Increased microvascular permeability caused by toxic oxygen metabolites is partly reversed by exchanging the perfusate in isolated rat lungs.
Toxic oxygen metabolites (TOM) released from stimulated phagocytes and lung tissue have been shown to injure the pulmonary microcirculation. In the present study we evaluated microvascular injury caused by TOM in rat lungs perfused with plasma. The injury, as indicated by an increase in vascular permeability, was assessed by determining the fluid filtration rate (FFR) after paralysing the pulmonary vascular bed with papaverine (0.1 mg/ml). TOM were generated by adding xanthine oxidase (XO) (0.05-0.125 U/ml) and hypoxanthine (HX) (1 mmol/l) to the perfusate. FFR was measured before, 30 and 60 min after addition of XO and HX. The following interventions were done: 1. the H2O2-scavenger catalase, 2. substitution of the perfusate after 30 min, 3. BW 755 C, a combined lipoxygenase and cyclooxygenase inhibitor, and 4. indomethacin, a cyclooxygenase inhibitor. Addition of XO and HX caused FFR to increase from 14 +/- 4 mg/min (mean +/- s.e. mean) at the onset to 56 +/- 7 mg/min and 86 +/- 10 mg/min after 30 and 60 min, respectively. Replacing the perfusate with fresh plasma after 30 min caused a significant reduction in FFR at 60 min, from 86 +/- 11 mg/min to 58 +/- 10 mg/min. Catalase prevented the increase in FFR. Indomethacin and BW 755 C had no effect on the increase in FFR. We conclude that TOM induced a partly reversible increase in microvascular permeability of isolated rat lungs. From previous studies, the activity of XO was expected to cease after 30 min. Therefore it is suggested that secondary products of TOM propagate the lung injury. The increase in permeability was not mediated by arachidonic acid metabolites.
Kjaeve
J
J
Department of Anesthesiology, University of Tromsø, Norway.
Vaage
J
J
Bjertnaes
L
L
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D002374:Catalase / Q000494:pharmacology; D007042:Hypoxanthines / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D010100:Oxygen / Q000633:toxicity*; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014969:Xanthine Oxidase / Q000494:pharmacology
D001095:Arachidonic Acids; D007042:Hypoxanthines; D016718:Arachidonic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D010208:Papaverine; D002374:Catalase; D014969:Xanthine Oxidase; D010100:Oxygen; D007213:Indomethacin