Sanguinate's effect on pial arterioles in healthy rats and cerebral oxygen tension after controlled cortical impact

Sanguinate, a polyethylene glycol-conjugated carboxyhemoglobin, was investigated for cerebral vasoactivity in healthy male Sprague-Dawley rats (Study 1) and for its ability to increase brain tissue oxygen pressure (PbtO(2)) after controlled cortical impact (CCI) - traumatic brain injury (TBI) (Study 2). In both studies ketamine-acepromazine anesthetized rats were ventilated with 40% O-2. In Study 1, a cranial window was used to measure the diameters of medium (50-100 mu m) and small-sized (<50 mu m) pial arterioles before and after four serial infusions of Sanguinate (8 mL/kg/h, cumulative 16 mL/kg IV), volume-matched Hextend, or normal saline. In Study 2, PbtO(2) was measured using a phosphorescence quenching method before TBI, 15 min after TBI (T15) and then every 10 min thereafter for 155 min. At T15, rats received either 8 mL/kg IV Sanguinate (40 mL/kg/h) or no treatment (saline, 4 mL/kg/h). Results showed: 1) in healthy rats, percentage changes in pial arteriole diameter were the same among the groups, 2) in TBI rats, PbtO(2) decreased from 36.5 +/- 3.9 mm Hg to 19.8 +/- 3.0 mm Hg at T15 in both groups after TBI and did not recover in either group for the rest of the study, and 3) MAP increased 16 +/- 4 mm Hg and 36 +/- 5 mm Hg after Sanguinate in healthy and TBI rats, respectively, while MAP was unchanged in control groups. In conclusion, Sanguinate did not cause vasoconstriction in the cerebral pial arterioles of healthy rats but it also did not acutely increase PbtO(2) when administered after TBI. Sanguinate was associated with an increase in MAP in both studies. (C) 2016 Elsevier Inc. All rights reserved.