Low-dose carbon monoxide inhalation prevents ischemia/reperfusion injury of transplanted rat lung grafts.
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.
Kohmoto
Junichi
J
Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Nakao
Atsunori
A
Kaizu
Takashi
T
Tsung
Allan
A
Ikeda
Atsushi
A
Tomiyama
Koji
K
Billiar
Timothy R
TR
Choi
Augustine M K
AM
Murase
Noriko
N
McCurry
Kenneth R
KR
D000280:Administration, Inhalation; D000818:Animals; D001784:Blood Gas Analysis; D002248:Carbon Monoxide / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D006085:Graft Survival; D018836:Inflammation Mediators / Q000097:blood; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
D018836:Inflammation Mediators; D002248:Carbon Monoxide