[Effect of etomidate on mitochondrial energy metabolism of rat livers in vitro].
OBJECTIVE
To investigate the change of energy metabolism in isolated rat liver mitochondria by the general anesthetic etomidate.


METHODS
Nine healthy male SD rats weighted 230-280 g were used to isolate liver mitochondria. According to randomized block design, the isolated liver mitochondria wered divided into three groups: control group, 0.4 microg/mL etomidate group, and 4 microg/mL etomidate group. Then the samples were incubated at 37 degrees C for 7 min. The fluorescence intensities of lipophilic cation Rhodamine-123 and forward light scatter (FSC) were analyzed by flow cytometry. The size of the adenine nucleotides (AMP, ADP, ATP) in mitochondria was measured by high performance liquid chromatography (HPLC). The energy charge (EC) = (ATP + 0.5ADP)/(ATP + ADP + AMP). The inorganic phosphorus method was used to measure the H(+)-ATPase hydrolytic activity and the oligomycin-sensitive H(+)-ATPase activity. The enzyme activity was express as nmol Pi/(mg pro x min).


RESULTS
The fluorescence intensities level of Rhodamine-123 in the 0.4 microg/mL etomidate group was higher than in the control group, but still lower than in the 4 microg/mL etomidate group (P<0.05). The size of FSC had no significant change in the 0.4 microg/mL etomidate group, whereas the 4 microg/mL etomidate group had increased size of FSC (P<0.05). Compared to the control group, no significant changes of content of adenine nucleotides, energy charge and hydrolytic activity of H(+)-ATPase were found in the 0.4 microg/mL etomidate group. However, the intra-mitochondrial ADP, ATP and energy charge levels decreased and the AMP increased in the 0.4 microg/mL etomidate group (P<0.05). The hydrolytic activity of H(+)-ATPase increased in the 4 microg/mL etomidate group (P<0.01), but it was not influenced by oligomycin (P>0.05).


CONCLUSIONS
Etomidate at 0.4 microg/mL has no significant effect on isolated rat liver mitochonddia, but at 4 microg/mL it can lead to distruption of mitochondrial energy metabolism.
Liu
Feng-zhi
FZ
Laboratory of Anesthesia and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhang
Wen-sheng
WS
Luo
Chao-zhi
CZ
D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D005045:Etomidate / Q000009:adverse effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D018686:Anesthetics, Intravenous; D005045:Etomidate