Abstract
Lipid emulsion (LE) therapy has been used to reduce overdose of bupivacaine (BPV)-induced cardiotoxicity. The TWIK-related potassium channel-1 (TREK-1) is inhibited by BPV and activated by polyunsaturated fatty acids, which are the main component in LE. These pharmacological properties inspired us to investigate whether the TREK-1 channel is associated with cell viability of H9c2 cardiomyoblasts affected by BPV and LE. Consistent with previous studies, BPV-induced cell death was reduced by LE treatment. The reduction in the TREK-1 expression level by BPV was alleviated by LE. The BPV cytotoxicity highly decreased in TREK-1 overexpressed cells but was the opposite in TREK-1 knocked-down cells. TREK-1 channel activators and inhibitors increased and decreased cell viability, respectively. BPV-induced depolarization of the plasma and mitochondrial membrane potential and increase in intracellular Ca2+ level were blocked by LE treatment. BPV-induced depolarization of membrane potential was reduced in TREK-1 overexpressed cells, indicating that TREK-1 channels mediate setting the resting membrane potentials as a background K+ channel in H9c2 cells. These results show that TREK-1 activity is involved in the BPV cytotoxicity and the antagonistic effect of LE in H9c2 cells and suggest that TREK-1 could be a target for action of BPV and LE.
Highlights
Bupivacaine, a local anesthetic of the amide group frequently used for spinal and epidural anesthesia during labor as well as for postoperative pain management, is more cardiotoxic compared with other local anesthetics [1]
To identify the effects of bupivacaine and lipid emulsion (LE) on the viability of H9c2 cells, H9c2 cells were treated with various concentrations of bupivacaine and/or LE for 24 h, and the cell viability was determined by MTT assay
The cells were treated with different concentrations of LE exposed to 1.2 mM bupivacaine to identify its protective effect on bupivacaine-induced cell death
Summary
Bupivacaine, a local anesthetic of the amide group frequently used for spinal and epidural anesthesia during labor as well as for postoperative pain management, is more cardiotoxic compared with other local anesthetics [1]. Bupivacaine may cause adverse drug reactions in the cardiovascular system, such as a negative inotropic effect, decrease in blood pressure and heart rate, alteration in electrical excitability, depressed contractility, and increased afterload through high plasma concentrations, lost Na+ channel binding properties, and block of other channels [2,3]. Bupivacaine affects many types of ion channels [4]. An overdose of bupivacaine induces vasodilation of blood vessels and circulatory collapse due to its cardiotoxicity. Attempts have been made to reduce these bupivacaine-induced systemic toxicities via lipid emulsion (LE) therapy.
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