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Objective: To determine influence of sevoflurane on changes in cerebrospinal fluid pressure in children presenting for lumbar puncture. Methods: Cerebrospinal fluid pressure, end tidal carbon dioxide, and end tidal sevoflurane concentration measurements were obtained at 2-minute intervals for a total of 10 minutes (T0 to T5). Because of concerns regarding patient safety and comfort, the study measurements were completed at the end of the lumbar procedure, starting with the closing pressure and when sevoflurane was stopped. Results: As end tidal sevoflurane concentration decreased, cerebrospinal fluid pressure initially increased up to T2 before decreasing back to around the initial point. There was no significant correlation between sevoflurane level and cerebrospinal fluid pressure. Both weight status and presence or absence of optic edema did not have a significant impact on pressure over time. However, there was a statistically significant difference in the cerebrospinal fluid pressure over time between those with spontaneous respirations compared to those without. Conclusions: There was no significant correlation between the end tidal sevoflurane concentration and cerebrospinal fluid pressure. Assisted ventilation did produce a statistically significant increase in cerebrospinal fluid pressure and suggests that the most accurate measurements are in those with spontaneous respirations., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. S. Aylward receives salary support from Biomarin pertaining to Batten Disease research, Biohaven Pharmaceuticals Holding Company Limited for a study on Rimegepant, and NeuroNEXT/NINDS a fellowship grant award. He also receives an honorarium as associate editor of Pediatric Neurology.

Background: In this study, gas tensions in cerebrospinal fluid (CSF) were prospectively evaluated as intraoperative markers for the detection of neurological deficits., Methods: Spinal fluid, serum, and heart lung machine (HLM) perfusate were monitored for gas tensions (po 2/pCo 2) and related parameters (pH, lactate, and glucose) during thoracoabdominal aortic repair and correlated with perioperative neurological examination and electrophysiological testing., Results: Forty-seven patients were assessed for the study, and 40 consecutive patients were finally included. The patients were divided into 3 groups: group A (23 patients, 57.5%): no clinical or laboratory signs of neurological damage; group B (14 patients, 35%) who developed subclinical deficits; and group C (3 patients, 7.5%) who had paraplegia. Significant intraoperative changes in CSF gas tensions were observed with postoperative paraplegia. Glucose ratio between serum and CSF showed higher variability in group C, confirming a damage of the blood-brain barrier (BBB)., Conclusion: Major neurological damage is reflected by early changes in CSF gas tensions and glucose variability, suggesting damage of the BBB in these patients., (© The Author(s) 2015.)

The acute in vitro brain slice model is a widely used neurophysiological research tool. When applying this method, most researchers continuously perfuse slices with carbogenated artificial cerebrospinal fluid (ACSF) to maintain pH balance and tissue oxygen delivery. Common wisdom suggests that static recordings are incompatible with submerged bath methodology because of deficiency in tissue oxygen supply. However, to our knowledge this has not been tested. In this study, we wanted to determine whether neocortical mouse slice viability could be maintained in the medium term (up to 2h) in a shallow, submerged recording bath under non-perfused, static conditions. Seizure-like events (SLEs) were generated in the slices utilizing no-magnesium ACSF and recorded for 2h under three conditions: (1) perfused ACSF condition (n=8), where slices were perfused continuously with carbogenated no-magnesium ACSF; (2) static ACSF condition (n=12), where slices were recorded in pre-carbogenated, but non-perfused (static) no-magnesium ACSF; and (3) static HEPES ACSF condition (n=12), where slices were recorded in non-perfused (static) no-magnesium ACSF with no pre-carbogenation but buffered with HEPES. SLE activity was stable for 2h across all three conditions. There was no statistically significant difference in SLE frequency, amplitude or length between static and perfused conditions. SLE frequency and amplitude were generally lower in the static HEPES buffer condition. The data indicate that robust and stable neocortical SLE activity can be generated for at least 2h in a submersion bath without ACSF perfusion if pH is adequately controlled., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In a model of aortic cross-clamping, we studied the use of a multiparameter sensor for measurement of cerebrospinal fluid (CSF) PO(2), PCO(2), and pH during and after aortic cross-clamping. The present study addressed the above-mentioned alterations and their relation according to time intervals. In 31 pigs, a sensor was introduced into the intrathecal space and epidural laser Doppler was used to measure spinal cord blood flow (SCF). By placing the aortic clamp at different levels, three different spinal cord ischemia groups were obtained (mild, moderate, and severe). CSF variables with SCF were studied for 25%, 50%, and 100% changes according to baseline level. In the clamping period, SCF decreased 71.5%, 40.0%, and 33.3% in groups 1, 2, and 3, respectively. CSF O(2) tension reached 0 in group 1, decreased 74.8% in group 2, and was 12.7% in group 3. CSF CO(2) tension increased 247.2% and 202.0% in groups 1 and 2, respectively, but slightly increased in group 3. The maximum reaction time of CSF O(2) tension was about 16.7-26.9min, although this range was 34.5-49.8min in CSF CO(2) tension. We recognized that O(2) tension reacts faster than PCO(2) and pH. It is possible for O(2) tension to be used faster than produced CO(2) in the ischemic medium, although it is known that the diffusion rate of CO(2) is much higher. Spinal cord O(2) tension monitoring is an important method to detect ischemic changes.

This study examined the role of pregnancy-induced changes in wakefulness (or non-chemoreflex) and central chemoreflex drives to breathe, acid-base balance and female sex hormones in the hyperventilation of human pregnancy. Thirty-five healthy women were studied in the third trimester (TM(3); 36.3+/-1.0 weeks gestation; mean+/-S.D.) and again 20.2+/-7.8 weeks post-partum (PP). An iso-oxic hyperoxic rebreathing procedure was used to evaluate wakefulness and central chemoreflex drives to breathe. At rest, arterialized venous blood was obtained for the estimation of arterial PCO(2) (PaCO(2)) and [H(+)]. Blood for the determination of plasma strong ion difference ([SID]), albumin ([Alb]), as well as serum progesterone ([P(4)]) and 17beta-estradiol ([E(2)]) concentrations was also obtained at rest. Wakefulness and central chemoreflex drives to breathe, [P(4)] and [E(2)], ventilation and V CO(2) increased, whereas PaCO(2) and the central chemoreflex ventilatory recruitment threshold for PCO(2) (VRTCO(2)) decreased from PP to TM(3) (all p<0.01). The reductions in PaCO(2) were not related to the increases in [P(4)] and [E(2)]. The alkalinizing effects of reductions in PaCO(2) and [Alb] were partly offset by the acidifying effects of a reduced [SID], such that arterial [H(+)] was still reduced in TM(3) vs. PP (all p<0.001). A mathematical model of ventilatory control demonstrated that pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, V CO(2) and cerebral blood flow account for the reductions in PaCO(2), [H(+)] and VRTCO(2). This is the first study to demonstrate that the hyperventilation and attendant hypocapnia/alkalosis of human pregnancy results from a complex interaction of pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, metabolic rate and cerebral blood flow.

