Faculty Profiles - BABA Hiroshsi

Papers - BABA Hiroshsi

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Extracorporeal Membrane Oxygenation for Anesthetic Management of Whole-Lung Lavage in a Patient with Pulmonary Alveolar Proteinosis Reviewed

IMAI Hidekazu, FURUTANI Kenta, SHIBUE Chieko, SAITO Takeshi, BABA Hiroshi

JJSCA 29 ( 7 ) 829 - 834 2009

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：THE JAPAN SOCIETY FOR CLINICAL ANESTHESIA

A 58-year-old woman presented with severe hypoxemia. Chest radiography showed patchy infiltrates in both lungs. A diagnosis of pulmonary alveolar proteinosis (PAP) was made. The patient needed whole-lung lavage (WLL) , and the support of extracorporeal membrane oxygenation (ECMO) was required during this procedure because of severe hypoxemia (PaO<sub>2</sub> 38mmHg, breathing ambient air) . We performed the ECMO-assisted left WLL without fatal hypoxemia. It is suggested that ECMO support enables PAP patients with severe hypoxemia to maintain good oxygenation during aggressive WLL and results in early patient recovery.

DOI： 10.2199/jjsca.29.829

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Other Link： http://search.jamas.or.jp/link/ui/2010053334

Spontaneous hyperactivity in mutant mice lacking the NMDA receptor GluRF epsilon 1 subunit is aggravated during exposure to 0.1 MAC sevoflurane and is preserved after emergence from sevoflurane anaesthesia Reviewed

A. B. Petrenko, T. Kohno, J. Wu, K. Sakimura, H. Baba

EUROPEAN JOURNAL OF ANAESTHESIOLOGY 25 ( 12 ) 953 - 960 2008.12

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background and objective: Patients who awake from sevoflurane anaesthesia with symptoms of agitation may have sonic underlying functional substrate that is sensitive to the low concentrations of anaesthetic encountered during emergence. One candidate for Such a substrate Could be neurocircuitry implied in the pathophysiology of both agitation and movement disorders with hyperactivity. We Postulated that hyperactive animals would show a further increase in activity in the presence of low concentrations of volatile anaesthetics, Such as sevoflurane. Methods: To confirm our hypothesis, we examined the effects of two subanaesthetic concentrations of sevoflurane, isoflurane and halothane (0.1, and 0.2 MAC (minimum alveolar concentration)) on spontaneous activity in N-methyl-D-aspartate receptor GluR epsilon 1 subunit knockout mice exhibiring locomotor hyperactivity in a novel environment and compared these results with those for wild-type controls. We also compared the effects of anaesthetic concentrations of sevoflurane (1.2 MAC) on mice activity during postanaesthesia recovery. Results: Out of the three anaesthetics used, only sevoflurane administered at 0.1 MAC caused a significantly different response between the two experimental groups. Exposure to this subanaesthetic concentration of sevoflurane reduced the activity of wild-type mice, whereas mutant animals showed a further increase in hyperactivity. The effects of 1.2 MAC sevoflurane anaesthesia on mice activity during postanaesthesia recovery also differed significantly between the two genotypes. Exposure to anaesthetic concentrations of sevoflurane had a sedative effect on wild-type mice, whereas Mutant mice preserved their high levels of activity upon emergence from the anaesthesia. Conclusions: The presence of an inherent anomaly in Mutant mice that becomes more manifest during exposure to 0.1 MAC sevoflurane and is still present after the emergence from sevoflurane anaesthesia Suggests the presence of and necessitates a search for some Putative substrate that may, by analogy, underlie emergence agitation in the clinical setting.

DOI： 10.1017/S0265021508004626

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Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord

