Reduced ischemia–reperfusion injury with rolipram in rat cadaver lung donors: effect of cyclic adenosine monophosphate

Abstract

Background. The perfusion of rat lungs retrieved from cadavers with a solution containing isoproterenol has been shown to ameliorate the ischemia–reperfusion injury seen in lungs retrieved after death, and this protective effect parallels increases in tissue cyclic adenosine monophosphate levels. In this study, we investigated the effect of rolipram, a phosphodiesterase inhibitor, on capillary permeability and lung cyclic adenosine monophosphate levels in lungs retrieved from circulation-arrested rats. Methods. Using an isolated perfused lung circuit, we retrieved lungs from circulation-arrested donor rats either ventilated with 100% oxygen or not ventilated for varying postmortem times. The lungs were reperfused with or without rolipram (2 μmol/L). The capillary filtration coefficient and wet to dry weight ratio, indicators of pulmonary vascular integrity, were determined, and tissue levels of adenine nucleotides and cyclic adenosine monophosphate were measured by high-performance liquid chromatography. Results. The capillary filtration coefficient was significantly reduced in nonventilated cadaver lungs reperfused with rolipram 120 minutes after death ( p < 0.05). Oxygen ventilation or reperfusion with rolipram had a similar effect on the capillary filtration coefficient. Cyclic adenosine monophosphate levels were significantly higher in rolipram-reperfused lungs retrieved 120 minutes after death in both oxygen-ventilated ( p < 0.01) and nonventilated ( p < 0.01) lungs. Conclusions. In lungs from nonventilated, circulation-arrested donors, reperfusion with rolipram reduces the ischemia–reperfusion injury that may be due to intracellular cyclic adenosine monophosphate. Alteration of perfusate may have an impact on capillary leak caused by antecedent ischemia. Thus, rolipram may be a useful adjunct in the preservation of donor lungs retrieved after death.