Time course of mitochondrial metabolism alterations to repeated injections of bupivacaine in rat muscle.
OBJECTIVE
Bupivacaine-induced myotoxicity is associated with mitochondrial bioenergetic alterations. The impact of the duration of bupivacaine treatment on mitochondrial energy production remains undetermined. Here, we assessed, in vivo, the alteration of mitochondrial metabolism following different durations of bupivacaine exposure (40, 56, or 112 hr) that correspond to 5, 7, or 14 repeated injections of 0.25% bupivacaine, respectively.


METHODS
Rats were divided randomly into seven different groups: one control group (no catheter); three groups with normal saline injections (1 mL x kg(-1)) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr, respectively; and three groups with 0.25% bupivacaine injections (1 mL x kg(-1)) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr. Psoas and gracilis muscle samples located within the bupivacaine infusion-diffusion space were investigated. To estimate mitochondrial respiratory capacity, the protein content of the mitochondrial respiratory chain apparatus was evaluated by measuring citrate synthase activity. To measure mitochondrial respiratory function, adenosine diphosphate-stimulated oxygen consumption was measured by polarography in saponin-skinned muscle fibres using glutamate-malate or succinate as energy substrates.


RESULTS
In psoas and gracilis muscles, saline solution had no effect on the two mitochondrial parameters. Bupivacaine induced a significant decrease in the citrate synthase activity in psoas (r(2) = 0.74; P < 0.001) and gracilis muscle (r(2) = 0.52; P < 0.001), and there was a significant decrease in the adenosine diphosphate-stimulated oxygen consumption using glutamate or succinate as substrates in both muscles (P < 0.001).


CONCLUSIONS
The severity of bupivacaine-induced myotoxicity is closely linked to the duration of bupivacaine exposure in the muscle fibres located close to the catheter tip.
Nouette-Gaulain
Karine
K
Laboratoire de physiopathologie mitochondriale, Université Victor Segalen Bordeaux 2, 33076, Bordeaux, France. karine.nouette-gaulain@chu-bordeaux.fr
Bringuier
Sophie
S
Canal-Raffin
Mireille
M
Bernard
Nathalie
N
Lopez
Sandrine
S
Dadure
Christophe
C
Masson
Françoise
F
Mercier
Jacques
J
Sztark
François
F
Rossignol
Rodrigue
R
Capdevila
Xavier
X
D000244:Adenosine Diphosphate / Q000008:administration & dosage; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D002950:Citrate (si)-Synthase / Q000187:drug effects / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D009135:Muscular Diseases / Q000139:chemically induced / Q000503:physiopathology; D010101:Oxygen Consumption / Q000187:drug effects; D011048:Polarography; D016658:Psoas Muscles / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000779:Anesthetics, Local; D000244:Adenosine Diphosphate; D002950:Citrate (si)-Synthase; D002045:Bupivacaine