Effects of general anaesthetic procedures on mitochondrial function of human skeletal muscle.
BACKGROUND
General anaesthetics inhibit mitochondrial function in animal models. However, very few studies have been performed in humans, and the results have not been conclusive.


METHODS
We prospectively studied the oxygen consumption and the individual enzyme activity of each complex of the mitochondrial respiratory chain of skeletal muscle mitochondria in 54 healthy individuals who underwent general anaesthesia for orthopaedic surgery. The control group (n = 54) was made up of individuals submitted to the same orthopaedic procedure under regional anaesthesia (n = 31), and patients who underwent muscle biopsies for diagnostic purposes by local anaesthesia (n = 23).


RESULTS
We found a significant decrease in the oxidation of glutamate (-36%), succinate (-25%) and ascorbate (-29%) in the general anaesthetic group compared with the controls (P < 0.001 for all substrates). The level of such inhibition was similar for volatile anaesthetics with strong (halothane) or weak (isoflurane) negative inotropic effect. By contrast, the enzymatic activity of all individual complexes and the coupling of oxidative phosphorylation did not differ between the two groups.


CONCLUSIONS
We conclude that during general anaesthetic procedures there is an extensive inhibition of substrate oxidation in human muscle mitochondria, and that it is not caused by a direct effect on complexes of the mitochondrial respiratory chain or through uncoupling oxidative phosphorylation.
Miró
O
O
Department of Internal Medicine, August Pi i Sunyer Biomedical Research Unit, (IDIBAPS) Hospital Clinic, Medical School, University of Barcelona, Catalonia, Spain.
Barrientos
A
A
Alonso
J R
JR
Casademont
J
J
Jarreta
D
D
Urbano-Márquez
A
A
Cardellach
F
F
D000765:Anesthesia, Conduction / Q000009:adverse effects; D000772:Anesthesia, Local / Q000009:adverse effects; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D001205:Ascorbic Acid / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006221:Halothane / Q000009:adverse effects; D006801:Humans; D066298:In Vitro Techniques; D007530:Isoflurane / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D013053:Spectrophotometry; D019802:Succinic Acid / Q000378:metabolism
D018685:Anesthetics, Inhalation; D018698:Glutamic Acid; D019802:Succinic Acid; D007530:Isoflurane; D010088:Oxidoreductases; D001205:Ascorbic Acid; D006221:Halothane