Biomedical subjects

K Shimoji

Publications and source records attributed to K Shimoji.

At least 55 records · Page 3Linked to original sources

PubMed1999

Direct inhibition of the N-methyl-D-aspartate receptor channel by high concentrations of opioids.

BACKGROUND: Electrophysiologic and receptor binding studies showed that some opioids have noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist properties. METHODS: The effects and mechanisms of action of various opioid compounds were examined on four kinds of heteromeric NMDA receptor channels, namely the epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1, and epsilon4/zeta1 channels, expressed in Xenopus oocytes. Furthermore, the action sites of opioids on NMDA receptor channels were investigated by site-directed mutagenesis. RESULTS: Meperidine inhibited four kinds of channels to a similar extent with inhibitor concentrations for half-control response (IC50s) of 210-270 microM. Morphine, fentanyl, codeine, and naloxone also inhibited NMDA receptor channels with affinities comparable to meperidine. Opioid inhibition exhibited voltage dependence and was quite effective at negative potentials. Opioids also shifted the inhibition curve of Mg2+ to the right. Furthermore, replacement of the conserved asparagine residue with glutamine in the channel-lining segment M2 of the zeta1 subunit, which constitutes the block sites of Mg2+ and ketamine, reduced the sensitivity to opioids, whereas that of the epsilon2 subunit barely affected the opioid sensitivity. CONCLUSIONS: These results, together with previous findings, suggest that the low-affinity NMDA receptor antagonist activity is a common characteristic of various opioid compounds, and that the inhibition is a result of channel-block mechanisms at the site, which partially overlaps with those of Mg2+ and ketamine. This antagonist property of opioids may be clinically significant in the spinal cord following epidural or intrathecal administration, after which the cerebrospinal fluid concentrations of some opioids reach the high micromolar level.

Amino Acid Sequence↗

PubMed1999

Effects of naloxone and morphine on acute hypoxic survival in mice.

OBJECTIVE: To investigate a role of the opiate system during acute hypoxic hypoxia, the effects of naloxone and morphine on hypoxic survival rate were investigated in awake adult mice. DESIGN: Prospective, randomized, animal trial. SETTING: University research laboratory. SUBJECTS: Male dd-Y mice (n = 864 in experiment I, n = 144 in experiment II, n = 30 in experiment III). INTERVENTIONS: The animals were placed in an airtight plastic chamber into which a continuous flow of 8 L/min 5% oxygen-95% nitrogen was passed. MEASUREMENTS AND MAIN RESULTS: One and 5 mg/kg naloxone had no significant effect on the survival rate of mice subjected to acute hypoxic hypoxia, whereas 10 mg/kg naloxone decreased the survival rate. On the other hand, 2 and 5 mg/kg morphine was shown to have a protective action against acute hypoxic hypoxia. The protective effects of 5 mg/kg morphine against hypoxia was even antagonized by 5 mg/kg naloxone, which did not itself show any significant effect on the survival rate. The oxygen consumption in the morphine-treated (5 mg/kg) mice was significantly (p < .05) lower (87.0% +/- 4.6%; mean +/- SE) than that in the saline-treated animals. CONCLUSIONS: The present study suggests that the endogenous opiate system does not play a significant role on the pathophysiology caused by acute hypoxic hypoxia and that the improved survival of the hypoxic animals by morphine is at least partly attributable to its depressant effect on oxygen consumption.

Analgesics, Opioid↗

PubMed1999

Enhanced beta-receptor-mediated vasorelaxation in hypoxic porcine coronary artery.

To investigate the beta-adrenoceptor-mediated responses in hypoxic coronary arteries, we studied the effect of isoproterenol (Iso) on isolated porcine coronary arteries contracted with endothelin-1 in media aerated with 0, 5, 7.5, and 95% O(2). The concentration-response curve of Iso was significantly shifted to the left by hypoxia (0 and 5% O(2)). In oxygenated and hypoxic arteries, 3 x 10(-8), 10(-6), and 10(-5) M Iso significantly increased the contents of cAMP. However, there was no difference in the increases of cAMP content induced by 3 x 10(-8) M Iso between oxygenated and hypoxic arteries. The content of cAMP induced by high concentrations of Iso (10(-6) and 10(-5) M) was significantly larger in hypoxic than in oxygenated arteries. Furthermore, the potentiation by hypoxia of the Iso-induced vasorelaxation was inhibited by glibenclamide and depolarization by KCl, but not by removal of endothelium and indomethacin. The vasodilatory response to forskolin and dibutyryl cAMP was unaffected by hypoxia. We conclude that activation of the ATP-sensitive K(+) channel may account for the potentiation of the response to Iso in hypoxic coronary arteries.

