A COMPARATIVE-STUDY OF THE EFFECTS OF ILOPROST AND PGE(1) ON PULMONARY ARTERIAL-PRESSURE AND EDEMA FORMATION IN THE ISOLATED-PERFUSED RAT LUNG MODEL

Isolated lungs from male Wistar rats (250-350 g) were perfused at a co nstant flow rate (10 ml/min, non-recirculating) with Krebs-Ringer-bica rbonate buffer containing 4.5% bovine serum albumin, and were ventilat ed at a positive pressure (60 breaths/min). Pulmonary arterial pressur e and lung weight las a measure of edema formation) were recorded cont inuously. After an equilibration period of 20 minutes the various test compounds were added to the perfusion fluid and experimental recordin g was continued for another 60 minutes. The effects of the stable PGI( 2)-mimetic, iloprost, of PGE(1), and of the biologically active PGE(1) -metabolite, 13,14-dihydro-PGE(1), were evaluated in this model (n=6). Iloprost showed slight, but not significant vasodilation; however, lu ng weight remained unchanged. PGE(1) and 13,14-dihydro-PGE(1) also cau sed slight vasodilation, but in contrast to iloprost these compounds i nduced distinct pulmonary edema. The lung weight gain was discernible at concentrations of 2.8 x 10(-6) mol/l (significant at 2.8 x 10(-5) m ol/l; p less than or equal to 0.05) and was accompanied by increases i n the wet-weight to dry-weight ratios. These findings were duplicated in a second set of experiments (n = 6) from which the same results wer e obtained. The results indicate that at high concentrations PGE(1) (a nd 13,14-dihydro-PGE(1)), but not iloprost, can induce pulmonary edema in rats probably by increasing the permeability of the pulmonary vasc ulature.