Yasuharu Kitani

The cerebral hemodynamic response to electrically induced seizures in man

The hemodynamic response to seizure has long been a topic for discussion in association with the neuronal damage resulting from convulsion. Electroconvulsive therapy (ECT) is an appropriate clinical model for the investigation of the cerebral physiology of seizure. In this study, we monitored the oxygenation state of brain tissue using near infrared (NIR) spectrophotometry, and flow velocity at the middle cerebral artery (MCA) using transcranial Doppler ultrasonography (tc-Doppler) in ninety cases where flow velocity at the middle cerebral artery (MCA) using transcranial Doppler ultrasonography (tc-Doppler) in ninety cases where ECT was prescribed to patients suffering from endogenous depression. Under general anesthesia with thiopental and succinyl choline, an electrical current was applied bilaterally at the minimal energy level. Throughout the therapy, end-tidal CO2 tension was maintained at 30-35 mmHg, and the SpO2 value was maintained above 98% by manual ventilation assistance. The total- and oxy-hemoglobin contents in the brain were reduced during the electrical shock, and then recovered to the pre-shock value (total-hemoglobin; 44.13 +/- 12.88 s after the shock, oxy-hemoglobin; 88.62 +/- 11.69 s after the shock). Subsequently, these values further increased beyond the preshock value. On the other hand, the deoxy-hemoglobin content increased for 90.73 +/- 15.88 s during and after the electrical shock, and decreased afterward. Reduction of cytochrome aa3 began 3.04 +/- 0.51 s after the electrical shock, and this was reoxygenated at 171.88 +/- 12.95 s after the shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional cerebral oxygen saturation during electroconvulsive therapy: monitoring by near-infrared spectrophotometry.

Electroconvulsive therapy (ECT) increases neuronal energy consumption and alters systemic hemodynamics.We examined the effects of ECT on regional cerebral oxygen saturation (rSO2) using a near-infrared spectrophotometer. Heart rate (HR), mean arterial blood pressure (MAP), and rSO2 were continuously monitored throughout ECT under general anesthesia in 43 patients. In all subjects, rSO2 changed in a consistent pattern during ECT, initially decreasing (-9.4% +/- 0.9%) just after application of the electrical current and subsequent increasing (8.7% +/- 0.9%) beyond the pre-ECT value. A close correlation was demonstrated between the increase in rSO2 and the mean blood pressure after the electrical shock (r2 = 0.832, P < 0.0001). We conclude that ECT initially may increase cerebral metabolic rate of oxygen more than cerebral blood flow and that rapidly increasing blood pressure transiently may overwhelm cerebral pressure autoregulation. (Anesth Analg 1996;83:726-30)

Nitrous Oxide Attenuates the Protective Effect of Isoflurane on Microtubule-Associated Protein2 Degradation During Forebrain Ischemia in the Rat

Recently, attention has been focused on the degradation of cytoskeletal proteins in animal models of cerebral ischemia, as the collapse of cytoskeletal proteins may be closely related to cytoskeletal disintegration and ultimate neuronal cell death. Among these proteins, microtubule-associated protein 2 (MAP2) has been shown to be highly vulnerable to ischemic injuries. To determine the degree of anesthetic effect on the collapse of cytoskeletal proteins, we compared the effect of three inhalation anesthetics; isoflurane, halothane, and nitrous oxide (N2O), on MAP2 degradation during 20 min of forebrain ischemia in the rat. Under equipotent anesthesia, forebrain ischemia was induced by the occlusion of the bilateral common carotid artery (CCA) combined with a lowering of mean arterial pressure (mAP) to 50 mmHg. After 20 min of ischemia, three regions of the brain, the frontoparietal cortex, brainstem, and hippocampus, were removed and separately homogenized. Subsequently, MAP2 of each region was measured using an enzyme-linked immunosorbent assay (ELISA). In the frontoparietal cortex and hippocampus, MAP2 was significantly protected from degradation when isoflurane was used combined with nitrogen (N2). However, the protective effects of isoflurane were drastically reduced when N2O was given instead of N2. These results suggest that the use of N2O should be discontinued when severe cerebral ischemia is accidentally incurred during anesthetic management.

