title: Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats.
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 hoursviaa 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.
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Noritomo
authors.initials: N
authors.lastname: Fujisaki
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; Senri Critical Care Medical Center, Saiseikai Senri Hospital, Suita, Osaka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kohama
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Kobe University Graduate School of Health Sciences, Kobe, Hyogo, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Kobe University Graduate School of Health Sciences, Kobe, Hyogo, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Urology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kanematsu
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Taihei
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sungsoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yumoto
authors.affiliation: Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Tsukahara
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Kotani
authors.affiliation: Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Atsunori
authors.identifier: 0000-0002-6818-2985
authors.initials: A
authors.lastname: Nakao
keywords: carbon monoxide; cardiac transplantation; cold preservation; donor; gene array; ischemia/reperfusion; pretreatment