Animals↗

PubMed1999

[Anesthetic management for pericardial fenestration in a hypertrophic cardiomyopathy (HCM) patient with massive pericardial effusion].

A 65 year-old male with HCM had progressively increased pericardial effusion. He also had atrial fibrillation (af), cardiac systolic dysfunction and chronic renal failure needing hemofiltration. Pericardial fenestration was carried out to improve diastolic function. Anesthetic management with fentanyl plus low-dose propofol infusion and postoperative analgesia with epidural morphine were effective for hemodynamic stability to prevent myocardial depression and to control ventricular response to atrial fibrillation. Intraoperative trans-esophageal echocardiography (TEE) monitoring was very useful for fluid therapy, inotropic support and estimation of systolic and diastolic function.

Aged↗

PubMed1999

[A case of partial Addison's disease activated with the administration of rifampicin (RFP)].

The patient was a 76 year-old female with tuberculous tendonitis, treated with anti-tuberculous drugs including rifampicin (RFP). About two weeks after the start of RFP, she noticed general malaise and started vomiting, and the laboratory data showed severe hyponatremia. Because of mild liver dysfunction, RFP was discontinued and her symptoms gradually improved. Abdominal X-ray and CT showed swellings and calcifications of adrenal glands bilaterally. Serum ACTH level was high and cortisole, 17-OHCS, and 17-KS levels were normal. Her response to rapid ACTH stimulation was blunted significantly. After another trial of RFP, she started to vomit and complain general malaise again. We diagnosed her as partial Addison's disease and administered hydrocortisone with RFP. After this treatment her improvement was rapid. It has been known that RFP causes induction of enzymes in hepatic microsomes which increase the catabolism of glucocorticoids. To avoid the risk of adrenal insufficiency, patients with insufficient adrenal hormone reserve should receive compensatory hydrocortisone while they are taking RFP.

Addison Disease↗

PubMed1999

[Anesthetic management of an infant with pulmonary atresia and ventricular septal defect accompanied by excess pulmonary blood flow for systemic-pulmonary shunt operation].

A 6-month-old infant had pulmonary atresia with ventricular septal defect (PA + VSD) accompanied by excess pulmonary artery flow via major aortopulmonary collateral artery, underwent aortopulmonary shunt with artificial graft under midazolam-fentanyl anesthesia. After the administration of protamine, arterial oxygen saturation gradually decreased. We suspected that hypotension and decrease in cardiac output induced by protamine caused the decrease in pulmonary blood flow via central shunt. It is suggested that pulmonary blood flow should be maintained by using an inotropic agent and a selective pulmonary arterial dilator such as prostaglandin E1 in a patient with PA + VSD after the institution of aorto-pulmonary shunt, because the patient with excess pulmonary flow has been reported to have high pulmonary resistance due to pulmonary abnormalities such as stenosis and thrombosis.

Anesthesia, Intravenous↗

PubMed1999

[Anesthetic management for mitral valve replacement in a patient with mitral stenosis and dilated cardiomyopathy].

A 42-year-old man with dilated cardiomyopathy and rheumatic mitral stenosis underwent mitral valve replacement. Prior intravascular fluid administration and infusion of dopamine and dobutamine stabilized hemodynamics during the induction of anesthesia. High-dose fentanyl at pre-cardiopulmonary bypass period and circulatory assist with milrinone and intraaortic balloon pumping after the bypass enabled us to obtain stable hemodynamics. Preoperative dobutamine stress test provided us the effective information for circulatory management in this patient.

Adult↗

PubMed1998

Ultrafine flexible spinal endoscope (myeloscope) and discovery of an unreported subarachnoid lesion.

