SEPARATE EFFECTS OF ISCHEMIA AND REPERFUSION ON VASCULAR-PERMEABILITY IN VENTILATED FERRET LUNGS

In systemic organs, ischemia-reperfusion injury is thought to occur during reperfusion, when oxygen is reintroduced to hypoxic ischemic tissue. In contrast, the ventilated lung may be more susceptible to injury during ischemia, before reperfusion, because oxygen tension will be high during ischemia and decrease with reperfusion. To evaluate this possibility, we compared the effects of hyperoxic ischemia alone and hyperoxic ischemia with normoxic reperfusion on vascular permeability in isolated ferret lungs. Permeability was estimated by measurement of filtration coefficient (K(f)) and osmotic reflection coefficient for albumin (sigma(alb)), using methods that did not require reperfusion to make these measurements. K(f) and sigma(alb) in control lungs (n = 5), which were ventilated with 14% O2-5% CO2 after minimal (15 +/- 1 min) ischemia, averaged 0.033 +/- 0.004 g . min-1 . mmHg-1 . 100 g-1 and 0.69 +/- 0.07, respectively. These values did not differ from those reported in normal in vivo lungs of other species. The effects of short (54 +/- 9 min, n = 10) and long (180 min, n = 7) ischemia were evaluated in lungs ventilated with 95% O2-5% CO2. K(f) and sigma(alb) did not change after short ischemia (K(f) = 0.051 +/- 0.006 g . min-1 . mmHg-1 . 100 g-1, sigma(alb) = 0.69 +/- 0.07) but increased significantly after long ischemia (K(f) = 0.233 +/- 0.049 g . min-1 . mmHg-1 . 100 g-1, sigma(alb) = 0.36 +/- 0.05). Thirty minutes of normoxic (14% O2 CO2) reperfusion with physiological salt solution containing 3 g/dl albumin-2 g/dl Ficoll and 175 mg/dl glucose after either 40 +/- 2 (short ischemia-reperfusion, n = 6) or 150 (long ischemia-reperfusion, n = 6) min of ischemia did not further alter permeability. These results suggest that ischemia-reperfusion injury in the ventilated ferret lung occurred primarily during ischemia rather than during reperfusion.