Acute mesenteric ischemia and reperfusion: Protective effects of recombinant soluble P-selectin glycoprotein ligand-1

The effects of recombinant soluble P-selectin glycoprotein ligand-1 (rsPSGL .Ig) were studied after 120 min of splanchnic artery occlusion and 120 min of reperfusion (SAO/R). SAO/R rats administered a low-affinity mutant form of rsPSGL.Ig exhibited signs of severe circulatory collapse with marked hyp otension, a survival time of only 37 +/- 16 min, and significant increases in intestinal myeloperoxidase (MPO) activity (P <0.01). In addition, SAO/R rats given rsPSGL.Ig low-affinity mutant showed severe endothelial dysfunct ion characterized by a blunted vasorelaxation to the endothelium-dependent vasodilator acetylcholine in comparison to sham-operated controls (30 +/- 9 % vs. 97 +/- 3%). Administration of rsPSGL.Ig (0.5 mg/kg) significantly imp roved mean arterial blood pressure and increased survival time to 107 +/- 1 3 min (P < 0.01). rsPSGL.Ig treatment also resulted in a significant attenu ation in both intestinal MPO activity as well as the SAO/R-induced decline in endothelium-dependent vasorelaxation of superior mesenteric artery rings (P < 0.01). In addition, rsPSGL.Ig attenuated in vitro neutrophil adherenc e to thrombin-stimulated superior mesenteric artery endothelium to a compar able degree as a P-selectin monoclonal antibody. These data suggest that rs PSGL.Ig provides beneficial effects by preserving endothelial function and attenuating neutrophil-endothelial cell interactions in the splanchnic circ ulation following ischemia-reperfusion.