Objective: To explore whether the carbon dioxide-bicarbonate (P(CO(2))-HCO(3)) buffering system in blood and cerebrospinal fluid (CSF) in diabetic ketoacidosis should influence the approach to ventilation in patients at risk of cerebral edema., Data Source: Medline search, manual search of references in articles found in Medline search, and use of historical literature from 1933 to 1967., Design: A clinical vignette is used--a child with severe diabetic ketoacidosis who presented with profound hypocapnia and then deteriorated--as a basis for discussion of integrative metabolic and vascular physiology., Study Selection: Studies included reports in diabetic ketoacidosis where arterial and CSF acid-base data have been presented. Studies where simultaneous acid-base, ventilation, respiratory quotient, and cerebral blood flow data are available., Data Extraction and Synthesis: We revisit a hypothesis and, by reassessing data, put forward an argument based on the significance of low [HCO(3)](CSF) and rising Pa(CO(2))- hyperventilation in diabetic ketoacidosis and the limit in biology of survival; repair of severe diabetic ketoacidosis and Pa(CO(2))-and mechanical ventilation., Conclusion: The review highlights a potential problem with mechanical ventilation in severe diabetic ketoacidosis and suggests that the P(CO(2))--HCO(3) hypothesis is consistent with data on cerebral edema in diabetic ketoacidosis. It also indicates that the recommendation to avoid induced hyperventilation early in the course of intensive care may be counter to the logic of adaptive physiology.

Objective: To determine whether high intracranial pressure (ICP) during spontaneous ventilation (SV) in anesthetized horses coincides with an increase in intracranial elastance (ie, change in ICP per unit change of intracranial volume)., Animals: 6 adult horses., Procedure: Anesthesia was induced and maintained in each horse for 5 hours with isoflurane at a constant dose equal to 1.2 times the minimum alveolar concentration. Direct ICP measurements were obtained by use of a strain gauge transducer inserted in the subarachnoid space, and arterial blood pressure was measured from a carotid artery. Physiologic responses were recorded after 15 minutes of normocapnic controlled ventilation (CV) and then after 10 minutes of SV. Aliquots (3 mL) of CSF were removed from each horse during SV until ICP returned to CV values. Slopes of pressure-volume curves yielded intracranial elastance., Results: Intracranial elastance ranged from 0.2 to 3.7 mm Hg/mL after removal of the first aliquot of CSF Slopes of pressure-volume curves were largest following removal of the initial CSF aliquot, but shallow portions of curves were detected at relatively high ICPs (25 to 35 mm Hg). A second-order relationship between SV ICP and initial intracranial elastance was found., Conclusions and Clinical Relevance: In horses anesthetized with isoflurane, small changes in intracranial volume can cause large changes in ICP Increased intracranial elastance could further exacerbate preexisting intracranial hypertension. However, removal of small volumes of CSF may cause rapid compensatory replacement from other intracranial compartments, which suggests steady-state maintenance of an increase in intracranial volume during isoflurane anesthesia in horses.

Several aspects of the central regulation of respiratory control have been investigated on brainstem-spinal cord preparations isolated from newborn rats whose dam was given 0.02% caffeine in water as drinking fluid during the whole period of pregnancy. Analysis of the central respiratory drive estimated by the recording of C4 ventral root activity was correlated to Fos ponto-medullary expression. Under normoxic conditions, preparations obtained from the caffeine-treated group of animals displayed a higher respiratory frequency than observed in the control group (9.2 +/- 0.5 versus 7.2 +/- 0.6 burst/min). A parallel Fos detection tends to indicate that the changes of the respiratory rhythm may be due to a decrease in neuronal activity of medullary structures such as the ventrolateral subdivision of the solitary tract, the area postrema, and the nucleus raphe obscurus. Under hypoxic conditions, the preparations displayed a typical hypoxic respiratory depression associated with changes in the medullary Fos expression pattern. In addition, the hypoxic respiratory depression is clearly emphasized after in utero exposure to caffeine and coincides with an increased Fos expression in the area postrema and nucleus raphe obscurus, two structures in which it is not increased in the absence of caffeine. Taken together, these results support the idea that in utero caffeine exposure could affect central respiratory control.

Spinal cord damage during and after thoracoabdominal aortic cross-clamping continues to be a major problem. Somatosensory and motor evoked potentials have been used to monitor spinal cord function but their value for predicting paraplegia has been controversial. The aim of this study was to measure biochemical markers in the cerebrospinal fluid (CSF) and correlate changes with spinal cord ischemia. Since neural tissue utilizes only glucose as substrate for its metabolism and energy supply, we measured changes of metabolites of anaerobe glycolysis. In a canine model in which general anesthesia was used, the thoracoabdominal aorta was cross-clamped proximally and distally for 60 min. Hemodynamic parameters, blood gases, and glucose level were monitored continuously. Blood and CSF sampling were performed at baseline, at 15, 30, and 55 min during cross-clamping, and at 5 and 15 min after aortic declamping. Levels of lactate (1.7 +/- 0.1 to 3.2 +/- 0.3 mmol/L), pCO2 (43 +/- 2 to 35 +/- 1.6 mmHg), and neuron-specific enolase (NSE) (5.17 +/- 0.5 to 13.0 +/- 3.5 mg/L) in CSF showed significant changes (p < 0.05) during clamping and reperfusion. Changes in CSF lactate and NSE levels correlate with the duration of spinal cord ischemia. These markers of ischemic metabolism appear suitable to monitor the degree of spinal cord ischemia during thoracoabdominal cross-clamping and may be useful to predict the efficacy of preventive methods.

Objective: To study the correlation between intrathecal PO2 and ultrastructural changes in the spinal cord during thoracic aortic occlusion in pigs., Material and Methods: In 18 pigs, online intrathecal oxygenation was monitored by a multiparameter Paratrend catheter (Biomedical Sensors, High Wycombe, United Kingdom) during 60 minutes' clamping of the proximal and distal descending thoracic aorta. The animals were randomly divided into 2 groups (A and B) depending on the level of distal aortic clamping. Distal aortic perfusion was restored through an aorto-iliac shunt, which also maintained low thoracic segmental perfusion of the spinal cord in group B. Perfusion-fixation technique was used before harvesting the spinal cord specimens, which later were evaluated with light and electron microscopy by an independent observer. Intrathecal parameters were interpreted as normal if PO2 was more than 0.8 kPa and PCO2 was less than 12 kPa, as intermediate ischemia if PO2 was 0.8 or less or PCO (2) was more than 12 kPa, and as absolute ischemia if PO2 was 0.8 or less and PCO2 was more than 12 kPa., Results: Among 6 animals with ultrastructural changes of absolute spinal cord ischemia-reperfusion injury, 5 also had absolute ischemia according to variables derived by the Paratrend catheter. The 2 methods were in agreement in 3 of 5 animals with intermediate ischemia-reperfusion changes and in 5 of 6 animals with normal findings. The accuracy of cerebrospinal fluid PO2 and PCO2 to predict electron microscopy-verified intermediate or absolute ischemia-reperfusion injury was 94%., Conclusions: Monitoring of intrathecal PO2 after clamping of the descending aorta correlated with ultrastructural changes in the spinal cord in this pig model.

