Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats

Noritomo Fujisaki, Keisuke Kohama, Takeshi Nishimura, Hayato Yamashita, Michiko Ishikawa, Akihiro Kanematsu, Taihei Yamada, Sungsoo Lee, Tetsuya Yumoto, Kohei Tsukahara, Joji Kotani, Atsunori Nakao

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Because inhaled carbon monoxide (CO) provides potent anti-inflammatory and antioxidant effects against ischemia reperfusion injury, we hypothesized that treatment of organ donors with inhaled CO would decrease graft injury after heart transplantation. Hearts were heterotopically transplanted into syngeneic Lewis rats after 8 hours of cold preservation in University of Wisconsin solution. Donor rats were exposed to CO at a concentration of 250 parts per million for 24 hours via a gas-exposure chamber. Severity of myocardial injury was determined by total serum creatine phosphokinase and troponin I levels at three hours after reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was performed on the heart graft tissue prior to implantation. Recipients of grafts from CO-exposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Although donor pretreatment with CO altered the expression of 49 genes expressly represented on the array, we could not obtain meaningful data to explain the mechanisms by which CO potentiated the protective effects.Pretreatment with CO gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac transplant model. A clinical report review indicated that CO-poisoned organ donors may be comparable to non-poisoned donors.

Original languageEnglish
Pages (from-to)122-129
Number of pages8
JournalMedical Gas Research
Volume6
Issue number3
DOIs
Publication statusPublished - Jul 1 2016

Keywords

  • Carbon monoxide
  • Cardiac transplantation
  • Cold preservation
  • Donor
  • Gene array
  • Ischemia/reperfusion
  • Pretreatment

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Anesthesiology and Pain Medicine

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