title: Beneficial effect of a nitric oxide donor in an ex vivo model of pig-to-human pulmonary xenotransplantation.
abstract: BACKGROUND
  Nitric oxide (NO) can reduce platelet adhesion and vascular resistance. Tempol can scavenge the reactive oxygen species (ROS) that induce tissue injury. As xenograft rejection attenuates endogenous NO production and generates ROS, we evaluated the potential effect of an NO donor (SIN-1, 3-morpholinosydnonimine) and tempol on hyperacute xenograft dysfunction using an ex vivo porcine lung perfusion model.
  
  
  METHODS
  For the evaluation of von Willebrand factor (vWF) secretion, human endothelial cells were stimulated with thrombin. Porcine lungs were perfused with either fresh human whole blood (unmodified control group [n = 4]), SIN-1 (n = 4), or SIN and tempol (n = 4).
  
  
  RESULTS
  SIN-1 and tempol significantly inhibited vWF secretion from endothelial cells in vitro. However, they did not suppress xenogeneic complement activation. In an ex vivo pulmonary perfusion model, SIN-1 improved pulmonary xenograft function by reducing pulmonary vascular resistance (PVR), inhibiting complement activation, and inhibiting thrombin generation. Combined treatment with tempol and SIN-1 potentiated PVR reduction, but slightly enhanced complement activation.
  
  
  CONCLUSIONS
  An NO donor is expected to improve pulmonary xenograft function through inhibition of vWF secretion, vasoconstriction, thrombin generation, and indirectly through inhibition of complement activation. The additional effects of tempol on an NO donor were not considered significant in an ex vivo xenograft system.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hee Sue
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.|Xenotransplantation Research Center and Transplantation Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.|Xenotransplantation Research Center and Transplantation Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: You
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.|Xenotransplantation Research Center and Transplantation Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jayoon
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Byungsu
authors.initials: B
authors.lastname: Yoo
authors.affiliation: Xenotransplantation Research Center and Transplantation Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Saebom
authors.initials: S
authors.lastname: Lee
authors.affiliation: Xenotransplantation Research Center and Transplantation Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Xenotransplantation Research Center and Transplantation Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ho Young
authors.initials: HY
authors.lastname: Hwang
authors.affiliation: Xenotransplantation Research Center and Transplantation Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yoohwa
authors.initials: Y
authors.lastname: Hwang
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.|Xenotransplantation Research Center and Transplantation Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Xenotransplantation Research Center and Transplantation Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D016040:Lung Transplantation; D008981:Molsidomine / Q000031:analogs & derivatives / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D010477:Perfusion; D020011:Protective Agents / Q000627:therapeutic use*; D013113:Spin Labels; D013552:Swine; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D003497:Cyclic N-Oxides; D020030:Nitric Oxide Donors; D020011:Protective Agents; D013113:Spin Labels; C002385:linsidomine; D008981:Molsidomine; C001803:tempol
keywords: ex vivo perfusion; nitric oxide; platelets; porcine lung; tempol; von Willebrand factor