THE EFFECTS OF PROPOFOL ON CEREBRAL HIGH-ENERGY METABOLITES, LACTATE,AND GLUCOSE IN NORMOXIC AND SEVERELY HYPOXIC RATS

Study was performed in Fischer-344 rats to test the effects of the int ravenous anesthetic propofol on cerebral content of high-energy metabo lites, glucose, and lactate in normoxic and severely hypoxic rats. Gen eral and local anesthetics (isoflurane, N2O 70%, pancuronium bromide, bupivacaine hydrochloride) were used for surgery (tracheostomy, femora l artery and vein cannulation, skull exposure, ligature of right-sided carotid and EEG needle electrodes only ill rats devoted to the hypoxi a study). For normoxia study, four groups of 7 rats each were treated for 60 min as it follows: the control group with N2O plus propofol veh icle and the other three with propofol 12.5, 25, or 50 mg kg(-1). h(-1 ) respectively. For the hypoxia-study five groups of 7 rats each were planned to have two control (one normoxic) and three propofol-treated groups, drug treatments being the above indicated and of 80 min. Durin g the last 20 min Pa-O2 was lowered to 15-20 mmHg. Pa-CO2 was maintain ed between 35-40 mmHg, rectal temperature at 37 degrees C, MABP near t o 100 mmHg and pH on the basal values during the whole procedure. Then brains were frozen in vivo, and cortical tissue was excised and analy zed for labile metabolites using fluorometric techniques. Propofol, at all the doses tested, did not alter the concentrations of adenine nuc leotides, phosphocreatine, lactate, pyruvate, or glucose in normoxic r ats. In rat brain, hypoxia did not produce significant changes in the concentrations of adenine nucleotides. PCr concentration was decreased both in the ligated and unligated side, and lactate levels exceeded 2 1 and 18 mu mol/g in the right and left cortices, respectively. While the lowest dose of propofol was ineffective in preventing PCr decrease and lactate increase, both 25 and 50 mg kg(-1). h(-1) significantly r educed those adverse effects of hypoxia.