Glutamate (GLU) is a neurotransmitter. Massive release of GLU and glycine (GLY) into the brain's extracellular space may be triggered by ischemia, and may result in acute neuronal lysis or delayed neuronal death. The aim of this study was to evaluate the possible relationship between hyperventilation and the level of GLU and GLY during brain ischemia. Rabbits were anesthetized with halothane and oxygen. Group 1 was allowed to hyperventilate (PaCO2 25-35 mmHg). PaCO2 was maintained throughout the study. Group 2 was a normal control group that maintained normocapnia. Two global cerebral ischemic episodes were produced. Microdialysate was collected during the peri-ischemic and reperfusion periods from the dorsal hippocampus. GLU and GLY concentrations were determined using high-performance liquid chromatography. In the control group, GLU and GLY were significantly elevated during each episode of ischemia; these levels returned to baseline within 10 minutes after reperfusion. In contrast, in the hyperventilation group GLU and GLY concentrations increased during ischemia, but they were not statistically significant. We were able to demonstrate that hypocapnia during periischemic period lowered extracellular GLU and GLY concentrations. These results can explain a part of the protective action of hypocapnia during cerebral ischemia.
Animal ; Brain Ischemia/*metabolism ; Glutamic Acid/*analysis ; Glycine/*analysis ; Hippocampus/*chemistry ; Hyperventilation/metabolism ; Hypocapnia/*metabolism ; Potassium/metabolism ; Potassium Channels/physiology ; Rabbits ; Support, Non-U.S. Gov't

The use of controlled hyperventilation during neurosurgical procedures prevents the deleterious effects of hypercarbia on the cerebral blood flow and intracranial pressure. hyperventilation with hypocarbia produces cerebral vasoconstriction, reduced cerebral blood flow and a reduction in brain size in the majority of patients with increased intracranial pressure. But since excessive cerebral vasoconstriction might induce cerebral ischemia, there has been much discussion concerning the optimal level of hypocarbia. Several studies have shown biochemical evidence of a change in cerebral glucose utilization to anaerobic metabolism during hypocarbia. In our investigation, the effect of hyperventilation on 10 neurosurgical patients was evaluated by blood gas analysis and the estimation of lackate and pyruvate in arterial blood and the cerebrospinal fluid. The results were as follows: 1) PaCO2 decreased from a prearesthetic value of 38+/-2.2 mmHg to 22+/-2.1mmHg 1 hour postinduction and 24+/-2.2mmHg at 2 hours due to hyperventilation. pH was 7.58+/-0.047 1 hour postinduction and 7.56+/-0.018 at 2 hours. PaO2 was 251+/-33.0mmHg 1 hour postinduction 1 hour and 215+/-20.9mmHg at 2 hours under a 50% inspired oxygen concentration(FiO2=0.5). 2) The arterial blood lactate value increased statistically significantly from a preanesthetic value of 9.3+/-1.5mg% to 11.8+/-1.47mg% 1 hour postinduction(p<0.01) to 12.5+/-1.53mg% at 2 hours(p<0.005). However all values were within the normal range(4.7+/-15.1mg%), and the lacte/pyruvate ratio did not change. 3) In the cerebrospinal fluid, pH was 7.45+/-0.057, PCO2 was 34+/-3.5mmHg and PO2 was 91+/-6.7mmHg following hyperventilation for 1 hour. The lactate value of the cerebrospinal fluid was 19.2+/-3.14mg%(normal range: 11.0~27.0mg%) and the lactate/pyruvate ration was 14.5+/-2.39. 4) No evidence of an excessive increase in CSF lactate was seen in any case. The above findings suggest that maintenance of an adequate oxygen concentration and a carbon dioxide value over 20mmHg would prevent cerebral ischemia following hypocarbia due to hyperventilation.
