The proper concentrations of dextrose and lidocaine in regenerative injection therapy: in vitro study

Background@#Prolotherapy is a proliferation therapy as an alternative medicine. A combination of dextrose solution and lidocaine is usually used in prolotherapy. The concentrations of dextrose and lidocaine used in the clinical field are very high (dextrose 10%-25%, lidocaine 0.075%-1%). Several studies show about 1% dextrose and more than 0.2% lidocaine induced cell death in various cell types. We investigated the effects of low concentrations of dextrose and lidocaine in fibroblasts and suggest the optimal range of concentrations of dextrose and lidocaine in prolotherapy. @*Methods@#Various concentrations of dextrose and lidocaine were treated in NIH-3T3. Viability was examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Migration assay was performed for measuring the motile activity. Extracellular signal-regulated kinase (Erk) activation and protein expression of collagen I and α-smooth muscle actin (α-SMA) were determined with western blot analysis. @*Results@#The cell viability was decreased in concentrations of more than 5% dextrose and 0.1% lidocaine. However, in the concentrations 1% dextrose (D1) and 0.01% lidocaine (L0.01), fibroblasts proliferated mildly. The ability of migration in fibroblast was increased in the D1, L0.01, and D1 + L0.01 groups sequentially. D1 and L0.01 increased Erk activation and the expression of collagen I and α-SMA and D1 + L0.01 further increased. The inhibition of Erk activation suppressed fibroblast proliferation and the synthesis of collagen I. @*Conclusions@#D1, L0.01, and the combination of D1 and L0.01 induced fibroblast proliferation and increased collagen I synthesis via Erk activation.

The proper concentrations of dextrose and lidocaine in regenerative injection therapy: in vitro study

Background@#Prolotherapy is a proliferation therapy as an alternative medicine. A combination of dextrose solution and lidocaine is usually used in prolotherapy. The concentrations of dextrose and lidocaine used in the clinical field are very high (dextrose 10%-25%, lidocaine 0.075%-1%). Several studies show about 1% dextrose and more than 0.2% lidocaine induced cell death in various cell types. We investigated the effects of low concentrations of dextrose and lidocaine in fibroblasts and suggest the optimal range of concentrations of dextrose and lidocaine in prolotherapy. @*Methods@#Various concentrations of dextrose and lidocaine were treated in NIH-3T3. Viability was examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Migration assay was performed for measuring the motile activity. Extracellular signal-regulated kinase (Erk) activation and protein expression of collagen I and α-smooth muscle actin (α-SMA) were determined with western blot analysis. @*Results@#The cell viability was decreased in concentrations of more than 5% dextrose and 0.1% lidocaine. However, in the concentrations 1% dextrose (D1) and 0.01% lidocaine (L0.01), fibroblasts proliferated mildly. The ability of migration in fibroblast was increased in the D1, L0.01, and D1 + L0.01 groups sequentially. D1 and L0.01 increased Erk activation and the expression of collagen I and α-SMA and D1 + L0.01 further increased. The inhibition of Erk activation suppressed fibroblast proliferation and the synthesis of collagen I. @*Conclusions@#D1, L0.01, and the combination of D1 and L0.01 induced fibroblast proliferation and increased collagen I synthesis via Erk activation.

Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine

BACKGROUND: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endotheliumdenuded rat aortas precontracted with phenylephrine. METHODS: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ([Ca2+]i) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. RESULTS: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100 mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced [Ca2+]i decrease in the aortas precontracted with phenylephrine. CONCLUSIONS: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine- induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

A Patient with Kikuchi's Disease: What Should Pain Clinicians Do?

