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We infused recombinant human tumor necrosis factor alpha (rhTNFJ, lymphotoxin (rhLT), and Escherichia coli 0111:B4 lipopolysaccharide (LPS) into anesthetized sheep with a lung lymph fistula to compare their effects on systemic and pulmonary bemodynamics, lung lymph dynamics, and eicosanoid release. rhTNF,, (25-150 pg/kg, n-6 sheep), but not rhLT (25 /ig/kg, n=3), rapidly increased lung lymph and plasma levels of 6-kcto-prostaglandin F la (6-k-PGF,,,) and caused profound systemic vasodilation and hypotension. Meclofenamate pretreatment (10 mg/kg) of three other sheep given 25 Mg/kg rhTNF., prevented the increase of lymph and plasma 6-k-PGF la levels, systemic vasodilation, and the early (<2 hrs) but not the late (4-6 hours) hypotension caused by rhTNF,,. LPS (1 /ug/kg, n = l l ) induced a briefer increase of lymph 6-k-PGF ln levels than did rhTNF a while plasma 6-k-PGF,,, levels did not increase. LPS induced more gradual hypotension than did rhTNF a but did not cause systemic vasodilation. LPS and rhTNF^ but not rhLT, increased lymph thromboxane Bj (TXBj) levels during the first hour of study, whereas only LPS acutely increased plasma TXB 2 levels. LPS caused acute pulmonary vasoconstriction and greater acute pulmonary artery hypertension than did either rhTNF,, or rhLT. Whereas LPS-treated sheep required less fluid transfusion than rhTNF a -treated sheep to maintain mean systemic arterial pressure greater than 50 mm Hg, LPS infusion caused a greater increase of lung lymph protein clearance. rhTNF,, caused minimal alterations of lung microvascular permeability. We conclude that eicosanoid mediators contribute importantly to differences of systemic and pulmonary hemodynamics caused by these agents in sheep.

A reference strain of Mycobacterium avium subspecies paratuberculosis was added to faecal larval cultures of Haemonchus contortus, Ostertagia circumcincta and Trichostrongylus colubrifonnis. Samples of the larvae produced were cultured for the presence of the bacterium in modified BACTEC 12B medium, both before and after exposure to gamma irradiation. The water used to wash the larvae off the faecal cultures was also tested for the presence of the bacterium. Positive growth was confirmed as M avium subspecies paratuberculosis by is0oo polymerase chain reaction and restriction endonuclease analysis of the product. M avium subspecies paratuberculosis was detected in the unirradiated larval suspensions and wash waters of all three nematode species, and in the irradiated H contortus larval suspension. Veterinary

Rapid protamine reversal of heparin anticoagulation in awake sheep caused, after 1 min, a approximately 15-fold increase of arterial plasma thromboxane B2 (TxB2) levels, a 4-fold rise of pulmonary vascular resistance (PVR), a 2-fold rise of pulmonary arterial pressure, and after 3 min, a 2-fold rise of ovine arterial plasma complement C3a levels (P less than 0.05). Infusion of nafamstat mesilate (FUT-175), a protease and complement pathway inhibitor, before protamine reduced these increases by approximately 60-90% (P less than 0.05). FUT-175 did not modify heparin + protamine-induced leukopenia, suggesting that FUT-175 incompletely blocked C5a production. We also learned that infusing protamine first and heparin 5 min later did not increase either plasma C3a or TxB2 levels or PVR while the activated clotting time increased only minimally. Thus, in awake sheep, the sequence of heparin and protamine infusion influences complement activation and pulmonary vasoconstriction. FUT-175 pretreatment reduces thromboxane release and pulmonary vasoconstriction probably by limiting complement activation.