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 (K_ATP) 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 K_ATP 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 K_ATP activity and enhanced K_ATP 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 K_ATP channels and indirect effects.

The goal of this study was to examine the effect of lipid emulsion on the vasodilation induced by ATP-sensitive potassium (K_ATP) channels in isolated rat aortae and the underlying mechanism. The effects of Intralipid, containing 100% long-chain fatty acids, and Lipofundin MCT/LCT, containing 50% long-chain fatty acids plus 50% medium-chain fatty acids, on the vasodilation induced by levcromakalim in endothelium-intact aorta with or without N^W-nitro-L-arginine methyl ester (L-NAME) and in endothelium-denuded aorta were examined. The effects of L-arginine, L-NAME, glibenclamide, and Lipofundin MCT/LCT, alone or combined, on the levcromakalim-induced vasodilation were examined. Lipofundin MCT/LCT inhibited the levcromakalim-induced vasodilation of isolated endothelium-intact aortae, whereas Intralipid did not. In addition, Lipofundin MCT/LCT had no effect on the levcromakalim-induced vasodilation of endothelium-denuded rat aortae and endothelium-intact aortae with L-NAME. L-arginine and Lipofundin MCT/LCT produced more levcromakalim-induced vasodilation than Lipofundin MCT/LCT alone. Glibenclamide inhibited levcromakalim-induced vasodilation. Levcromakalim did not significantly alter endothelial nitric oxide synthase phosphorylation, whereas Lipofundin MCT/LCT decreased cyclic guanosine monophosphate. Lipofundin MCT/LCT did not significantly alter levcromakalim-induced membrane hyperpolarization. Taken together, these results suggest that Lipofundin MCT/LCT inhibits the vasodilation induced by levcromakalim by inhibiting basally released endothelial nitric oxide, which seems to occur through medium-chain fatty acids.

Intravenous sedative drugs are commonly administered during regional anesthesia. However, reducing the excessive use of sedatives while providing adequate sedation is important from the clinical perspective, since the use of sedatives can cause considerable complications. We hypothesized that the application of earmuffs and eye masks would help reduce the sedative dose required to maintain proper sedation by blocking external stimuli. Patients who underwent orthopedic surgery under spinal anesthesia were randomly allocated to the control (no intervention) or intervention group (wearing earmuffs and eye masks). Intravenous sedation was administered using target-controlled infusion of propofol. The target concentration was controlled to maintain a Modified Observer’s Assessment of Alertness and Sedation score of 3 or 4. The primary outcome was the intraoperative propofol requirement. We also investigated the incidence of apnea, and patient satisfaction. Propofol requirement was significantly lower in the intervention group than that in the control group (2.3 (2.0–2.7) vs. 3.1 (2.7–3.4) mg·kg⁻¹·h⁻¹; p < 0.001). Intraoperative apnea occurred less frequently (p = 0.038) and patient satisfaction was higher (p = 0.002) in the intervention group compared to the control group. This study demonstrated that the use of earmuffs and eye masks during sedation was associated with lower propofol requirement and improved sedation quality.

This study aimed to examine the effect of lipid emulsion on the vasodilation induced by a toxic dose of amlodipine in isolated rat aorta and elucidate its mechanism, with a particular focus on nitric oxide. The effects of endothelial denudation, N^W-nitro-L-arginvine methyl ester (L-NAME), methylene blue, lipid emulsion, and linolenic acid on the amlodipine-induced vasodilation and amlodipine-induced cyclic guanosine monophosphate (cGMP) production were examined. Furthermore, the effects of lipid emulsion, amlodipine, and PP2, either alone or combined, on endothelial nitric oxide synthase (eNOS), caveolin-1, and Src-kinase phosphorylation were examined. Amlodipine-induced vasodilation was higher in endothelium-intact aorta than in endothelium-denuded aorta. L-NAME, methylene blue, lipid emulsion, and linolenic acid inhibited amlodipine-induced vasodilation and amlodipine-induced cGMP production in the endothelium-intact aorta. Lipid emulsion reversed the increased stimulatory eNOS (Ser1177) phosphorylation and decreased inhibitory eNOS (Thr495) phosphorylation induced via amlodipine. PP2 inhibited stimulatory eNOS, caveolin-1, and Src-kinase phosphorylation induced via amlodipine. Lipid emulsion inhibited amlodipine-induced endothelial intracellular calcium increase. These results suggest that lipid emulsion attenuated the vasodilation induced via amlodipine through inhibiting nitric oxide release in isolated rat aorta, which seems to be mediated via reversal of stimulatory eNOS (Ser1177) phosphorylation and inhibitory eNOS (Thr495) dephosphorylation, which are also induced via amlodipine.

