Faculty Profiles - BABA Hiroshsi

No evidence for the development of acute analgesic tolerance during and hyperalgesia after prolonged remifentanil administration in mice Reviewed

Hideaki Ishii, Andrey B. Petrenko, Tatsuro Kohno, Hiroshi Baba

MOLECULAR PAIN 9 11 2013.3

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) are undesirable effects of opioids that have been reported in both animals and humans. However, the development of AOT and OIH in cases of potent, short-acting mu-opioid receptor agonist remifentanil administration remains controversial. It has been suggested that the emergence of AOT and OIH by remifentanil could be dose and infusion duration dependent, i.e., low dose and short infusions may lead to negative results. In this study, we determined whether AOT and OIH could be elicited by prolonged, continuous administration of remifentanil at maximally tolerable doses in C57BL/6 mice.
Results: The analgesic effects of continuously administered remifentanil [by short (1 h) and prolonged (4 h) intraperitoneal infusions] were studied. These experiments involved repeated measurements of thermal thresholds during remifentanil administration. Therefore, particular attention was paid to prevent cumulative tissue injury, which could mimic pronociceptive effects of remifentanil. To exclude the possibility of pseudoAOT during infusion, we used brief cooling of all ipsilateral hindpaws that exhibited analgesic response. Thermal thresholds remained steadily elevated over a 1-h period during continuous administration at infusion rates of 120, 180, and 240 mg/kg/h, which indicated no AOT development. To exclude the possibility of pseudoOIH after infusion, intact contralateral hindpaws were used for all postinfusion threshold measurements. Thermal thresholds at each infusion rate returned to the baseline values within 15 min after the termination of the administration. They did not decrease below the baseline values during 1 h following infusion, which indicated no OIH development. Similar threshold dynamics were also observed for thermal and mechanical testing modalities in animals infused at 120 mg/kg/h for 4 h as well as in animals with rapidly attained and maintained maximum analgesia for 3 h.
Conclusions: These results suggest that neither intra-infusion AOT nor postinfusion OIH develops in mice receiving continuous remifentanil when the possibility of cumulative tissue injury mimicking AOT or OIH is carefully avoided.

File： Ishii(Mol Pian, 2013).pdf

DOI： 10.1186/1744-8069-9-11

Increased brain monoaminergic tone after the NMDA receptor GluN2A subunit gene knockout is responsible for resistance to the hypnotic effect of nitrous oxide Reviewed

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

EUROPEAN JOURNAL OF PHARMACOLOGY 698 ( 1-3 ) 200 - 205 2013.1

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

N-methyl-D-aspartate (NMDA) receptors can be inhibited by inhalational anesthetics in vitro at clinically relevant concentrations. Here, to clarify the role of NMDA receptors in anesthetic-induced unconsciousness, we examined the hypnotic properties of isoflurane, sevoflurane and nitrous oxide in NMDA receptor GluN2A subunit knockout mice. The hypnotic properties of inhalational anesthetics were evaluated in mice in the loss of righting reflex (LORR) assay by measuring the 50% concentration for LORR (LORR ED50). Knockout mice displayed isoflurane and sevoflurane LORR ED50 values similar to wild-type controls, indicating no significant contribution of these receptors to the hypnotic action of halogenated anesthetics. However, compared with wild-type controls, mutant mice displayed larger isoflurane LORR ED50 values in the presence of nitrous oxide, indicating a resistance to this gaseous anesthetic. Knockout mice have enhanced brain monoaminergic activity which occurs secondary to NMDA receptor dysfunction, and the observed resistance to the isoflurane LORR ED50-sparing effect of nitrous oxide could be abolished by pretreatment with the dopamine D-2 receptor antagonist droperidol or with the serotonin 5-HT (2A), receptor antagonist ketanserin. Thus, resistance to nitrous oxide in knockout mice appears to be a secondary phenomenon of monoaminergic origin and not a direct result of impaired NMDA receptor function. Our results indicate that NMDA receptors are not critically involved in the hypnotic action of conventionally-used inhalational anesthetics. Also, they suggest that increased brain monoaminergic tone can diminish the effects of general anesthesia. Finally, they provide further evidence that changes secondary to genetic manipulation can explain the results obtained in global knockouts. (C) 2012 Elsevier B.V. All rights reserved.

