Time course of endothelial-neutrophil interaction in splanchnic artery ischemia-reperfusion

Splanchnic artery occlusion and reperfusion (SAO/R) results in a severe for m of circulatory shock that has a high mortality rate. To examine the time course of the early events involved in SAO/R, occlusion of the superior mes enteric artery (SMA) and the celiac artery (120 min) were followed by reper fusion periods of 0, 2.5, 5, 20, 30, 60, or 120 min. Relaxation of isolated SMA vascular rings to the endothelium-dependent vasodilator ACh was unimpa ired following 120 min of ischemia (86 +/- 5%); however, significant (P < 0 .01) reductions in endothelium-dependent vasorelaxation were observed follo wing 2.5 min (53 +/- 6%) of reperfusion with severe dysfunction (P < 0.001) observed at 20 min (29 +/- 4%). Neutrophil adherence to the endothelium in creased as a function of reperfusion time with a 2.3-fold increase observed at 20 min (P < 0.01) and a 3.4-fold increase observed at 120 min (P < 0.00 1). Intestinal myeloperoxidase activity was significantly increased 30 min after reperfusion (P < 0.05), whereas surface expression of P-selectin prog ressively increased at 5 (P < 0.05) and 30 min (P < 0.001) postreperfusion. These findings demonstrate that endothelial dysfunction is a very early ev ent in the pathophysiology of SAO/R, subsequently resulting in increased su rface expression of P-selectin and the adherence of neutrophils to the endo thelium that leads to neutrophil accumulation in the splanchnic viscera.