title: Successful prolonged ex vivo lung perfusion for graft preservation in rats.
abstract: OBJECTIVE
  Ex vivo lung perfusion (EVLP) strategies represent a new frontier in lung transplantation technology, and there have been many clinical studies of EVLP in lung transplantation. The establishment of a reliable EVLP model in small animals is crucial to facilitating translational research using an EVLP strategy. The main objective of this study was to develop a reproducible rat EVLP (R-EVLP) model that enables prolonged evaluation of the explanted lung during EVLP and successful transplantation after EVLP.
  
  
  METHODS
  The donor heart-lung blocks were procured with cold low-potassium dextran solution and immersed in the solution for 1 h at 4 °C. And then, the heart-lung blocks were flushed retrogradely and warmed up to 37 °C in a circuit perfused antegradely with acellular perfusate. The perfusate was deoxygenated with a gas mixture (6% O2, 8% CO2, 86% N2). The perfusion flow was maintained at 20% of the entire cardiac output. At 37 °C, the lungs were mechanically ventilated and perfusion continued for 4 h. Every hour, the perfused lung was evaluated for gas exchange, dynamic lung compliance (Cdyn) and pulmonary vascular resistance (PVR).
  
  
  RESULTS
  R-EVLP was performed for 4 h. Pulmonary oxygenation ability (pO2/pCO2) was stable for 4 h during EVLP. It was noted that Cdyn and PVR were also stable. After 4 h of EVLP, pO2 was 303 ± 19 mmHg, pCO2 was 39.6 ± 1.2 mmHg, PVR was 1.75 ± 0.10 mmHg/ml/min and Cdyn was 0.37 ± 0.03 ml/cmH2O. Lungs that were transplanted after 2 h of R-EVLP resulted in significantly better post-transplant oxygenation and compliance when compared with those after standard cold static preservation.
  
  
  CONCLUSIONS
  Our R-EVLP model maintained stable lung oxygenation, compliance and vascular resistance for up to 4 h of perfusion duration. This reliable model should facilitate further advancement of experimental work using EVLP.
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Noda
authors.forename: Norihisa
authors.initials: N
authors.lastname: Shigemura
authors.forename: Yugo
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Jay K
authors.initials: JK
authors.lastname: Bhama
authors.forename: Jonathan
authors.initials: J
authors.lastname: D'Cunha
authors.forename: James D
authors.initials: JD
authors.lastname: Luketich
authors.forename: Christian A
authors.initials: CA
authors.lastname: Bermudez
mesh_terms: D000818:Animals; D008168:Lung / Q000601:surgery*; D016040:Lung Transplantation / Q000295:instrumentation / Q000379:methods; D008297:Male; D009926:Organ Preservation / Q000295:instrumentation / Q000379:methods; D051381:Rats; D015424:Reperfusion / Q000295:instrumentation / Q000379:methods; D019737:Transplants / Q000502:physiology / Q000601:surgery
keywords: Ex vivo lung perfusion; Lung transplantation; Organ preservation