STUDY DESIGN: Introduction of a new diagnostic procedure and a report on its usefulness. OBJECTIVES: To introduce a new endoscope (myeloscope) developed for the examination of the spinal canal and to present a previously unreported subarachnoid condition as a cause of paraparesis revealed by it. SUMMARY OF BACKGROUND DATA: In spite of the availability of advanced imaging technology, there still exists a significant number of patients with spinal diseases in whom a diagnosis cannot be made. Direct visualization of the pathologic area is required in these patients. Recent advances in fiberoptics have made this possible. METHODS: The endoscope consisted of a fiberscope with an external diameter of 0.5, 0.9, or 1.4 mm. It was inserted into the subarachnoid space in the lumbar spine and carefully advanced cranially. Since 1987, this examination has been performed on 18 patients aged 7 to 69 years who had pain or other neurologic symptoms of unknown origin. RESULTS: The surface of the spinal cord, roots, properties of the arachnoid membrane, and small vessels could be observed clearly. The scope could be advanced as far as the upper cervical spine. Cotton-candy-like proliferation of fibrous tissue was identified by myeloscopy in four paraparetic patients who had clinical and radiologic features similar to those of a spinal cord herniation. The fibrous tissue beat on the spinal cord with the pulsation of the spinal fluid. Resection of the fibrous tissue with conventional surgery resulted in neurologic improvement. Complications included one case of meningitis in the early period and five cases of postspinal headache. No nerve injury was apparent. CONCLUSIONS: Myeloscopy provides detailed information about the subarachnoid space and even reveals dynamic conditions that cannot be identified during open surgery or at autopsy. It will bring new concepts to the diagnosis of spinal diseases.

Adolescent↗

PubMed1998

Muscarinic facilitation of GABA release in substantia gelatinosa of the rat spinal dorsal horn.

1. Blind patch clamp recordings were made from substantia gelatinosa (SG) neurones in the adult rat spinal cord slice to study the mechanisms of cholinergic modulation of GABAergic inhibition. 2. In the majority of SG neurones tested, carbachol (10 microM) increased the frequency (677 % of control) of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs). A portion of these events appeared to result from the generation of spikes by GABAergic interneurones, since large amplitude IPSCs were eliminated by tetrodotoxin (1 microM). 3. The effect of carbachol on spontaneous IPSCs was mimicked by neostigmine, suggesting that GABAergic interneurones are under tonic regulation by cholinergic systems. 4. The frequency of GABAergic miniature IPSCs in the presence of tetrodotoxin (1 microM) was also increased by carbachol without affecting amplitude distribution, indicating that acetylcholine facilitates quantal release of GABA through presynaptic mechanisms. 5. Neither the M1 receptor agonist McN-A-343 (10-300 microM) nor the M2 receptor agonist, arecaidine (10-100 microM), mimicked the effects of carbachol. All effects of carbachol and neostigmine were antagonized by atropine (1 muM), while pirenzepine (100 nM), methoctramine (1 microM) and hexahydrosiladifenidol hydrochloride, p-fluoro-analog (100 nM) had no effect. 6. Focal stimulation of deep dorsal horn, but not dorsolateral funiculus, evoked a similar increase in IPSC frequency to that evoked by carbachol and neostigmine. The stimulation-induced facilitation of GABAergic transmission lasted for 2-3 min post stimulation, and the effect was antagonized by atropine (100 nM). 7. Our observations suggest that GABAergic interneurones possess muscarinic receptors on both axon terminals and somatodendritic sites, that the activation of these receptors increases the excitability of inhibitory interneurones and enhances GABA release in SG and that the GABAergic inhibitory system is further controlled by cholinergic neurones located in the deep dorsal horn. Those effects may be responsible for the antinociceptive action produced by the intrathecal administration of muscarinic agonists and acetylcholinesterase inhibitors.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1998

Intracellular acidification induced by membrane depolarization in rat hippocampal slices: roles of intracellular Ca2+ and glycolysis.

