Effects of intermittent femoral nerve injections of bupivacaine, levobupivacaine, and ropivacaine on mitochondrial energy metabolism and intracellular calcium homeostasis in rat psoas muscle.
BACKGROUND
Long-acting local anesthetics cause muscle damage. Moreover, long-acting local anesthetics act as uncoupler of oxidative phosphorylation in isolated mitochondria and enhance sarcoplasmic reticulum Ca(2+) release. The aim of the study was to evaluate effects of perineural injections of local anesthetics on mitochondrial energetic metabolism and intracellular calcium homeostasis in vivo.


METHODS
Femoral nerve block catheters were inserted in adult male Wistar rats. Rats were randomized and received seven injections (1 ml/kg) of bupivacaine, levobupivacaine, ropivacaine, or isotonic saline at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle was quickly dissected from next to the femoral nerve. Local anesthetic concentrations in muscle were determined. Oxidative capacity was measured in saponin-skinned fibers. Oxygen consumption rates were measured, and mitochondrial adenosine triphosphate synthesis rate was determined. Enzymatic activities of mitochondrial respiratory chain complexes were evaluated. Local calcium release events (calcium sparks) were analyzed as well as sarcoplasmic reticulum calcium content in saponin-skinned fibers.


RESULTS
Eight hours after the last injection, psoas muscle concentration of local anesthetics was less than 0.3 microg/g tissue. Adenosine triphosphate synthesis and adenosine triphosphate-to-oxygen ratio were significantly decreased in the muscle of rats treated with local anesthetics. A global decrease (around 50%) in all of the enzyme activities of the respiratory chain was observed. Levobupivacaine increased the amplitude and frequency of the calcium sparks, whereas lower sarcoplasmic reticulum calcium content was shown.


CONCLUSIONS
Bupivacaine, levobupivacaine, and ropivacaine injected via femoral nerve block catheters induce a deleterious effect in mitochondrial energy, whereas only levobupivacaine disturbs calcium homeostasis.
Nouette-Gaulain
Karine
K
Laboratoire de Physiologie Mitochondriale, Unité INSERM U688, Université Victor Ségalen Bordeaux 2, Bordeaux, France.
Sirvent
Pascal
P
Canal-Raffin
Mireille
M
Morau
Didier
D
Malgat
Monique
M
Molimard
Mathieu
M
Mercier
Jacques
J
Lacampagne
Alain
A
Sztark
François
F
Capdevila
Xavier
X
D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005267:Femoral Nerve / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D000077554:Levobupivacaine; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D016658:Psoas Muscles / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D000077554:Levobupivacaine; D002118:Calcium; D002045:Bupivacaine