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 intravenous anesthetic propofol on cerebral content of high-energy metabolites, glucose, and lactate in normoxic and severely hypoxic rats. General and local anesthetics (isoflurane, N(2)O 70%, pancuronium bromide, bupivacaine hydrochloride) were used for surgery (tracheostomy, femoral artery and vein cannulation, skull exposure, ligature of right-sided carotid and EEG needle electrodes only in rats devoted to the hypoxia study). For normoxia study, four groups of 7 rats each were treated for 60 min as it follows: the control group with N(2)O plus propofol vehicle and the other three with propofol 12.5, 25, or 50 mg x kg(-1) x 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. During the last 20 min Pa(O(2)) was lowered to 15-20 mmHg. Pa(CO(2)) was maintained between 35-40 mmHg, rectal temperature at 37 degrees C, MABP near to 100 mmHg and pH on the basal values during the whole procedure. Then brains were frozen in vivo, and cortical tissue was excised and analyzed for labile metabolites using fluorometric techniques. Propofol, at all the doses tested, did not alter the concentrations of adenine nucleotides, phosphocreatine, lactate, pyruvate, or glucose in normoxic rats. 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 21 and 18 micromol/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 x kg(-1) x h(-1) significantly reduced those adverse effects of hypoxia.
Ori
C
C
Department of Anesthesiology and Critical Care Medicine, Universit degli Studi di Padova, Italy. carloori@ipdunidx.unipd.it
Cavallini
L
L
Freo
U
U
Ruggero
S
S
Ermani
M
M
Pizzolato
G
G
Dam
M
M
D000227:Adenine Nucleotides / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D000227:Adenine Nucleotides; D018686:Anesthetics, Intravenous; D010725:Phosphocreatine; D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose; D010100:Oxygen; D015742:Propofol