Cerebrospinal fluid acid-base balance in newborns

In adults, cerebrospinal fluid (CSF) acid-base balance is an important determinant of cerebral blood flow, ventilatory drive, and state of consciousness. Sixteen lumbar punctures were performed on newborns (mean gestational age, 33.8 weeks; range, 26 to 44 weeks). The mean CSF pH was 7.366 units, 0.036 less than the mean capillary blood pH (NS). The mean CSF arterial carbon dioxide tension (PCO2) was 40.3 mm Hg, 6.7 greater than the mean blood PCO2 (p less than 0.01). The mean bicarbonate ion concentration in CSF was 21.8 mEq/L, 1.2 greater than that in blood (NS). Acid-base determinations in CSF of neonates with intraventricular hemorrhage did not differ significantly from those of neonates with otherwise normal CSF. These acid-base values are similar to those found in adults and did not vary with gestational age, suggesting that mechanisms to establish this acid-base gradient are developed by 26 weeks' gestation.     

Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT). European Atrial Fibrillation Trial (EAFT) study groups.

OBJECTIVE: To assess independent predictors of hemorrhage in 651 anticoagulated patients. BACKGROUND: An excess incidence of major bleeding (7% per year) in patients with nondisabling cerebral ischemia of presumed arterial origin treated with oral anticoagulation led to early termination of the Stroke Prevention In Reversible Ischemia Trial (SPIRIT). METHODS: The relationship between known risk factors and hemorrhage was assessed by univariate and multivariate analyses. We compared the risk factors with those in 225 patients anticoagulated because of cerebral ischemia with atrial fibrillation in the European Atrial Fibrillation Trial (EAFT). RESULTS: Leukoaraiosis (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.4 to 5.3) and age older than 65 years (HR 1.9, 95% CI 1.0 to 3.4) were independent predictors of all anticoagulation-related hemorrhages in SPIRIT. The incidence of intracranial bleeding in SPIRIT was 3.7% per year; this incidence increased by a factor of 1.37 for each 0.5 unit international normalized ratio (INR). Patients with cerebral ischemia of presumed arterial origin had a 19 times (95% CI 2.4 to 150) higher risk of intracranial hemorrhages than those with atrial fibrillation after correcting for baseline differences between SPIRIT and EAFT patients. CONCLUSIONS: In addition to the intensity of anticoagulation, leukoaraiosis and age older than 65 years are independent risk factors for bleeding in patients anticoagulated because of cerebral ischemia of presumed arterial origin. These patients have a higher inherent risk of anticoagulation-related intracranial hemorrhages than patients with atrial fibrillation.     

严重脑外伤后血和脑脊液酸碱平衡变化

通过测定14例脑外伤病人血和脑脊液PO_2、PCO_2、pH、HCO_3~-水平,我们观察到严重脑外伤后出现脑脊液代谢性酸中毒,动脉血呼吸性碱中毒和低氧血症。脑脊液pH值与颅内压水平呈密切的负相关关系。脑脊液pH值是较敏感的预后指标。     

Cerebral blood flow, cerebral metabolism and cerebrospinal fluid biochemistry in brain-injured patients after exposure to hyperbaric oxygen.

A series of head-injured patients, in coma, were treated with hyperbaric oxygen (OHP) at 2.5 atm. Cerebral blood flow (CBF), cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGL), and lactate (CMRL act), and various cerebrospinal fluid (CSF) parameters were measured before and 2 h after the treatment. Pre-OHP and post-OHP average values of arterial blood and CSF lactate, and CMRL act were higher than normal, while CBF, CMRO2 and CSF oxygen pressure (PO2) were lower. CBF tended to increase after OHP in some patients and to decrease in others. This discrepancy and the conflicting results of the literature can be tentatively explained in assuming that there is a different effect of OHP on normal brain circulation as compared to impaired brain circulation. Changes of cerebral metabolic rates were inconsistent and did not relate to changes of CBF, except with repeated studies of the same patient. A correlation was found between the variations of CMRGL and those of arterial blood and CSF glucose content. CSF PO2, CSF acid-base balance, and CSF lactate content did not vary, and arterial PO2 showed a consistent fall. In two patients who were neurologically improved after OHP exposure, the CBF and metabolic changes were not the same.     