Anesthesia* ; Blood Gas Analysis ; Brain ; Brain Ischemia ; Carbon Dioxide ; Cerebrospinal Fluid* ; Glucose ; Humans ; Hydrogen-Ion Concentration ; Hyperventilation* ; Intracranial Pressure ; Lactic Acid ; Metabolism ; Neurosurgical Procedures ; Oxygen ; Pyruvic Acid ; Vasoconstriction

In order to determine the relationship between acid-base balance and K+ metabolism in patients whi controlled respiration during surgery, 20 patients under general anesthesia were studied. Anesthesia was induced with 2% thiopental and was maintained with halothane. Suxamethonium was used for intubation. During surgery, the respiration of the patient was controlled by a volume controlled respirator with tidal volume of 800ml and a rate of 12/min. Blood and urine samples were collected before anesthesia, and 30 and 60 minutes thereafter. REsults were as follows: Hyperventilation induced by artificial respiration during surgical anesthesia produced a significant decrease in PaCO2 from 36.1+/-1.3mmHg to 19.9+/-1.5mmHg at 30 min, and to 20.1+/-1.7mmHg at 60 min. Hyperventilation increased arterial pH from 7.41+/-0.008 to 7.49+/-0.028 at 30 min, and 7.47+/-0.011 at 60 min. Hyperventilation produced a significant decrease in serum concentration of K+ from 4.04+/-0.12 to 3.75+/-0.08mEq/l at 30min, and 3.62+/-0.05 mEq/l at 60min. Urinary excrets of K+ was not significantly altered during the hour of the hyperventilation. These results suggest that hypokalemia followed by respiratory alkasisis mainly due to the movement of K+ from extracellular to intracellular compartments rather than a change in renal excretion of K+.
Acid-Base Equilibrium ; Anesthesia ; Anesthesia, General ; Halothane ; Humans ; Hydrogen-Ion Concentration* ; Hyperventilation* ; Hypokalemia ; Intubation ; Metabolism* ; Potassium* ; Respiration ; Respiration, Artificial ; Succinylcholine ; Thiopental ; Tidal Volume ; Ventilators, Mechanical

BACKGROUND: There are therapies to lower intracranial pressure (ICP) including head elevation, hyperventilation, diuretics injection, intravenous mannitol, hypothermia, cerebrospinal fluid drainage, and cerebral resection in neurosurgical patients. However in recent reports, hyperventilation followed by mannitol administration may lead to cerebral ischemia. Therefore, we investigated the effect of 0.5-1.0 g/kg mannitol administration on jugular venous oxygen saturation (SjVO2) and cerebral arterial- jugular venous oxygen content difference (AVDO2) at PaCO2 25-30 mmHg and 35-40 mmHg in patients undergoing neurosurgery. METHODS: We studied 17 patients undergoing neurosurgery in the Ajou University Hospital. Anesthesia was induced with fentanyl, midazolam, thiopental, and vecuronium, and maintained with O2-Air-Isoflorane, a continuous infusion of fentanyl, and vecuronium. Patients were divided into two groups. Group 1 (n = 10) which is PaCO2 25-30 mmHg and Group 2 (n = 7) which is PaCO2 35-40 mmHg by controlling ventilator. Measurements of SjVO2 and AVDO2 in following time intervals: I = preinjection of mannitol, II = postinjection 20 minutes of mannitol, III = postinjection 40 minutes of mannitol were obtained for each group. 0.5-1.0 g/kg mannitol was administered intravenously just at duramater opening. RESULTS: Hemodynamics and hematologics were not significantly different among the two groups. SjVO2 of each group are as follows; Group 1; I (70.3+/-8.1%), II (66.3+/-6.9%), III (69.1+/-7.9%) and Group 2; I (78.6+/-7.4%), II (75.1+/-8.1%), III (76.0+/-11.2%). Hyperventilation significantly decreased SjVO2. AVDO2 was not significantly different but SjVO2 in II was significantly decreased compared with I and III in Group 1 (20% patients). CONCLUSIONS: Mannitol produced a change of SjVO2 and AVDO2 during hyperventilation. Therefore, intravenous mannitol during hyperventilation should be given cautiously according to the patients status because it may cause cerebral ischemia in critical patients.