Hideaki Ishii, Tatsuro Kohno, Tomohiro Yamakura, Miho Ikoma, Hiroshi Baba

EUROPEAN JOURNAL OF NEUROSCIENCE 27 ( 12 ) 3182 - 3190 2008.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Dexmedetomidine is a highly specific, potent and selective alpha(2)-adrenoceptor agonist. Although intrathecal and epidural administration of dexmedetomidine has been found to produce analgesia, whether this analgesia results from an effect on spinal cord substantia gelatinosa (SG) neurons remains unclear. Here, we investigated the effects of dexmedetomidine on postsynaptic transmission in SG neurons of rat spinal cord slices using the whole-cell patch-clamp technique. In 92% of the SG neurons examined (n = 84), bath-applied dexmedetomidine induced outward currents at -70 mV in a concentration-dependent manner, with the value of effective concentration producing a half-maximal response (0.62 mu M). The outward currents induced by dexmedetomidine were suppressed by the alpha(2)-adrenoceptor antagonist yohimbine, but not by prazosin, an alpha(1)-, alpha(2B)- and alpha(2C)-adrenoceptor antagonist. Moreover, the dexmedetomidine-induced currents were partially suppressed by the alpha(2C)-adrenoceptor antagonist JP-1302, while simultaneous application of JP-1302 and the alpha(2A)-adrenoceptor antagonist BRL44408 abolished the current completely. The action of dexmedetomidine was mimicked by the alpha(2A)-adrenoceptor agonist oxymetazoline. Plots of the current-voltage relationship revealed a reversal potential at around -86 mV. Dexmedetomidine-induced currents were blocked by the addition of GDP-beta-S [guanosine-5'-O-(2-thiodiphosphate)] or Cs+ to the pipette solution. These findings suggest that dexmedetomidine hyperpolarizes the membrane potentials of SG neurons by G-protein-mediated activation of K+ channels through alpha(2A)- and alpha(2C)-adrenoceptors. This action of dexmedetomidine might contribute, at least in part, to its antinociceptive action in the spinal cord.

DOI： 10.1111/j.1460-9568.2008.06260.x

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Taurine activates glycine and gamma-aminobutyric acid A receptors in rat substantia gelatinosa neurons Reviewed

Jun Wu, Tatsuro Kohno, Stefan K. Georgiev, Miho Ikoma, Hideaki Ishii, Andrey B. Petrenko, Hiroshi Baba

NEUROREPORT 19 ( 3 ) 333 - 337 2008.2

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Taurine has been suggested to modulate nociceptive information at the spinal cord level. In this study, the pharmacological properties of taurine were investigated in adult rat substantia gelatinosa (SG) neurons using whole-cell patch-clamp method. We found that taurine seemed to have higher efficacy than glycine on glycine receptors in SG neurons. An increase in chloride conductance was responsible for taurine-induced currents. Taurine at 0.3 mM activated glycine receptors, whereas at 3 mM activated both glycine and gamma-aminobutyric acid A receptors. The currents activated by coapplication of taurine and glycine are cross inhibitive. Altogether these results show that taurine might represent another important neurotransmitter or modulator in SG neurons, which may be involved in antinociception.

File： Wu(Neuroreport,2008).pdf

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Nitrous oxide inhibits glutamatergic transmission in spinal dorsal horn neurons Reviewed

Stefan K. Georgiev, Tatsuro Kohno, Miho Ikorna, Tomohiro Yamakura, Hiroshi Baba

PAIN 134 ( 1-2 ) 24 - 31 2008.1

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

The effects of nitrous oxide (N2O) are thought to be mediated by several pharmacological pathways at different levels of the central nervous system. Here, we focus on excitatory glutamatergic transmission in the superficial dorsal horn of the spinal cord with respect to its importance for the nociceptive processing. The effects of 50% N2O on electrically evoked and spontaneous excitatory glutamatergic transmission and on the response to exogenous administration of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptor agonists were examined in lamina II neurons of adult rat spinal cord slices using the whole-cell patch-clamp technique. Peak amplitudes of A delta- and C-fiber evoked monosynaptic NMDA- and AMPA-receptor-mediated excitatory postsynaptic currents (EPSCs) were decreased in the presence of N2O. N2O reduced the peak amplitude and integrated area of exogenous NMDA- and AMPA-induced currents. Moreover NO changed the distribution of miniature EPSC amplitude, but not frequency distribution in most neurons. N20 inhibits glutamatergic transmission in the superficial dorsal horn by modulating the NMDA- and AMPA-receptors. Our findings raise the possibility that the antinociceptive effect of N2O may be directly mediated at the level of the spinal cord. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.pain.2007.03.026

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術後神経障害をきたした10症例の検討 Reviewed

若井綾子, 岡本学, 馬場洋

ペインクリニック 29 ( 12 ) 1653 - 1659 2008

[Introduction: position of the research on anesthetic mechanisms from the anesthesiologist's perspectives]. Reviewed