Acid-base equilibrium in cerebrospinal fluid following intracranial surgery]

In 48 patients the acid-base equilibrium in the CSF and blood was determined on the 2nd day after intracranial operation. In the postopertive period various disturbances of this equilibrium were found which were probably various stages of metabolic acidosis compensation in the CSF which was a reflection of metabolic (lactate) acidosis developing primarily in the damaged brain area. On the basis of determinations it was found that changes in the CSF of the type of metabolic acidosis (21 cases) corresponded most frequently to respiratory alkalosis in the blood (11 cases). Changes of the type of respiratory acidosis in the CSF(13 cases) corresponded usually to metabolic alkalosis in the blood (7 cases). The development of metabolic acidosis in patients in severe and moderately severe condition (19 cases) was associated with poor prognosis as to survival since the mortality in this group was 10 (about 53%). The favourable effect of dehydrating treatment may be due also to facilitation of passage of bicarbonates from the blood into the cerebral tissue and CSF since their level is increased in the blood during metabolic alkalosis (during a decrease in the extracellular space) resulting from dehydration.     

Cerebrospinal fluid lactate and pyruvate concentrations in patients with malignant hypertension

Summary Lactate and pyruvate concentrations and acid-base parameters in cerebrospinal fluid (CSF) and arterial blood were measured in 21 patients with malignant hypertension (MHT), 19 with benign hypertension (BHT) and 21 normotensive subjects (NT). Average values for CSF lactate and lactate/pyruvate (L/P) ratio were significantly higher in MHT (1.90±10mM/1, 19.2±1.0) than in either BHT (1.50±0.05 mM/1, 15.7±0.7) or NT (1.44±0.04 mM/1, 15.7±0.4). There was a linear correlation between CSF lactate and CSF pressure (r=0.565, P<0.01), and the latter was also related to mean arterial pressure exceeding 150 mm Hg (r=0.553, P<0.01). Such increases in the acid metabolites in CSF indicate that brain metabolism becomes anaerobic in MHT, probably due to increased intracranial prssure. Increased cerebrovascular permeability is also discussed as participating in causal mechanisms.

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Zusammenfassung Bei 21 Patienten mit maligner Hypertonie, 19 mit benigner Hypertonie und 21 mit normalem Blutdruck wurden in Blut und Liquor die Lactat- und Pyruvatkonzentrationen sowie die Säure-Basen-Parameter gemessen. Die Werte für das Lactat bzw. für das Lactat-Pyruvat-Verhältnis im Liquor waren bei Patienten mit maligner Hypertonie signifikant höher (1,90±0,10 mM/1, 19,2±1,0) als bei den Patienten mit benigner Hypertonie (1,50±0,05 mM/1, 15,7±0,7) bzw. bei normotensiven Individuen (1,44±0,04 mM/1, 15,7±0,4). Es bestand eine lineare Korrelation zwischen den Lactatwerten und dem Druck im Liquor (r=0,565, P<0,01), wobei dies außerdem korrelierte mit einem mittleren arteriellen Blutdruck von mehr als 150 mm Hg (r=0,553, P<0,01). Diese Zunahme in den Säuremetaboliten im Liquor weist darauf hin, daß der Hirnstoffwechsel bei maligner Hypertonie in eine anaerobe Phase tritt, wahrscheinlich wegen des erhöhten intrakraniellen Druckes. Es wird auch die Möglichkeit einer erhöhten cerebralen Gefäßdurchlässigkeit als mitbeteiligter Mechanismus erwogen.