Anesthesia ; Brain Ischemia ; Cerebrospinal Fluid ; Diuretics ; Drainage ; Fentanyl ; Head ; Hemodynamics ; Humans ; Hyperventilation* ; Hypothermia ; Injections, Intravenous ; Intracranial Pressure ; Mannitol* ; Metabolism* ; Midazolam ; Neurosurgery ; Oxygen ; Thiopental ; Vecuronium Bromide ; Ventilators, Mechanical

TCF4 (transcription factor 4; E2-2, ITF2) is a transcription factor that when haplo-insufficient causes Pitt-Hopkins Syndrome (PTHS), an autism-spectrum disorder that is associated with pervasive developmental delay and severe intellectual disability. The TCF4 gene is also a risk factor with highly significant linkage to schizophrenia, presumably via overexpression of the TCF4 gene product in the central nervous system. This review will present an overview of the clinical manifestations of PTHS and relate those clinical attributes to the underlying molecular genetics of TCF4. In order to provide a molecular biological context for the loss of function of TCF4 in PTHS, the review will also present a brief overview of the basic biochemistry of TCF4-mediated regulation of cellular and neuronal gene expression. In the final section of this review, I will discuss and speculate upon possible roles for the TCF4 transcription factor in neuronal function and comment upon how understanding these roles may give new insights into the molecular neurobiology of human cognition.
Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/*metabolism ; Disease Models, Animal ; Facies ; Humans ; Hyperventilation/diagnosis/*genetics/pathology ; Intellectual Disability/diagnosis/*genetics/pathology ; Neurons/metabolism/pathology ; *Transcription, Genetic

The sudden onset of respiratory acidosis or alkalosis due to inadequate ventilation during general inhalation anesthesia may influence the action of neuromuscular blocking agents. In virtro animal studies by Funk et al.(1980) suggested that the neuromuscular blocking action of Org NC 45(NC) was minimally depressed above pH 7.68 and significantly potentiated under acidotic conditions(pH 7.05). They proposed that this was the result of an increase in NC metabolism by alkaline hydrolysis in the alkalotic state and greater molecular stability during acidosis. This study was performed to determine the effects of the neuromuscular blocking action of NC during respiratory acidosis and alkalosis. The patients were divided in to 3 groups: 1, ll & lll and experienced normocarbia, hypocarbia and hypercarbia, respectively. Hypocarbia was induced by hyperventilation and hypercarbia by adjustment of a rebreathing valve in the CO2 absorber in the semiclosed system. Simultaneously, arterial blood samples were collected from radial arteries for arterial blood gas analysis including pH and pCO2. Following the administration of succinylcholine(SCC) and the recovery of a 75% twitch height, ED95 of NC was given to the patient and the results were recorded by an evoked electromyograph (NMT, Datex). The results are follows: 1) The number of patients in groups l, ll and lll were 22, 13 and 8, respectively. The patients in each group were evenly distributed with respect to age, body weight and anesthesia. 2) The end-tidal CO2 tension in group l, ll and lll group was 38.86+/-4.62, 20.23+/-2.42 and 52.00+/-4.86mmHg, and the arterial pCO2(pH) was 37.36+/-5.71(7.461+/-0.054), 23.00+/-1.51(7.649+/-0.032) and 53.29+3.35 mmHg(7.314+/-0.026), resptectively. The end-tidal CO2 tension, arterial CO2 tension and pH in group ll and lll were significantly different from those of group l(p<0.05). 3) The onset time of SCC in group ll and lll was shorter than that in group l (p<0.05), but within 1 min in all groups. The duration of SCC in group lll(19.56+/-6.15min) was longer than that in group l (14.74+/-4.56min) (p<0.05). 4) Although there was no significant difference among the groups with respect to onset time and duration, the recovery index in group ll(10.29+/-2.21min) was significantly different from group l and lll(14.76+/-5.26 and 13.50+/-13.67 min, respectively) (p<0.05). After administration of NC in 5 min intervals, twitch tension was measured and the results were inserted into a regression equation which emphasized the delayed recovery in group lll(r=0.87). In conclusion, the recovery index in alkalosis shortened and the initial twitch tension in acidosis following NC administration was delayed compared to that in normocapnis and alkalosis. Patients with alkalosis may require more frequent doses of NC and continuous monitoring following repeated or continuous infusion in acidosis.
