Abstract W P84: Post-ischemic Intra-arterial Infusion of Liposome-encapsulated Hemoglobin Suppresses Endothelial and Neutrophil Inflammatory Activation Accompanied by Maintaining Microvascular Perfusion in Rat Cerebral Ischemia Reperfusion Model

Abstract

Background: Liposome-encapsulated hemoglobin (LEH) containing human hemoglobin (Hb) is an artificial oxygen carrier with 1/40th the size of erythrocytes. We previously demonstrated that post-ischemic intra-arterial (IA) infusion of LEH for 2 hours can reduce ischemia reperfusion (I/R) injury in the rat transient MCAO model (2013, ISC Honolulu). In the present study we examine whether short-time (15-minute) infusion of LEH can also have the same effect on I/R injury and explore the mechanism of the effect. Methods: Male SD rats were subjected to 2-hour MCAO and then were divided into three groups: 1) LEH group (n=9) infused with LEH (20 ml/kg) through the recanalized internal carotid artery for 15 minutes, 2) vehicle group (n=8) infused with saline (20 ml/kg) in the same manner as the LEH group, and 3) control group subjected to recanalization only (n=8). Results: Compared with the control and vehicle groups, the LEH group showed significantly better neurological score, smaller infarction and brain edema, and less Evans blue leakage (p<0.01). MPO expression, MMP-9 expression and activity, and ICAM-1 expression in the LEH group were also significantly lower than those in the control and vehicle groups (p<0.01). LEH visualized by immunostaining with anti-human Hb antibody in the LEH group was distributed in significantly more microvessels (p<0.01) compared with rat erythrocyte visualized by immunostaining with anti-rat Hb antibody in the control group (Figure). Conclusions: Short-time IA infusion of LEH can reduce I/R injury like long-time infusion. This therapeutic approach is likely to suppress endothelial and neutrophil inflammatory activation accompanied by maintaining microvascular perfusion because of LEH’s small size compared with erythrocyte.