Serum and urine levels of phenol following phenol blocks

RésuméChez 20 patients atteints de maladie vasculaire périphérique chronique on a mesuré les concentrations du phénol dans le sang et ľurine après un bloc sympathique thoracique on lombaire avec 4–10 ml de sept pour cent de phénol aqueux.Les temps pour atteindre la concentration maximale (tmax), les concentrations maximales (Cmax), les temps de latence (Tlag), les demi-vies ďélimination apparente (ttel) et la surface des courbes de concentrations sériques (AUC) furent détermines. Les valeurs de tmax, Cmax Ttag, t{tel} et AUC étaient de 18.8 ± 2.5min, 3.01 ± 0.28μ,g-ml-1 5.3 ± 1.6min, 30.3 ± 2.8mm, et 365 ± 41 μ,g ml-1 min-1, respectivement, pour le phénol non conjugu±. Quant aux valeurs pour le phénol conjugué, elles étaient respectivement 54.9 ± 4.5 min, 4.15 ± 0.25μg·ml-1, 9.9 ± 5.9min, 64.0 ± 7.3min, et 838 ± 95 μg·ml-1 ·min-1 Ľexcrétion urinaire cumulative sous forme conjuguée après 8 heures variait de 31 à 63 pour cent de la dose administràe.Ces ràsultats indiquent que le phénol a une demi-vie très courte et qu’il est excrété rapidement dans éurine conjugué au sulfate.

Effect of chemical sympathectomy on muscle blood flow.

Lumbar chemical sympathectomy using 5 percent phenol in glycerin alleviated intermittent claudication and improved cutaneous blood flow. This technic permits instituting physiotherapy and exercises to improve collateral circulation. The procedure was performed 56 times on 29 cases. No significant complication was observed. Muscle blood flow (MBF) was measured by 133Xe clearance, at rest and following exercise. Total blood flow (TBF) of the leg was measured by the impedance method, and increased cutaneous blood flow was confirmed by thermogram and photoplethysmogram.TBF increased significantly following exercise after sympathectomy. The ratio of MBF at rest and after exercise increased significantly in m. gastrocnemius, a white muscle, but was not significant in m. anterior tibialis, a red muscle.Chemical lumbar sympathectomy also produces preganglionic neurolysis to suppress vascular hypersensitivity after surgical ganglionectomy.

Nitrous oxide, but not xenon, affects the signaling in the neuronal growth cone.

1. Xenon (Xe) is an inert gas with the anesthetic property. To investigate whether Xe affects the neural network formation, the authors examined the biochemical characteristics of growth cones prepared from rat forebrains at different perinatal periods, in comparison with inhalation of N2O. 2. Fetal or neonatal rats were exposed to an atmosphere containing inhalational anesthetics (70% Xe or N2O) or the control atmosphere (30% O2 and 70% N2) for 6 h. After the exposure, isolated growth cone particles (IGCs) were prepared from their forebrains using a subcellular fractionation method. Protein composition, Ca2+-dependent protein phosphorylation, protein kinase C (PKC) activity, and degradation of PKC in the IGCs were compared among three groups. 3. No apparent change of protein composition in IGCs was observed by electrophoresis. Ca2+dependent phosphorylation of GAP-43 and MARCKS protein, and PKC activity in IGCs significantly decreased after exposure to N20. The degradation of PKC increased significantly after inhalation of N2O. 4. The authors concluded that Xe dose not change the above biochemical characteristic of the growth cones, suggesting that Xe is free from the teratogenic effect on the neuronal network formation and that Xe is a safe anesthetics for the perinatal neuronal development.

GABAA receptor in growth cones: The outline of GABAA receptor-dependent signaling in growth cones is applicable to a varitey of α-subunit species

The growth cone is responsible for axonal elongation and pathfinding by responding to various modulators for neurite growth, including neurotransmitters. We demonstrated an outline of the gamma aminobutyric acid (GABA)A‐dependent signaling in growth cones. Here, we examined the effects of the modulators of GABAA receptor on the signaling in growth cones. Phenobarbital or propofol, acting on β‐subunit, enhanced the [Cl‐]infi change and [Ca2+]i elevation by the GABA stimulation to isolated growth cones. Besides, propofol enhanced GABA‐dependent phosphorylation of growth‐associated protein of 43 kDa (GAP‐43) by protein kinase C. In contrast, an α‐subunit acting agent diazepam did not modulate any of the above signals. Next, we examined the effect of the developmental change of α‐subunit on the outline of the GABAA‐dependent signaling in growth cones. We also found that the amounts of several different α‐subunit isoforms developmentally increased or decreased in growth cone membrane (GCM), but that the affinity and density of the [3H]diazepam binding sites were similar to those in adult synaptic membrane. Taken together, our results strongly suggest that each step of GABAA‐dependent signaling in GCM is not modified by diazepam, indicating that the signaling pathway mediated by GABAA receptor in growth cones is applicable to any compositional change of α‐subunit isoforms. J. Neurosci. Res. 58:407–416, 1999.