File： Petrenko(Eur J Pharmacol,2013).pdf

DOI： 10.1016/j.ejphar.2012.10.034

Underlying mechanisms of pain evoked by tranexamic acid in the spinal dorsal horn neurons

Ohashi Nobuko, Sasaki Mika, Ohashi Masayuki, Kamiya Yoshinori, Baba Hiroshi, Kohno Tatsuro

PAIN RESEARCH 31 ( 1 ) 9 - 20 2013

Language：Japanese Publisher：JAPANESE ASSOCIATION FOR STUDY OF PAIN

Tranexamic acid (TXA) is an antifibrinolytic agent widely used to reduce blood loss during surgery. However, a serious adverse effect of TXA is seizure due to inhibition of γ–aminobutyric acid (GABA) and glycine receptors in cortical neurons. These receptors are also present in the spinal cord, and antagonism of these receptors in spinal dorsal horn neurons produces painrelated phenomena, such as allodynia and hyperalgesia. Moreover, some patients who are injected intrathecally with TXA develop severe back pain. However, no previous studies have investigated whether TXA modulates the GABA and glycine receptors in dorsal horn neurons. We hypothesized that TXA inhibits both GABA and glycine receptors in dorsal horn neurons,resulting in producing pain. Here, we investigated the effects of TXA by using behavioral measures in rats and found that TXA produces behaviors indicative of spontaneous pain and allodynia. We then performed wholecell patch–clamp experiments that showed that TXA inhibits GABAA and glycine receptors in spinal dorsal horn neurons. Finally, we also showed that TXA facilitates activation of the extracellular signal–regulated kinase in the spinal cord. These results indicated that TXA produces pain by inhibiting GABAA and glycine receptors directly located on postsynaptic sites of the recorded SG neurons. In addition, TXA enhances the excitability of excitatory interneurons via blockade of GABAergic and glycinergic postsynaptic inhibition, which facilitates excitatory transmission to the SG neurons indirectly.

DOI： 10.11154/pain.31.9

CiNii Article

Other Link： http://search.jamas.or.jp/link/ui/2016213404

Should We Use Psychostimulant Drugs to Boost the Emergence from General Anesthesia? Reviewed

Andrey B. Petrenko, Misako Takamatsu, Hiroshi Baba

ANESTHESIOLOGY 117 ( 6 ) 1393 - 1394 2012.12

When Similar Is Not Alike: Decreased Sensory Thresholds After Intravenous Infusion of Remifentanil May Not Be Remifentanil-Induced Hyperalgesia Reviewed

Andrey B. Petrenko, Hideaki Ishii, Tatsuro Kohno, Hiroshi Baba

ANESTHESIA AND ANALGESIA 115 ( 4 ) 977 - 977 2012.10

橈骨動脈カニューレに対する固定法の工夫前向きランダム化臨床試験

大橋宣子, 古谷健太, 本田博之, 馬場洋

臨床麻酔 36 ( 10 ) 1457 - 1462 2012.10

Language：Japanese Publisher：真興交易(株)医書出版部

橈骨動脈カニューレの開存性を維持することは重要であるが、ドレッシング材の添付文書(conventional method)に従い固定した場合でも、カニューレの閉塞や圧波形の描出不良をしばしば経験する。この問題を改善するため、新しい固定法(pillow method)を考案した。今回、対象症例102例をランダムにconventional methodとpillow methodに割り当てpillow methodの有効性を検討した。その結果、pillow methodによる固定は動脈カニューレの開存を良好に維持することができ、より細いカニューレでも安定した動脈圧モニタリングが行えることが示唆された。(著者抄録)

The Mu Opioid Receptor Modulates Neurotransmission in the Rat Spinal Ventral Horn Reviewed

Hiroyuki Honda, Yasuhiko Kawasaki, Hiroshi Baba, Tatsuro Kohno

ANESTHESIA AND ANALGESIA 115 ( 3 ) 703 - 712 2012.9

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

BACKGROUND: Opioids inhibit excitatory neurotransmission and produce antinociception through mu opioid receptors (MORs). Although MORs are expressed in the spinal ventral horn, their functions and effects are largely unknown. Therefore, we examined the neuromodulatory effects of mu opioids in spinal lamina IX neurons at the cellular level.
METHODS: The effects of the selective mu agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]Jenkephalin (DAMGO) on synaptic transmission were examined in spinal lamina IX neurons of neonatal rats using the whole-cell patch-clamp technique.
RESULTS: DAMGO produced outward currents in 56% of the lamina IX neurons recorded, with a 50% effective concentration of 0.1 mu M. Analysis of the current-voltage relationship revealed a reversal potential of approximately -86 mV. These currents were not blocked by tetrodotoxin but were inhibited by Ba2+ or a selective mu antagonist. Moreover, the currents were suppressed by the addition of Cs+ and tetraethylammonium or guanosine 5'-[beta-thi]diphosphate trilithium salt to the pipette solution. In addition, DAMGO decreased the frequency of spontaneous excitatory and inhibitory postsynaptic currents, and these effects were unaltered by treatment with tetrodotoxin.
CONCLUSION: Our results suggest that DAMGO hyperpolarizes spinal lamina IX neurons by G protein-mediated activation of K+ channels after activation of MORs. Furthermore, activation of MORs on presynaptic terminals reduces both excitatory and inhibitory transmitter release. Although traditionally opioids are not thought to affect motor function, the present study documents neuromodulatory effects of mu opioids in spinal lamina IX neurons, suggesting that MORs can influence motor activity. (Anesth Analg 2012;115:703-12)

