Tadahide Totoki

Possible mechanism of irreversible nerve injury caused by local anesthetics: detergent properties of local anesthetics and membrane disruption.

BackgroundIrreversible nerve injury may result from neural membrane lysis due to the detergent properties of local anesthetics. This study aimed to investigate whether local anesthetics display the same properties as detergents and whether they disrupt the model membrane at high concentrations. MethodsConcentrations at which dodecyltrimethylammonium chloride and four local anesthetic (dibucaine, tetracaine, lidocaine, and procaine) molecules exhibit self-aggregation in aqueous solutions were measured using an anesthetic cation-sensitive electrode. Light-scattering measurements in a model membrane solution were also performed at increasing drug concentrations. The concentration at which drugs caused membrane disruption was determined as the point at which scattering intensity decreased. Osmotic pressures of anesthetic agents at these concentrations were also determined. ResultsConcentrations of dodecyltrimethylammonium chloride, dibucaine, tetracaine, lidocaine, and procaine at which aggregation occurred were 0.15, 0.6, 1.1, 5.3, and 7.6%, respectively. Drug concentrations causing membrane disruption were 0.09% (dodecyltrimethylammonium chloride), 0.5% (dibucaine), 1.0% (tetracaine), 5.0% (lidocaine), 10.2% (procaine), and 20% (glucose), and osmotic pressures at these concentrations were 278, 293, 329, 581, 728, and 1,868 mOsm/kg H2O, respectively. ConclusionsThese results show that all four local anesthetics form molecular aggregations in the same manner as dodecyltrimethylammonium chloride, a common surfactant. At osmotic pressures insufficient to affect the membrane, local anesthetics caused membrane disruption at the same concentrations at which molecular aggregation occurred. This shows that disruption of the model membrane results from the detergent nature of local anesthetics. Nerve membrane solubilization by highly concentrated local anesthetics may cause irreversible neural injury.

Proper shoulder position for subclavian venipuncture: a prospective randomized clinical trial and anatomical perspectives using multislice computed tomography.

Background:Although the Trendelenburg position and shoulder bracing are recommended for safe subclavian venipuncture, the optimal shoulder position remains unclear. The current study observed spatial relations between the subclavian vein and surrounding structures using multislice computed tomography to determine optimal shoulder position for safe subclavian venipuncture and then conducted a small follow-up clinical trial to confirm these findings. Methods:Thoracic multislice computed tomography was performed for seven adult volunteers at three shoulder positions: elevated (up); neutral; and lowered caudally (down). Overlap and distance between the clavicle and the subclavian vein and the diameter of the subclavian vein were measured. Anatomical relations between the subclavian artery and vein were also observed. The success rate for subclavian venipuncture was then compared between the up and down shoulder positions in 30 patients. Results:In the multislice computed tomography study, the mean overlap ratios between clavicle and subclavian vein in the up, neutral, and down positions were 33.5, 36.9, and 40.0%, respectively. Overlap increased with lower shoulder position (up < neutral < down; P < 0.05). The mean distances between the clavicle and the subclavian vein in the up, neutral, and down positions were 6.8, 5.0, and 3.6 mm, respectively. Again, distance decreased with lower shoulder position (up < neutral < down; P < 0.05). The diameter of the subclavian vein did not differ among the three shoulder positions. The success rate for subclavian venipuncture was significantly higher in the down position compared with the up position (P = 0.003). Conclusions:Lowered shoulder position increases both overlap and proximity between the clavicle and the subclavian vein, producing a more constant relation between the clavicle and the subclavian vein, without affecting vein diameter. Proper use of a lowered shoulder position should thus increase the safety and reliability of subclavian venipuncture compared with other shoulder positions.

