Lipid emulsion inhibits the cardiac toxicity caused by chloroquine via inhibition of reactive oxygen species production / 대한마취과학회지

Background@#Lipid emulsion (LE) is effective in treating intractable cardiac depression induced by the toxicity of highly lipid-soluble drugs including local anesthetics. However, the effect of LE on chloroquine (CQ)-evoked cardiac toxicity remains unclear. This study aimed to examine the effect of Lipofundin MCT/LCT, an LE, on the cardiotoxicity caused by CQ in H9c2 rat cardiomyoblasts and elucidate the underlying cellular mechanism. @*Methods@#The effects of CQ (1 × 10-4 M), LE, and the reactive oxygen species (ROS) scavengers mitotempo and N-acetyl-L-cysteine (NAC), alone or combined, on cell viability and migration, apoptosis, ROS production, calcium levels, mitochondrial membrane potential, and adenosine triphosphate (ATP) were examined. Additionally, the effects of LE on the activities of catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) induced by CQ were assessed. @*Results@#Pretreatment with LE, mitotempo, or NAC reversed the reduction in cell migration and viability, mitochondrial membrane potential, and ATP levels evoked by CQ, and inhibited the increase in cleaved caspase-3, ROS, and calcium concentration induced by CQ. LE inhibited the increase in Bax expression, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, MDA activity, and late apoptosis, and reversed the reduction in SOD and CAT activity induced by CQ. CQ did not significantly affect cleaved caspase-8 expression, and LE did not significantly affect CQ concentration. @*Conclusions@#Collectively, these results suggest that LE (Lipofundin MCT/LCT) inhibits the cardiotoxicity and late apoptosis induced by CQ toxicity via the intrinsic mitochondrial apoptotic pathway that is associated with direct inhibition of ROS production.

Mechanisms underlying lipid emulsion resuscitation for drug toxicity: a narrative review / 대한마취과학회지

Currently, lipid emulsion (LE) is widely used to treat local anesthetic systemic toxicity (LAST). LE also ameliorates intractable cardiovascular collapse caused by lipid-soluble non-local anesthetic drug toxicity. This review aims to provide the underlying mechanism of LE resuscitation in drug toxicity (including LAST) and a detailed description of LE treatment and to discuss further research directions. We searched for relevant articles using the following keywords: “local anesthetic systemic toxicity or LAST or toxicity or intoxication or poisoning” and “Intralipid or lipid emulsion”. The underlying mechanisms of LE treatment can be classified into indirect and direct effects. One indirect effect known as the lipid shuttle is a commonly accepted mechanism of LE treatment. The lipid shuttle involves the absorption of highly lipid-soluble drugs (e.g., bupivacaine) from the heart and brain through the lipid phase, which are then delivered to the muscle, adipose tissue, and liver for storage and detoxification. The direct effects include inotropic effects, fatty acid supply, attenuation of mitochondrial dysfunction, glycogen synthase kinase-3β phosphorylation, and inhibition of nitric oxide. These mechanisms appear to act synergistically to treat drug toxicity. The recommended protocol for LE treatment of LAST is as follows: a bolus administration of 20% LE at 1.5 ml/kg over 2–3 min followed by 20% LE at 0.25 ml/kg/min. LAST most commonly occurs after intravenous administration of local anesthetics. However, non-local anesthetic drugs that cause drug toxicity are orally administered. Further studies are needed to determine the optimal dosing schedule of LE treatment for non-local anesthetic drug toxicity.

Iatrogenic common carotid artery rupture during neck surgery rescued using covered stent: A case report

Carotid artery rupture during head and neck surgery is a catastrophic, life-threatening emergency. Although recent incidence has declined, it still occurs in many patients. Hemorrhage from the carotid artery is usually massive and uncontrollable. Fast, aggressive treatment to prevent hemodynamic instability is required. Even if patients survive this event, they may experience severe neurological sequelae. A ruptured carotid artery is usually controlled by direct compression and arterial ligation. However, apart from the inherent difficulty of operation, these traditional surgical treatments are associated with high morbidity and mortality. In the past two decades, endovascular management has become a mainstay of carotid rupture treatment. We report a case of successful recovery without any sequelae after cardiovascular collapse due to an unintentional common carotid artery (CCA) rupture during neck surgery. The exposed CCA was treated with a covered stent. In such a case, multidisciplinary cooperation is crucial.

The effect of sugammadex on the vascular tone of isolated rat aorta / 대한마취과학회지

No abstract available.

