Tumor necrosis factor-a in ischemia and reperfusion injury in rat lungs

Khimenko, Pavel L., G. J. Bagby, J. Fuseler, and Aubrey E. Taylor. Tumor necrosis factor-a in ischemia and reperfusion injury in rat lungs. J. Appl. Physiol. 85(6): 2005–2011, 1998.—The effects of both recombinant rat tumor necrosis factor-a (TNF-a) and an anti-TNF-a antibody were studied in isolated buffer-perfused rat lungs subjected to either 45 min of nonventilated [ischemia-reperfusion (I/R)] or air-ventilated (V̇/R) ischemia followed by 90 min of reperfusion and ventilation. In the I/R group, the vascular permeability, as measured by the filtration coefficient (Kfc), increased threeand fivefold above baseline after 30 and 90 min of reperfusion, respectively (P , 0.001). Over the same time intervals, the Kfc for the V̇/R group increased fiveand tenfold above baseline values, respectively (P , 0.001). TNF-a measured in the perfusates of both ischemic models significantly increased after 30 min of reperfusion. Recombinant rat TNF-a (50,000 U), placed into perfusate after baseline measurements, produced no measurable change in microvascular permeability in control lungs perfused over the same time period (135 min), but I/R injury was significantly enhanced in the presence of TNF-a. An anti-TNF-a antibody (10 mg/rat) injected intraperitoneally into rats 2 h before the lung was isolated prevented the microvascular damage in lungs exposed to both I/R and V̇/R (P , 0.001). These results indicate that TNF-a is an essential component at the cascade of events that cause lung endothelial injury in short-term I/R and V̇/R models of lung ischemia.