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Biomedical subjects

K Shimoji

Publications and source records attributed to K Shimoji.

At least 37 records · Page 2Linked to original sources

Involvement of presurgical pain in preemptive analgesia for orthopedic surgery: a randomized double blind study.

Preemptive analgesia (PA) is effective in animal models but its clinical effectiveness remains controversial. We examined the effect of preexisting pain on PA. Subjects were recruited from patients needing orthopedic surgery. Some had presurgical pain (fracture surgery and arthritic surgery), while others had no presurgical pain (removal surgery for a tumor, nail or plate). Epidural morphine or a saline control was given preemptively before surgery and maintained until skin closure. Following skin closure, naloxone or placebo was injected intravenously to erase the aftereffects of the morphine. After total recovery, the PCA pump was set to inject epidural morphine. Pain intensity after surgery was measured by a visual analogue scale (VAS), and the amount of morphine used within 48h after surgery. PA was significantly effective for removal surgery, but ineffective for fracture or arthritic surgery. For the fracture and arthritic surgery PA treatment groups, there was a significant correlation between pre- and postsurgical (6h) spontaneous pain, while the corresponding control groups showed no significant correlation. Postsurgical VAS values in the fracture and arthritic surgery control groups increased significantly compared with presurgical VAS values. PA was effective when presurgical pain was absent, but ineffective when presurgical pain was present. We propose that central sensitization is already established by presurgical pain, and preserved until the termination of surgery. The ineffectiveness of PA did not depend on whether the pain was acute (fracture surgery) or chronic (arthritic surgery).

Adult↗

Complete recovery of consciousness in a patient with decorticate rigidity following cardiac arrest after thoracic epidural injection.

A 46-yr-old man with dysaesthesia (burning sensation) following herpes zoster in the left upper chest region was treated with a single thoracic (T2/T3) epidural injection (1.0% lidocaine 3 ml + 0.125% bupivacaine 3 ml) as an outpatient. Twenty minutes after the injection, a nurse noticed the patient to be unconscious with dilated pupils, apnoea and cardiac arrest. Following immediate cardiopulmonary resuscitation, the patient was treated with an i.v. infusion of thiamylal sodium 2-4 mg kg-1 h-1 and his lungs were mechanically ventilated. When the patient developed a characteristic decorticate posture, mild hypothermia (oesophageal temperature, 33-34 degrees C) was induced. On the 17th day of this treatment, after rewarming (35.5 degrees C) and discontinuation of the barbiturate, the patient responded to command. Weaning from the ventilator was successful on the 18th day. About 4 months after the incident, the patient was discharged with no apparent mental or motor disturbances. We suggest that mild hypothermia with barbiturate therapy may have contributed to the successful outcome in this case.

Analgesia, Epidural↗

N-methyl-D-aspartate receptor channel block by meperidine is dependent on extracellular pH.

UNLABELLED: Large concentrations of meperidine inhibit N-methyl-D-aspartate-(NMDA) receptor channels by channel block mechanisms. Extracellular pH regulates the activity and drug sensitivity of NMDA-receptor channels. We examined the influence of extracellular pH on sensitivity to meperidine of epsilon/zeta heteromeric NMDA-receptor channels expressed in Xenopus oocytes. Inhibition of epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1, and epsilon4/zeta1 channels by meperidine was dependent on pH, with more inhibition at acidic pH and less inhibition at alkaline pH. The degree of voltage-dependence of meperidine block was only slightly affected by changes in pH, whereas affinity for meperidine was greatly reduced at alkaline pH. Furthermore, interaction of meperidine with Mg(2+) block was reduced at alkaline pH. Because the percentage of the protonated form of meperidine is only slightly affected by pH, changes in properties of the meperidine binding site may be involved in mechanisms of alteration of meperidine potency by pH. IMPLICATIONS: At acidic pH the potency of meperidine for N-methyl-D-aspartate-receptor channels was increased. Any antinociceptive and neuroprotective benefit from the N-methyl-D-aspartate-receptor antagonist property of meperidine may be pH dependent.

