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 (cA MP), We examined the effect of db-cAMP against lung injury caused by c old 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 f or 15 hours), In the fresh group, the lung was flushed with the preser vative solution and reperfusion was performed immediately, In the cont rol group and the db-cAMP group, the lung was flushed either with the solution or with a combination of the solution plus db-cAMP, respectiv ely, and preserved at 4 degrees C for 15 hours, The lung was reperfuse d 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 ini tiation of reperfusion, being as low as those in the fresh group and s ignificantly 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 protect ion of the vascular endothelium.