To elucidate the mechanism of pHi changes induced by membrane depolarization, the variations in pHi and [Ca2+]i induced by a number of depolarizing agents, including high K+, veratridine, N-methyl-D-aspartate (NMDA) and ouabain, were investigated in rat hippocampal slices by the fluorophotometrical technique using BCECF or fura-2. All of these depolarizing agents elicited a decrease in pHi and an elevation of intracellular calcium ([Ca2+]i) in the CA1 pyramidal cell layer. The increases in [Ca2+]i caused by the depolarizing agents almost completely disappeared in the absence of Ca2+ (0 mM Ca2+ with 1 mM EGTA). In Ca2+ free media, pHi acid shifts produced by high K+, veratridine or NMDA were attenuated by 10-25%, and those produced by ouabain decreased by 50%. Glucose-substitution with equimolar amounts of pyruvate suppressed by two-thirds the pHi acid shifts induced by both high K+ and NMDA. Furthermore, lactate contents were significantly increased in hippocampal slices by exposure to high K+, veratridine or NMDA but not by ouabain. These results suggest that the intracellular acidification produced by these depolarizing agents, with the exception of ouabain, is mainly due to lactate accumulation which may occur as a result of accelerated glycolysis mediated by increased Na+-K+ ATPase activity. A Ca2+-dependent process may also contribute to the intracellular acidification induced by membrane depolarization. Since an increase in H+ concentration can attenuate neuronal activity, glycolytic acid production induced by membrane depolarization may contribute to the mechanism that prevents excessive neuronal excitation.

Acids↗

PubMed1998

Sensitivity of the N-methyl-D-aspartate receptor channel to butyrophenones is dependent on the epsilon2 subunit.

The effects of three kinds of butyrophenones, haloperidol, droperidol and spiperone, on the N-methyl-D-aspartate (NMDA) receptor channel were examined on the epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1 and epsilon4/zeta1 heteromeric NMDA receptor channels, expressed in Xenopus oocytes. Micromolar concentrations of haloperidol selectively inhibited the epsilon2/zeta1 channel, whereas the epsilon1/zeta1, epsilon3/zeta1 and epsilon4/zeta1 channels were enhanced or minimally affected by higher concentrations of haloperidol. Similarly, droperidol and spiperone inhibited the epsilon2/zeta1 channel more strongly than the other epsilon/zeta channels, although sensitivities of the epsilon2/zeta1 channel to droperidol and spiperone were lower than those to haloperidol. These results suggest that the sensitivities of the NMDA receptor channels to butyrophenones are dependent on the epsilon2 subunit. Furthermore, the replacement with glutamine of the conserved asparagine residue in segment M2, which constitutes the Mg2+ block sites, of the epsilon2 and zeta1 subunits (the mutations epsilon2-N589Q and zeta1-N598Q, respectively) reduced the sensitivities to haloperidol. The mutation zeta1-N598Q reduced the sensitivities to haloperidol more effectively than the mutation epsilon2-N589Q. These results, together with previous findings, suggest that the haloperidol block sites of the NMDA receptor channel partially overlap the Mg2+ block sites.

Amino Acid Substitution↗

PubMed1998

Differential inhibitory effects of thiopental, thiamylal and phenobarbital on both voltage-gated calcium channels and NMDA receptors in rat hippocampal slices.

Although it is known that there are some pharmacological differences between the structurally similar barbiturates, the underlying mechanism of action remains unclear. We have compared the effects of thiopental, thiamylal and phenobarbital on both voltage-gated calcium channels (VGCC) and N-methyl-D-aspartate (NMDA) receptors in rat hippocampal slices by determining changes in intracellular calcium ([Ca2+]i). Experiments were performed in adult rat hippocampal slices perfused with Krebs solution (37 degrees C). Concentrations of [Ca2+]i in the pyramidal cell layer of the CA1 region were measured using a calcium indicator dye, fura-2. To activate VGCC and NMDA receptors, slices were exposed to K+ 60 mmol litre-1 (< or = 60 s) and NMDA 100 mumol litre-1 (30 s), respectively. Thiopental, thiamylal and phenobarbital were present 5 min before, during and 1 min after high K+ or NMDA application. Both thiamylal and thiopental (50-600 mumol litre-1) attenuated the increases in [Ca2+]i produced by high K+ or NMDA in a concentration-dependent manner, while phenobarbital 50-1000 mumol litre-1 only slightly attenuated the [Ca2+]i increase produced by high K+ at concentrations of more than 200 mumol litre-1 and was ineffective on the [Ca2+]i response produced by NMDA. Although the increases in [Ca2+]i caused by membrane depolarization with high K+ were reduced equally with thiamylal and thiopental, thiamylal was more effective in attenuating the increase in [Ca2+]i produced by NMDA receptor activation than thiopental. We conclude that the depressant effects of barbiturates on both VGCC and NMDA receptors varied between agents. Differential inhibition of both VGCC and NMDA receptors may determine the pharmacological properties of barbiturates and their ability to protect neurones against ischaemia.