The mechanism of hypocapnic constriction of the cerebral vasculature under conditions of altered acid-base balance has not been investigated. As K(ATP) channels and NO have been implicated in hypocapnic constriction, this study investigated their roles in the constriction due to lowered pCO(2) in hypercapnic rabbits with acute metabolic alkalosis. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. Lowering blood pCO(2) from initial baseline hypercapnic levels to near normocapnic and hypocapnic levels constricted basilar artery by 10.2+/-0.8% (4) and 16.2+/-0.6% (44), respectively (means+/-S.E., n), as determined in an in situ cranial window preparation. The constrictions were maintained for 4-5 h and return of pCO(2) to hypercapnic levels relaxed the constriction. Changing the suffusate pH to either the pH of the cerebral spinal fluid observed during initial baseline hypercapnia or following lowered pCO(2) did not alter the magnitude of constriction due to lowered pCO(2). Neither 0.3 mM N(G)-monomethyl-L-arginine monoacetate, an NO synthase inhibitor, nor 10 microM glibenclamide, a K(ATP) channel blocker, altered the magnitude of hypocapnic constriction. These results demonstrated that under conditions of acute metabolic alkalosis and accompanying compensatory hypercapnia, subsequent pCO(2) reduction induces prolonged constriction of the basilar artery that is independent of (1) cerebral spinal fluid pH over a physiologic range, and (2) NO and K(ATP) channels.

Cisternal samples of cerebrospinal fluid (CSF) were analyzed for protein, albumin, sodium (Na), potassium (K), and calcium (Ca) content in 21 control subjects and 64 patients who had experienced acute stroke. A second cisternal CSF sample was taken in 37 of the stroke patients after 2-3 weeks treatment with the calcium antagonist nimodipine. Increased permeability of the blood-brain barrier was reflected by the significantly higher CSF/serum ratio of albumin in stroke patients than in control subjects (0.0046 vs. 0.0028,p = 0.0012). Serum and CSF concentrations of Na, K, and Ca did not differ between control subjects and stroke patients. In control subjects and in stroke patients, concentration of calcium in cisternal CSF ([Ca]) was smaller than values reported by others in lumbar samples. In stroke patients, the pH of CSF was lower than that of simultaneously taken blood (7.38 vs. 7.44, p < 0.001). No differences between stroke patients and control subjects were found for the cisternal CSF/serum ratios of Na (1.0 and 0.99), K (0.61 and 0.63), and Ca (0.25 and 0.24). When patients and controls were pooled together, CSF total [Ca] correlated weakly with serum total [Ca] (Spearman r = 0.28, p = 0.014) and with serum ionized [Ca] (Spearman r = 0.27, p = 0.016). After 2-3 weeks of nimodipine treatment, CSF [Ca] was significantly lower in the subgroup treated with 60 mg nimodipine four times daily (240 mg/d) than with 30 mg four times daily. A nimodipine dosage of 30 mg four times daily (120 mg/d) did not affect CSF [Ca]. A 240 mg daily dosage, but not a 120 mg daily dosage, of nimodipine may affect the Ca transport system in humans at the choroid plexus.

The most feared complication of thoracoabdominal clamping is the paraplegia or paraparesis following ischemic injury of the spinal cord. Early intraoperative recognition of this complication has not been solved yet. In our earlier experiment we found significant alterations of CSF glucose, lactate, pCO2 and Neuron Specific Enolase (NSE) levels during 60 minutes thoracoabdominal aortic clamping in dogs. The analysis of these parameters proved to be proper to follow metabolism of the spinal cord during this type of surgery. In our present paper we studied protective effect of regional hypothermia using peridural cooling by registration of above parameters. Statistical analysis of our data showed prevention of production of anaerobe metabolites in animals with icy peridural irrigation. The biochemical approach is appropriate for monitoring effectiveness of regional hypothermia of the spinal cord during aortic surgery.

Objective: To determine the feasibility and usefulness of continuous cerebrospinal fluid pH and gas tension monitoring in critically ill neurosurgical patients., Design: Prospective, observational study., Setting: Neurosurgical intensive care unit in a teaching hospital., Patients: Five critically ill neurosurgical patients (GCS < 8) requiring intensive care intracranial pressure monitoring and intermittent positive pressure ventilation., Interventions: Placement of a Paratrend 7 sensor into the external ventricular drain., Measurements and Main Results: The cerebrospinal fluid (CSF) pH, PCO2 and PO2 were recorded at 1-min intervals. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were recorded at 15-min intervals. The mean baseline CSF pH, O2 and PO2 values were 7.28 +/- 0.08 pH units, 44 +/- 6 torr and 43 +/- 27 torr, respectively. The ranges of CSF pH, PCO2 and PO2 observed during the study were 6.3-7.8 pH units, 37-150 torr and 4-150 torr, respectively. A statistically significant correlation between ICP, CPP and CSF gas tensions occurred in patient 3. Significant changes in CSF PO2 and pH were observed with augmentation of CPP and preceded clinical improvement in patient 4. There were no complications attributable to sensor placement. CSF gas tensions and pH values obtained from patients 3 and 4 suggest that these measurements may be an indicator of cerebral perfusion., Conclusions: Continuous CSF gas tension measurements in critically ill patients are possible and may be an indicator of adequacy of cerebral perfusion. The relative merits and limitations of the technique are discussed.