Lipid emulsion inhibits vasodilation induced by a toxic dose of bupivacaine by suppressing bupivacaine-induced PKC and CPI-17 dephosphorylation but has no effect on vasodilation induced by a toxic dose of mepivacaine

BACKGROUND: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. METHODS: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ([Ca²⁺]ᵢ) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. RESULTS: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in [Ca²⁺]ᵢ. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. CONCLUSIONS: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

Lipid emulsion inhibits vasodilation induced by a toxic dose of bupivacaine by suppressing bupivacaine-induced PKC and CPI-17 dephosphorylation but has no effect on vasodilation induced by a toxic dose of mepivacaine

BACKGROUND: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. METHODS: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ([Ca²⁺]ᵢ) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. RESULTS: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in [Ca²⁺]ᵢ. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. CONCLUSIONS: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

Prognostic Value of Serum Ferritin in Terminally Ill Cancer Patients / 한국호스피스완화의료학회지

PURPOSE: Predicting life expectancy of terminally ill cancer patients is very important. In many studies, ferritin is detected at higher levels in the sera of cancer patients, and higher ferritin level correlates with aggressiveness of disease and poor outcomes of patients. This study evaluated a prognostic role of serum ferritin levels in terminally ill cancer patients. METHODS: This study enrolled 65 terminally ill cancer patients from March through June 2012. We assessed routine laboratory findings including serum ferritin levels as well as demographic and clinical characteristics of the patients. To examine the association between serum ferritin levels and patient's characteristics, we used Spearman's correlation analysis, Wilcoxon's rank sum test or Kruskal-Wallis test, as appropriately. For multivariate analysis, Cox's proportional hazard regression model was used to evaluate significance of serum ferritin levels as a prognostic factor. RESULTS: A negative correlation between serum ferritin levels and survival time was found. After adjusting for sex, age, performance status, creatinine levels and white blood cell counts, serum ferritin levels were significantly associated with survival time. CONCLUSION: Even at the very end of life of terminal cancer patients, serum ferritin levels were an independent prognostic factor for survival.

Lipid Emulsions Enhance the Norepinephrine-Mediated Reversal of Local Anesthetic-Induced Vasodilation at Toxic Doses

PURPOSE: Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. MATERIALS AND METHODS: The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6x10-4 M levobupivacaine, 2x10-3 M ropivacaine, and 7x10-3 M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. RESULTS: Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3x10-3 M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. CONCLUSION: Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.

Inter-arm Differences in Simultaneous Blood Pressure Measurements in Ambulatory Patients without Cardiovascular Diseases / 가정의학회지

BACKGROUND: It has traditionally been known that there is normally a difference in blood pressure (BP) between the two arms; there is at least 20 mm Hg difference in the systolic blood pressure (SBP) and 10 mm Hg difference in the diastolic blood pressure (DBP). However, recent epidemiologic studies have shown that there are between-arm differences of 10 mm Hg. In women, 89.6% of patients had IAD in SBP of 10 mm Hg or IAD in DBP of > 10 mm Hg. Gangneung Asan Hospital clinical series of patients showed that the absolute IAD in SBP had a significant correlation with cardiovascular risk factors such as the 10-year Framingham cardiac risk scores and higher BP in men and higher BP in women. However, the absolute IAD in SBP and DBP had no significant correlation with the age, obesity, smoking, drinking, hyperlipidemia, diabetes, metabolic syndrome, and renal function. CONCLUSION: Our results showed that there were no significant between-arm differences in simultaneous BP measurements. It was also shown that most of the ambulatory patients without cardiovascular diseases had an IAD in SBP of < 10 mm Hg and an IAD in DBP of < 6 mm Hg.

Differences in Blood Pressure Measurements Obtained Using an Automatic Oscillometric Sphygmomanometer Depending on Clothes-Wearing Status / 가정의학회지

BACKGROUND: According to the current guidelines for blood pressure monitoring, clinicians are recommended to measure blood pressure by completely exposing the upper arm. However, it is a common practice that blood pressure is measured with the cuff placed over the sleeve or with the sleeve rolled up. We therefore conducted this study to examine whether there are any differences in blood pressure measurements among the three different settings: the sleeve group, the rolled sleeve group, and the bare arm group. METHODS: We conducted the current study in 141 male and female adult patients who visited our clinical department. In these patients, we took repeatedly blood pressure measurements using the same automatic oscillometric device on three different settings. Then, we analyzed the results with the use of randomized block design analysis of variance. RESULTS: The mean values of systolic blood pressure (SBP) between the first reading and those of the second reading were 128.5 +/- 10.6 mm Hg in the sleeve group, 128.3 +/- 10.8 mm Hg in the rolled sleeve group, and 128.3 +/- 10.7 mm Hg in the bare arm group. These results indicate that there were no significant differences among the three groups (P = 0.32). In addition, the mean values of diastolic blood pressure (DBP) between the first reading and those of the second reading were 80.7 +/- 6.1 mm Hg in the sleeve group, 80.7 +/- 6.1 mm Hg in the rolled sleeve group, and 80.6 +/- 5.9 mm Hg in the bare arm group. These results indicate that there were no significant differences among the three groups (P = 0.77). In addition, based on the age, sex, past or current history of hypertension or diabetes mellitus, the thickness of sleeve, weight, a drinking history, and a smoking history, there were no significant differences in SBP and DBP among the three groups. CONCLUSION: There were no significant differences in blood pressure measurements between the three different settings (the sleeve group, the rolled sleeve group, and the bare arm group).

