Effects of low-dose Beraprost sodium, a stable prostaglandin I2 analogue, on reperfusion injury to rabbit lungs

We investigated the effects of low-dose Beraprost sodium (BPS), a stable prostaglandin I-2 (PGI(2)) analogue, on microvascular permeability and the plasma concentrations of thromboxane and adenosine 3',5'-cyclic monophosphate (cAMP) in blood-perfused rabbit lungs subjected to ischemia-reperfusion (I/R). After an ischemic insult for 2 h, saline as a vehicle, 3 pmol/L of BPS (BPS-1), 150 to 300 pmol/L of BPS (BPS-2), 900 pmol/L of BPS (BPS-3), or 60 mu mol/L of indomethacin (IND) was administered into the reservoir, then the lungs were reperfused and reventilated for 1 h. Vascular permeability was assessed by determining the microvascular filtration coefficient (K-f, ml/min/mm Hg/100 g wet lung). I/R resulted in increases in vascular resistance, K-f, and thromboxane. BPS-2, BPS-3, and IND inhibited the increase in vascular resistance, and BPS-3 and IND attenuated the increases in K-f and thromboxane. BPS-3 increased, but IND decreased, the concentrations of cAMP in the perfusate. Perfusate thromboxane released after reperfusion was significantly correlated with K-f. We conclude that cyclooxygenase products play a critical role in I/R-induced lung vascular injury and that 900 pmol/L of BPS inhibits the production of thromboxane and enhances the permeability barrier via a cAMP-elevating effect. However, vasodilatory action of BPS may exacerbate the reperfused lung injury by increasing the flow through injured capillaries via inhibition of thromboxane-induced vasoconstriction.