Acid-Base Equilibrium ; Acidosis ; Acidosis, Respiratory ; Alkalosis ; Anesthesia ; Anesthesia, Inhalation ; Animals ; Arterial Pressure ; Blood Gas Analysis ; Body Weight ; Humans ; Hydrogen-Ion Concentration ; Hydrolysis ; Hyperventilation ; Metabolism ; Neuromuscular Blockade* ; Neuromuscular Blocking Agents ; Radial Artery ; Vecuronium Bromide* ; Ventilation

We performed experiments to study the effects of acutely increased inracranial pressure on cereral gas metabolism. The results and findings were reported to The Journal of Catholic Medical College,(Vol. 24) 1973. We thereafter evaluated cerebral gas metabolism of fifty patients with acute cerebral lesions. Cerebral gas metabolism was measured by determining the pO2, pCO2, and pH values of arterial and venous blood and of the cerebrospinal fluid. Samplings of venous blood were obtained from the internal jugular vein. In the determination of the pH, pO2 and pCO2 of arterial and venous blood and cerebro-spinal fluid, the "Radiometer BMS 3 with Digital Acid-Base Analyser PHM 72" was used. These 50 patients had their gas metabolism measured at interval of 2 or 3 days, from the time of their admission to the time of either their recovery or death. The following observations were made 1. The 50 patients studied and observed included. a) Brain contusion 13 cases. b) Epidural or subdural hematoma 11 cases. c) Skull fracture 10 cases. d) Intracerebral hemorrhage 5 cases. e) Scalp laceration 1 cases. f) Arteriovenous malformation or cerebral rete 5 cases. g) Traumatic subarachnoid hemorrhage 1 cases. h) Intracranial aneurysm 4 cases. 2. There 50 patients have been subdivided according to level of consciousness as follows: a) Group A-Those who were alert with no neurological deficit. b) Group B-Those who were drowsy with mild neurological deficit. c) Group C-Those who were stuporous with severe neurological deficit. d) Group D-Those who were in coma. 3. It was observed that the pH, pO2, and pCO2 content of the arterial and venous blood and cerebrospinal fluid of those in Group A were within normal ranges. 4. Many cases classified under Group B had respiratory alkalosis of the arterial blood. However those who recovered or became worse revealed no noticeable changes in the cerebral gas metabolism studies. 5. Many cases classified under Group C had respiratory alkalosis in their arterial blood but only a few showed metabolic acidosis in the cerebrospinal fluid. However the patients who became worse manifested a marked metabolic acidosis in the cerebrospinal fluid. 6. Several patients in Group D had severe respiratory alkalosis as well as metabolic alkalosis in their arterial blood and marked metabolic acidosis in the their cerebrospinal fluid. 7. "Luxury perfusion syndrome" was not seen in any of the fifty cases studied. 8. Only a few cases manifested arterial hypoxemia in the all group. We believe this was due to the fact that tracheostomy and hyperventilation were done in the early stages with the aim of reducing the raised intracranial pressure.
Acidosis ; Alkalosis ; Alkalosis, Respiratory ; Anoxia ; Arteriovenous Malformations ; Brain Injuries ; Brain* ; Cerebral Hemorrhage ; Cerebrospinal Fluid ; Coma ; Consciousness ; Hematoma, Subdural ; Humans ; Hydrogen-Ion Concentration ; Hyperventilation ; Intracranial Aneurysm ; Intracranial Pressure ; Jugular Veins ; Lacerations ; Metabolism ; Perfusion ; Reference Values ; Scalp ; Skull Fractures ; Stupor ; Subarachnoid Hemorrhage, Traumatic ; Tracheostomy