Tumor necrosis factor-alpha in ischemia and reperfusion injury in rat lungs.
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.
Khimenko
P L
PL
Department of Physiology, College of Medicine, University of South Alabama, Mobile, Alabama 36688, USA.
Bagby
G J
GJ
Fuseler
J
J
Taylor
A E
AE
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004727:Endothelium / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000503:physiopathology*; D055370:Lung Injury; D008297:Male; D010477:Perfusion; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D000906:Antibodies; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha