A leporine model to investigate tumour necrosis factor alpha (TNF alpha) secretion after peripheral vein or mesenteric vein lipopolysaccharide injection was devised. Mesenteric vein injection provoked lower arterial concentrations after 90 minutes (median (range), 2.81, (0.75-11.96) ng/ml) than peripheral vein injection (7.00 (4.27-14.95) ng/ml (p less than 0.05)). Mesenteric vein injection after 10 minutes' warm hepatic ischaemia, which impairs hepatic clearance, provoked higher median arterial TNF alpha values at 90 minutes (7.98 (2.85-21.48) ng/ml) than in normal animals (p less than 0.05). Portal vein endotoxaemia induced less TNF alpha production than systemic endotoxaemia unless hepatic clearance was impaired, thus the major source of TNF alpha in systemic endotoxaemia is probably extrahepatic.
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