The protective effect of lipid emulsion in preventing bupivacaine-induced mitochondrial injury and apoptosis of H9C2 cardiomyocytes

Abstract

Lipid emulsion (LE) has been shown to be effective in the resuscitation of bupivacaine-induced cardiac arrest, but the precise mechanism of this action has not been fully elucidated. Pursuant to this lack of information on the mechanism in which LE protects the myocardium during bupivacaine-induced toxicity, we explored mitochondrial function and cell apoptosis. H9C2 cardiomyocytes were used in study. Cells were randomly divided in different groups and were cultivated 6 h, 12 h, and 24 h. The mitochondria were extracted and mitochondrial ATP content was measured, as was mitochondrial membrane potential, the concentration of calcium ion (Ca2+), and the activity of Ca2+-ATP enzyme (Ca2+-ATPase). Cells from groups Bup1000, LE group, and Bup1000LE were collected to determine cell viability, cell apoptosis, and electron microscopy scanning of mitochondrial ultrastructure (after 24 h). We found that LE can reverse the inhibition of the mitochondrial function induced by bupivacaine, regulate the concentration of calcium ion in mitochondria, resulting in the protection of myocardial cells from toxicity induced by bupivacaine.

Lipid Emulsion for Treating Local Anesthetic Systemic Toxicity

“…These results appear to be associated with inhibition of the mitochondrial permeability transition pore opening 51 , 52 . These previous reports suggest that lipid emulsion-mediated recovery from bupivacaine-induced cardiac toxicity was associated with the reversal of the reduced fatty acid supply and ATP production or the mitochondrial dysfunction induced by toxic doses of bupivacaine 49 - 52 . In another study, lipid emulsion enhanced the mitochondrial respiratory function of myocardial cells and produced slight bupivacaine entrapment in bupivacaine-induced cardiac depression of pigs 53 .…”

“…Furthermore, pretreatment with ATP abolished the myocardial depression induced by bupivacaine in an isolated rabbit right atrial model 50 . Lipid emulsion attenuated apoptosis induced by toxic doses of bupivacaine through inhibition of the bupivacaine-induced enhanced oxidative stress and mitochondrial dysfunction in H9c2 rat cardiomyoblasts 51 , 52 . These results appear to be associated with inhibition of the mitochondrial permeability transition pore opening 51 , 52 .…”

“…Lipid emulsion attenuated apoptosis induced by toxic doses of bupivacaine through inhibition of the bupivacaine-induced enhanced oxidative stress and mitochondrial dysfunction in H9c2 rat cardiomyoblasts 51 , 52 . These results appear to be associated with inhibition of the mitochondrial permeability transition pore opening 51 , 52 . These previous reports suggest that lipid emulsion-mediated recovery from bupivacaine-induced cardiac toxicity was associated with the reversal of the reduced fatty acid supply and ATP production or the mitochondrial dysfunction induced by toxic doses of bupivacaine 49 - 52 .…”

Electroacupuncture pretreatment alleviates myocardial injury through regulating mitochondrial function

“…Mitochondrial calcium ion concentrations were measured using Fluo-3 AM in accordance with previous study [7]. Fluo-3 AM was added to resuspended mitochondria and incubated for 1h.…”

“…Evidently, bupivacaine inhibits MRCC-I activity in a dose-dependent manner, accounting for alterations in mitochondrial energy uxes [10]. Bupivacaine negatively regulates fatty acid oxidation and oxidative phosphorylation and inhibits the activity of mitochondrial carnitine transferases, thereby reducing the synthesis of adenosine triphosphate (ATP) required for myocardial contractility [7]. Bupivacaine also inhibits the aerobic respiration of the mitochondria; speci cally, decoupling of oxidative phosphorylation alters MMP and inhibits mitochondrial respiration, resulting in the production of reactive oxygen species (ROS) in the mitochondria and triggering the mitochondrial pathway of apoptosis [11].…”