Ex vivo application of carbon monoxide in University of Wisconsin solution to prevent intestinal cold ischemia/reperfusion injury

A. Nakao, H. Toyokawa, A. Tsung, M. A. Nalesnik, D. B. Stolz, J. Kohmoto, A. Ikeda, K. Tomiyama, T. Harada, T. Takahashi, R. Yang, M. P. Fink, K. Morita, A. M.K. Choi, N. Murase

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75 Citations (Scopus)

Abstract

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.

Original languageEnglish
Pages (from-to)2243-2255
Number of pages13
JournalAmerican Journal of Transplantation
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 1 2006
Externally publishedYes

Keywords

  • Carbon monoxide
  • Guanylyl cyclase
  • Heme oxygenase
  • Ischemia/reperfusion
  • Vascular endothelial cell
  • cGMP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Nakao, A., Toyokawa, H., Tsung, A., Nalesnik, M. A., Stolz, D. B., Kohmoto, J., Ikeda, A., Tomiyama, K., Harada, T., Takahashi, T., Yang, R., Fink, M. P., Morita, K., Choi, A. M. K., & Murase, N. (2006). Ex vivo application of carbon monoxide in University of Wisconsin solution to prevent intestinal cold ischemia/reperfusion injury. American Journal of Transplantation, 6(10), 2243-2255. https://doi.org/10.1111/j.1600-6143.2006.01465.x