Baba H, Wu J, Wakai A, Ogawa M, Fujiwara N

Masui. The Japanese journal of anesthesiology 56 Suppl S83 - 8 2007.11

Mutation of alpha(1G) T-type calcium channels in mice does not change anesthetic requirements for loss of the righting reflex and minimum alveolar concentration but delays the onset of anesthetic induction Reviewed

Andrey B. Petrenko, Mika Tsujita, Tatsuro Kohno, Kenji Sakimura, Hiroshi Baba

ANESTHESIOLOGY 106 ( 6 ) 1177 - 1185 2007.6

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background: T-type calcium channels regulate neuronal membrane excitability and participate in a number of physiologic and pathologic processes in the central nervous system, including sleep and epileptic activity. Volatile anesthetics inhibit native and recombinant T-type calcium channels at concentrations comparable to those required to produce anesthesia. To determine whether T-type calcium channels are involved in the mechanisms of anesthetic action, the authors examined the effects of general anesthetics in mutant mice lacking alpha(1G) T-type calcium channels.
Methods: The hypnotic effects of volatile and intravenous anesthetics administered to mutant and C57BL/6 control mice were evaluated using the behavioral endpoint of loss of righting reflex. To investigate the immobilizing effects of volatile anesthetics in mice, the minimum alveolar concentration (MAC) values were determined using the tail-clamp method.
Results: The 50% effective concentration for loss of righting reflex and MAC values for volatile anesthetics were not altered after alpha(1G) channel knockout. However, mutant mice required significantly more time to develop anesthesia/hypnosis after exposure to isoflurane, halothane, and sevoflurane and after intraperitoneal administration of pentobarbital.
Conclusions: The 50% effective concentration for loss of righting reflex and MAC values for the volatile anesthetics were not altered after alpha(1G) calcium channel knockout, indicating that normal functioning of alpha(1G) calcium channels is not required for the maintenance of anesthetic hypnosis and immobility. However, the timely induction of anesthesia/hypnosis by volatile anesthetic agents and some intravenous anesthetic agents may require the normal functioning of these channel subunits.

File： Petrenko(Anesthesiology,2007.pdf

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Iteration of high-frequency stimulation enhances long-lasting excitatory responses in the spinal dorsal horn of rats: Characterization by optical imaging of signal propagation Reviewed

Mayumi Ogawa, Misako Takamatsu, Manabu Okamoto, Hiroshi Baba, Kenji Seo, Naoshi Fujiwara

NEUROSCIENCE RESEARCH 57 ( 3 ) 467 - 472 2007.3

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

To investigate plastic changes in nociceptive sensitivity of the dorsal horn, slow excitatory responses elicited by iteration of high-frequency stimulation were spatiotemporally observed in spinal cord slices of young-adult rats using membrane excitation imaging techniques. Single-pulse stimulation to the dorsal root elicited membrane excitation in lamina II, and high-frequency pulse-train stimulation evoked long-lasting excitation that expanded widely in the dorsal horn. Iteration of high-frequency stimulation enhanced the strength and extent of the excitatory responses, but such augmentation of the excitatory responses disappeared in the presence of an NMDA receptor antagonist (CPP) and was hindered by an NK1 receptor antagonist (L-703.606). The results suggest that activation of both NMDA and NK1 receptors is involved in the enhancement of slow excitatory responses evoked by iteration of high-frequency stimulation. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

File： Ogawa M(Neuroscience Research,2007).pdf

DOI： 10.1016/j.neures.2006.11.011

Investigational Questionnaire Concerning Epidural Anesthesia in Perioperative Anticoagulant Therapy Reviewed

SATO Tsuyoshi, OKAMOTO Manabu, HONMA Takayuki, BABA Hiroshi

27 ( 4 ) 332 - 338 2007

脊髄後角におけるデクスメデトミジンの作用 Reviewed

石井秀明, 河野達郎, 馬場洋

脊髄機能診断学 29 ( 1 ) 34 - 39 2007

Five Cases of Severe Hypotension upon Red Blood Cell Transfusion through a Potassium Adsorption Filter Reviewed

HIRAISHI Mai, OHKURO Michiya, TOBITA Toshiyuki, BABA Hiroshi

27 ( 7 ) 684 - 688 2007

亜酸化窒素の脊髄第Ⅱ層における作用 Reviewed

Georgiev S, 河野達郎, 生駒美穂, 馬場洋

脊髄機能診断学 29 ( 1 ) 27 - 33 2007

Introduction: Position of the research on anesthetic mechanisms from the anesthesiologist's perspectives Reviewed