Analgesics, Opioid↗

The stereoselective effects of ketamine isomers on heteromeric N-methyl-D-aspartate receptor channels.

UNLABELLED: The effects of S(+)- and R(-)-ketamine on heteromeric N-methyl-D-aspartate receptor channels were investigated on the epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1, and epsilon4/zeta1 channels expressed in Xenopus oocytes. S(+)-ketamine inhibited all four epsilon/zeta channels more effectively than R(-)-ketamine. The inhibitor concentrations for half-control response for S(+)-ketamine were quite similar among the four channels with 0.44-0.56 microM. However, the inhibitor concentrations for half-control response for R(-)-ketamine varied slightly among the four channels with 1.0 microM for epsilon2/zeta1 and epsilon3/zeta1 channels and 1.9-2.0 microM for epsilon1/zeta1 and epsilon4/zeta1 channels. Thus, the potency ratio of S(+)- and R(-)-ketamine for heteromeric channels was only slightly different among the epsilon/zeta channels. IMPLICATIONS: The potency order and ratio of ketamine isomers for inhibition of N-methyl-D-aspartate receptor channels may not be so different between the brain region and the developmental stage.

Analgesics↗

The effects of nicardipine on dynamic cerebral autoregulation in patients anesthetized with propofol and fentanyl.

UNLABELLED: We investigated the effects of nicardipine on dynamic cerebral pressure autoregulation in 13 normal adult patients undergoing gynecologic or orthopedic surgery. Anesthesia was induced and maintained with propofol and fentanyl. Hypotension to a mean arterial pressure of 60-65 mm Hg was induced and maintained with a continuous infusion of nicardipine. Time-averaged mean blood flow velocity in the right middle cerebral artery was measured continuously by using transcranial Doppler ultrasonography. The cerebral autoregulatory responses were activated by releasing thigh cuffs. The actual blood flow velocity in the right middle cerebral artery response to acute change in mean arterial pressure was fitted to 1 of 10 computer-generated curves to determine the dynamic rate of cerebral autoregulation (dRoR), and the best fitting curve was used. The autoregulation test was repeated until two values of dRoR were obtained at baseline and during induced hypotension. Nicardipine significantly reduced dRoR values of 13.1% +/- 3.6%/s at baseline to 8.3% +/- 2.6%/s during hypotension (P: < 0.01). During deliberate hypotension induced by nicardipine, the cerebral dynamic autoregulatory response is impaired in normal adult patients. IMPLICATIONS: During deliberate hypotension induced by nicardipine, the cerebral dynamic autoregulatory response is impaired in normal adult patients.

Adjuvants, Anesthesia↗

Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 1): effects on axon terminals of GABAergic and glycinergic neurons.

BACKGROUND: The activation of descending norepinephrine-containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha2 receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa. METHODS: Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated. RESULTS: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 microM) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected. This augmentation was mimicked by an alpha1-receptor agonist, phenylephrine (10-60 microM), and inhibited by alpha1-receptor antagonists prazosin (0.5 microM) and 2-(2,6-dimethoxyphenoxyethyl) amino-methyl-1,4-benzodioxane (0.5 microM). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine. CONCLUSION: These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha1 receptors, thus providing a mechanism underlying the clinical use of alpha1 agonists with local anesthetics in spinal anesthesia.

Adrenergic alpha-Agonists↗

Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 2): effects on somatodendritic sites of GABAergic neurons.

BACKGROUND: It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons. In the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are "GABAergic." METHODS: A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied. RESULTS: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 microM) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents. These increases were blocked by tetrodotoxin (1 microM). The effects of norepinephrine were mimicked by the alpha1-receptor agonist phenylephrine (10-80 microM) and inhibited by the alpha1-receptor-antagonist WB-4101 (0.5 microM). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 microM). CONCLUSION: The observations suggest that GABAergic interneurons possess somatodendritic alpha1 receptors, and activation of these receptors excites inhibitory interneurons. The alpha1 actions reported herein may contribute to the analgesic action of intrathecally administered phenylephrine.

Adrenergic alpha-1 Receptor Agonists↗

Actions of midazolam on GABAergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices.