Kikuchi's disease (KD) is an idiopathic and self-limiting necrotizing lymphadenitis that predominantly occurs in young females. It is common in Asia, and the cervical lymph nodes are commonly involved. Generally, KD has symptoms and signs of lymph node tenderness, fever, and leukocytopenia, but there are no reports on treatment for the associated myofacial pain. We herein report a young female patient who visited a pain clinic and received a trigger point injection 2 weeks before the diagnosis of KD. When young female patients with myofascial pain visit a pain clinic, doctors should be concerned about the possibility of KD, which is rare but can cause severe complications.

Propofol has delayed myocardial protective effects after a regional ischemia/reperfusion injury in an in vivo rat heart model / 대한마취과학회지

BACKGROUND: It is well known that propofol protects myocardium against myocardial ischemia/reperfusion injury in the rat heart model. The aim of this study was to investigate whether propofol provides a protective effect against a regional myocardial ischemia/reperfusion injury in an in vivo rat heart model after 48 h of reperfusion. METHODS: Rats were subjected to 25 min of left coronary artery occlusion followed by 48 h of reperfusion. The sham group received profopol without ischemic injury. The control group received normal saline with ischemia/reperfusion injury. The propofol group received profopol with ischemia/reperfusion injury. The intralipid group received intralipid with ischemia/reperfusion injury. A microcatheter was advanced into the left ventricle and the hemodynamic function was evaluated. The infarct size was determined by triphenyltetrazolium staining. The serum level of cardiac troponin-I (cTn-I) was determined by ELISA (enzyme-linked immunosorbent assay). RESULTS: Propofol demonstrated protective effects on hemodynamic function and infarct size reduction. In the propofol group, the +dP/dt(max) (P = 0.002) was significantly improved compared to the control group. The infarct size was 49.8% of the area at risk in the control group, and was reduced markedly by administration of propofol to 32.6% in the propofol group (P = 0.014). The ischemia/reperfusion-induced serum level of cTn-I was reduced by propofol infusion during the peri-ischemic period (P = 0.0001). CONCLUSIONS: Propofol, which infused at clinically relevant concentration during the peri-ischemic period, has delayed myocardial protective effect after regional myocardial ischemia/reperfusion injury in an in vivo rat heart model after 48 h of reperfusion.

The effect of propofol on myocardial protection after regional ischemia-reperfusion injury in an in vivo rat heart model / 대한마취과학회지

BACKGROUND: It is known that propofol protects myocardium against a global ischemia-reperfusion injury in the isolated rat heart model. The aim of this study was to investigate whether propofol, at a clinically relevant concentration infused during the peri-ischemic period, also provides a protective effect against a regional myocardial ischemia-reperfusion injury in vivo. METHODS: Rats were subjected to 25 minutes of coronary artery occlusion followed by 24 hours of reperfusion. Propofol or intralipid was administrated during 35 minutes starting 5 minutes before the onset of ischemia until 5 minutes after the onset of reperfusion. A micromanometer catheter was advanced into the left ventricle and the hemodynamic function was evaluated. The infarct size was determined by triphenyltetrazolium staining after 24 hours of reperfusion. RESULTS: Propofol administration during the peri-ischemic period demonstrated protective effects on hemodynamic function and infarct size reduction. In the control group, the peak rate of the ventricular pressure increase (+dP/dt(max))(P = 0.0001) and the peak rate of the intraventricular pressure decline (-dP/dt(max))(P = 0.0001) were significantly decreased compared to the sham group. In the propofol group, the +dP/dt(max) (P = 0.003) and -dP/dt(max) (P = 0.002) were significantly improved compared to the control group. The infarct size was 47.6% of the area at risks in the control group, and was reduced markedly by administration of propofol during the peri-ischemic period to 26.2% in the propofol group (P = 0.004). CONCLUSIONS: Propofol, at a clinically relevant concentration infused during the peri-ischemic period, have protective effect after regional myocardial ischemia-reperfusion injury in an in vivo rat heart model.