Objective: To describe the effects of tromethamine, a putative treatment for metabolic acidosis, and to compare its biochemical effects with those of sodium bicarbonate., Design: Randomized intervention study with repeated measures., Animals: 16 healthy horses, 3 to 17 years old, weighing 391 to 684 kg., Methods: Ten horses received 3 mEq/kg tromethamine and six received 3 mEq/kg sodium bicarbonate. Samples of venous blood and cerebrospinal fluid (CSF) were collected at intervals before and after drug administration. Heart rate and breathing rate were also recorded at intervals., Results: Median standard base excess increased significantly (P < .05) from baseline immediately after both bicarbonate and tromethamine. These increases were not significantly different between treatments. Standard base excess returned toward baseline but remained significantly increased 3 hours after infusion of either treatment. After tromethamine, there was a significant decrease in plasma sodium concentration that lasted for at least 90 minutes. After sodium bicarbonate, no change in plasma sodium concentration was detected. Both sodium bicarbonate and tromethamine increased carbon dioxide tension in venous blood and CSF. Despite venous alkalemia, the pH of CSF decreased after both treatments., Conclusions: Tromethamine and sodium bicarbonate have similar alkalinizing ability. Tromethamine causes hyponatremia, whereas both tromethamine and sodium bicarbonate increase carbon dioxide tension in venous blood and CSF., Clinical Relevance: If hyponatremia, hypercarbia, and acidosis of the CSF occur after tromethamine is given to horses with existing metabolic acidosis, some of the potential advantages of tromethamine may prove theoretical rather than practical.

Cerebrospinal fluid (CSF) gas tension measurements have been used as a marker of cerebral oxygenation in animal models and in human studies. Discrepancies in the measurement of PCO2 and PO2 in non-blood solutions by standard blood gas analyzers have been described. The CSF is a physiological non-blood fluid with an ability to carry only dissolved O2 or CO2. The aim of this experiment was to determine the bias and precision of CSF pCO2 and pO2 measurements of a contemporary blood gas analyzer and a continuous gas sensor. CSF from human patients was tonometered to known PCO2 and PO2 using standard calibration gases in a bubble tonometer. Following equilibration, a continuous measurement of the partial pressure of gases in the CSF in the tonometer solution was made using a calibrated Paratrend 7 gas sensor (Biomedical Sensors, Bucks., UK) inserted into the equilibration chamber of the tonometer and continuous CSF pH, PCO2 and PO2 measurements recorded at 1-min intervals. After equilibration, a 3-ml CSF sample was aspirated anaerobically from the tonometer and analysed in duplicate using an ABL 620 (Radiometer, Copenhagen) blood gas analyser. The measured pCO2 and pO2 from the ABL 620 blood gas analyser and the Paratrend 7 sensor were paired with the expected values to calculate bias and precision. Small offsets in PCO2 and large offsets in PO2 measurement were seen with the ABL 620 blood gas analyser. This study brings into question clinical decisions based on CSF PO2 measurements. The implications for calibrating CSF sensors against CSF gas measurements are discussed.

Objective: To determine normal acid-base status of the CSF and to compare it with changes during acute hypercapnia in equine neonates., Animals: 10 clinically normal foals between 1 and 12 days old., Procedure: CSF and arterial and venous blood samples were collected every 15 minutes during 45 minutes of normocapnia and 90 minutes of hypercapnia in isoflurane-anesthetized foals. CSF samples were collected via a subarachnoid catheter placed in the atlanto-occipital space., Results: Comparison of blood and CSF gases during normocapnia indicated that CSF was significantly more acidic than blood. The lower pH was attributable to higher CO2 and lower bicarbonate concentrations than those in blood. During hypercapnia, CSF CO2 increased and pH decreased parallel to changes in blood, but changes were not a great as similar changes in venous blood, indicating that some degree of buffering occurs in the CSF of foals., Conclusions: Normal CSF acid-base status in equine neonates is similar to that in other domestic species. The blood-brain and blood-CSF interfaces in neonates allow rapid diffusion of CO2, but allow only slow diffusion of bicarbonate. Equine neonates are capable of buffering respiratory-induced acid-base changes in the CSF, but the buffering capacity is less than that of the vascular compartment., Clinical Relevance: Neonatal foals may develop severe respiratory compromise, resulting in hypoxemia and hypercapnia. Because the ability of the CSF to buffer acid-base changes in neonates is reduced, hypercapnia may contribute to the CNS abnormalities that often develop in sick neonates. Thus, normal blood gas values should be maintained in diseased equine neonates.

To assess the possible relationship between changes in acid-base state of cerebrospinal fluid (CSF) and enhanced spread of spinal anaesthesia during pregnancy, we have measured CSF pH, carbon dioxide tension (PCO2) and HCO3- values in 73 women undergoing spinal anaesthesia with hyperbaric amethocaine 8 mg. Patients were allocated to one of four groups according to gestational period: non-pregnant group (n = 13), first trimester group (8-13 weeks, n = 19), second trimester group (14-26 weeks, n = 11) and third trimester group (27-39 weeks, n = 30). The pH of the CSF was greater in the second and third trimester groups than in the non-pregnant group. CSF PCO2 decreased by 0.53-0.8 kPa throughout pregnancy. CSF HCO3- was decreased throughout pregnancy. Overall, no clinically significant correlation was found between maximum cephalad spread of analgesia and CSF pH, PCO2 or HCO3-. We conclude that pregnancy-induced changes in acid-base state of CSF have little effect on the spread of spinal anaesthesia, although there is a clinically different spread of spinal anaesthesia between non-pregnant and pregnant states.

A compartmental transport model is developed, capable of predicting the evolution of CO2, HCO-3 and H+ in the cerebrovascular system. In the model, the transport of these components is simulated at a subset of three compartments: cerebrospinal fluid (CSF), capillary-choroid plexus and brain tissue, belonging to a seven compartmental assembly representing the entire brain. The remaining ones are; artery, vein, venous sinus and jugular bulb. The model accounts for advection associated with non-steady perfusion fluxes across semi-previous boundaries. Pressures, associated with perfusion, are solved in the seven-compartment model. The three-compartment transport model also takes into account changes in compartmental volume due to displacement of its boundaries, diffusion through boundaries and rate of generation of substances by chemical reactions. A first-order reaction rate is assumed in the CSF compartment. A parameter estimation method is then developed to assess boundary diffusivities from time-averaged observed values of perfusion pressure, tension of carbon dioxide, pH values, and concentration of free hydrogen and bicarbonate ions. An equation of state describing the regulation of flow from arteries to capillaries, as a function of CO2 tension in the CSF, is then suggested. Upon solving all coupled mass balance equations, and for a pre-evaluated perfusion pressure in the artery and capillary compartments, one can estimate the change in arteries to capillaries conductance at every time step. Boundary diffusivities between the capillary, cerebrospinal fluid and brain tissue compartments, were estimated. A sensitivity analysis proves the consistency between model predictions and available clinical observations, this, in terms of the influence of the parameter associated with CO2 metabolic rate on CO2 tension. It was shown that decrease of this tension caused an abrupt pressure fall at the first instant which later increased to an asymptotic value. This, however, was not evident in the capillaries at which pressure slightly falls and then remains constant.

