Beneficial effect of a nitric oxide donor in an ex vivo model of pig-to-human pulmonary xenotransplantation

Hee Sue Park, Ji Eun Kim, Hyun Ju You, Jayoon Gu, Byungsu Yoo, Saebom Lee, Hyun Joo Lee, Ho Young Hwang, Yoo Hwa Hwang, Hyun Kyung Kim, Young Tae Kim

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalXenotransplantation
Volume22
Issue number5
DOIs
StatePublished - 1 Sep 2015

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Heterologous Transplantation
Nitric Oxide Donors
Heterografts
Swine
Complement Activation
Lung
von Willebrand Factor
Thrombin
Vascular Resistance
Reactive Oxygen Species
Nitric Oxide
Endothelial Cells
Perfusion
Vasoconstriction
tempol
Blood Platelets
Control Groups
Wounds and Injuries

Keywords

  • ex vivo perfusion
  • nitric oxide
  • platelets
  • porcine lung
  • tempol
  • von Willebrand factor

Cite this

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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.",
keywords = "ex vivo perfusion, nitric oxide, platelets, porcine lung, tempol, von Willebrand factor",
author = "Park, {Hee Sue} and Kim, {Ji Eun} and You, {Hyun Ju} and Jayoon Gu and Byungsu Yoo and Saebom Lee and Lee, {Hyun Joo} and Hwang, {Ho Young} and Hwang, {Yoo Hwa} and Kim, {Hyun Kyung} and Kim, {Young Tae}",
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doi = "10.1111/xen.12195",
language = "English",
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Beneficial effect of a nitric oxide donor in an ex vivo model of pig-to-human pulmonary xenotransplantation. / Park, Hee Sue; Kim, Ji Eun; You, Hyun Ju; Gu, Jayoon; Yoo, Byungsu; Lee, Saebom; Lee, Hyun Joo; Hwang, Ho Young; Hwang, Yoo Hwa; Kim, Hyun Kyung; Kim, Young Tae.

In: Xenotransplantation, Vol. 22, No. 5, 01.09.2015, p. 391-398.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Beneficial effect of a nitric oxide donor in an ex vivo model of pig-to-human pulmonary xenotransplantation

AU - Park, Hee Sue

AU - Kim, Ji Eun

AU - You, Hyun Ju

AU - Gu, Jayoon

AU - Yoo, Byungsu

AU - Lee, Saebom

AU - Lee, Hyun Joo

AU - Hwang, Ho Young

AU - Hwang, Yoo Hwa

AU - Kim, Hyun Kyung

AU - Kim, Young Tae

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

KW - ex vivo perfusion

KW - nitric oxide

KW - platelets

KW - porcine lung

KW - tempol

KW - von Willebrand factor

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VL - 22

SP - 391

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JF - Xenotransplantation

SN - 0908-665X

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