BackgroundPolynitroxylation of hemoglobin confers superoxide dismutase–mimetic and peroxidase activity and may protect from reperfusion injury in addition to facilitating oxygen transport. We determined whether transfusion of polynitroxylated PEGylated hemoglobin (PNPH) is protective in the rat filament model of 2 hours of middle cerebral artery occlusion (MCAO). Methods and ResultsTransfusion of 10 mL/kg of PNPH at 20 minutes of MCAO reduced infarct volume by over 70% (n=10). To determine whether PNPH might act by promoting vasodilation, pial arteriolar diameter in the distal MCA border region was measured in closed cranial windows. With no transfusion, MCAO induced an initial dilation (36±2% ±SE) that subsided by 2 hours (5±4%; n=8). With PNPH transfusion at 20 minutes of MCAO, the initial dilation (31±3%) was better maintained at 2 hours (21±4%; n=7; P