, Hiroshi Date

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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 41°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.

Original languageEnglish
Pages (from-to)1093-1099
Number of pages7
JournalJournal of Heart and Lung Transplantation
Volume33
Issue number10
DOIs
Publication statusPublished - 2014 Oct 1

Keywords

  • ex vivo lung
  • lung transplantation
  • marginal donor
  • perfusion fibrinolytic
  • plasmin
  • treatment

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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