This study investigated the interaction between vagal afferent input and central chemosensitivity in modulating the respiratory motor output of in vitro brain stem-spinal cord preparations from adult bullfrogs. With this preparation, the spatiotemporal distribution of respiratory-related motor output emulated that of intact bullfrogs; that is, the fictive breathing pattern was mostly episodic. Recordings from cranial motor nerves (V and X) showed that, without peripheral feedback, increasing the PCO2 of the mock cerebrospinal fluid (thereby reducing pH from 8.3 to 7.7) caused a modest increase in respiration-related burst frequency. When the pulmonary branch of a vagus nerve was stimulated phasically (2 V, 20 Hz, 0.2 ms) during each fictive breath to simulate afferent pulmonary stretch receptor feedback 1) the responsiveness of the preparation to the same changes in pH was augmented nearly threefold and 2) the breathing pattern remained episodic. It appears, therefore, that episodic breathing is an intrinsic property of the central nervous system in bullfrogs. It is concluded that there is a strong interaction between vagal feedback and central chemodetection in controlling the temporal relationships that characterize this episodic breathing pattern.

The dynamic exchange of CO2 and HCO-3 between the central circulation and peripheral sites such as the cerebrospinal fluid (CSF) is not completely understood. To examine this we administered a tracer dose of NaHCO3 labeled with the stable isotope 13C into the central circulation of nine 3- to 4-wk-old anesthetized, instrumented piglets. Serial samples of arterial and venous blood, breath, and CSF were obtained to determine the 13C/12C ratio by isotope-ratio mass spectrometry. Gas-exchange and hemodynamic parameters were obtained through standard techniques. The patterns of tracer washout in venous blood, arterial blood, and breath were nearly indistinguishable from each other, and the mean residence time was 113 +/- 24 min (average +/- SD). In contrast, the CSF 13C/12C ratio was not equivalent to that in venous blood, arterial blood, or breath until 20 min after tracer administration. Tracer washout data were used to determine the best-fit three-exponential-term equation and to calculate compartmental parameters of a three-compartment mammillary system in which CO2 and HCO3- residing in the central compartment (compartment 1) exchanges relatively rapidly with one peripheral compartment (compartment 2) and slowly with the other (compartment 3). The turnover time for the CSF was 6.8 +/- 2.5 min and the estimate for compartment 2 was 7.1 +/- 3.7 min. Accordingly, CSF appears to be one of the rapidly interchanging peripheral compartments.

Data on canine cisternal cerebrospinal fluid (CSF) ions in acute respiratory alkalosis are limited and fragmentary. We hypothesized that with the fall in arterial PCO2 (PaCO2) and in the face of normal osmoregulation, CSF [Na+] remains relatively constant and CSF [Na+-Cl-] narrows to account in part for the fall in CSF [HCO3-]. We therefore measured blood and CSF acid-base variables and ions of two groups of pentobarbital-anesthetized, mechanically ventilated dogs (n = 10 in each group). In the control group, PaCO2 was kept constant and changes in serum and CSF ions were minimal. In Group II (acute respiratory alkalosis), both PaCO2 and cisternal CSF PCO2 decreased by 10 mm Hg. Five hours after induction of respiratory alkalosis, mean CSF [HCO3-] decreased significantly by 4.4 +/- 1.2 mEq/L (mean +/- SD). The fall in CSF [HCO3-] was similar to changes in CSF strong ion difference (SID = Na(+)+K(+)+Ca(2+)+Mg(2+)-CL(-)-lactate), which decreased 4.4 +/- 1.9 mEq/L. Concentrations of the four major CSF cations did not change significantly. Cisternal CSF lactate rose significantly by 1.2 +/- 0.9 mEq/L, accounting for 25% of the change in CSF [HCO3-]. The remaining (75%) change in CSF [HCO3-] was accounted for by changes in CSF [Cl-].

Changes in ventilatory rate affect arterial blood pH and PCO2 within seconds to minutes, but the corresponding acute changes for cerebrospinal fluid (CSF) pH and PCO2 have been as well documented. Using our previously-described swine model of brain retraction ischemia, we examined changes in arterial and CSF pH and PCO2 with acute changes in ventilation in four animals. Newly developed fluorescent dye technology permitted near-instantaneous recording of CSF pH and PCO2 during acute hyperventilation (end-tidal PCO2 of 20 mm Hg) and acute hypoventilation (end-tidal PCO2 of 50 mm Hg). The Puritan-Bennett 3300 Intra-Arterial Blood Gas Monitor (PB3300) was used with the sensor placed in the CSF in the interhemispheric fissure posterior to the corpus callosum. The following data were gathered at 5, 15, 30, and 60 minutes after the ventilatory change: arterial pH and PCO2, end-tidal CO2, laser-Doppler cerebral blood flow, and CSF pH and PCO2. The baseline (normoventilation) values for arterial and CSF pH and PCO2 in swine were comparable to those in humans: arterial pH 7.44 and PCO2 43 mm Hg; CSF pH 7.31 and PCO2 55 mm Hg. Changes in pH and PCO2 with hyperventilation and hypoventilation occurred rapidly in both arterial blood and CSF. Steady-state values were reached within 15 minutes for hypoventilation, and 30 minutes for hyperventilation. The correlation between arterial and CSF values for both pH and PCO2 at 5, 15, 30, and 60 minutes were all very highly significant (P < 0.001) except for arterial and CSF PCO2 at 5 minutes (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

By studying early postmortem changes in cerebrospinal fluid (CSF) it is possible to draw conclusions as to premortem focal brain cell injury and terminal brain ischemia. Cisternal fluid (CF) from 40 different adult cadavers with no known neurological disorder was analyzed and compared with known in vivo values. They were divided into four groups (n = 10 in each group), CF samples taken 2, 4, 10, and 24 h after death. The enzyme activity of CK and CK-BB (EC 2.7.3.2) increased linearly and statistically significantly 4-24 h postmortem (P < 0.001) the 2 h values being already 10 to 20 times higher than in vivo, LD and its isoenzymes 1 to 3 (EC 1.1.1.27) distinctly 10 to 24 h after death. Glucose and pyruvate concentrations in the CF declined, as did Na+ and Cl-. Lactate and K+ increased over time. The earliest statistically significant changes between different timepoints were seen in lactate, pyruvate and K+ concentrations. The GABA concentration was already more than 170 times at 2 h postmortem, and glutamate more than 20 times higher than in vivo. The concentrations of alanine, glycine, lysine, histidine, isoleucine, phenylalanine, and tyrosine were 2 to 3 times higher at 2 h postmortem than during life. The concentrations of all amino acids and ammonia increased linearly and statistically significantly (P < 0.001) in the CF 4 to 24 h postmortem.

