Recombinant soluble P-selectin glycoprotein ligand-1 protects against myocardial ischemic reperfusion injury in cats

Objective: Neutrophils (PMNs) contribute importantly to the tissue injury a ssociated with ischemia and subsequent reperfusion of a vascular bed. The e ffects of a recombinant soluble human form of P-selectin glycoprotein ligan d-l (rsPSGL.Ig) on PMN-endothelial cell interactions were investigated in a well established model of feline myocardial-ischemia reperfusion injury. M ethods: Cats were subjected to 90 min of myocardial ischemia followed by 27 0 min of reperfusion. Results: Administration of rsPSGL.Ig (1 mg/kg) just p rior to reperfusion resulted in a significant reduction in myocardial necro sis compared to that in cats administered a low affinity mutant form of rsP SGL.Ig (1 mg/kg) (16+/-3 vs. 42+/-7% of area-at-risk, P<0.01). Cardioprotec tive effects were confirmed by significant (P<0.05) reductions in plasma cr eatine kinase activity in cats treated with rsPSGL.Ig. Inhibition of PMN-en dothelial cell interactions was evidenced by a significant attenuation in c ardiac myeloperoxidase activity (P<0.01) and reduced PMN adherence to ische mic-reperfused coronary endothelium (P<0.001). In addition, rsPSGL.Ig treat ment significantly (P<0.01) preserved endothelium-dependent vasorelaxation in ischemic-reperfused coronary arteries. Conclusion: These results demonst rate that the administration of a recombinant soluble PSGL-1 reduces myocar dial reperfusion injury and preserves vascular endothelial function, which is largely the result of reduced PMN-endothelial cell interactions. (C) 199 9 Elsevier Science B.V. All rights reserved.