A Median Epidural Septum Is Not a Common Cause of Unilateral Epidural Blockade

Unilateral blockade is occasionally seen with continuous and single-injection lumbar epidural anesthesia. Technical failure and presence of a median epidural septum have been suggested as causes of unilateral blockade (1-7). Median epidural septa have been observed under direct epiduroscopy and computed tomography-epidurography (8,9). We hypothesized that if a median epidural septum is a factor in the development of a unilateral blockade (by acting as a diffusion barrier to the local anesthetics extending from one side to the other), the pressure in the epidural space and subsequent cephalocaudad spread of the epidural anesthesia would be greater in the presence of unilateral blocks than in the presence of bilateral blocks. To investigate the cause of unilateral blockade, we compared the spread of lumbar epidural anesthesia when unilateral and when bilateral.

Lidocaine spray used to capture a live Clinostomum parasite causing human laryngitis.

This case report describes a patient who developed Clinostomum laryngitis after eating raw fresh-water fish. Parasite removal was performed under general anesthesia using a laryngomicroscopic method. Because it was difficult to capture the worm intact using forceps, it was sprayed with 8% lidocaine solution. This immediately inhibited peristaltic movement of the parasite allowing easy retrieval without tearing any part of the organism, thus facilitating parasite identification.

Tramadol produces outward currents by activating μ-opioid receptors in adult rat substantia gelatinosa neurones

1 An action of a tramadol metabolite, mono‐O‐dimethyl‐tramadol (M1), on substantia gelatinosa (SG) neurones in adult rat spinal cord slices was examined by using the whole‐cell patch‐clamp technique. 2 In 41% of the neurones examined, superfusing M1 produced an outward current at −70 mV; this response reversed at a potential close to the equilibrium potential for K+. M1 current hardly declined and persisted for >30 min after its washout. 3 M1 current correlated in amplitude with current produced by μ‐opioid receptor agonist DAMGO in the same neurone, and largely reduced in amplitude in the presence of μ‐opioid receptor antagonist CTAP but not α2‐adrenoceptor antagonist yohimbine. In a neurone where M1 had no effect on holding currents, noradrenaline produced an outward current at −70 mV. 4 The amplitude of the M1 response, relative to that of the DAMGO response, exhibited an EC50 value of 300 μM. 5 We conclude that M1 produces a persistent hyperpolarization by activating μ‐opioid receptors in adult rat SG neurones. This could contribute to at least a part of pain alleviation produced by tramadol.

Cutaneous distribution of sympathetic postganglionic fibers from stellate ganglion: A retrograde axonal tracing study using wheat germ agglutinin conjugated with horseradish peroxidase

Sympathetic postganglionic cells of the stellate ganglion (SG) projecting to the skin in young dogs were labeled retrogradely with wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP). After application of WGA-HRP into the dermis and/or subcutaneous tissue of the upper extremity, numerous labeled cells were observed in the SG. The sympathetic postganglionic fibers from the SG were distributed in the skin area between the third cervical vertebra and the level of the thirteenth rib. These fibers decreased in number toward the rostral and caudal skin area with a peak on the upper extremity. Sympathetic postganglionic cells in the SG projecting to these skin areas were found ipsilaterally to the injection side. No labeled cells were observed in the SG after injecting WGA-HRP into the epidermis and/or subcutaneous tissue of the face, the level of the second cervical vertebra, and the lower extremity.Sympathetic postganglionic neurons of the SG which project in the cervical and thoracic sympathetic trunks were labeled retrogradely with unconjugated horseradish peroxidase (HRP) applied to the cut end of the sympathetic trunks proximal to the SG. The application was made in the cervical sympathetic trunk (CST) caudal to the superior cervical ganglion (SCG). In the thoracic sympathetic trunk (TST), the application was made between the fourth and fifth thoracic sympathetic ganglia (T4 and T5), and between T10 and T11. Labeled cell bodies were observed in SG bilaterally.

