Amino acids counteract the inhibitory effect of fentanyl on hepatocyte oxidative metabolism.
OBJECTIVE
Hypothermia is common after major surgery in newborns and can be triggered by intraoperative fentanyl analgesia. Recent studies have found that fentanyl inhibits hepatocyte mitochondrial oxidative metabolism, which is proportional to thermogenesis. In adults it has been shown that amino acids have a thermogenic effect, although the biochemical basis of this phenomenon is not known. The aim of this study was to test the hypothesis that amino acids counteract the inhibition of neonatal hepatocyte oxygen consumption by fentanyl.


METHODS
Hepatocytes were isolated from suckling rats, and O2 consumption was measured polarographically. In experiment A hepatocytes were incubated with (1) palmitate alone (control), (2) palmitate plus fentanyl, (3) palmitate plus fentanyl plus amino acids, and (4) palmitate plus amino acids. In experiment B the effects of essential and nonessential amino acids were tested separately. In experiment C, to investigate whether the effect of amino acids is intramitochondrial, hepatocytes were incubated with amino acids plus inhibitors of mitochondrial respiration.


RESULTS
In experiment A, fentanyl significantly inhibited O2 consumption (P = .006). This inhibition was reversed by amino acids (P < .001). In experiment B, both essential and nonessential amino acids reversed the effect of fentanyl (P < .001). In experiment C, there was no difference in O2 consumption in the presence of myxothiazol among the groups indicating that amino acids affect intramitochondrial O2 consumption.


CONCLUSIONS
(1) Amino acids abolish the inhibitory effect of fentanyl on hepatocyte oxidative metabolism. (2) Amino acids affect intramitochondrial O2 consumption and therefore thermogenesis. (3) Perioperative administration of amino acids in neonates may help to prevent hypothermia and its deleterious effects.
Zamparelli
M
M
Department of Paediatric Surgery, Institute of Child Health and Great Ormond Street Hospital for Children, London, England.
Eaton
S
S
Spitz
L
L
Pierro
A
A
D000759:Adjuvants, Anesthesia / Q000037:antagonists & inhibitors*; D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001833:Body Temperature Regulation / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D005283:Fentanyl / Q000037:antagonists & inhibitors*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity
D000759:Adjuvants, Anesthesia; D000596:Amino Acids; D005283:Fentanyl