Development of Operation System

We are gradually developing a total hospital information system known as GUNMAS (Gunma University Network for Medical-Hospital- Information Archiving System). an operation system is also being developed as part of Gunmas.

Pharmacological evalution of cilostazol by thermograms of patients with chronic arterial occlusive disease

AIM OF INVESTIGATION: This study examines the interaction between ____________________. 5-HTlA receptors and opioids in the control of nociception in the rat an METHODS: The tail-flick response to heat and pressure was examined. All drugs were _______ given s.c. Morphine was applied 20 min prior to testing and 5-HTlA ligands 10 min before morphine: that is, 30 min prior to testing. Full ~-HT~A agonists could not be tested in rats since they elicited spontaneous tail-flicks (1). RESULTS: The full 5-HTlA agonists, -2----8-OH-DPAT, lisuride and 5-MeODMT, the partial agonists, buspirone, gepirone, ipsapirone and flesinoxan and the antagonists, BMY 7378, alprenolol and spiperone all failed to significantly modify the response to heat and pressure in rats and mice not treated with morphine. Each of the 5-HTlA agonists and partial agonists dose-dependently antagonised the antinociceptive action of morphine in mice and rats. Dose-response curves to morphine were shifted in parallel to the right. Thus, this antagonism could be overcome by increasing the dose of morphine. The action of morphine could be both prevented and reversed. The time-course of action of morphine was unaffected. The antinociception induced by a further mu-agonist, sufentanil, was also blocked. The 5-HTlA antagonists did not attenuate the action of morphine. Further, l-PP, the metabolite of buspirone, was also inactive. The full and partial agonists employed have significant affinity at alpha 1, alpha 2 and D2 receptors. However, idazoxan, prazosin and pimozide, antagonists at alpha 2, alpha 1 and D2 receptors, respectively, did not antagonize morphine under these conditions. CONCLUSION: 11 5-HTlA ligands do not detectably modify responses to acute nociceptive __________ heat or pressure stimuli in rodents. 21 An agonist action at 5-HTlA functionally antagonises opioid-induced antinociception. 3) These data may be of both physiological and clinical significance in view of the therapeutic use of 5-HTlA ligands in man. (1) M.J. Millan, K. Bervoets and F.C. Colpaert, Neurosci. Lett., in press.

A prolonged relief of cancer pains by electro-coagulation of the pituitary gland

Gunma University Hospital,Maebashi,Gunma,JAPAN,371. Purpose: An electric stumulation on the pituitary gland causes a transient pain relief for cancer patients. In order to prolong this pain relief, authors coagulated the site on inquiring to patient as to pain relief followed by electric stimulation of pituitary gland. Methods: (1) Under fluoroscope, C-shaped bipolar electrode laid on near to the pars intermedia of the pituitary gland transphenoidally. When patients state pain relief on elec-tric stimulation (25cps, 4,%9volts, 0.2msec square wave), the site was coagulated by radiofrequency. (Bio-electronics lesion generator). (2) With concent by patients, SSEP, threshold of pain and CSF by spinal tap obtained before and after 24hrs. Non-invasive measurement of r-CBF and r-CMR02 obtained by positron emission CT scanning (PET) of the brain. Result: 12 out of 15 cases relieve pain, but prolonged complete pain relief over 2 month obtained only two out of survived 9 cases. AVP (B-arginine Vasopressin) in CSF increased over 100 times in complete pain relieved as well as raised pain threshold together with prolonged latency in late component of SSEP. PET exhibited depressed rCMR02 in the whole brain while rCBF was not changed. Conclusion: Electrocoagulation of the pituitary gland is effective to relieve cancer pain as well as NALP. Meanwhile the pituitary function kept intact.