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: Huacheng Zhou, Hua Qian, Jinfeng Liu, Daling Zhu, Wengang Ding, Peng Pan, Di Jin, Juan Wang, Wenzhi Li
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 30 Issue 4 Pg. 460-6 (Apr 2011) ISSN: 1557-3117 [Electronic] United States
• PMID: 21216159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Carbon Monoxide
• Biliverdine

Topics

• Animals
• Antioxidants (administration & dosage)
• Biliverdine (administration & dosage)
• Brain Death
• Carbon Monoxide (administration & dosage)
• Male
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy, prevention & control)