Dimethylsulfoxide potentiates the nerve conduction-blocking effect of lidocaine without augmentation of the intracellular lidocaine concentration in the giant axon of crayfish in vitro.

The purpose of this study was to investigate how dimethylsulfoxide (DMSO) potentiates the blocking action of lidocaine. A giant axon removed from a crayfish was used to investigate nerve conduction and intracellular lidocaine concentration. The maximum values of the differential waveform (dV/dt max) calculated from evoked action potentials were used for evaluating an inhibition of nerve conduction. The inhibition of the dV/dt max in low-frequency stimulation (tonic block) and high-frequency stimulation (phasic block) after perfusion of 1 mm lidocaine with or without 0.2 vol % DMSO, in which the concentration of DMSO alone had no anesthetic effect, was measured to evaluate the potentiating action of DMSO. The intracellular lidocaine concentration was measured via a lidocaine-sensitive glass microelectrode during 30 min of perfusion of 1 mm lidocaine alone or in combination with DMSO. When applied without lidocaine, DMSO caused a dose-dependent nerve conduction block when used at concentrations >1 vol %. The dV/dt max in the tonic block was significantly decreased when 0.2 vol % DMSO was added to the lidocaine solution (P = 0.004). In the phasic block, there was no significant potentiating action of DMSO. There were no significant differences in the intracellular lidocaine concentrations with or without DMSO. The potentiating effects of DMSO were observed only in the condition of low-frequency stimulation and were not related to the intracellular lidocaine concentration in the giant axon of crayfish in vitro.

The effect of pulsed radiofrequency current on mechanical allodynia induced with resiniferatoxin in rats.

BACKGROUND: Pulsed radiofrequency (PRF) is a popular pain treatment modality. The effect of PRF current on neuropathic pain has not been examined in detail. We investigated the effect of PRF current on mechanical allodynia induced with resiniferatoxin (RTX) in rats, especially regarding the influence of the duration of allodynia before PRF procedures and that of exposure time to PRF. METHODS: Adult male Sprague-Dawley rats (weighing 250-400 g) received a single intraperitoneal injection of RTX (200 microg/kg) under 2 to 3% sevoflurane anesthesia. Rats in group S(2) (n = 5) were assigned to receive PRF current to the right sciatic nerve for 2 minutes 1 week after RTX treatment; rats in group M(2) (n = 6), PRF current for 2 minutes 3 weeks after RTX treatment; rats in group L(2) (n = 7), PRF current for 2 minutes 5 weeks after RTX treatment; rats in group S(4) (n = 5), PRF current for 4 minutes 1 week after RTX treatment; rats in group S(6) (n = 5), PRF current for 6 minutes 1 week after RTX treatment; and rats in group S(0) (n = 3), no PRF current was delivered. Instead, the needle and electrode were inserted at proper points for 6 minutes 1 week after RTX treatment. All rats were evaluated for sensitivity to mechanical stimulation with von Frey filaments and to thermal stimulation with a thermal testing apparatus and for motor function using placing and grasping reflexes before injection of RTX, every week after injection of RTX, and 1, 2, 3, 4, and 5 weeks after PRF treatment. RESULTS: The paw withdrawal thresholds of both hindpaws 1 week after RTX treatment were significantly lower than the pre-RTX baseline in all groups. In groups S(2), S(4), S(6), and M(2), after PRF procedures, the ipsilateral paw withdrawal thresholds significantly increased. A statistically significant difference was detected between the PRF-treated and PRF-untreated hindpaws. The ipsilateral-contralateral paw withdrawal thresholds after PRF procedures in group S(2) were significantly higher than those in groups M(2) and L(2). Between groups M(2) and L(2), significant differences were found 1, 2, 4, and 5 weeks after PRF procedures. The ipsilateral-contralateral paw withdrawal thresholds in group S(6) were significantly higher than those in groups S(2) and S(4) 5 weeks after PRF procedures. No significant difference was found between groups S(2) and S(4) at any time. After PRF procedures, no difference in the withdrawal latency after heat stimulation and no motor disturbance were observed at any time in all groups. CONCLUSIONS: PRF treatment was more effective when applied in the early stages of mechanical allodynia (1 week) in rats. Increased exposure time to PRF current from 2 to 6 minutes showed a significant antiallodynic effect without motor impairment. We propose the application of PRF current for 6 minutes adjacent to the nerve as soon as possible when allodynia appears.

