Time course of mitochondrial metabolism alterations to repeated injections of bupivacaine in rat muscle

Abstract

Purpose 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 mLÁkg -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 mLÁkg -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 saponinskinned 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 diphosphatestimulated 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. RésuméObjectif La myotoxicite´induite par bupivacaı¨ne est associe´e à des alte´rations du me´tabolisme e´nerge´tique mitochondrial. Nous ne connaissons pas l'impact de la dure´e d'un traitement de bupivacaı¨ne sur la production e´nerge´tique mitochondriale. Dans cette e´tude, nous avons e´value´in vivo l'alte´ration du me´tabolisme mitochondrial al a suite de diffe´rentes dure´es d'exposition a`la bupivacaı¨ne (40, 56 ou 112 h), ce qui correspond respectivement a`cinq, sept ou 14 injections re´pe´te´es de bupivacaı¨ne a`0,25 %. Méthode Les rats ont e´te´randomise´s en sept groupes diffe´rents: un groupe te´moin (pas de cathe´ter); trois groupes avec des injections de se´rum physiologique (1 mLÁkg -1 ) toutes les huit heures via un cathe´ter au niveau du nerf fe´moral pendant 40, 56 et 112 h, respectivement; et trois groupes recevant des injections de bupivacaı¨ne a`0,25 % (1 mLÁkg -1 ) toutes les huit heures via un cathe´ter au niveau du nerf fe´moral pendant 40, 56 et 112 h. Des e´chantillons du muscle psoas et du muscle gracilis situe´s dans l'espace de diffusion de la bupivacaı¨ne ont e´te´examine´s. Le contenu prote´inique ...

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