Dibutyryl cyclic adenosine monophosphate attenuates lung injury caused by cold preservation and ischemia-reperfusion.

Abstract

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. 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. 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. We conclude that db-cAMP attenuates the lung injury by cold preservation and ischemia-reperfusion, at least partly by protection of the vascular endothelium.