Anesthetics, Intravenous↗

PubMed1998

Headache after attempted epidural block: the role of intrathecal air.

BACKGROUND: Postmeningeal puncture headache (PMPH) is typically attributed to the loss of cerebrospinal fluid (CSF). However, when it occurs after an attempted epidural puncture, it may be due to either CSF loss or, potentially, to the subarachnoid injection of air used as a part of "loss-of-resistance" testing. This study was performed to examine the relation between intrathecal air and PMPH. METHODS: Using a loss-of-resistance test with an air-filled (n = 1,812; air group) or saline-filled (n = 1,918; saline group) syringe, epidural block was performed in patients with acute or chronic pain. The dura was judged to be perforated not only when backflow of CSF was recognized in the needle but also when signs and symptoms solely attributable to meningeal perforation were seen, such as high spinal blockade or severe motor blockade. The incidence, onset time, and duration of PMPH in the air and saline groups were compared. In all patients with signs of meningeal perforation, brain computed tomography was examined. RESULTS: The incidence of PMPH in the air group (32 cases) was significantly higher than that in the saline group (5 cases), although the occurrences of meningeal perforation between the air (48 cases) and saline (51 cases) groups did not differ significantly. Intrathecal air bubbles were detected on brain computed tomography in both the deep supraspinal structures such as the ventricles, Silvian fissures and cisterns, and the superficial subarachnoid space in 30 of 32 patients with PMPH in the air group, whereas no intrathecal air bubbles were seen in the saline group. PMPH was significantly more rapid in onset and shorter in duration in the air group than that in the saline group. CONCLUSIONS: The use of air for loss-of-resistance testing during epidural block was associated with a higher incidence of PMPH, which might be attributable to subarachnoid air injection and CSF leakage.

Adolescent↗

PubMed1998

Thiopental inhibits increases in [Ca2+]i induced by membrane depolarization, NMDA receptor activation, and ischemia in rat hippocampal and cortical slices.

BACKGROUND: This study examined the effects of thiopental on intracellular calcium ([Ca2+]i) changes induced by membrane depolarization, N-methyl-D-aspartate (NMDA) receptor activation, and ischemia. METHODS: Experiments were performed in brain slices prepared from Wistar rats. [Ca2+]i measurements were taken on the CA1 pyramidal cell layer of the hippocampus or layers II to III of the somatosensory cortex using the fura-2 fluorescence technique. Membrane depolarization and NMDA receptor activation were induced by exposing slices to 60 mM K+ and 100 microM NMDA, respectively. In vitro ischemia was induced by superfusing slices with glucose-free Krebs solution equilibrated with 95% nitrogen and 5% carbon dioxide. Thiopental was applied 5 min before application of high K+ and NMDA, or before in vitro ischemia. RESULTS: Ischemia for 15 min produced a characteristic [Ca2+]i increase in both hippocampal and cortical slices. Thiopental prolonged the latency to the appearance of the [Ca2+]i plateau and reduced the magnitudes of increase in [Ca2+]i 8, 10, and 15 min after the onset of ischemia. Thiopental also suppressed the high K+- and NMDA-induced [Ca2+]i increases. The NMDA-induced [Ca2+]i increases were attenuated to a greater extent in cortical slices than were those in hippocampal slices. The inhibition of thiopental on the 200-microM NMDA-mediated [Ca2+]i response was confirmed in cultured cortical neurons. CONCLUSIONS: The results indicate that thiopental attenuates ischemia-induced [Ca2+]i increases in the hippocampus and cortex in vitro, probably because of its inhibition of both voltage-gated calcium channels and NMDA receptors. The regionally different inhibition of thiopental on NMDA receptors may relate to its region-specific action against ischemia.