BACKGROUND: Although intrathecal administration of midazolam has been found to produce analgesia, how midazolam exerts this effect is not understood fully at the neuronal level in the spinal cord. METHODS: The effects of midazolam on either electrically evoked or spontaneous inhibitory transmission and on a response to exogenous gamma-aminobutyric acid (GABA), a GABA(A)-receptor agonist, muscimol, or glycine were evaluated in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. RESULTS: Bath-applied midazolam (1 microM) prolonged the decay phase of evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by GABA(A) receptors, without a change in amplitudes, while not affecting glycine receptor-mediated miniature inhibitory postsynaptic currents in both the decay phase and the amplitude. Either GABA- or muscimol-induced currents were enhanced in amplitude by midazolam (0.1 microM) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 microM); glycine currents were, however, unaltered by midazolam. CONCLUSIONS: Midazolam augmented both the duration of GABA-mediated synaptic current and the amplitude of GABA-induced current by acting on the GABA(A)-benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.

2-Amino-5-phosphonovalerate↗

Preemptive analgesia by intravenous low-dose ketamine and epidural morphine in gastrectomy: a randomized double-blind study.

BACKGROUND: Morphine and ketamine may prevent central sensitization during surgery and result in preemptive analgesia. The reliability of preemptive analgesia, however, is controversial. METHODS: Gastrectomy patients were given preemptive analgesia consisting of epidural morphine, intravenous low-dose ketamine, and combinations of these in a randomized, double-blind manner. Postsurgical pain intensity was rated by a visual analog scale, a categoric pain evaluation, and cumulative morphine consumption. RESULTS: Preemptive analgesia by epidural morphine and by intravenous low-dose ketamine were significantly effective but not definitive. With epidural morphine, a significant reduction in visual analog scale scores at rest was observed at 24 and 48 h, and morphine consumption was significantly lower at 6 and 12 h, compared with control values. With intravenous ketamine, visual analog scale scores at rest and morphine consumption were significantly lower at 6, 12, 24, and 48 h than those in control subjects. The combination of epidural morphine and intravenous ketamine provided definitive preemptive analgesia: Visual analog scale scores at rest and morphine consumption were significantly the lowest at 6, 12, 24, and 48 h, and the visual analog scale score during movement and the categoric pain score also were significantly the lowest among the groups. CONCLUSION: The results suggest that for definitive preemptive analgesia, blockade of opioid and N-methyl-d-aspartate receptors is necessary for upper abdominal surgery such as gastrectomy; singly, either treatment provided significant, but not definitive, postsurgical pain relief. Epidural morphine may affect the spinal cord segmentally, whereas intravenous ketamine may block brain stem sensitization via the vagus nerve during upper abdominal surgery.

Aged↗

[Anesthetic management of thrombectomy for left ventricular huge mobile thrombus].

A 45 year-old male underwent thrombectomy for huge mobile thrombus and aneurysmectomy in the left ventricle. Despite of the patient's preoperative poor cardiac function and difficulties in weaning from cardiopulmonary bypass, he could recover with the aid of left ventricular bypass for 6 days without complications such as thromboembolism. Intraoperative transesophageal echocardiography was useful in observation of thrombus, decision making in the adaptation and type-selection of mechanical ventricular support, and evaluation of its efficacy.

Anesthesia, Intravenous↗

[Anesthetic management with veno-venous extracorporeal membrane oxygenator (VV-ECMO) in a patient with severe tracheobronchial stenosis].

We conducted an anesthetic management to perform tracheostomy and tracheolysis in a 33 year-old female with severe stenosis extending to the lower trachea and right main bronchus. The minimal diameter of the stenotic lesion of the trachea was 3 mm according to the preoperative examinations including tomography, CT scan and magnetic resonance imaging. Since there was a high risk of airway collapse during anesthetic induction that could have made ventilation impossible, we decided to apply VV-ECMO to support gas-exchange prior to anesthetic induction. Blood gas analysis showed good results, and sufficient oxygenation and stable circulation were achieved during surgical procedures. Total intravenous anesthesia with propofol and fentanyl could provide adequate depth of anesthesia during surgery and rapid recovery with good spontaneous respiration after the termination of the infusion. VV-ECMO was a useful method to support gas-exchange in a case not requiring circulatory assistance without uneven oxygenation sometimes observed in VA-ECMO.