Lacking of Aiolos accelerates pre-mature B cell apoptosis mediated by BCR signaling through elevation in cytochrome c release.

Antigen binding to B cell receptor (BCR) of pre-mature B lymphocytes leads to their apoptosis, while binding to BCR of mature B lymphocytes induces their activation and proliferation. The former binding is believed to be a mechanism so as to exclude B cell clones leading to protection from auto-immune diseases. Cross-linking of BCR of pre-mature B cells, including chicken DT40 cells, with anti-immunoglobulin antibody induces their apoptosis. The PMA/ionomycin treatments, which mimic BCR stimulation, are used to study intracellular signal transduction of B lymphocytes. Here, by analyzing the Aiolos-deficient DT40 cell line, Aiolos(-/-), we reveal that the lack of Aiolos accelerates apoptosis of DT40 cells mediated by BCR signaling. Moreover, the Aiolos-deficiency and BCR signaling cooperatively control this apoptosis through dramatically elevated cytochrome c release from mitochondria to cytosol and elevated caspase (caspase-3, 8 and 9) activities, resulting in drastically diminished amounts of ICAD followed by increased DNA fragmentation. Re-expression study reveals that the shorter isoform of Aiolos (Aio-2) controls PMA/ionomycin-mediated apoptosis via up-regulation and down-regulation of the PKCdelta and bak genes, respectively. These findings could be a powerful trigger to resolve molecular mechanisms of negative selection of B lymphocytes and also auto-immune diseases.

The effect of lidocaine on cholinergic neurotransmission in an identified reconstructed synapse.

BACKGROUND: The presynaptic effect of lidocaine on cholinergic synaptic transmission is unclear because of the difficulty in identifying presynaptic neurons and the complexity of the central nervous system in vivo. To clarify the effect of lidocaine on cholinergic synapse, we reconstructed a cultured soma-soma chemical synapse model consisting of two identified visceral dorsal 4 (VD4) and left pedal e-1 (LPeD1) neurons from the snail, Lymnaea stagnalis, in vitro, and used it to determine how lidocaine affects cholinergic synaptic transmission. METHODS: The response to acetylcholine and excitatory postsynaptic potential (EPSP) amplitude was recorded in the reconstructed chemical synaptic transmission model composed of VD4 and LPeD1 neurons. The currents for acetylcholine measurements were made under voltage-clamp in the presynaptic VD4 and postsynaptic LPeD1 neurons. RESULTS: Lidocaine inhibited both EPSP and the response for acetylcholine of the postsynaptic neuron. EPSP amplitude was reduced in a voltage-dependent manner in the presynaptic neuron, and lidocaine induced a hyperpolarization shift of the voltage-dependent inactivation curves of EPSP amplitude. CONCLUSIONS: Lidocaine inhibits cholinergic synaptic transmission with a voltage-dependent inactivation of EPSP amplitude through the membrane potential depolarization of presynaptic neurons.

Effects of landiolol on the cardiovascular response during tracheal extubation.

The objective of this study was to investigate the effect of landiolol on the cardiovascular responses to emergence from anesthesia and tracheal extubation. Fifty-nine patients without cardiovascular disorders who were scheduled for tympanoplasty were randomly allocated to receive a loading dose of landiolol at 0.125 mg x kg(-1) x min(-1) for 1 min, followed by an infusion at 0.01 mg x kg(-1) x min(-1) (group L1), 0.02 mg x kg(-1) x min(-1) (group L2), 0.03 mg x kg(-1) x min(-1) (group L3), or 0.04 mg x kg(-1) x min(-1) (group L4). At the end of surgery, sevoflurane and nitrous oxide were discontinued, and landiolol was started. The mean arterial pressure (MAP), heart rate (HR), and rate pressure product (RPP) in the four groups were compared before anesthesia induction, just after extubation, 5 min after extubation, 10 min after extubation, and at discharge from the operating room. Just after extubation compared with the baseline, the MAP increased significantly in all groups; the HR increased in groups L1 and L2; and the RPP increased in all groups, except for group L4. Continuous administration of landiolol, at 0.03 or 0.04 mg x kg(-1) x min(-1), may prevent the increases in HR and RPP, respectively, that occur at the emergence from anesthesia and tracheal extubation.