Anesthetics, Intravenous↗

PubMed1998

[Anesthetic management for renal tumor extending to the inferior vena cava].

A 58 year-old woman underwent radical nephrectomy, thrombectomy and ileo-cecal resection for renal tumor with thrombus involving the inferior vena cava and ascending colon cancer. In a patient having tumor thrombus extending to the vena cava, recognition of the position of the thrombus is important for surgical and anesthetic management in pre- and intra-operative periods. Transesophageal echocardiography (TEE) enabled us to visualize the real-time movement and deformity of thrombus by surgical manipulation and compression during operation. TEE seemed also very useful not only in understanding the hemodynamics during operation but also in detecting the residual tumor and the blood flow in liver and the inferior vena cava after operation.

Anesthesia, Inhalation↗

PubMed1997

Prior brain injury protects death from local anaesthetic-induced convulsion.

Minor brain injury was inflicted with a small hypodermic needle at four sites from the scalp 7 days before the production of convulsion by i.p. injection of 100 mg/kg lidocaine in mice. The latency to convulsion and survival rate were significantly longer and higher, respectively, in the brain-injured group than in the sham-operated one. Thus, the results suggest that a protective mechanism develops in the injured brain against asphyxia caused by lidocaine convulsion.

Anesthetics, Local↗

PubMed1997

NMDA induces a biphasic change in intracellular pH in rat hippocampal slices.

As alterations in intracellular pH (pH(i)) tend to exert a profound effect on the properties of cells, this study was undertaken to examine NMDA-induced changes in pH(i) in rat hippocampal slices using the BCECF fluorescent technique. The 'resting' pH(i) in the CA1 pyramidal cell layers was 6.93 +/- 0.07 (mean +/- S.D., n = 72 slices) in 25 mM HCO3-/5% CO2-buffered solution at 37 degrees C. Exposure of hippocampal slices to NMDA in the range of 10-1000 microM produced a biphasic change in pH(i): an initial transient alkaline shift was followed by a long-lasting acid shift. Dizocilpine (10 microM) but not CNQX (40 microM) blocked the NMDA-induced changes in pH(i). In 0 Ca medium (0 mM Ca2+ supplemented 1 mM EGTA, referred to as 0 Ca), pH(i) acid shift caused by NMDA (20 microM) declined by about 11%, whereas the initial alkaline shift almost completely disappeared. In an independent experiment, the NMDA-induced increase in intracellular Ca2+ ([Ca2+]i) was reduced by more than 80% in 0 Ca medium. Glucose substitution using equimolar pyruvate (as an energy-yielding substrate) suppressed this NMDA-induced pH(i) acid shift by two-thirds, while the NMDA-induced pH(i) alkaline shift was enhanced. Fluoride (10 mM), a glycolytic inhibitor, abolished NMDA-induced pH(i) acid shift. Furthermore, the lactate content of hippocampal slices was markedly increased following exposure to NMDA. In conclusion, activation of NMDA receptors in rat hippocampal slices evokes a biphasic change in pH(i). The initial alkaline shift is suggested to be associated with calcium influx, and the following acid shift may be caused by an increase in lactate production through the acceleration of glycolysis, as well as the increased [Ca2+]i. The pH(i) acid shift produced by the increased lactate may contribute to proton modulation of the NMDA receptor and NMDA-induced cell injury or death.

Animals↗

PubMed1997

[Anesthetic managements for pericardiectomy of three patients with constrictive pericarditis].

We experienced three patients with constrictive pericarditis who underwent pericardiectomy. Percutaneous cardiopulmonary support (PCPS) was carried out in two patients because of unstable hemodynamics caused by massive bleeding or cardiac compression due to surgical manipulation. In the other patient with severe tachycardia, we prepared PCPS before the induction of anesthesia, and could manage the whole course of anesthesia satisfactorily. It is suggested that PCPS is the most reliable way to support hemodynamics during anesthesia in patients with constrictive pericarditis.

Anesthesia↗