An 11-year-old girl with reflex sympathetic dystrophy successfully treated by thoracoscopic sympathectomy

Abstract We report on an 11‐year‐old girl with reflex sympathetic dystrophy (RSD) complaining of severe pain in her right upper extremity. Oral administration of narcotics or non‐steroid anti‐inflammatory drugs gave no relief in pain. Thoracoscopic electrocauterization of the thoracic sympathetic ganglion at the level of T3 was performed 3 months after the start of symptoms, and brought complete resolution of pain.

Congenital absence of the internal carotid artery diagnosed during investigation of trigeminal neuralgia

Abstract. Congenital absence of the unilateral internal carotid artery (ICA) was found in a patient during MR imaging examination for right trigeminal neuralgia. Magnetic resonance angiography showed complete absence of the right ICA and a large tortuous basilar artery (BA). The source images revealed a deformed right trigeminal nerve resulting from compression by the BA. Computed tomography of the skull base showed absence of the right carotid canal, suggesting agenesis of the right ICA. Longstanding hemodynamic stress may have caused the BA to become extremely tortuous, resulting in the trigeminal neuralgia.

Acetazolamide-induced increase in blood flow to rabbit organs is confirmed using colored microspheres

SummaryInhibitors of carbonic anhydrase activity have been found to increase blood and organPCO2 and to increase blood flow (BF) in individual organs. To determine whether carbonic anhydrase inhibition coordinately induces an increase in BF in several organs, we assayed the effect of the carbonic anhydrase inhibitor, acetazolamide (AZ), on BF in rabbit organs using the colored microsphere (CM) assay. Eight female white rabbits were anesthetized with ketamine and urethane, and administered three sequential doses of 4 mg/kg AZ. After each dose, the rabbits were injected with 9 × 105 CMs of different colors, and arterial blood was collected. We found that AZ had no effect on blood pressure, body temperature, hemoglobin conentration, orPaCO2. In contrast, 12 mg/kg AZ significantly increasedPaO2 and significantly decreased base excess. When we measured organ BF, we observed, in response to 12 mg/kg AZ, an 82% increase in brain BF and a 55% increase in kidney BF, but no change in BF of the liver, stomach wall, or abdominal muscle. These findings suggest that the inhibition of carbonic anhydrase activity by AZ, which decreases the rate of CO2 conversion to HCO3-, causes the retention of CO2 in tissues and organs, and thus increases BF in specific organs. Administration of carbonic anhydrase inhibitors, such as AZ, may increase BF to the brain and kidney without reducingPaO2, thereby increasing the supply of oxygen in conditions involving hypoxia such as ischemia and shock.

NOS II inhibition restores attenuation of endothelium-dependent hyperpolarization in rat mesenteric artery exposed to lipopolysaccharide.

Abstract: The aim of this study was to assess the effects of lipopolysaccharide (LPS) exposure on the endothelium-dependent hyperpolarization in the rat mesenteric artery using isometric tension recordings and electrophysiological studies. Mesenteric arterial rings of male Sprague-Dawley rats were incubated with LPS for 6 hours. All experiments were performed in the presence of indomethacin to inhibit the formation of vasoactive prostanoids. Contraction to phenylephrine was significantly reduced in rings incubated with LPS, which was restored in the presence of Nω-nitro-L-arginine methyl ester (L-NAME). l-NAME resistant relaxation to acetylcholine was attenuated in LPS-treated rings. LPS exposure hyperpolarized resting membrane potentials of arterial smooth muscle cells, which was repolarized by incubation with either L-NAME or 1400W, a selective inhibitor of nitric oxide synthase II (NOS II). Endothelium-dependent hyperpolarization to acetylcholine was attenuated in arteries incubated with LPS, while incubation with LPS and 1400W restored EDHF-mediated hyperpolarization. LPS-induced membrane potential change was mimicked by incubation with either SIN-1 or diethylamine NONOate, a donor of nitric oxide. These data suggest that LPS exposure attenuates EDHF-mediated both relaxation and hyperpolarization in the rat mesenteric artery. The possible mechanisms underlying decreased EDHF-mediated responses might be due to, at least in some part, massive nitric oxide induced by NOS II.