[A patient undergoing surgery for gastric cancer four weeks after insertion of a drug-eluting coronary stent].

We report a patient who underwent gastrectomy four weeks after a coronary stent insertion. A 79-year-old man suffering from unstable angina was transferred to our hospital and a sirolimus-eluting coronary stent was inserted into his right coronary artery. The day after receiving the coronary stent, the patient began vomitting bloody gastric fluid. Endoscopic findings showed Borrmann type 3 gastric cancer and a distal partial gastrectomy was scheduled four weeks after stent insertion. One week before the operation, the patient's aspirin and ticlopidine regimen was replaced with heparin injection, which was then discontinued twelve hours before the operation. After confirmation that his activated coagulation time was normalized, an epidural catheter was inserted and anesthesia was induced with midazolam 3.0 mg, fentanyl 0.1 mg and vecuronium 7.0 mg. Then propofol administration was began with a simulated blood concentration of 2 microg x ml(-1). Anesthesia was maintained using propofol infusions and intermittent epidural injections of local anesthetics. Hypotension was treated using an infusion of dopamine. The surgery was successfully performed and the patient was intensively monitored in the ICU. Heparin was restarted three days after the operation, and replaced with antiplatelet therapy five days after the operation. Six months after his gastrectomy, the patient underwent a right colon resection for invasive carcinoma. No complication, such as stent thrombosis or bleeding, occurred during the perioperative period.

Lidocaine increases intracellular sodium concentration through a Na+-H+ exchanger in an identified Lymnaea neuron.

BACKGROUND: The intracellular sodium concentration ([Na(+)]in) is related to neuron excitability. For [Na(+)]in, a Na(+)-H(+) exchanger plays an important role, which is affected by intracellular pH ([pH]in). However, the effect of lidocaine on [pH]in and a Na(+)-H(+) exchanger is unclear. We used neuron from Lymnaea stagnalis to determine how lidocaine affects [pH]in, Na(+)-H(+) exchanger, and [Na(+)]in. METHODS: Intracellular sodium imaging by sodium-binding benzofuran isophthalate and intracellular pH imaging by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein were used to measure [Na(+)]in and [pH]in. Measurements for [Na(+)]in were made in normal, Na(+) free saline, with modified extracellular pH, and a Na(+)-H(+) exchanger antagonist [(5-N-ethyl-N-isopropyl amiloride, N-methylisopropylamiloride, and 5-(N,N-hexamethylene)-amiloride) pretreatment trials. Furthermore, [Na(+)]in and [pH]in were recorded simultaneously. From 0.1 to 10 mM, lidocaine, mepivacaine, bupivacaine, prilocaine, and QX-314 were evaluated. RESULTS: Lidocaine, mepivacaine, and prilocaine increased the [Na(+)]in in a dose-dependent manner. In contrast, QX-314 did not change the [Na(+)]in at each dose. In the Na(+) free saline or in the presence of each Na(+)-H(+) exchanger antagonist, lidocaine failed to increase [Na(+)]in. Lidocaine, mepivacaine, and prilocaine induced a significant decrease in [pH]in below baseline with an increase in [Na(+)]in. In contrast, QX-314 did not change the [pH]in. These results demonstrated that lidocaine increases [Na(+)]in through Na(+)-H(+) exchanger activated by intracellular acidification, which is induced by the proton trapping of lidocaine. This [Na(+)]in increase and [pH]in change induces cell toxicity. CONCLUSION: Lidocaine increases the [Na(+)] through a Na(+)-H(+) exchanger by proton trapping.

Lysophosphatidic acid-LPA1 receptor-Rho-Rho kinase-induced up-regulation of Nav1.7 sodium channel mRNA and protein in adrenal chromaffin cells: enhancement of 22Na+ influx, 45Ca2+ influx and catecholamine secretion.

