Splanchnic artery occlusion
shock was induced in anesthetized rats by clamping the splanchnic arteries for 45 min. The survival rate, plasma levels of
thromboxane B2 (TxB2) and
6-keto-PGF1 alpha, serum and peritoneal levels of macrophage
tumor necrosis factor (
TNF alpha), the phagocytotic and killing activity of peritoneal macrophages and white blood cells count were evaluated. Shocked rats died within 2 h, while all
sham-shocked rats survived more than 6 h. Plasma TxB2 and
6-keto-PGF1 alpha levels were increased in rats subjected to splanchnic artery occlusion
shock compared to the levels in
sham-shocked animals. Serum and peritoneal macrophage
TNF alpha levels were undetectable in
sham-shocked rats, whereas shocked rats exhibited increased levels of
TNF alpha. Moreover, splanchnic artery occlusion
shock reduced peritoneal macrophage phagocytotic and killing activity, and also produced severe
leukopenia. A specific receptor antagonist of
platelet activating factor (PAF), L-652, 731 (an i.v. bolus of 3.2 mg/kg 2 min after removal of the clamps followed, 5 min thereafter, by a continuous infusion of 0.16 mg/kg per min for 30 min) significantly increased the survival rate, lowered plasma TxB2 levels and reduced both serum and macrophage
TNF alpha levels in shocked rats. In addition,
L-652,731 completely restored macrophage phagocytosis, partially improved macrophage killing and significantly inhibited
leukopenia. Finally, the administration of
L-652,731 had beneficial effects on the cardiovascular changes induced by splanchnic artery occlusion
shock. These findings are consistent with the involvement of PAF in splanchnic artery occlusion
shock and indicate that PAF produces
shock through direct and indirect (TxB2-mediated and
TNF alpha-mediated) actions.