Creatine kinase (CK) and its brain-specific isoenzyme (CK-BB), neuron-specific enolase (NSE), neural cell adhesion molecule (NCAM) and the ions sodium, potassium, chloride and calcium were measured both in CSF and serum and inorganic phosphate in CSF in order to assess their prognostic value in total brain ischemia due to cardiac arrest. The samples were collected at 4, 28 and 76 h after resuscitation. Twenty consecutive patients resuscitated from ventricular fibrillation or asystole were included in the study. Nine of the patients recovered consciousness (recovered) but eleven remained comatose (disabled). The follow-up period was 2 years after which only one patient was still alive. The earliest statistically significant differences between neurologically recovered and disabled patient groups were seen in CSF inorganic phosphate (P = 0.030) already at 4 h and CK-BB (P = 0.046) and NSE (P = 0.020) activity at 28 h. Later, at 76 h after the resuscitation CSF NSE differentiated the groups most clearly (P = 0.014). The values were higher in the disabled patients. A negative correlation between CSF parameters and Glasgow Coma scores was also seen at these timepoints. Statistically significant differences between the groups were seen in both CSF and blood pCO2, pO2, base excess (BE) and actual bicarbonate (HCO3-). CSF or serum NCAM has no prognostic value in anoxic-ischemic coma. The results suggest that in CSF CK-BB and NSE are useful prognostic indicators of hypoxic brain injury when measured 28-76 h after cardiac arrest whereas blood samples have no prognostic value.

The classical Grodins model of chemical respiratory control is analysed. Scaling and asymptotic analysis are used to reduce the model drastically to a much simplified form. In essence, the model consists of two separate controllers due to oxygen and carbon dioxide. The authors focus on the carbon dioxide controller, and show that it can be considered as two coupled delay recruitment equations. While, in normal circumstances, steady ventilation is stable, it is shown that, by varying controlling parameters, periodic and chaotic solutions may be obtained.

To determine whether cerebrospinal fluid (CSF) Cl- has a role in determining the stimulus to the central respiratory chemoreceptors under conditions of constant CSF pH, CO2, and HCO3- concentrations, the ventral medullary surface of the anesthetized rat was perfused with mock CSF of various ion composition and pH. Four mock CSF perfusates were used: two normal pH control perfusions and two acidic solutions. One acidic perfusate was formulated in the traditional manner by substituting Cl- for HCO3-. The second acidic perfusate, and one of the normal pH control perfusates, had approximately 15% of the Cl- replaced with isethionate, an impermeant strong anion. When the two acidic solutions were perfused over the ventral medulla, consistently larger increases in both tidal volume and minute ventilation were observed with the isethionate-containing acidic solution, despite conditions of identical pH and PCO2. The unequal ventilatory effects of the two acidic perfusions suggest that Cl- transport may be a factor determining the stimulus to the central respiratory chemoreceptors.

Objective: To further the understanding of lactate-induced panic in patients with panic disorder, the authors examined cisternal lactate and carbon dioxide levels in nonhuman primates after infusions of sodium lactate comparable to those used in studies of human beings., Method: CSF and venous blood lactate, pH, PCO2, PO2, and bicarbonate were measured in five ketamine-anesthetized nonhuman primates, without mechanical ventilation, before and after they underwent infusions of sodium lactate. In addition, the same measurements were made for three of the five subjects who were given saline infusions., Results: Despite the development of the characteristic peripheral biochemical effects of infused sodium lactate--increased lactate and bicarbonate levels and metabolic alkalosis--no increases in central lactate or carbon dioxide levels were observed. Saline infusions produced no biochemical effects on venous and cisternal measures., Conclusions: The results of this study are in keeping with previous findings of nonpermeability of the blood-brain barrier to anionic compounds such as lactate. They therefore support theories of lactate panic based on cognitive and/or brainstem misevaluation of peripheral somatic sensations.

The exact location of the central respiratory chemoreceptors sensitive to changes in PCO2 has not yet been determined. To avoid the confounding effects of the cerebral circulation, we used the in vitro brain stem-spinal cord of neonatal rats (1-5 days old) to identify areas within 500 microns of the ventral surface of the medulla where changes in PCO2 evoked a sudden increase in the rate of respiratory neural activity. The preparation was superfused with mock cerebrospinal fluid (CSF) while maintained at constant temperature (26 +/- 1 degrees C) and pH (7.34). Respiratory frequency increased linearly with decreases in superfusate pH (r2 = 0.92, P less than 0.001), indicating that the respiratory circuitry for the detection of CO2 and stimulation of breathing was intact in this preparation. The search for central chemoreceptors was performed with a specially designed micropipette that allowed microejection of 2-10 nl of mock CSF equilibrated with different CO2-O2 gas mixtures. The pipette was advanced in 50- to 100-microns steps by use of a microdrive to a maximum depth of 500 microns from the surface of the ventral medulla. Depending on the location of the micropipette, ejection of CO2-acidified mock CSF at depths of 100-350 microns below the ventral surface of the medulla stimulated neural respiratory output. Using this response as an indication of the location of central respiratory chemoreceptors, we found that chemoreceptive elements were located in a column in the ventromedial medulla extending from the hypoglossal rootlets caudally to an area 0.75 mm caudal to VI nerve in the rostral medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

To estimate whether H+ is the unique stimulus of the medullary chemosensor, ventilatory effects of HCO3- and/or CO2 applied on the ventral medullary surface using an improved superfusion technique and of CO2 inhalation were compared in halothane-anesthetized spontaneously breathing rats. Superfusion with low [HCO3-]-acid mock cerebrospinal fluid (CSF) (normal Pco2) induced a significant increase in ventilation, with an accompanying reduction in endtidal Pco2 (PETco2). High [HCO3-]-alkaline CSF depressed ventilation. Changes in Pco2 of superfusing CSF, on the other hand, had no significant effect despite the similar changes in pH. Simultaneous decrease in [HCO3-] and Pco2 of mock CSF with normal pH also maintained stimulated respiration. CO2 inhalation during superfusion with various [HCO3-] solutions caused further increase in ventilation as PETco2 increased. The results suggest that the surface area of the rat ventral medulla contains HCO3- (or H+)-sensitive respiratory neural substrates which are, however, little affected by CO2 in the subarachnoid fluid. A CO2 (or CO2-induced H+)-sensitive chemosensor responsible for the increase in ventilation during CO2 inhalation may exist elsewhere functionally apart from the HCO3- (or H+)-sensitive sensor in the examined surface area.