In cultured bovine adrenal chromaffin cells, chronic (> or = 24 h) treatment with lysophosphatidic acid (LPA) augmented veratridine-induced 22Na+ influx via Na(v)1.7 by approximately 22% (EC(50) = 1 nmol/L), without changing nicotine-induced 22Na+ influx via nicotinic receptor-associated channel. LPA enhanced veratridine (but not nicotine)-induced 45Ca2+ influx via voltage-dependent calcium channel and catecholamine secretion. LPA shifted concentration-response curve of veratridine for 22Na+ influx upward, without altering the EC(50) of veratridine. Ptychodiscus brevis toxin-3 allosterically enhanced veratridine-induced 22Na+ influx by twofold in non-treated and LPA-treated cells. Whole-cell patch-clamp analysis showed that peak Na+ current amplitude was greater by 39% in LPA (100 nmol/L for 36 h)-treated cells; however, I-V curve and steady-state inactivation/activation curves were comparable between non-treated and LPA-treated cells. LPA treatment (> or = 24 h) increased cell surface [3H]saxitoxin binding by approximately 28%, without altering the K(d) value; the increase was prevented by cycloheximide, actinomycin D, or Ki16425, dioctylglycerol pyrophosphate 8:0 (two inhibitors of LPA(1) and LPA3 receptors), or botulinum toxin C3 (Rho inhibitor), Y27632 (Rho kinase inhibitor), consistent with LPA(1) receptor expression in adrenal chromaffin cells. LPA raised Nav1.7 mRNA level by approximately 37%. Thus, LPA-LPA(1) receptor-Rho/Rho kinase pathway up-regulated cell surface Nav1.7 and Nav1.7 mRNA levels, enhancing veratridine-induced Ca2+ influx and catecholamine secretion.

The effects of centrally administered dexmedetomidine on cardiovascular and sympathetic function in conscious rats.

BACKGROUND: The alpha2-receptor is expressed in the brain, including the hypothalamus, where it is implicated in autonomic nervous system control. The effects of systemic administration of dexmedetomidine (DEX) on cardiovascular responses are well known; however, little is known about the effects of central administration of DEX on cardiovascular responses in conscious animals. In this study, we explored the effects and the mechanism of intracerebroventricularly (icv) administered DEX on cardiovascular responses and sympathetic nerve activity in conscious, unrestrained rats. METHODS: We administered DEX (0.5, 1, and 2 microg/kg) icv and measured the mean arterial blood pressure (MAP), heart rate (HR), and plasma catecholamine in conscious rats (n = 58). Rats were also administered atropine (n = 8), propranolol (n = 8), or hexamethonium (n = 8) to assess the influence of vagal or sympathetic efferent activity in the DEX-induced responses. Some of the rats underwent carotid sinus and aortic nerve denervation to exclude the effect of the baroreceptor reflex. RESULTS: Intracerebroventricular administration of DEX dose-dependently decreased MAP, HR, and plasma norepinephrine. Large dose of DEX decreased plasma epinephrine. The amplitude of MAP reduction induced by DEX was reduced by hexamethonium or propranolol. The amplitude of HR reduction was reduced by atropine or propranolol. The amplitude of MAP and HR reduction induced by DEX were smaller in hexamethonium-pretreatment rats than in intact ones. The amplitude of MAP and HR reduction induced by DEX were larger in sinus and aortic nerve denervation rats than in intact ones. CONCLUSIONS: These results indicate that icv administration of DEX decreases MAP by sympathetic inhibition and decreases HR by sympathetic inhibition and vagal stimulation.

[Burst spikes induced by lidocaine in the ganglion of Lymnaea stagnalis].