File： Honda(A & A,2012).pdf

DOI： 10.1213/ANE.0b013e318259393d

Use of aortic occlusion balloon catheter for sacral giant cell tumor resection Reviewed

Hiroyuki Honda, Takayuki Yoshida, Chieko Shibue, Hiroshi Baba

Japanese Journal of Anesthesiology 61 ( 6 ) 610 - 613 2012.6

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

We report 2 patients for whom anesthetic management using aortic occlusion balloon catheter (AOBC) was performed thrice. A 14-year-old boy and a 43-year-old man with sacral giant cell tumor underwent tumor resection. In both patients, transcatheter arterial embolization (TAE) was performed several times before the operation. Before the surgery, an AOBC was inserted via the right femoral artery. For tumor resection, the AOBC was inflated, and a slight decrease in hemorrhage was observed. The occlusion was maintained for 40-55 min, with a loss of 1,400-3,700 ml of blood. In case 1, moderate bleeding from the epidural venous plexus was observed. In case 2, packed red blood cell transfusion was needed, and the patient returned to surgery for hemostasis. Because the AOBC could not decrease the severity of venous hemorrhage, we expected increased hemorrhage with an increase in the extent of surgery. In addition, preoperative multiple TAE might lead to the development of collateral circulation around the sacrum and augment the amount of blood loss in that region. Although the AOBC could reduce intraoperative hemorrhage, uncontrollable bleeding may occur if the sacral giant cell tumor shows extensive dissemination.

Scopus

仙骨部巨細胞腫切除術に大動脈遮断バルーンカテーテルを使用した2症例 Reviewed

本田博之, 吉田敬之, 渋江智栄子, 馬場洋

麻酔 61 ( 6 ) 610-3 - 613 2012.6

Language：Japanese Publisher：克誠堂出版(株)

症例1は14歳男性で、仙骨部の巨細胞腫に対し経カテーテル動脈塞栓術(TAE)を2回行ったが縮小せず、摘出手術となった。腫瘍は仙骨内を占拠し、一部脊柱管内に進展していた。麻酔導入後、出血量制御のため右大腿動脈よりシースを挿入し、大動脈遮断バルーンカテーテル(AOBC)の先端を第2〜3腰椎間に留置した。腫瘍操作直前にバルーンを膨らませ、血栓予防のためヘパリンを静注した。操作が脊柱管に及んだ際に硬膜外静脈叢からの出血が生じたが、閉鎖時間55分、総出血量1390mlで手術を終了した。残存腫瘍に対する再手術も同様に行った。症例2は43歳男性で、仙骨部の巨細胞腫に対しTAEを6回行ったが疼痛が増強し、摘出術を施行した。症例1と同様にAOBCの留置と操作を行ったが、腫瘍切除に伴って比較的大量に出血し、大動脈閉鎖時間50分、総出血量3705mlであった。手術5時間後に神経圧迫症状が出現し血腫除去・止血術を要したが、症状は軽快し退院に至った。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J01397&link_issn=&doc_id=20120607150010&doc_link_id=%2Fad3msuie%2F2012%2F006106%2F011%2F0610-0613%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fad3msuie%2F2012%2F006106%2F011%2F0610-0613%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Milnacipran inhibits glutamatergic N-Methyl-D-Aspartate receptor activity in Spinal Dorsal Horn Neurons Reviewed

Tatsuro Kohno, Masafumi Kimura, Mika Sasaki, Hideaki Obata, Fumimasa Amaya, Shigeru Saito

