Sulfatide reduces leucocyte accumulation and reverts vascular failure in splanchnic artery occlusion shock

Selectin-mediated leucocyte accumulation is implicated in the pathogenesis of splanchnic artery occlusion. Sulfatide is recognized by P-selectin and b locks this adhesion molecule. We investigated the effects of sulfatide in r ats subjected to splanchnic artery occlusion shock. Anaesthetized rats, sub jected to total occlusion of the superior mesenteric artery and the coeliac trunk for 45 min developed severe shock resulting in death within 85-90 mi n after the release of occlusion. Sham operated animals were used as contro ls. Splanchnic artery occlusion shocked rats had marked hypotension, enhanc ed levels of tumor necrosis factor-alpha (TNF-alpha) in serum and macrophag es, leucopenia and increased ileal leucocyte accumulation, studied by the m eans of myeloperoxidase activity. Furthermore, aortae from shocked rats sho wed marked hyporeactivity to phenylephrine (1 nM-10 mu M), reduced responsi veness to acetylcholine (10 nM-10 mu M) and an increased staining for P-sel ectin in the vasculature. In vivo administration of sulfatide (10 mg/kg, i. v., 5 min after occlusion of the splanchnic arteries) increased survival ra te (90%, 4 h after splanchnic artery occlusion shock), enhanced mean arteri al blood pressure, reduced serum TNF-alpha (37 +/- 11 U/ml vs. 398 +/- 18 U /ml), ameliorated leucopenia and reduced ileal myeloproxidase activity (1.2 +/- 0.4 U/g tissue vs. 8.2 +/- 0.8 U/g tissue). Aortae from splanchnic art ery occlusion shocked rats treated with sulfatide exhibited a greater contr actile response to phenylephrine and improved responsiveness to acetylcholi ne. Moreover sulfatide-treated rats showed a reduced staining for P-selecti n in the aorta and in the superior mesenteric artery. Finally, passive immu nization with specific monoclonal antibodies raised against P-selectin sign ificantly protected from the lethality induced by splanchnic artery occlusi on shock. Our results suggest that sulfatide protects against splanchnic ar tery occlusion shock. (C) 1998 Elsevier Science B.V. All rights reserved.