EFFECTS OF NALMEFENE, CG3703, TIRILAZAD, OR DOPAMINE ON CEREBRAL BLOOD-FLOW, OXYGEN DELIVERY, AND ELECTROENCEPHALOGRAPHIC ACTIVITY AFTER TRAUMATIC BRAIN INJURY AND HEMORRHAGE

Hemorrhage after traumatic brain injury (TBI) in cats produces signifi cant decreases in cerebral oxygen delivery (DcereO2) and electroenceph alographic (EEG) activity. To determine whether effective treatments f or the separate insults of TBI and hemorrhagic shock would also prove effective after the clinically relevant combination of the two, we mea sured the effects of a K-opiate antagonist (nalmefene), an inhibitor o f lipid peroxidation (tirilazad), a thyrotropin-releasing hormone anal og (CG3703), a clinically useful presser agent (dopamine) or a saline placebo on cerebral blood flow (CBF), and EEG activity after TBI and m ild hemorrhagic hypotension. Cats (n = 40, 8 per group) were anestheti zed with 1.6% isoflurane in N2O:O-2 (70:30) and prepared for fluid-per cussion TBI and microsphere measurements of CBF. Cats were randomized to receive nalmefene (1 mg/kg), tirilazad (5 mg/kg), CG3703 (2 mg/kg), dopamine (20 mu g.kg(-1) min(-1)) or a saline placebo (2 mi, 0.9% NaC l). Animals were injured (2.2 atm), hemorrhaged to 70% of preinjury bl ood volume, treated as just described and resuscitated with a volume o f 10% hydroxyethyl starch equal to shed blood. CBF was determined and EEG activity recorded before injury, after hemorrhage, and 0, 60, and 120 min after resuscitation (RO, R60, and R120). CBF increased signifi cantly after resuscitation (RO) in the nalmefene-and CG3703-treated gr oups. CBF did not differ significantly from baseline in any group at R 60 or R120. DcereO2 was significantly less than baseline in the saline -, dopamine-, and tirilazad-treated groups at R60 and in the dopamine- , tirilazad-, and CG3703-treated groups at R120. EEG activity remained unchanged in the nalmefene-treated group but deteriorated significant ly at R60 or R120 compared to baseline in the other groups. Nalmefene and CG3703 preserved the hyperemic response to hemodilution (otherwise antagonized by TBI), and nalmefene prevented the deterioration in Dce reO2 and EEG activity that occurs after TBI and hemorrhage.