In order to study the role of CO2 and acid-base status in contributing to ventilatory drive, skate were exposed to normoxic hypercapnia (PICO2 = 7.5 Torr) under conditions where the primary O2 drive would remain unaltered. Blood O2 transport was markedly insensitive to CO2, with no Root effect and only a small Bohr effect. Red blood cell pHi was not preferentially regulated, and there was no evidence of RBC swelling or nucleoside triphosphate adjustment. Although there were no changes in arterial O2 levels during hypercapnia, ventilation immediately increased 2.7-fold through large changes in stroke volume and small changes in frequency, and declined only slightly through 24-48 h. PaCO2 equilibrated rapidly with PICO2, driving down arterial pHa, which was 65% corrected through HCO3- accumulation by 24 h. In contrast, the extradural fluid outside the brain equilibrated only very slowly, and was clearly not involved in the ventilatory stimulation. Increased ventilation during hypercapnia may be related to depression in pHa.

This study examined the possible role(s) of central acid-base stimuli in the increase in ventilation induced by hypercapnia in the skate, a response that is not due to an O2 signal (Graham et al., Respir. Physiol., 1990, 80: 251-270). Skate were sampled for cerebrospinal fluid (CSF) acid-base status, intracellular pH of the brain (14C-DMO method), and pHi in other tissues throughout 24 h of exposure to PICO2 = 7.5 Torr. CSF PCO2 rapidly equilibrated with the elevated PaCO2. Despite the much lower non-HCO3- buffer capacity in the CSF, CSF pH was not depressed to the same extent as blood pHa. CSF pH was also regulated rapidly, returning to control levels by 8-10 h, whereas pHa remained significantly depressed at 24 h. Similarly, the pHis of the weakly buffered brain and heart ventricle were initially compensated more rapidly than those of more strongly buffered white muscle and red blood cells. However, brain pHi adjustment slowed markedly after 4 h and stabilized at only 70% compensation by 20-24 h, suggesting that brain intracellular acidosis may play a role in the long-term increase in ventilation. CSF and brain were the only compartments which did not exhibit an apparent compounding metabolic acidosis during the initial stages of hypercapnic exposure. While these results illustrate the primacy of central acid-base regulation, they do not support a role for CSF pH in the long-term elevation of ventilation in response to hypercapnia. Depressions in pHa and brain pHi appear the two most likely candidates for proximate stimuli.

The concentration of total lactate in cisternal fluid increased threefold, from 12.3 +/- 2.1 to 37.6 +/- 8.9 mg/dl, during a 20-min intravenous infusion of 1 M racemic sodium lactate (10 mEq/kg) in 3 anesthetized, mechanically ventilated baboons. Rises in cisternal lactate lagged behind arterial lactate increases, but occurred during the time interval in which susceptible humans typically panic in response to lactate infusion. Subsequent to cisternal lactate increases, cisternal pH and HCO3- concentration progressively increased during a 105-min interval following lactate infusion. No consistent changes in cisternal pCO2 occurred during or subsequent to lactate infusion. These preliminary findings fail to support the hypothesis that lactate-induced panic is mediated by increasing central nervous system pCO2. Instead, these data demonstrate that lactate can rapidly increase in the central nervous system during lactate infusion, suggesting new lines of investigation for studying the mechanisms responsible for lactate-induced panic.

The purpose of this study was to investigate the effects of bumetanide, an inhibitor of NaCl cotransport on cisternal cerebral spinal fluid (CSF) acid-base balance during acute respiratory acidosis (ARA). We measured blood and CSF acid-base variables in two groups (N = 7 in each) of anesthetized paralyzed and mechanically ventilated dogs with bilateral ligation of renal pedicles (to eliminate saluresis). After baseline samples were obtained (-1 h) bumetanide (0.5 mg/kg) was administered intravenously within 15 min (group 2); group 1 received equal volume of diluted saline. ARA was induced 1 h later (0 h) and was maintained for 5 h. In both groups PaCO2 was maintained between 55 to 60 mm Hg. Mean cisternal CSF PCO2 was 42.8 +/- 2.6, and 43.8 +/- 2.5 mm Hg, respectively in group 1 and group 2 and rose approximately 20 mm Hg during ARA. In group 1, CSF [HCO3-] was 22.0 +/- 1.0, 24.8 +/- 0.6, and 25.4 +/- 1.6 mEq/L, respectively at 0, 2 1/2, and 5 h; respective values for group 2 were 22.9 +/- 1.5, 24.7 +/- 1.4, and 26.1 +/- 1.3 mEq/L. Comparing the two groups, respective values were not significantly different from each other. Similarly, between the two groups changes in CSF [Na(+)-Cl-] during ARA were not significantly different from each other. Based on our results we conclude that at the dose used in the present study bumetanide does not change ionic composition and acid-base balance of cisternal CSF when compared to controls. Because changes in CSF [Na(+)-Cl-] during ARA were similar in both groups, any inhibition of Cl- influx into CSF by bumetanide should have been proportional to that of Na+.

In 35 unconscious patients suffering from traumatic brain injury and subjected to controlled hyperventilation within 12 hours of the acute trauma, we measured continuously the intraventricular pressure (IVP), ventricular fluid lactate, pyruvate, L/P ratio, pH and bicarbonate during the first 4 posttraumatic days, and related the findings to the clinical course. In patients in whom the follow-up study did not reveal severe mental impairment or dementia, the ventricular fluid lactate never exceeded 4 mmol/litre. In this group, the IVP level never exceeded 40 mmHg/hour, and the mean pressure/day never exceeded 20 mmHg. In half of the patients in whom dementia, vegetative survival or death occurred, ventricular fluid lactate exceeded 4 mmol/litre; the IVP level/hour exceeded 40 mmHg in two of 23 patients, and the mean pressure/day exceeded 20 mmHg in nine of 23 patients. The prognostic value of pyruvate was of less importance, although a significant increase in patients with a poor outcome was seen. No prognostic conclusions could be drawn from ventricular fluid, L/P ratio, pH and bicarbonate.

Time and temperature effects on postmortem cerebrospinal fluid samples from 60 adult mongrel dogs were studied. After death the dogs were held at 4, 20, or 37 degrees C for intervals of 3, 6, 12, 24, or 48 h. Antemortem and postmortem cerebrospinal fluid was evaluated for sodium, chloride, potassium, urea nitrogen, glucose, creatinine, calcium, phosphorus, and carbon dioxide. Sodium and urea nitrogen values remained stable. Chloride may be of forensic science value. Low levels of postmortem calcium might indicate antemortem hypocalcemia; high levels of postmortem glucose may indicate antemortem hyperglycemia. Calcium and creatinine levels increased slightly but continually after death; carbon dioxide values dropped.

