Gamma-Hydroxybutyrate: cerebral metabolic, vascular, and protective effects.

Abstract

The cerebral protection afforded by each of several preparations of gamma-hydroxybutyrate (GHB) was examined in the hypoxic (FiO2 = 0.05) mouse model. The greatest increase in survival time (85%) occurred after pretreatment with 300 mg/kg given as buffered gamma-butyrolactone (GBL). Compared with previous studies employing the same hypoxic model, this increase was less than that observed with certain barbiturates and equal to that observed with certain anesthetics. The cerebral and systemic metabolic and vascular effects of each of several preparations of GHB were examined in a canine model. The cerebral metabolic rate for oxygen (CMRO2) tended to increase after GHB 100 mg/kg, then progressively decreased after cumulative doses of 600 mg/kg and 1100 mg/kg. The greatest depression in CMRO2 (48%) occurred with 1100 mg/kg given as unbuffered GBL. With each preparation and at every dose, a reduction in cerebral blood flow (CBF) exceeded the reduction in CMRO2. The major systemic effect was an almost two-thirds reduction in cardiac output at the largest doses. Assuming no species difference the cerebral protection observed with GHB is probably limited by both the reduction in cardiac output and the unfavorable relationship of cerebral oxygen supply to demand (CBF/CMRO2). Brain biopsies taken after the cumulative dose of GHB 1100 mg/kg showed a trend toward lower phosphocreatine levels and higher lactate and lactate/pyruvate levels than in untreated dogs.