BACKGROUND: To investigate the burst spikes (BS) induced by lidocaine in the ganglion of Lymnaea stagnalis, we used a multielectrode dish for extracellular recording in many points simultaneously. METHODS: Ganglion of Lymnaea stagnalis was placed in the multielectrode dish that has 64 planar microelectrodes. After the basal electrophysiological recordings of neuronal activity in the ganglion, the lidocaine concentrations were increased from 1 to 1,000 microg x ml(-1). RESULTS: A sequence of changes was observed. The initial stage was represented before first BS. Second stage was during first BS (lidocaine concentrations were between 18 +/- 3 and 105 +/- 69 microg x ml(-1)). Third stage was the period before the second BS. The fourth stage was during second BS (lidocaine concentrations were more than 670 +/- 254 microg x ml(-1)). Basic unit frequency of firing were 83 +/- 33% at first stage, 91 +/- 280% at second stage, 77 +/- 29% at third stage, and 50 +/- 41% at fourth stage (P < 0.05) compared to control (100%). CONCLUSIONS: The results of this study showed that the lidocaine induced BS with low and high lidocaine concentrations have different mechanisms in the central nervous system of Lymnaea stagnalis.

Activation of a G protein-coupled inwardly rectifying K+ current and suppression of Ih contribute to dexmedetomidine-induced inhibition of rat hypothalamic paraventricular nucleus neurons.

BACKGROUND: Alpha2-adrenoceptor agonist has been reported to produce inhibition of arginine vasopressin release, diuresis, and sympatholytic effects. However, its mechanisms of central action remain incompletely understood. Hypothalamic paraventricular nucleus (PVN) neurons, which are in direct contact with noradrenergic synapses and are controlled by the hyperpolarization-activated currents, are called Ih (H current). The effect of dexmedetomidine, a highly selective and potent agonist, at alpha2 adrenoceptors on Ih is unknown. The purpose of this study was to examine the effects of dexmedetomidine on the PVN neuron, which is involved in the arginine vasopressin release and autonomic regulation. METHODS: The authors investigated the effects of dexmedetomidine on the membrane properties in PVN magnocellular neurons and an Ih in PVN parvocellular neurons with a whole cell patch clamp technique using a rat brain slice preparation. RESULTS: Dexmedetomidine dose-dependently hyperpolarized PVN magnocellular neurons. In the voltage clamp mode, dexmedetomidine induced an outward current, with a reversal potential of -94 mV, and this was shown to depend on the external concentration of K. Pretreatment with Ba or peptide toxin tertiapin blocked hyperpolarization induced by dexmedetomidine. The effect of dexmedetomidine was blocked by an alpha2-adrenoceptor antagonist, yohimbine. Ih was suppressed dose dependently by dexmedetomidine in PVN parvocellular neurons. Pretreatment with Cs occluded the Ih suppression by dexmedetomidine. Yohimbine blocked the Ih suppression by dexmedetomidine. The Ih sensitive to dexmedetomidine was weakly modulated by intracellular cyclic adenosine monophosphate. CONCLUSIONS: Dexmedetomidine inhibited PVN magnocellular neurons by activation of the G protein-coupled inwardly rectifying K current and inhibited PVN parvocellular neurons by suppression of Ih.

Prolongation of intrathecal and sciatic nerve blocks using a complex of levobupivacaine with maltosyl-beta-cyclodextrin in rats.

BACKGROUND: We used a cyclodextrin-based drug delivery system, consisting of levobupivacaine complexed with maltosyl-beta-cyclodextrin (G2-beta-CD), in spinal and sciatic nerve blocks in rats to investigate prolongation of the local anesthetic effect. METHODS: Rats were assigned to four groups (n = 6 in each) and received intrathecally 30 microL of 1% levobupivacaine complexed with 0 (control), 50, 100, or 200 mM of G2-beta-CD. Muscle tone and tail flick latency were studied after intrathecal administration. Four more groups (n = 6) of rats received a sciatic nerve block with 0.5% or 1% levobupivacaine complexed with either 0 or 100 mM of G2-beta-CD. The time course of changes in proprioception, motor function, and nociception after circumferential subcutaneous administration to the sciatic nerve was examined. RESULTS: With the intrathecal block, all rats stopped tail movement immediately after injection of the local anesthetic. The mean time to recovery of muscle tone with 1% levobupivacaine complexed with 100 mM (80.0 +/- 8.9 min) and 200 mM (91.7 +/- 7.0 min) of G2-beta-CD was significantly longer than that of the control group (38.3 +/- 3.1 min), but tail flick latency was not prolonged. With the sciatic nerve block, all rats were temporarily immobilized after levobupivacaine injection. The anesthetic effects of 0.5% levobupivacaine with 100 mM of G2-beta-CD were twice as long as those for 0.5% levobupivacaine alone, and those of 1% levobupivacaine with 100 mM of G2-beta-CD were 1.4 times longer than those for 1% levobupivacaine alone. CONCLUSIONS: The complex of levobupivacaine with G2-beta-CD prolonged the anesthetic effect of levobupivacaine in both intrathecal and sciatic nerve blocks in rats.

