Linoleic Acid Attenuates the Toxic Dose of Bupivacaine-Mediated Reduction of Vasodilation Evoked by the Activation of Adenosine Triphosphate-Sensitive Potassium Channels

Abstract

The goal of this study was to investigate the effect of lipid emulsion on a toxic dose of local anesthetic-mediated reduction of vasodilation evoked by the ATP-sensitive potassium (KATP) channel agonist levcromakalim. The effect of lipid emulsion (LE) and linoleic acid on the local anesthetic-mediated reduction of vasodilation and membrane hyperpolarization evoked by levcromakalim was assessed in isolated endothelium-denuded vessels (rat aorta and mesenteric artery) and aortic vascular smooth muscle cells. The effect of LE and linoleic acid on KATP channel activity in transfected HEK-293 cells was investigated, as was the effect of LE on bupivacaine concentration. The efficacy of LE in attenuating the local anesthetic-mediated reduction of vasodilation evoked by levcromakalim was correlated with the lipid solubility of the local anesthetic. Linoleic acid attenuated the bupivacaine-mediated reduction of vasodilation evoked by levcromakalim. LE decreased the bupivacaine-mediated reduction of membrane hyperpolarization evoked by levcromakalim but did not significantly alter the mepivacaine-mediated reduction. LE and linoleic acid both reversed the bupivacaine-mediated decrease of KATP activity and enhanced KATP activity. LE decreased the bupivacaine concentration. Linoleic acid may be the major contributor to LE-induced attenuation of bupivacaine-mediated reduction of vasodilation evoked by levcromakalim via the direct activation of KATP channels and indirect effects.

Lipid emulsion attenuates extrinsic apoptosis induced by amlodipine toxicity in rat cardiomyoblasts

“…17 Moreover, lipid emulsion and linoleic acid alone enhanced ATP-sensitive potassium channel activity in HEK-293 cells, transfected with Kir6.2 and SUR2. 24 In our study, the phosphoinositide-3 kinase inhibitor LY 294002 and ATP-sensitive potassium channel inhibitor glibenclamide partially reversed lipid emulsion-mediated attenuation of decreased cell viability and cell count induced by amlodipine at toxic doses (Figure 2B and 2C). Taking into consideration data from previous studies, our results suggest that lipid emulsion-mediated protection from decreased cell viability seems to be partially mediated via the activation of phosphoinositide-3 kinase and ATP-sensitive potassium channels in cardiomyoblasts.…”

“…Taking into consideration data from previous studies, our results suggest that lipid emulsion-mediated protection from decreased cell viability seems to be partially mediated via the activation of phosphoinositide-3 kinase and ATP-sensitive potassium channels in cardiomyoblasts. 16,17,22 –24 It has been reported that lipid emulsion inhibits the expression of cleaved caspase-8 and/or Bax induced by bupivacaine, verapamil, doxorubicin, and malathion at toxic doses in rat cardiomyoblasts and lung tissue. 15,18,21,25,26 In the present study, lipid emulsion inhibited amlodipine (10 −5 M)-induced increase in cleaved caspase-3 and capase-8 expression (Figure 3A and 3B).…”

Lipofundin MCT/LCT Inhibits Levcromakalim-Induced Vasodilation by Inhibiting Endothelial Nitric Oxide Release

“…Intralipid is mainly used to treat local anaesthetic systemic toxicity, and Lipofundin MCT/LCT is sometimes used to treat local anaesthetic systemic toxicity [19][20][21][22][23][24]. Although lipid emulsion alleviates the toxic dose of bupivacaine-mediated inhibition of vasodilation induced by the K ATP channel agonist levcromakalim primarily by scavenging effects regarded as indirect action, Intralipid may provide a more favourable effect than Lipofundin MCT/LCT on the maintenance of vasodilation induced by K ATP channel activation mediated through the pathophysiological state caused by local anaesthetic systemic toxicity [25]. However, this study has some limitations.…”

“…The membrane potential in VSMCs cultured on poly-L-lysine-coated glass coverslips was recorded under current-clamp mode (I = 0) using the whole-cell patch clamp technique as described previously [25]. Membrane potentials were amplified with a patch clamp amplifier (Axopatch 200B, Axon Instruments, Union City, CA, USA).…”

Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase

“…Isolated rat thoracic aortae were prepared for isometric tension measurement as described previously by our laboratory [14,15]. Male Sprague-Dawley rats (250-300 grams) were euthanized with 100% carbon dioxide supplied via a small hole in the cage.…”