Recombinant soluble P-selectin glycoprotein ligand-1 protects against myocardial ischemic reperfusion injury in cats.
OBJECTIVE
Neutrophils (PMNs) contribute importantly to the tissue injury associated with ischemia and subsequent reperfusion of a vascular bed. The effects of a recombinant soluble human form of P-selectin glycoprotein ligand-1 (rsPSGL.Ig) on PMN-endothelial cell interactions were investigated in a well established model of feline myocardial-ischemia reperfusion injury.


METHODS
Cats were subjected to 90 min of myocardial ischemia followed by 270 min of reperfusion.


RESULTS
Administration of rsPSGL.Ig (1 mg/kg) just prior to reperfusion resulted in a significant reduction in myocardial necrosis compared to that in cats administered a low affinity mutant form of rsPSGL.Ig (1 mg/kg) (16 +/- 3 vs. 42 +/- 7% of area-at-risk, P < 0.01). Cardioprotective effects were confirmed by significant (P < 0.05) reductions in plasma creatine kinase activity in cats treated with rsPSGL.Ig. Inhibition of PMN-endothelial cell interactions was evidenced by a significant attenuation in cardiac myeloperoxidase activity (P < 0.01) and reduced PMN adherence to ischemic-reperfused coronary endothelium (P < 0.001). In addition, rsPSGL.Ig treatment significantly (P < 0.01) preserved endothelium-dependent vasorelaxation in ischemic-reperfused coronary arteries.


CONCLUSIONS
These results demonstrate that the administration of a recombinant soluble PSGL-1 reduces myocardial reperfusion injury and preserves vascular endothelial function, which is largely the result of reduced PMN-endothelial cell interactions.
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002415:Cats; D002448:Cell Adhesion; D003331:Coronary Vessels; D003402:Creatine Kinase / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000627:therapeutic use*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D019007:P-Selectin; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use