     

CEREBRAL LACTATE, PYRUVATE and ATP CONCENTRATIONS, and ARTERIAL ACID-BASE BALANCE AT VARIOUS TIME INTERVALS FOLLOWING BILATERAL CAROTID ARTERY OCCLUSION IN NORMOTENSIVE and SPONTANEOUSLY HYPERTENSIVE RATS

Cerebral lactate, pyruvate and adenosine triphosphate (ATP), and arterial acid-base balance were measured in normotensive rats (NTR) and spontaneously hypertensive rats (SHR) at various time intervals following bilateral carotid occlusion. In SHR, a great and progressive increase in cerebral lactate and lactate/pyruvate ratio (L/P ratio) during the first 5–6 hours after occlusion was followed by a gradual decrease as the time interval increased. Cerebral ATP in SHR decreased as cerebral lactate increased, and an inverse relationship was observed between lactate and ATP. On the other hand, in NTR, there were minimal changes in cerebral lactate and L/P ratio following carotid occlusion. These results suggest that bilateral carotid occlusion might cause severe ischemic damages of the brain in SHR, but not in NTR. the hemodynamic factor as a cause of cerebral ischemia in hypertensives is discussed.     

Cerebrospinal fluid lactate and pH in patients with acute severe head injury.

Cerebral ventricular fluid (CSF) lactate and pH were measured repeatedly in 21 comatose patients with severe head injury during the first three weeks after trauma. In addition, regional cerebral 133Xe blood flow (rCBF) was measured two to four times in each patient at various time intervals, depending on the indications for carotid angiography, and the pressure in the cerebral ventricular system (IVP) was measured continuously. The series was divided into three groups: (1) patients with local cortical cerebral lesions, (2) patients with brain-stem symptoms, and (3) patients with both local cortical lesions and brain-stem symptoms. The results showed that a high CSF lactate level in patients with severe acute brain injury suggested severe and extensive brain lesions and predicted a poor outcome of the injury. In the individual patients, increasing CSF lactate foreboded clinical deterioration, whereas decreasing CSF lactate indicated recovery. The CSF pH was decreased in most patients, but very low pH levels (below 7.20) were seen only in three patients who all had a poor outcome. Correlation was not observed between CSF lactate and rCBF or between CSF pH and rCBF. It is concluded that repeated determination of CSF lactate and pH during the post-traumatic period may be a valuable tool in the assessment of the course and outcome of the brain injury.     

Effects of hypercapnia and arterial hypotension and hypertension on cerebrospinal fluid pulse pressure and intracranial volume-pressure relationships.

In twelve anaesthetised, ventilated dogs the effects of hypercapnia and pharmacologically induced arterial hypotension and hypertension on the interrelation between volume-pressure response (VPR) and cerebro-spinal fluid (CSF) pulse pressure were studied during continuous inflation of a supratentorial extradural balloon. Hypercapnia did not significantly affect the intracranial volume-pressure relationships, but did cause a significant increase in gradient of the relationship between CSF pulse pressure and intracranial pressure (ICP). Alteration of the arterial blood pressure showed opposite effects on VPR and CSF pulse pressure. A decrease in VPR and an increase in pulse pressure were observed during arterial hypotension; the reverse was found during arterial hypertension. The discrepancy between the effects on VPR and CSF pulse pressure of the variables under study was explained by changes in the transient increase in cerebral blood volume per cardiac cycle. On the basis of the results of this study it will be possible, during clinical ICP monitoring, to interpret changes in the CSF pulse pressure to ICP ratio in terms of changes in intracranial volume-pressure relationships.     

Brain energy metabolism and intracranial pressure in idiopathic adult hydrocephalus syndrome

BACKGROUND: The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance. OBJECTIVE: To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter. METHODS: A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate. RESULTS: When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p < 0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage. CONCLUSIONS: Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.     

Use of ventricular cerebrospinal fluid lactate measurement to diagnose cerebrospinal fluid infection in patients with intraventricular haemorrhage.

