Dibutyryl cyclic adenosine monophosphate attenuates lung injury caused by cold preservation and ischemia-reperfusion.
OBJECTIVE
Dibutyryl adenosine 3',5'cyclic monophosphate (db-cAMP) is a membrane-permeable analog of adenosine 3',5'cyclic monophosphate (cAMP). We examined the effect of db-cAMP against lung injury caused by cold preservation and ischemia-reperfusion.


METHODS
Rats were divided into three groups (each n = 6) according to the presence or absence of db-cAMP in the preservative solution and cold ischemia (4 degrees C for 15 hours). In the fresh group, the lung was flushed with the preservative solution and reperfusion was performed immediately. In the control group and the db-cAMP group, the lung was flushed either with the solution or with a combination of the solution plus db-cAMP, respectively, and preserved at 4 degrees C for 15 hours. The lung was reperfused for 60 minutes in an ex vivo rat lung perfusion model.


RESULTS
The shunt ratios of the reperfused lung in the db-cAMP group were 4.0% +/- 1.6% and 3.4% +/- 1.2% 10 and 60 minutes, respectively, after the initiation of reperfusion, being as low as those in the fresh group and significantly lower than those in the control group (p < 0.01). The wet/dry weight ratio of the lung tissue after reperfusion was 5.99 +/- 1.50 in the db-cAMP group, which was similar to that in the fresh group (5.45 +/- 0.23) and significantly lower than that in the control group (14.20 +/- 3.43) (p < 0.01). Electron microscopic examination showed less damage in the pulmonary arterial endothelium in the db-cAMP group.


CONCLUSIONS
We conclude that db-cAMP attenuates the lung injury by cold preservation and ischemia-reperfusion, at least partly by protection of the vascular endothelium.
Nakamura
T
T
Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University, Japan.
Hirata
T
T
Fukuse
T
T
Ueda
M
M
Hitomi
S
S
Wada
H
H
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D003080:Cold Temperature; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure; D008168:Lung / Q000098:blood supply; D016040:Lung Transplantation; D008297:Male; D008854:Microscopy, Electron; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors
D019188:Organ Preservation Solutions; D003994:Bucladesine