In this study, we examined whether aortic contraction, induced by the alpha-2 adrenoceptor agonist dexmedetomidine, is involved in the transactivation of the epidermal growth factor receptor (EGFR) in isolated endothelium-denuded rat aortas. Additionally, we aimed to elucidate the associated underlying cellular mechanisms. The effects of the alpha-2 adrenoceptor inhibitor rauwolscine, EGFR tyrosine kinase inhibitor AG1478, Src kinase inhibitors PP1 and PP2, and matrix metalloproteinase inhibitor GM6001 on EGFR tyrosine phosphorylation and c-Jun NH₂-terminal kinase (JNK) phosphorylation induced by dexmedetomidine in rat aortic smooth muscles were examined. In addition, the effects of these inhibitors on dexmedetomidine-induced contraction in isolated endothelium-denuded rat aorta were examined. Dexmedetomidine-induced contraction was inhibited by the alpha-1 adrenoceptor inhibitor prazosin, rauwolscine, AG1478, PP1, PP2, and GM6001 alone or by a combined treatment with prazosin and AG1478. AG1478 (3 × 10⁻⁶ M) inhibited dexmedetomidine-induced contraction in isolated endothelium-denuded rat aortas pretreated with rauwolscine. Dexmedetomidine-induced EGFR tyrosine and JNK phosphorylation were inhibited by rauwolscine, PP1, PP2, GM6001, and AG1478. Furthermore, dexmedetomidine-induced JNK phosphorylation reduced upon EGFR siRNA treatment. Therefore, these results suggested that the transactivation of EGFR associated with dexmedetomidine-induced contraction, mediated by the alpha-2 adrenoceptor, Src kinase, and matrix metalloproteinase, caused JNK phosphorylation and increased calcium levels.

Dexmedetomidine is widely used to induce sedation in the perioperative period. This study examined the effect of hypothermia (33 and 25 °C) on dexmedetomidine-induced contraction in an endothelium-intact aorta with or without the nitric oxide synthase inhibitor N^W-nitro-L-arginine methyl ester (L-NAME). In addition, the effect of hypothermia on the contraction induced by dexmedetomidine in an endothelium-denuded aorta with or without a calcium-free Krebs solution was examined. The effects of hypothermia on the protein kinase C (PKC), myosin light chain (MLC₂₀) phosphorylation, and Rho-kinase membrane translocation induced by dexmedetomidine were examined. Hypothermia inhibited dexmedetomidine-induced contraction in the endothelium-intact aorta with L-NAME or endothelium-denuded aorta. Hypothermia had almost no effect on the dexmedetomidine-induced contraction in the endothelium-denuded aorta with the calcium-free Krebs solution; however, the subsequent contraction induced by the addition of calcium was inhibited by hypothermia. Conversely, the transition from profound hypothermia back to normothermia reversed the hypothermia-induced inhibition of subsequent calcium-induced contractions. Hypothermia inhibited any contraction induced by KCl, PDBu, and NaF, as well as PKC and MLC₂₀ phosphorylation and Rho-kinase membrane translocation induced by dexmedetomidine. These results suggest that hypothermia inhibits dexmedetomidine-induced contraction, which is mediated mainly by the impediment of calcium influx and partially by the attenuation of pathways involving PKC and Rho-kinase activation.