MOLECULAR PAIN 8 45 2012.6

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Antidepressants, which are widely used for treatment of chronic pain, are thought to have antinociceptive effects by blockade of serotonin and noradrenaline reuptake. However, these drugs also interact with various receptors such as excitatory glutamatergic receptors. Thermal hyperalgesia was induced by intrathecal injection of NMDA in rats. Paw withdrawal latency was measured after intrathecal injection of antidepressants. The effects of antidepressants on the NMDA and AMPA-induced responses were examined in lamina II neurons of rat spinal cord slices using the whole-cell patch-clamp technique. The effects of milnacipran followed by application of NMDA on pERK activation were also investigated in the spinal cord.
Results: Intrathecal injection of milnacipran (0.1 mu mol), but not citalopram (0.1 mu mol) and desipramine (0.1 mu mol), followed by intrathecal injection of NMDA (1 mu g) suppressed thermal hyperalgesia. Milnacipran (100 mu M) reduced the amplitude of NMDA (56 +/- 3 %, 64 +/- 5 % of control)-, but not AMPA (98 +/- 5 %, 97 +/- 5 % of control)- mediated currents induced by exogenous application and dorsal root stimulation, respectively. Citalopram (100 mu M) and desipramine (30 mu M) had no effect on the amplitude of exogenous NMDA-induced currents. The number of pERK-positive neurons in the group treated with milnacipran (100 mu M), but not citalopram (100 mu M) or desipramine (30 mu M), followed by NMDA (100 mu M) was significantly lower compared with the NMDA-alone group.
Conclusions: The antinociceptive effect of milnacipran may be dependent on the drug's direct modulation of NMDA receptors in the superficial dorsal horn. Furthermore, in addition to inhibiting the reuptake of monoamines, glutamate NMDA receptors are also important for analgesia induced by milnacipran.

File： Kohno(Mol Pain,2012).pdf

DOI： 10.1186/1744-8069-8-45

[Perioperative brachial plexus injury caused by hyperabduction of the upper extremity in a patient with Ehlers-Danlos syndrome in the prone position]. Reviewed

Nobuko Ohashi, Kenta Furutani, Hideaki Ishii, Hiroshi Baba

Masui. The Japanese journal of anesthesiology 61 ( 6 ) 626 - 8 2012.6

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

A 26-year-old woman with Ehlers-Danlos syndrome (EDS) underwent posterior spinal fusion with instrumentation for scoliosis. General anesthesia was maintained using propofol and remifentanil. The procedure was performed examining the motor evoked potential (MEP) and somatosensory evoked potential (SSEP) of the lower extremities with the patient placed in the prone position. The procedure was completed successfully without major cardiovascular or respiratory complications. The duration of anesthesia was 821 min. When drapes were removed, we noticed that the right shoulder was in a hyperabduction position. After emergence from anesthesia, it was observed that the right upper extremity was paralyzed. Thereafter, brachial plexus injury, which may have been due to intraoperative malpositioning, was diagnosed. Brachial plexus injury is the most common among the nerve injuries resulting from intraoperative malpositioning. Patients with EDS are thought to be at high risk for the complications and it has also been reported that patients with joint hypermobility, such as that in EDS or Marfan syndrome, are highly susceptible to nerve injury. Intraoperative monitoring of the MEP and SSEP in the upper extremities should be considered for early detection and prevention of brachial plexus injury in patients with EDS who are thought to be at high risk.

Effect of Xenon on Excitatory and Inhibitory Transmission in Rat Spinal Ventral Horn Neurons Reviewed

Tomohiro Yamamoto, Hiroyuki Honda, Hiroshi Baba, Tatsuro Kohno

ANESTHESIOLOGY 116 ( 5 ) 1025 - 1034 2012.5

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

Background: The minimum alveolar concentration is determined in the spinal cord rather than in the brain. Xenon inhibits glutamatergic excitatory synaptic transmission in the dorsal horn neurons. However, its actions in the ventral horn neurons have not been investigated.
Methods: The effects of 50 or 75% xenon on excitatory and inhibitory synaptic transmission were examined in the spinal lamina IX neurons of neonatal rats by using a whole cell patch clamp technique.
Results: Fifty percent xenon inhibited the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid-induced currents (amplitudes = 72 +/- 9% and integrated area = 73 +/- 13% of the control values), and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid receptor-mediated electrically evoked excitatory postsynaptic currents (amplitudes = 69 +/- 13% of the control values). Seventy-five percent xenon similarly inhibited alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid-induced currents. However, xenon had no effect on the N-methyl-D-aspartate-induced currents or N-methyl-D-aspartate receptor-mediated electrically evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There were no discernible effects on the currents induced by gamma-aminobutyric acid or glycine or on miniature inhibitory postsynaptic currents.
Conclusions: Xenon inhibits alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid receptor-mediated glutamatergic excitatory transmission in the spinal lamina IX neurons via a postsynaptic mechanism. In contrast, there are no substantial effects on N-methyl-D-aspartate receptor-mediated or inhibitory synaptic transmission. The suppressive effects on excitatory synaptic transmission in the ventral horn neurons partly account for the mechanism behind xenon's ability to produce immobility in response to noxious stimuli and to determine the minimum alveolar concentration.