Adult↗

Actions of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord.

1. The actions of opioid receptor agonists on synaptic transmission in substantia gelatinosa (SG) neurones in adult (6- to 10-week-old) rat spinal cord slices were examined by use of the blind whole-cell patch-clamp technique. 2. Both the mu-receptor agonist DAMGO (1 microM) and the delta-receptor agonist DPDPE (1 microM) reduced the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) which were monosynaptically evoked by stimulating Adelta afferent fibres. Both also decreased the frequency of miniature EPSCs without affecting their amplitude. 3. In contrast, the kappa-receptor agonist U-69593 (1 microM) had little effect on the evoked and miniature EPSCs. 4. The effects of DAMGO and DPDPE were not seen in the presence of the mu-receptor antagonist CTAP (1 microM) and the delta-receptor antagonist naltrindole (1 microM), respectively. 5. Neither DAMGO nor DPDPE at 1 microM affected the responses of SG neurones to bath-applied AMPA (10 microM). 6. Evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by either the GABAA or the glycine receptor, were unaffected by the mu-, delta- and kappa-receptor agonists. Similar results were also obtained in SG neurones in young adult (3- to 4-week-old) rat spinal cord slices. 7. These results indicate that opioids suppress excitatory but not inhibitory synaptic transmission, possibly through the activation of mu- and delta- but not kappa-receptors in adult rat spinal cord SG neurones; these actions are presynaptic in origin. Such an action of opioids may be a possible mechanism for the antinociception produced by their intrathecal administration.

Animals↗

Unique radiological appearance of a microcystic meningioma.

A 35-year-old female presented with partial complex seizures. Computed tomography (CT) showed a slightly high density mass over the right frontal convexity, with heterogeneous contrast enhancement. T1-weighted magnetic resonance (MR) imaging showed the tumour as a hypo-intense lesion, with faint reticular enhancement after intravenous injection of gadolinium-diethylenetriaminepenta-acetic acid. The tumour was totally removed. The specimen was extremely soft and moist. The histological diagnosis was microcystic meningioma. The tumour cells were composed of typical meningothelial cells and stellate cells. The degenerative character of the tumour may be reflected in the poor enhancement on CT and MR imaging. This faint enhancement effect may be a neuro-imaging characteristic indication of this rare microcystic variant of meningioma.

Adult↗

Subunit- and site-specific pharmacology of the NMDA receptor channel.

N-Methyl-D-aspartate (NMDA) receptor channels play important roles in various physiological functions such as synaptic plasticity and synapse formation underlying memory, learning and formation of neural networks during development. They are also important for a variety of pathological states including acute and chronic neurological disorders, psychiatric disorders, and neuropathic pain syndromes. cDNA cloning has revealed the molecular diversity of NMDA receptor channels. The identification of multiple subunits with distinct distributions, properties and regulation, implies that NMDA receptor channels are heterogeneous in their pharmacological properties, depending on the brain region and the developmental stage. Furthermore, mutation studies have revealed a critical role for specific amino acid residues in certain subunits in determining the pharmacological properties of NMDA receptor channels. The molecular heterogeneity of NMDA receptor channels as well as their dual role in physiological and pathological functions makes it necessary to develop subunit- and site-specific drugs for precise and selective therapeutic intervention. This review summarizes from a molecular perspective the recent advances in our understanding of the pharmacological properties of NMDA receptor channels with specific references to agonists binding sites, channel pore regions, allosteric modulation sites for protons, polyamines, redox agents, Zn2+ and protein kinases, phosphatases.

Animals↗

Effects of nicardipine-, nitroglycerin-, and prostaglandin E1-induced hypotension on human cerebrovascular carbon dioxide reactivity during propofol-fentanyl anesthesia.

