Low-dose carbon monoxide inhalation prevents ischemia/reperfusion injury of transplanted rat lung grafts.

Abstract

BACKGROUND:

Carbon monoxide (CO), a byproduct of heme catalysis by heme oxygenases, has been shown to provide protection against ischemia/reperfusion (I/R) injury. We examined the cytoprotective effect of CO at a low concentration on cold I/R injury of transplanted lung grafts.

METHODS:

Orthotopic left lung transplantation was performed in syngenic Lewis to Lewis rat combination. Grafts were preserved in University of Wisconsin solution at 4 degrees C for 6 hours. Donors and/or recipients were exposed to CO (250 ppm) in air for 1 hour before surgery and then continuously post-transplantation.

RESULTS:

Blood oxygen partial pressure of graft pulmonary veins in the CO-treated group versus the air-treated group was significantly higher. The increase of messenger RNA of inflammatory mediators such as interleukin-6, tumor necrosis factor-alpha, inducible nitric oxide synthase, and cycloooxygenase-2 was markedly inhibited in the CO-treated group. The expression of phosphorylated-extracellular signal-regulated protein kinase 1/2 was significantly reduced in the CO-treated group. CO treatment reduced the number of infiltrating macrophages into the lung grafts. Vascular endothelial cells detected by CD31 stain were well preserved in CO-treated grafts, while those in air-treated grafts were faint and interrupted.

CONCLUSIONS:

These results demonstrate that exogenous low-dose CO treatment of donors and recipients can prevent lung I/R injury and significantly improve function of lung grafts after extended cold preservation and transplantation.

• Authors: Junichi Kohmoto, Atsunori Nakao, Takashi Kaizu, Allan Tsung, Atsushi Ikeda, Koji Tomiyama, Timothy R Billiar, Augustine M K Choi, Noriko Murase, Kenneth R McCurry
• Journal: Surgery (Surgery) Vol. 140 Issue 2 Pg. 179-85 (Aug 2006) ISSN: 0039-6060 [Print] United States
• PMID: 16904967 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Carbon Monoxide

Topics

• Administration, Inhalation
• Animals
• Blood Gas Analysis
• Carbon Monoxide (administration & dosage)
• Drug Administration Schedule
• Graft Survival
• Inflammation Mediators (blood)
• Lung Transplantation (adverse effects)
• Male
• Rats
• Rats, Inbred Lew
• Reperfusion Injury (etiology, prevention & control)