56 S83-88 - 88 2007

Effects of ketamine on acute somatic nociception in wild-type and N-methyl-D-aspartate (NMDA) receptor epsilon 1 subunit knockout mice Reviewed

AB Petrenko, T Yamakura, AR Askalany, T Kohno, K Sakimura, H Baba

NEUROPHARMACOLOGY 50 ( 6 ) 741 - 747 2006.5

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Although the properties of ketamine appear to be well characterized, there is a lot of ambiguity in the literature regarding its analgesic effects. After careful selection of proper experimental conditions and drug doses, we systematically characterized the effects of systemic ketamine on acute somatic nociception in mice and examined the role of the NMDA receptor epsilon 1 subunit in mediating its analgesia. Intraperitoneal administration of ketamine was not analgesic in any of the phasic pain assays (thermal, mechanical, electrical) applied to C57BL/6 (wild-type) and NMDA receptor epsilon 1 subunit knockout (mutant) mice. Surprisingly, rather than being analgesic for thermal nociception, ketamine showed pronociceptive properties in case of low-intensity heat stimulation in wild-type mice. In the formalin test (tonic pain), ketamine significantly reduced phase 2 nociceptive behavior in both wild-type and mutant mice. These data indicate that in wild-type mice ketamine has no analgesic effect on phasic pain in normal somatic tissues, but alleviates tonic pain after inflammation. Such analgesic spectrum of ketamine can be fully explained by its NMDA receptor antagonist properties. The results for the mutant mice suggest that the epsilon 1 subunit of the NMDA receptor does not mediate the analgesic effects of ketamine in tonic pain. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuropharm.2005.11.019

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Actions of midazolam on excitatory transmission in dorsal horn neurons of adult rat spinal cord Reviewed

T Kohno, A Wakai, T Ataka, M Ikoma, T Yamakura, H Baba

ANESTHESIOLOGY 104 ( 2 ) 338 - 343 2006.2

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background: Although intrathecal administration of midazolam, a water-soluble imidazobenzodiazepine derivative, has been found to produce analgesia, how it exerts this effect at the neuronal level in the spinal cord is not fully understood.
Methods: The effects of midazolam on electrically evoked and spontaneous excitatory transmission were examined in lamina H neurons of adult rat spinal cord slices using the whole cell patch clamp technique.
Results: Bath-applied midazolam (1 mu m) diminished A delta- and C-fiber evoked polysynaptic excitatory postsynaptic currents in both amplitude and integrated area. However, it affected neither A delta- and C-fiber evoked monosynaptic excitatory postsynaptic currents in amplitude nor miniature excitatory postsynaptic currents in amplitude, frequency, and decay time constant. In the presence of a benzodiazepine receptor antagonist, flumazenil (5 mu m), midazolam (1 mu m) did not diminish A delta-fiber evoked polysynaptic excitatory postsynaptic currents, suggesting that midazolam modulate the gamma-aminobutyric acid interneurons in the dorsal horn.
Conclusions: Midazolam reduced excitatory synaptic transmission by acting on the gamma-aminobutyric acid type A/benzodiazepine receptor in interneurons, leading to a decrease in the excitability of spinal dorsal horn neurons. This may be a possible mechanism for the antinociception by midazolam in the spinal cord.

File： Kohno(Anesthesiology,2006).pdf

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Actions of norepinephrine and isoflurane on inhibitory synaptic transmission in adult rat spinal cord substantia gelatinosa neurons Reviewed

SK Georgiev, A Wakai, T Kohno, T Yamakura, H Baba

ANESTHESIA AND ANALGESIA 102 ( 1 ) 124 - 128 2006.1

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Volatile inhaled anesthetics and nitrous oxide (N2O) are often used together in clinical practice to produce analgesia. Because the analgesic effect of N2O is, at least in part, mediated by norepinephrine (NE) release in the spinal cord, we examined the interaction between isoflurane (ISO) and NE in the adult rat spinal cord with respect to central nociceptive information processing. The effects of clinically relevant concentrations of ISO (1 MAC) and NE (20 mu M) on spontaneous inhibitory transmission in substantia gelatinosa (SG) neurons were examined using the blind whole-cell patch-clamp method. ISO prolonged the decay time and increased the total charge transfer of spontaneous inhibitory postsynaptic currents. NE increased the frequency and mean amplitude of inhibitory postsynaptic currents and the charge transfer as well. Coapplication of both drugs led to an additive increase of the charge transfer and frequent temporal summation of inhibitory postsynaptic currents. We conclude that both ISO and NE enhance the inhibitory synaptic transmission in the rat SG neurons and their interaction is additive, suggesting that ISO may add to the analgesic action of N2O at the spinal cord dorsal horn level.