STUDY OBJECTIVE: To investigate the effects of nicardipine-, nitroglycerin-, and prostaglandine E1-induced hypotension on cerebrovascular carbon dioxide (CO2) reactivity over a wide range of arterial CO2 tension (PaCO2) (PaCO2; range 25 to 50 mmHg). DESIGN: Prospective, randomized study. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 36 ASA physical status I and II patients without cerebrovascular disease, hypertension, or diabetes mellitus, undergoing an elective abdominal surgery. INTERVENTIONS: Patients were randomly allocated to one of three groups (nicardipine-, nitroglycerin-, or prostaglandin E1-induced hypotension group; 12 in each group). Anesthesia was induced and maintained with a bolus dose, followed by a continuous infusion of propofol (6.7 +/- 1.5 mg/kg/hr) and fentanyl (1.68 +/- 0.4 micrograms/kg/hr). Deliberate hypotension of mean arterial pressure 55 to 60 mmHg was induced and maintained with a bolus dose, followed by a continuous infusion of nicardipine (6.80 +/- 0.75 micrograms/kg/min), nitroglycerin (3.20 +/- 1.10 micrograms/kg/min), or prostaglandin E1 (0.103 +/- 0.052 microgram/kg/min). MEASUREMENTS AND MAIN RESULTS: Time-averaged mean red blood cell velocity in the right middle cerebral artery (Vmca) at PaCO2 ranging from 25 to 50 mmHg was measured with transcranial Doppler ultrasonography. A minimum of six simultaneous measurements of Vmca and PaCO2 were obtained during baseline and deliberate hypotension in each patient. Absolute slope between Vmca and PaCO2 during baseline and deliberate hypotension was determined individually by linear regression analysis. Absolute slope was treated as the variable, because it yielded a significant close correlation coefficient (r > 0.95; p < 0.05). Comparisons between baseline and deliberate hypotension were made by analysis of variance for repeated measures. Mean absolute slope was significantly reduced from 1.88 +/- 0.57 cm/sec/mmHg (mean +/- SD) to 1.21 +/- 0.46 in the nicardipine group (p < 0.05), from 1.75 +/- 0.69 to 1.35 +/- 0.47 in the nitroglycerin group (p < 0.05), and from 1.95 +/- 0.89 to 1.33 +/- 0.70 (p < 0.05) in the prostaglandin E1 group, respectively. CONCLUSION: Nicardipine-, nitroglycerin-, and prostaglandin E1-induced hypotension attenuate the human cerebrovascular CO2 reactivity during propofol-fentanyl anesthesia.

Adult↗

The effectiveness of preemptive analgesia varies according to the type of surgery: a randomized, double-blind study.

UNLABELLED: The reliability of preemptive analgesia is controversial. Its effectiveness may vary among anatomical areas or surgical types. We evaluated preemptive analgesia by epidural morphine in six surgery types in a randomized, double-blind manner. Pain intensity was rated using a visual analog scale, a verbal report, and a measurement of postsurgical morphine consumption. Preemptive analgesia was effective in limb surgery and mastectomy, but ineffective for gastrectomy, hysterectomy, herniorrhaphy, and appendectomy. Relief of postsurgical pain in hemiorrhaphy was more rapid than that in the other surgery types. Preemptive analgesia was effective in limb surgery and mastectomy, but not in surgeries involving laparotomy, regardless of whether the surgery was major (gastrectomy and hysterectomy) or minor (herniorrhaphy and appendectomy). These results suggest that viscero-peritoneal nociception is involved in postsurgical pain. The abdominal viscera and peritoneum are innervated both heterosegmentally (in duplicate or triplicate by the vagus and/or phrenic nerves) and segmentally (by the spinal nerves). Therefore, supraspinal and/or cervical spinal neurons might be sensitized, despite the blockade of the segmental nerves with epidural morphine. The rapid retreat of the pain after hemiorrhaphy suggests that central sensitization remits soon after minor surgery, but that in appendicitis, it may be protracted by additional noxious stimuli, such as infection. IMPLICATIONS: Epidural preemptive analgesia was reliably effective in limb and breast surgeries but ineffective in abdominal surgery, suggesting involvement of the brainstem and cervical spinal cord via the vagus and phlenic nerves.

Aged↗