PO2 MODULATION OF PARAQUAT-INDUCED MICROVASCULAR INJURY IN ISOLATED DOG LUNGS

We determined the effects of paraquat (PQ) concentrations ranging from 10-3 to 10-2 M and three levels of venous PO2 [hypoxia (41 ± 3 Torr), normoxia (147 ± 8 Torr), and hyperoxia (444 ± 17 Torr)] in the presence of 4 x 10-3 M PQ on microvascular permeability in isolated blood-perfused dog lungs. Capillary filtration coefficient (K(f,c)) increased and isogravimetric capillary pressure (Pc,i) decreased 3 h after perfusion with 10-2 M PQ (n = 7) and 5 h after perfusion with 4 x 10-3 M PQ (n = 6) but not with 10-3 M PQ (n = 4). In hyperoxic lungs perfused with 4 x 10-3 M PQ, K(f,c) increased to nine times the base-line value 5 h after PQ [0.-15 ± 0.01 to 1.35 ± 0.25 (SE) ml · min-1 · cmH2O-1 · 100 g-1]. Pc,i significantly decreased from a base-line value of 9.4 ± 0.2 to 7.1 ± 0.4 cmH2O at 3 h. In hypoxic lungs perfused with 4 x 10-3 M PQ (n = 5), Pc,i and K(f,c) changes were not significantly different from those in normoxic lungs treated with PQ. Thus both hyperoxia and an increased dose of PQ shortened the latent period and increased the severity of the PQ-induced microvascular permeability lesion, but hypoxia failed to prevent the PQ damage.