Pretreatment with Polynitroxyl Albumin (PNA) Inhibits Ischemia-Reperfusion Induced Leukocyte-Endothelial Cell Adhesion

Recently published evidence indicates that polynitroxylated albumin (PNA) protects tissues against ischemia/reperfusion (I/R) injury, possibly by enhancing tissue redox activity. The objective of this study was to determine if PNA treatment alters the leukocyte-endothelial cell adhesion that is normally elicited by I/R. PNA, human serum albumin (HSA) or saline were administered (i.v.) 5 min before reperfusion. Venular diameter, red blood cell velocity, wall shear rate, systemic hematocrit, systemic arterial pressure, as well as the number of adherent and emigrated leukocytes were monitored in rat mesenteric venules before and after 20 min of ischemia and 30 min of reperfusion. In saline-treated rats, I/R elicited a 5.3-fold increase in leukocyte adhesion and a 1.8-fold increase in leukocyte emigration. HSA-treated animals exhibited 4.0 and 2.3-fold increases in leukocyte adherence and emigration, respectively. In PNA-treated rats, the number of adherent leukocytes increased only 2.1-fold increase in adherent leukocytes, while leukocyte emigration was completely inhibited. The PNA-induced attenuation of leukocyte adherence/emigration could not be attributed to alterations in systemic or local hemodynamics (red blood cell velocity or wall shear rate). PNA was also shown to be a potent inhibitor of xanthine-xanthine oxidase mediated adhesion of human neutrophils to cultured human endothelial cells. These findings indicate that PNA may protect tissues against I/R injury by attenuating leukocyte-endothelial cell adhesion.