File： Georgiev(A&A,2006).pdf

DOI： 10.1213/01.ane.0000184829.25310

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Difference of the effects of options on primary afferents-mediated nociceptive transmission in the spinal dorsal horn Reviewed

Ikoma M, Kohno T, Baba H

The Joural of Functional Diagnosis of the Spinal Cord 28 ( 1 ) 32 - 40 2006

Possible role of the N-methyl-d-aspartate receptor GluRε1 subunit in ketamine hypnosis and analgesia Reviewed

Tomohiro Yamakura, Andrey B. Petrenko, Hiroshi Baba, Kenji Sakimura

International Congress Series 1283 137 - 142 2005.11

Language：English Publishing type：Research paper (scientific journal)

Ketamine is an IV anesthetic and analgesic with N-methyl-d-aspartate receptor (NMDAR)-blocking properties at clinically relevant concentrations. Functional NMDARs are composed by assembly of GluRζ1 (NR1) subunit with GluRε1-4 (NR2A-D) subunits, which confer unique properties on native NMDARs. Mutant mice lacking the ε1 subunit, which is widely expressed postnatally in normal animals, were found to be resistant to ketamine-induced loss of the righting reflex (hypnosis). Surprisingly, they were also more resistant to hypnotic action of pentobarbital, which does not interact with the NMDARs at clinically relevant concentrations. These results suggest the difficulties with interpretation of altered anesthetic sensitivity in global knockouts. Although the ability of ketamine to produce somatic analgesia even at subanesthetic doses in humans is well recognized, administration of ketamine did not result in elevation of pain thresholds to thermal stimuli (phasic pain model) in wild-type and mutant mice. Ketamine dose-dependently reduced nociceptive behavior (paw licking/biting) in the second phase of the formalin test (tonic pain model) in both wild-type and mutant mice. These results argue against the contribution of the ε1 subunit to ketamine analgesia in this nociceptive assay. © 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ics.2005.07.042

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Effect of agmatine on heteromeric N-methyl-D-aspartate receptor channels Reviewed

AR Askalany, T Yamakura, AB Petrenko, T Kohno, K Sakimura, H Baba

NEUROSCIENCE RESEARCH 52 ( 4 ) 387 - 392 2005.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Endogenous polyamines like spermine are known to have four distinct effects on recombinant N-methyl-D-aspartate (NMDA) receptor channels: voltage-dependent inhibition, glycine-dependent Stimulation, glycine-independent stimulation and decreased affinity to the agonist (L-glutamate). These effects are highly dependent on the constituting F subunits (epsilon 1-r4) of the recombinant NMDA receptor channels. Agmatine reportedly inhibits native NMDA receptor channels in cultured hippocampal neurons. In the present investigation, the effects of agmatine on the epsilon/zeta heteromeric NMDA receptor channels expressed in Xenopus laevis oocytes were examined using the two-electrode voltage clamp method. Agmatine inhibited the four epsilon/zeta (epsilon 1/zeta 1, epsilon 2/zeta 1, epsilon 4/zeta 1 and epsilon 4/zeta 1) channels with similar sensitivity (an IC50 value of about 300 mu M at -70 mV). This effect was dependent on the membrane potential and was more pronounced at hyperpolarized membrane potentials (vottage-dependent inhibition). Agmatine did not exhibit other stimulatory (glycine-dependent and -independent effects) or inhibitory (decreased affinity to L-glutamate) effects. These properties are similar to the pharmacological profile of well-characterized NMDA receptor channel blockers like phencyclidine and ketamine. Thus, regarding the effects on the NMDA receptor channels, agmatine is not like other endogenous polyamines rather it acts as a channel blocker. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2005.05.002

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Papers - BABA Hiroshsi