Dixyrazine, a phenothiazine derivative, can prevent brain oedema induced by intracarotid injection of protamine sulphate

The present study was performed to determine whether an opening of the blood-brain barrier (BBB) induced by intracarotid infusion of protamine sulphate necessarily leads to brain oedema and, if so, whether dixyrazine, a phenothiazine, can prevent the oedema. Evans blue albumin was used to detect BBB opening. Endogenous serum albumin was determined in CSF sampled before and after protamine infusion. The brain specific gravity, a sensitive indicator of brain oedema, was determined one hour after intracarotid infusion of 5 or 10 mg protamine sulphate in 100 or 200 microliters solvent in rats. Both doses opened the BBB and the CSF albumin was significantly increased (p less than 0.05 for 5 mg and p less than 0.01 for 10 mg protamine sulphate). However, only 10 mg protamine significantly reduced the specific gravity in the cerebral cortex and basal ganglia in the right (injected) hemisphere. Pretreatment with dixyrazine 10 mg/kg completely prevented the brain oedema and significantly reduced the albumin increase in CSF. We conclude that a) a moderate opening of BBB induced by 5 mg protamine sulphate does not lead to brain oedema and b) dixyrazine can prevent the brain oedema induced by 10 mg protamine sulphate.