Journal of Applied Physiology
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J Appl Physiol 85: 2005-2011, 1998;
8750-7587/98 $5.00
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Vol. 85, Issue 6, 2005-2011, December 1998

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

Pavel L. Khimenko1, G. J. Bagby2, J. Fuseler3, and Aubrey E. Taylor1

1 Department of Physiology, College of Medicine, University of South Alabama, Mobile, Alabama 36688; 2 Department of Physiology, Louisiana State University Medical Center, New Orleans 70112; and 3 Department of Medicine, Louisiana State, University Medical Center, Shreveport, Louisiana 71130

The effects of both recombinant rat tumor necrosis factor-alpha (TNF-alpha ) and an anti-TNF-alpha antibody were studied in isolated buffer-perfused rat lungs subjected to either 45 min of nonventilated [ischemia-reperfusion (I/R)] or air-ventilated (V/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 three- and fivefold above baseline after 30 and 90 min of reperfusion, respectively (P < 0.001). Over the same time intervals, the Kfc for the V/R group increased five- and tenfold above baseline values, respectively (P < 0.001). TNF-alpha measured in the perfusates of both ischemic models significantly increased after 30 min of reperfusion. Recombinant rat TNF-alpha (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-alpha . An anti-TNF-alpha 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 V/R (P < 0.001). These results indicate that TNF-alpha is an essential component at the cascade of events that cause lung endothelial injury in short-term I/R and V/R models of lung ischemia.

cytokines; microvascular permeability


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