The Effect of the Spinal Block Level on the Requirements of Propofol for Sedation / 대한마취과학회지

BACKGROUND: It has been reported that spinal anesthesia has a sedative effect and so this decreases the hypnotic requirement of intravenous anesthetic. Therefore, we have conducted a prospective randomized study to investigate the effect of the spinal anesthesia level on the hypnotic requirements for conscious sedation. METHODS: Forty adult patients were scheduled to undergo spinal anesthesia, and they were randomly allocated to one of the two groups. After subarachnoid injection of 0.5% hyperbaric bupivacaine 16 mg, the patients in group 1 and group 2 were maintained in a reversed Trendelenburg position and a Trendelenburg position, respectively. After fifteen minutes, the target controlled infusion of propofol was started for achieving a target concentration of 1 microgram/ml, and the mean BIS for 1 min was checked after an effect site concentration (Ce) of 1 microgram/ml was reached. The target controlled infusion of propofol was restarted at a target concentration (Tc) of 1.5 microgram/ml, and the mean BIS for 1 min was checked after the Ce level of 1.5 microgram/ml was reached. RESULTS: The mean BIS at 1 microgram/ml Ce was 90.0 +/- 8.5 and 77.8 +/- 10.3 in group 1 and group 2, respectively. The mean BIS at 1.5 g/ml Ce was 73.6 +/- 19.4 and 60.0 +/- 13.1, respectively. CONCLUSIONS: There was a significant difference in the requirements of propofol for conscious sedation between the below T12 block group and the above T4 block group.

Cardiac Arrest due to Severe Hypokalemia during Barbiturate Coma Therapy in a Patient with Severe Acute Head Injury: A case report / 대한마취과학회지

An emergency left frontotemporal craniectomy with direct neck clipping and hematoma removal was performed in a 36-year-old man with a ruptured left middle cerebral artery aneurysm and sylvian hematoma. Because of severe brain swelling postoperatively, we induced barbiturate coma therapy to treat his intractable brain swelling. He had an initial loading dose of sodium thiopental (5 mg/kg) followed by continuous infusion of sodium thiopental (5 mg/kg/hour). The lowest potassium concentration recorded during the barbiturate coma therapy was 1.1 mmol/L; necessitating treatment with cardiac massage, epinephrine, and atropine because of asystole and severe bradycardia. However, he did not recover from cardiac arrest. We present here a case of cardiac arrest due to severe life threatening hypokalemia that occurred during barbiturate coma therapy.

The Effect of Spinal Anesthesia and Intrathecal Clonidine on the Propofol Hypnotic Requirements for Conscious Sedation / 대한마취과학회지

BACKGROUND: It is stated frequently that patients with spinal block may be drowsy, although they may not have received any sedative drugs. Intrathecal clonidine increase the duration of sensory and motor blockades, and also has a sedative effect. Thus we conducted this study to investigate the effects of spinal anesthesia and intrathecal clonidine on propofol hypnotic requirements. METHODS: Forty-five adult patients scheduled to undergo local or spinal anesthesia were enrolled in this study. Group 1 included patients on local anesthesia, group 2 were patients on spinal anesthesia with 0.5% hyperbaric bupivacaine, and group 3 were patients on spinal anesthesia with 0.5% hyperbaric bupivacaine and 75microgram clonidine. The target controlled infusion (TCI) of propofol was started at a target concentration of 1microgram/ml. We checked the lowest BIS during 5 min observation after the effect site concentration (Ce) had been reached (1microgram/ml). The TCI of propofol was then restarted at a target concentration of 1.5microgram/ml and we checked the lowest BIS during 5 min observation after the Ce had been reached (1.5microgram/ml). We also checked the Ce when the BIS reached 80 and 70. RESULTS: The minimum BIS's at 1 microgram/ml Ceiiwere 86.9 +/- 11.3 (Group 1), 80.5 +/- 8.5 (Group 2) and 66.9 +/- 15.5 (Group 3), and the minimum BIS's at 1.5microgram/ml Ce were 76.0 +/- 13.4, 62.9 +/- 12.4, 48.5 +/- 13.7, respectively. The Ce's of propofol at BIS 80 were checked initially at 1.4 +/- 0.5microgram/ml (Group 1), 1.1 +/- 0.3microgram/ml (Group 2) and 0.8 +/- 0.3microgram/ml (Group 3). The Ce's of propofol at BIS 70 were 1.8 +/- 0.6microgram/ml, 1.4 +/- 0.3microgram/ml and 1.0 +/- 0.3microgram/ml, respectively. The Ce's of Group 2 and Group 3 at BIS 80 and BIS 70 were statistically lower than those of Group 1 (P < 0.05), and the Ce's of Group 3 at BIS 80 and BIS 70 were statistically lower than those of Group 2 (P < 0.05). CONCLUSIONS: Spinal anesthesia and intrathecal clonidine reduce the requirement of propofol for conscious sedation. The Ce of propofol for conscious sedation is 1.4-1.8microgram/ml for local anesthesia, 1.1-1.4microgram/ml for spinal anesthesia with 0.5% hyperbaric bupivacaine, and 0.6-1.0microgram/ml for spinal anesthesia with 0.5% hyperbaric bupivacaine and 75microgram clonidine.