File： Yamamoto(Anesthesiology,2012).pdf

DOI： 10.1097/ALN.0b013e31825037a1

Intranasal Application of Xenon: A Shortcut to the Brain or Just a Longer Way to It through the Lungs? Reviewed

Andrey B. Petrenko, Hiroshi Baba

ANESTHESIOLOGY 116 ( 3 ) 736 - 737 2012.3

Acute Airway Obstruction and Tracheal Laceration during Gastrostomy Placement in an Infant with Tracheoesophageal Fistula Reviewed

Hideaki Ishii, Hiroyuki Honda, Tatsuro Kohno, Hiroshi Baba

ANESTHESIOLOGY 116 ( 2 ) 485 - 487 2012.2

Alternative site for median nerve blockade allowing early functional rehabilitation after hand surgery Reviewed

Tatsunori Watanabe, Ippei Watanabe, Masahiro Koizumi, Andrey B. Petrenko, Hiroshi Baba

CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE 59 ( 1 ) 58 - 62 2012.1

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

In this report we describe an alternative approach to catheter placement for continuous selective median nerve blockade. It spared the finger movements and therefore allowed early postoperative rehabilitation in a patient who underwent surgical repair of the index finger flexor tendon.
A patient with a complicated history of traumatic index finger flexor tendon rupture, surgical repair, failed rehabilitation due to poor postoperative pain control, adhesion formation, and subsequent rerupture due to tenolysis was admitted for reconstructive surgery. This time, a continuous regional block was used. Although the insertion of a catheter at the wrist level would have spared the anterior interosseous branch of the median nerve and preserved finger movements, a more distant site had to be chosen to avoid proximity to the surgical wound. Therefore, under combined ultrasonography and neurostimulation guidance, the catheter was inserted in the proximal one-third of the patient's forearm distal to the branching-off point of the anterior interosseous nerve. Continuous ropivacaine infusion was initiated and maintained until being stopped on the afternoon of the third postoperative day, providing good analgesia without interfering with postoperative physiotherapy, which was successfully completed during this hospitalization.
Placement of a catheter for continuous median nerve blockade in the proximal one-third of the forearm for effective postoperative pain-free rehabilitation after hand surgery should be considered in cases in which the surgical incision extends toward the patient's wrist. The block site can be readily identified by a combined use of ultrasonography and neurostimulation guidance.

File： Watanabe(Can J Anes,2012).pdf

DOI： 10.1007/s12630-011-9613-4

気道確保に注意を要した小児巨大乳頭浮腫の1例 Reviewed

大西毅, 飛田俊幸, 馬場洋

日本臨床麻酔学会誌 32 ( 5 ) 791 - 794 2012

Tissue Doppler imaging is useful for predicting the need for inotropic support after cardiac surgery Reviewed

Hidekazu Imai, Satoshi Kurokawa, Miki Taneoka, Hiroshi Baba

JOURNAL OF ANESTHESIA 25 ( 6 ) 805 - 811 2011.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

Low preoperative left ventricular ejection fraction (EF) is a predictor of the need for inotropic support after cardiac surgery. However, EF can be misinterpreted and difficult to measure in some cases. The purpose of this study was to compare the value of preoperative EF and intraoperative tissue Doppler imaging variables in predicting the need for postoperative inotropic support.
Forty-eight consecutive adult patients undergoing cardiac surgery were enrolled in this study. Systolic mitral annular velocity (S (m)), early diastolic mitral annular velocity (E (m)), the ratio of E (m) to late diastolic mitral annular velocity (E (m)/A (m)), and the ratio of early diastolic transmitral velocity to E (m) (E/E (m)) were measured using transesophageal echocardiography before median sternotomy. The primary outcome was the need for inotropic support for 12 or more hours after surgery. Preoperative, intraoperative, and echocardiographic characteristics were analyzed to determine the independent predictors of the need for postoperative inotropic support.
Postoperative inotropic support was required for a parts per thousand yen12 h in 26.7% of patients. Multivariate logistic regression identified only cardiopulmonary bypass (CPB) time as an independent predictor of inotropic support (odds ratio, 1.015; 95% CI, 1.004-1.025; P = 0.004). Additional analysis was performed in the 25 patients with a CPB time of a parts per thousand yen200 min. In this analysis, only S (m) was significantly associated with the need for inotropic support for a parts per thousand yen12 h.
This study suggests that those patients who have decreased S (m) and extended CPB times are more likely to require inotropic support after surgery, independent of a preserved left ventricular EF.

File： Imai(JA, 2011).pdf

DOI： 10.1007/s00540-011-1231-3