Lipid emulsion-mediated reversal of toxic-dose aminoamide local anesthetic-induced vasodilation in isolated rat aorta / 대한마취과학회지

BACKGROUND: Intravenous lipid emulsion has been used to treat systemic toxicity of local anesthetics. The goals of this in vitro study were to determine the ability of two lipid emulsions (Intralipid(R) and Lipofundin(R) MCT/LCT) to reverse toxic dose local anesthetic-induced vasodilation in isolated rat aortas. METHODS: Isolated endothelium-denuded aortas were suspended for isometric tension recording. Vasodilation was induced by bupivacaine (3 x 10(-4) M), ropivacaine (10(-3) M), lidocaine (3 x 10(-3) M), or mepivacaine (7 x 10(-3) M) after precontraction with 60 mM KCl. Intralipid(R) and Lipofundin(R) MCT/LCT were then added to generate concentration-response curves. We also assessed vasoconstriction induced by 60 mM KCl, 60 mM KCl with 3 x 10(-4) M bupivacaine, and 60 mM KCl with 3 x 10(-4) M bupivacaine plus 1.39% lipid emulsion (Intralipid(R) or Lipofundin(R) MCT/LCT). RESULTS: The two lipid emulsions reversed vasodilation induced by bupivacaine, ropivacaine, and lidocaine but had no effect on vasodilation induced by mepivacaine. Lipofundin(R) MCT/LCT was more effective than Intralipid(R) in reversing bupivacaine-induced vasodilation. The magnitude of lipid emulsion-mediated reversal of vasodilation induced by high-dose local anesthetics was as follows (from highest to lowest): 3 x 10(-4) M bupivacaine-induced vasodilation, 10(-3) M ropivacaine-induced vasodilation, and 3 x 10(-3) M lidocaine-induced vasodilation. CONCLUSIONS: Lipofundin(R) MCT/LCT-mediated reversal of bupivacaine-induced vasodilation was greater than that of Intralipid(R); however, the two lipid emulsions equally reversed vasodilation induced by ropivacaine and lidocaine. The magnitude of lipid emulsion-mediated reversal of vasodilation appears to be correlated with the lipid solubility of the local anesthetic.

Optical characteristics of resin composite before and after polymerization / 대한치과보존학회지

OBJECTIVES: The aim of this study was to evaluate the optical characteristics such as color and translucency changes before and after light curing, to quantify the CQ and to measure refractive indices of body and opaque shade of resin composites materials. MATERIALS AND METHODS: Resin composites used in this study were A2 body and A2 opaque shade of Esthet-X, Filtek supreme, Gradia Direct, Clearfil Majesty and Beautifil?? Color and translucency changes before and after light curing were evaluated by colorimeter, the CQ was quantified by GC-MS and refractive index changes were measured by spectroscopic ellipsometer. RESULTS: Translucency parameter (TP) was significantly increased after curing. The CQ content of body shades are higher than that of opaque shades in all resin composites. Refractive index increased after polymerization in all materials and significant difference in Deltarefractive index was found between body and opaque shade (significance level 0.05). CONCLUSIONS: For an accurate shade match, direct shade matching of resin composite should be performed by using the cured material.

A Case of Successful Correction of Subclavian Steal Syndrome by Percutaneus Transluminal Angioplasty with Stenting Who Found Incidentally Significant Interarm Blood Pressure Difference / 가정의학회지

A case of successful correction of subclavian steal syndrome by percutaneous transluminal angioplasty with stenting in a male patient who found incidentally significant interarm blood pressure difference. Small difference in blood pressure (BP) between two arms is a relatively common. Significant interarm BP difference is a potential marker of peripheral vascular disease such as subclavian artery stenosis and a predictor of cardiovascular disease. The subclavian steal syndrome is a condition that results from stenosis of subclavian artery proximal to the vertebral artery. The resulting symptoms are vertebrobasilar insufficiency symptoms due to reversal of blood flow from the contralateral vertebral and basilar artery into the ipsilateral upper extremity vessels and arm ischemic symptoms. Stenotic lesion of subclavian artery has traditionally been treated surgically. However recent trends are undergoing a paradigm shift from open surgery to endovascular approach. We report a patient with subclavian steal syndrome who found incidentally 35 mmHg interarm systolic BP difference. It was successfully treated by percutaneus transradial angioplasty with stenting on stenotic lesion of the subclavian artery.