A comparative study of the effects of iloprost and PGE1 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 constant flow rate (10 ml/min, non-recirculating) with Krebs-Ringer-bicarbonate buffer containing 4.5 % bovine serum albumin, and were ventilated at a positive pressure (60 breaths/min). Pulmonary arterial pressure and lung weight (as a measure of edema formation) were recorded continuously. After an equilibration period of 20 minutes the various test compounds were added to the perfusion fluid and experimental recording was continued for another 60 minutes. The effects of the stable PGI2-mimetic, iloprost, of PGE1, and of the biologically active PGE1-metabolite, 13,14-dihydro-PGE1, were evaluated in this model (n = 6). Iloprost showed slight, but not significant vasodilation; however, lung weight remained unchanged. PGE1 and 13, 14-dihydro-PGE1 also caused slight vasodilation, but in contrast to iloprost these compounds induced 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) mol/l; p < or = 0.05) and was accompanied by increases in the wet-weight to dry-weight ratios. These findings were duplicated in a second set of experiments (n = 6) from which the same results were obtained. The results indicate that at high concentrations PGE1 (and 13,14-dihydro-PGE1), but not iloprost, can induce pulmonary edema in rats probably by increasing the permeability of the pulmonary vasculature.
Misselwitz
B
B
Research Laboratories of Schering AG, Berlin, Germany. BERND.MISSELWITZ@SCHERING.DE
Bräutigam
M
M
D000527:Alprostadil / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D016285:Iloprost / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects*; D011654:Pulmonary Edema / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; C069881:13,14-dihydroprostaglandin E1; D000527:Alprostadil; D016285:Iloprost