[Central action of orexins on sympathetic outflow and cardiovascular function with a focus on the paraventricular nucleus of the hypothalamus].

Orexins were initially reported as regulators of food intake. More recent reports suggest that they might play roles in the multiple functions of neuronal systems, causing medical conditions such as narcolepsy, a sleep disorder. Orexins and their receptors (OX1R and OX2R) are distributed in the neural tissue and brain regions involved in the autonomic and neuroendocrine control. Within the hypothalamus, orexin fibers and orexin receptors, especially OX2R, are found extensively in the paraventricular nucleus (PVN) of the hypothalamus. The PVN is an integrative center of the autonomic nervous system and the neuroendocrine system. Thus, orexins may play a role in the regulation of cardiovascular and autonomic nervous systems. This article provides a summary of our studies, in which we used direct recording of renal sympathetic nerve and PVN neuronal activities in conscious freely-moving rats and the in vitro whole cell patch-clamp technique to examine the direct effect of orexins on PVN neurons using a hypothalamic slice. Functional studies demonstrated that intracerebroventricularly (i.c.v.) administered orexins evoke increases in blood pressure, heart rate, and sympathetic nerve activity and depolarize both the magno- and parvo-cellular neurons through the activation of non-selective cation channels. The present studies suggest that PVN plays a role as one of the efferent pathways of orexin-induced activation of the sympathetic outflow.

[Plasma levobupivacaine concentrations following epidural administration of levobupivacaine conjugated with or without maltosyl-beta-cyclodextrin].

BACKGROUND: To investigate the pharmacokinetics of complexation of levobupivacaine with maltosyl-beta-cyclodextrin, the plasma concentrations of levobupivacaine were measured following epidural administration of levobupivacaine conjugated with maltosyl-beta-cyclodextrin or levobupivacaine alone in a rabbit model. METHODS: Rabbits were randomly divided into two groups, levobupivacaine (1%) group (n = 6) and levobupivacaine (1%) conjugated with maltosyl-beta-cyclodextrin (100 mM) group (n = 6). One ml of each solution was randomly injected through an epidural catheter placed at L5-6. The plasma levobupivacaine concentrations were measured before and 5, 10, 15, 30, 60, 120, 240, 360, and 480 min after injection. RESULTS: The plasma levobupivacaine concentrations were significantly higher in the levobupivacaine conjugated with maltosyl-beta-cyclodextrin group than in levobupivacaine group at 5 min (1,465 +/- 311, 1,033 +/- 347 ng x ml(-1)), 10 min (1,068 +/- 237, 731 +/- 191), and 15 min (958 +/- 311, 605 +/- 118). There were no differences in area under the curve (1,551 +/- 387, 1,176 +/- 154 ng x hr x ml(-1)) and elimination half life (100 +/- 54, 78 +/- 37 min) between the two groups. CONCLUSIONS: The results of this study indicated that the absorption of levobupivacaine conjugated with maltosyl-beta-cyclodextrin from the epidural space and the elimination from the blood were similar to plain levobupivacaine.

[Epidural infusion of low dose bupivacaine after combined spinal-epidural anesthesia using needle through needle method provided no analgesic effect on postoperative pain after caesarian section].