The pH and PCO2 values measured by the Astrup technique were compared in cerebrospinal fluid (CSF) obtained using two different sampling techniques: 1) a direct or in vivo technique and 2) the widely accepted syringe sampling technique. In 65 pairs of measurements in 9 dogs it was found that the pH was always overestimated and the PCO2 always underestimated in the syringe sample when compared to the in vivo sample. The equations describing the relationships are as follows: 1) pH (syringe = 0.995 pH (in vivo) + 0.084 and 2) PCO2 (syringe) = 0.873 PCO2 (in vivo) + 0.2. The amount by which the syringe sample underestimated the true PCO2 value increased with the absolute PCO2 value, consistent with the possibility of there being a diffusional loss of CO2 during the transfer of CSF from the syringe to the pH electrode (PCO2 (in vivo)- PCO2 (syringe) = 2.4, 4.9, 7.5, and 10.0 mmHg at in vivo PCO2's of 20, 40, 60, and 80 mmHg). This study indicates that the technique used for sampling CSF is crucial to the expected accuracy of the results and that the number of transfers of CSF during the sampling and measurement procedures should be minimized in order to obtain reliable results.

Unanesthetized adult female ponies were studied near sea level (250 m) and during sojourns to 3400 m (N=6) and 4300 m (N=7) altitude. The pH, PCO2, and PO2 of arterial blood and pH and PCO2 of cerebrospinal fluid (CSF) were measured under conditions of acute (1 hr) and chronic (1-45 days) hypoxia. Cerebrospinal fluid was sampled from the cisterna magna of the awake pony and arterial blood withdrawn from an indwelling arterial catheter. In both groups of animals, PaCO2 decreased slightly after 1 hr of hypoxia (delta PaCO2= - 0.6 mm Hg at 3400 m; - 3.9 mm Hg at 4300 m), decreased further after 1-5 days at high altitude (delta PaCO2= - 7.2 mm Hg at 3400 m; - 12.3 mm Hg at 4300 m) and then increased significantly after 6 days of chronic hypoxia (delta PaCO2= + 4.1 mm Hg at 3400 m; + 4.7 mm Hg at 4300 m). Although PaO2 decreased markedly during acute hypoxia, subsequent changes in PaCO2 at high altitude did not alter PaO2 from that observed during acute hypoxia (PaO2=52 mm Hg at 3400 m; 41 mm Hg at 4300 m). The pH of CSF increased during acute hypoxia (delta pH= + 0.013 unit at 3400 m; + 0.033 unit at 4300 m) and became more alkaline after 1-2 days at high altitude (delta pH= + 0.031 unit at 3400 m; + 0.064 unit at 4300 m). At 4300 m, CSF pH remained alkaline to control values throughout sojourn. Under these conditions of chronic hypocapnic hypoxia, CSF pH was imperfectly regulated and regulated in a magnitude equal to (3400 m) or less than (4300 m) arterial blood. Furthermore, the similarity of relative changes in CSF [HCO3-] and arterial [HCO3-] during chronic hypoxia may indicate a passive regulation of CSF [HCO3-] rather than local 'CSF-specific' mechanisms as previously proposed.

If 100% O2 produces hyperventilation by increasing central CO2 due to cerebral vasoconstriction or dimished reduction of oxyhemoglobin, then, there should be a parallel decrease in alveolar and CSF PCO2 during O2 breathing in neonates. To test this hypothesis, we measured ventilation, alveolar PCO2 and CSF PCO2, pH and HCO2 before and 10-20 min after infants began breathing 100% O2. With 100% O2, minute ventilation increased from 0.193 +/- (SE) 0.013 (n = 7) to 0.252 +/- 0.013 liter/min/kg (p less than 0.015), PACO2 decreased from 42 +/- 2 to 38 +/- 2 mm Hg (p less than 0.005), CSF PCO2 decreased from 51 +/- 1 to 44 +/- 1 mm Hg (p less than 0.015), and pH increased from 7.308 +/- 0.013 to 7.354 +/- 0.013 (p less than 0.05). CSF bicarbonate decreased, but not significantly. These findings, showing a trend toward alkalosis, suggest that the neonate, like the adult man, induces hyperventilation during hyperoxia via an increase in PCO2 at the central level.

Effects of body temperature on the ventilatory control system were studied in 17 anaesthetized cats. At different body temperatures (stabilized within 0.1 degrees C) CO2 response curves were measured in each cat. In with chloralose-urethan anaesthetized cats it was found that in the body temperature range of 34-40 degrees C, in which neither shivering nor panting occurred, no statistically significant trend with temperature was found in the slope (S) and the extrapolated intercept on the PaCO2-axis (B) of the linear CO2 response curve during hyperoxia as well as hypoxia. In two with pentobarbital anaesthetized cats similar results were obtained. The resting ventilation (at FICO2 = 0) did not change significantly, while the resting PaCO2 during hyperoxia showed a trend to increase with temperature just reaching the level of significance (P less than 0.05). Breathing frequency increased significantly with temperature (P less than 0.0005). When body temperature was elevated above 41 degrees C both the slope (S) and the intercept of the CO2 response curve (B) decreased. In three cats ventriculo-cisternal perfusion was performed and no apparent influence of body temperature was found on the relation between the PCSFCO2 and PETCO2 and on the VE-PCSFCO2 response curves. These findings show that body temperature has no important modifying effect on the ventilatory response to CO2 in anaesthetized cats in the temperature range of 34-40 degrees C.

Blood in mouth, nose, and eye tissues of birds cools by evaporation, then flows to a cephalic vascular heat exchanger, the ophthalmic rete. There, acting as a heat sink, blood from the evaporative surfaces cools arterial blood flowing counter-current to it toward the brain. The brain thus remains cooler than the body core. Data for unanesthetized domestic pigeons (Columba livia) suggest that in addition to losing heat, blood perfusing the evaporative surfaces also exchanges oxygen and carbon dioxide with air. In the heat exchanger, this blood apparently gives up oxygen to, and gains carbon dioxide from, arterial blood. The consequent increase in oxygen and decrease in carbon dioxide in the brain's arterial blood enhance diffusion of these gases in, and oxygen supply to, the brain. Such events may help birds maintain the brain's oxygen supply during the high systemic demand of exercise and at the reduced oxygen availability of high altitude.

By means of the Astrup apparatus (Blood Microsystem BMS 2) acid-base indices in blood and cerebro-spinal fluid of clinically healthy Merino sheep at the age of one year (15 head) and of two or three years (41 head) were determined. Blood collected anaerobically from v. jugularis and liquor collected by means of the suboccipital punction in heparinized syringes and/or caplaris and liquor collected by means of the suboccipital punction in heparinized syringes and/or capillaries were examined immediately after the collection. Following indices were obtained and re-counted according to nomograms: actual pH, partial CO2 pressure--pCO2 base excess--BE, base buffer--BB, standard bicarbonate--SB, actual bicarbonate--AB, total CO2--tCO2 (Tables I, II). Indices of pH, pCO2, BE and BB indicated statistically significant differences in values when comparing liquor with venous blood (in younger ewes). As the values of the sheep cerebro-spinal fluid indices examined are not to be found in literature, the above stated values can be recommended to be used as basic values for a given age group.