Vascular Smooth Muscle Adenosine Triphosphate (ATP)-Sensitive Potassium Channel and Anesthetics / 대한마취과학회지

Adenosine triphosphate-sensitive potassium channel (KATP channel) closed by intracellular adenosine triphosphate (ATP) appears widely distributed in the vascular system. Activation of vascular smooth muscle KATP channel with hyperpolarizing agents such as lemakalim results in membrane hyperpolarization, a consequent reduction in calcium influx through voltage-dependent calcium channel, and leads to vessel relaxation. In contrast to KATP channel activation in vascular smooth muscle cell, KATP channel-induced hyperpolarization of endothelial cells results in an increase in calcium influx, which could stimulate the production of nitric oxide and prostacyclin from the endothelial cell. KATP channels response to change in the cellular metabolic status like ischemia and hypoxia, and are the target of a variety of synthetic and endogenous vasoactive substance. KATP channel openers are used as therapeutic agent for cardiovascular disease. Endogenous KATP channel-induced vasodilation is functionally important because it has been shown to modulate the pulmonary vasoconstrictor response to hypoxia and systemic hypotension in the pulmonary circulation, enhance tissue perfusion in response to hypoxia and severe hypotension in the systemic circulation. In virtro, halothane and intravenous anesthetics attenuated KATP channel agonist, lemaklim-induced vasodilation. The coronary vasodilation by volatile anesthetics such as isoflurane, enflurane and halothane was associated with activation of KATP channel in coronary artery. Further investigation is required to determine signal transduction pathway in detail stimulated by KATP channel agonist in human blood vessel and effect of anesthetics on the KATP channel-induced signal transduction, and role of KATP channel of pathophysiology of vascular disease such as hypertension, angina.

General Anesthesia for a Cesarean Section in a Patient with a Brain Tumor: A case report / 대한마취과학회지

A 28-year-old primigravida at 33 weeks gestation was referred to our hospital because of aggravation of seizures which occurred intermittently for the past 2 years. A brain magnetic resonance imaging scan taken at 33 weeks gestation showed a large brain tumor (7X5X4 cm) in the left high frontal lobe. She had a cesarean section under general anesthesia at 38 weeks and 1 day gestation. General anesthesia was induced with thiopental 250 mg, succinylcholine 75 mg and lidocaine 60 mg after a vecuronium 0.8 mg intravenous injection. The hyperventilation and mannitol used to reduce increased intracranial pressure (ICP) in this patient may be harmful and detrimental to the fetus before delivery. Achieving both ICP control and fetal well being at the same time during a cesarean section can be challenging to anesthesiologists. We report the anesthetic management of a cesarean section in a patient with a large brain tumor.