title: Protection against lung graft injury from brain-dead donors with carbon monoxide, biliverdin, or both.
abstract: BACKGROUND
  The process of brain death can induce acute lung injury in donors and aggravate ischemia-reperfusion injury in grafts. Carbon monoxide (CO) and biliverdin (BV) have been shown to attenuate ischemia-reperfusion injury. We therefore examined if the administration of both CO and BV provide enhanced cytoprotection against lung graft injury from brain-dead (BD) rat donors.
  
  
  METHODS
  Brain death was induced in all donors, after which they were observed for 1.5 hours and then underwent lung transplantation. The recipients were ventilated with 40% oxygen (control group), ventilated with 250 ppm CO in 40% oxygen (CO group), treated with BV (35 mg/kg) intraperitoneally (BV group), or treated with CO and BV conjointly (COBV group) before transplantation (n = 8 each group). The recipients were sacrificed 2 hours after lung transplantation by exsanguination. Serum levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  CO and/or BV treatment attenuated partial pressure of arterial oxygen (Pao(2))/fraction of inspired oxygen (Fio(2)) aggravation in the recipients after reperfusion, reduced the wet weight/dry weight ratio, decreased the lung injury score, inhibited the activity of myeloperoxidase in grafts, and decreased serum levels of IL-8 and TNF-α compared with the control group (p < 0.05). The COBV group had significantly decreased malonaldehyde levels and increased superoxide dismutase levels in lung grafts compared with the CO group (p < 0.05). The static pressure-volume curve of the lungs was ameliorated in the CO group, BV group, and COBV group compared with the control group (p < 0.05).
  
  
  CONCLUSIONS
  CO and BV exert protective effects through anti-inflammatory and anti-oxidant mechanisms, and dual treatment provided enhanced cytoprotection against lung graft injury from BD rat donors.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital, Harbin Medical University, and Hei Long Jiang Province Key Lab of Research on Anesthesiology and Critical Care Medicine, Harbin, China.
authors.forename: Huacheng
authors.initials: H
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Qian
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
authors.forename: Wengang
authors.initials: W
authors.lastname: Ding
authors.forename: Peng
authors.initials: P
authors.lastname: Pan
authors.forename: Di
authors.initials: D
authors.lastname: Jin
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001664:Biliverdine / Q000008:administration & dosage*; D001926:Brain Death; D002248:Carbon Monoxide / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D002248:Carbon Monoxide; D001664:Biliverdine