BACKGROUND: In order to evaluate the analgesic efficacy of low dose epidural bupivacaine infusion with and without morphine after caesarean section we performed combined spinal-epidural anesthesia (CSEA) using needle through needle method. Three different epidural analgesic regimens were compared retrospectively. METHODS: The number of analgesic use during 24 hours after operation was compared. Patients were categorized into three groups; group N : intraoperative bolus epidural morphine (2.5 mg) alone, group L : bolus morphine (2.5 mg) plus epidural bupivacaine infusion (32 ml of 0.2% bupivacaine) at a rate of 2.1 ml x hr(-1), group M : bolus morphine (2.4 mg) plus epidural bupivacaine-morphine (33 ml of 0.2% bupivacaine containing morphine 2.3 mg) infusion at a rate of 2.1 ml x hr(-1). Used analgesics included pentazocine 15 mg i.m., diclofenac 25 mg suppo. and loxoprofen 60 mg p.o.. RESULTS: The mean number of analgesic use during the first 24 hours in group M (0.29 +/- 0.46) was significantly smaller than those of group N (0.97 +/- 0.91) and group L (0.84 +/- 0.95). Percentage of patients requiring no analgesic during the first 24 hours was significantly less in group M (70.8%) than in group N (33.4%) and group L (42.1%). CONCLUSIONS: A 2.1 ml x hr(-1) infusion of epidural bupivacaine has no analgesic effect after caesarean section under CSEA using NTN method.

Increase in intracellular Ca2+ concentration is not the only cause of lidocaine-induced cell damage in the cultured neurons of Lymnaea stagnalis.

PURPOSE: To determine whether the increase in intracellular Ca2+ concentration induced by lidocaine produces neurotoxicity, we compared morphological changes and Ca2+ concentrations, using fura-2 imaging, in the cultured neurons of Lymnaea stagnalis. METHODS: We used BAPTA-AM, a Ca2+ chelator, to prevent the increase in the intracellular Ca2+ concentration, and Calcimycin A23187, a Ca2+ ionophore, to identify the relationship between increased intracellular Ca(2+) concentrations and neuronal damage without lidocaine. Morphological changes were confirmed using trypan blue to stain the cells. RESULTS: Increasing the dose of lidocaine increased the intracellular Ca2+ concentration; however, there was no morphological damage to the cells in lidocaine at 3 x 10(-3) M. Lidocaine at 3 x 10(-2) M increased the intracellular Ca2+ concentration in both saline (from 238 +/- 63 to 1038 +/- 156 nM) and Ca2+-free medium (from 211 +/- 97 to 1046 +/- 169 nM) and produced morphological damage and shrinkage, with the formation of a rugged surface. With the addition of BAPTA-AM, lidocaine at 3 x 10(-2) M moderately increased the intracellular Ca2+ concentration (from 150 +/- 97 to 428 +/- 246 nM) and produced morphological damage. These morphologically changed cells were stained dark blue with trypan blue dye. The Ca2+ ionophore increased the intracellular Ca2+ concentration (from 277 +/- 191 to 1323 +/- 67 nM) and decreased it to 186 +/- 109 nM at 60 min. Morphological damage was not observed during the 60 min, but became apparent a few hours later. CONCLUSION: These results indicated that the increase in intracellular Ca2+ concentration is not the only cause of lidocaine-induced cell damage.

Alteration of regional cerebral blood flow in patients with chronic pain--evaluation before and after epidural spinal cord stimulation.

BACKGROUND: Chronic pain is defined as intractable pain caused by abnormal pain transmission or impairment of the pain control system per se. Alteration of regional cerebral blood flow (rCBF) is known to occur under the presence of pain stimulation. Epidural spinal cord stimulation (SCS) is occasionally effective in relieving the symptom. OBJECTIVE: The aim of the current study is to investigate the alteration of rCBF in baseline condition and to find the association between the rCBF change and the efficacy of SCS in chronic pain. METHODS: A total of 18 patients underwent Tc-99m-HMPAO SPECT before and after SCS. Analysis with three-dimensional stereo-tactic surface projections (3D-SSP) with stereo-tactic extraction estimation (SEE) software was adopted to evaluate the rCBF. We assessed the extent score of the abnormal region in each segment (rate of the coordinates with a Z-value that exceeds three kinds of threshold value 2.0, 2.5 and 3.0 in all coordinates within a segment). According to the therapeutic response defined by visual analogue scale, we categorized patients into two groups, the good responder (GR) group (n=12) and poor responder (PR) group (n=6). In the analysis, we compared the extent score in the following two conditions. (1) Comparison between the PR group and normal control group under both baseline condition and after SCS. (2) Comparison between the GR group and normal control group under both baseline condition and after SCS. RESULTS: (1) In the PR group, increased rCBF was observed in left thalamus, bilateral precuneus and bilateral cerebellum under the baseline condition. After SCS, the range of these increased rCBF areas localized but remained. Decrease of rCBF was noted in bilateral subcallosal gyrus, superior temporal gyrus (STG) and bilateral anterior cingulate gyrus (ACG). They localized after SCS, but remained. (2) In the GR group, increased rCBF areas were noted in bilateral precuneus and bilateral cerebellum under the baseline condition. After SCS, they localized in bilateral precuneus but those of bilateral cerebellum remained. Decreased rCBF area was noted in bilateral subcallosal gyrus, STG and bilateral ACG under the baseline. After SCS, they localized in bilateral subcallosal gyrus and bilateral STG. In contrast, they enlarged in bilateral ACG. CONCLUSION: Chronic pain patients demonstrated abnormal rCBF distribution on both baseline and post SCS conditions. Increased rCBF of thalamus and precuneus under both conditions in the PR group and decreased rCBF of ACG under post SCS conditions in the GR group were characteristic patterns. Tc-99m-HMPAO SPECT with 3D-SSP and SEE analysis is likely objective and effective in monitoring and evaluating therapeutic outcome by SCS in chronic pain. In addition, it provides information that is useful in the selection of SCS candidates.

A comparison of intracellular lidocaine and bupivacaine concentrations producing nerve conduction block in the giant axon of crayfish in vitro.

Clinically, lidocaine requires a larger concentration than bupivacaine to block nerves. Bupivacaine has a higher lipid solubility, tissue permeability, and affinity for sodium channels than lidocaine, resulting in greater anesthetic potency. Local anesthetics require access to the sodium channel from the intracellular milieu. In this study, we sought to determine the intracellular concentration of lidocaine and bupivacaine when a nerve was blocked in the giant axon of a crayfish. A solution of lidocaine or bupivacaine was perfused, and a nerve block was determined as the absence of an evoked action potential after tonic or phasic electrical stimulation. The intracellular lidocaine or bupivacaine concentration was measured using a lidocaine- or bupivacaine-sensitive glass micro-electrode. A phasic block was more effectively and rapidly achieved with a smaller concentration of bupivacaine than with lidocaine. The intracellular concentration and intra- to extracellular ratios were significantly larger with lidocaine than with bupivacaine when nerve conduction was blocked. These findings suggest that bupivacaine has a higher potency than lidocaine, at least in the giant axon of a crayfish in vitro. The implications of the present results are that bupivacaine is a more potent nerve block and produces a use-dependent (phasic) block at smaller concentrations than lidocaine.

[A case of anaphylactic shock due to an antibiotic used preoperatively].

We report a case of an anaphylactic reaction due to a preoperatively administered antibiotic. A 72-year-old man scheduled to undergo cholecystectomy and choledocholithotomy received a cefoperazone infusion after being turned to a lateral position for insertion of an epidural catheter. Immediately after local injection of lidocaine, he, complained of inguinal itching. His systolic blood pressure then decreased to 60 mmHg and complained of discomfort and vomited. Soon, his systolic blood pressure decreased to 40 mmHg and he lost consciousness. Antibiotic infusion was stopped and he was returned to a prone, head-down position. His Spo2 decreased to 90%, and oxygen was administered. Following ephedrine 10 mg injection, his systolic blood pressure increased to 80 mmHg and he became conscious, but an erhythemic area appeared on his precordial region. Repeated epinephrine 0.05 mg injection restored his blood pressure to the preoperative level. Since a blood sample obtained 15 minutes after the event revealed high serum IgE levels, he was diagnosed as IgE-mediated anaphylactic reaction. Subsequent intradermal tests were tentatively positive to cefoperazone and negative to lidocaine. Surgery was successfully performed using cefotiam, which was also negative in a preoperative intradermal test.