Early diagnosis of ventriculostomy-associated cerebrospinal fluid (CSF) infection in acute neurosurgical patients can be difficult. The use of prophylactic antibiotics in intraventricular or subarachnoid haemorrhage decreases the sensitivity of cell counts, Gram staining and bacterial culture as diagnostic tools. We prospectively collected clinical and cerebrospinal data for 16 patients with intraventricular haemorrhage, with an external ventricular drain inserted, with or without spontaneous subarachnoid haemorrhage. Three (18.8%) patients had cerebrospinal fluid infection, with appropriate changes in antibiotic regimens needed. All three patients had CSF lactate levels of >4 mmol/L (6.4 mmol/L, 7.8 mmol/L, 7.9 mmol/L). Eleven out of 13 patients without CSF infection had CSF lactate levels of below 4 mmol/L. The two patients with CSF lactate levels of 4-6 mmol/L were grade 5 subarachnoid haemorrhage patients, one with renal impairment. Using a cut-off lactate level of 4 mmol/L, the positive predictive value was 60% and negative predictive value was 100% for CSF infection. A CSF lactate level of above 4 mmol/L should prompt suspicion of CSF infection in intraventricular haemorrhage patients with an external ventricular drain.     

Elevated cerebrospinal fluid lactate/pyruvate ratio in Machado-Joseph disease

To identify the metabolic alterations related to mitochondrial functions in Machado-Joseph disease (MJD), we analyzed the cerebrospinal fluid (CSF) levels of lactate, pyruvate, and citric acid cycle intermediates by high performance liquid chromatography (HPLC) in 7 Japanese patients with that disease and then measured some mitochondrial enzymes. Their mean age was 46 years. Diseased controls were matched by age to the patients studied. The CSF level of lactate was significantly elevated, pyruvate was significantly decreased, and the lactate/pyruvate (L/P) ratio was significantly elevated in the patients with MJD. There were no significant differences of citric acid cycle intermediates of the CSF between the patients and the controls. We measured the native and dichloroacetate (DCA)-activated pyruvate dehydrogenase complex (PDHC) activities, and mitochondrial electron transport activities in 3 patients with MJD, and found these activities to be normal. Therefore, the increased CSF lactate, increased lactate/pyruvate ratio, and decreased pyruvate may reflect the decreased regional cerebral blood flow rather than metabolic derangement of the mitochondria.     

Implications of vascular endothelial growth factor, sFlt-1, and sTie-2 in plasma, serum and cerebrospinal fluid during cerebral ischemia in man.

The relation between cerebral ischemia and local release of angiogenic factors was investigated after subarachnoid hemorrhage (SAH) in humans. Time-dependent concentration-changes of vascular endothelial growth factor (VEGF), sFlt-1 and sTie-2 extracted from plasma, serum, and cerebrospinal fluid (ventricular, cisternal, and lumbar) were analyzed in 15 patients surgically treated for ruptured aneurysms of the anterior circulation (Hunt and Hess grades I-V). Data were related to brain Po2 (Pbro2) and cerebral energy metabolites (extracellular lactate, pyruvate, glutamate, and glycerin concentrations) as well as clinical and radiologic reference data. Delayed impairment of cerebral perfusion secondary to progressive microcirculatory alterations was associated with reduced local Pbro2 and energy metabolism (increased lactate-pyruvate ratio, glutamate and glycerine levels). Elevated serum/plasma and CSF concentrations of VEGF, sFlt-1, and sTie-2 matched the scale of ischemic tissue hypoxia. Excessive VEGF/sFlt-1 and sTie-2 levels were related to Pbro2 values consistently less than 5 mm Hg, glutamate concentrations greater than 300 micromol/L, lactate-pyruvate ratio greater than 300, cerebral infarction, and reduced outcome (P < 0.01). Delayed microcirculatory impairment was mirrored by distinct elevation of cisternal and arterial VEGF and sFlt-1 concentrations, suggesting local induction of angiogenesis. Arterial levels of VEGF, sFlt-1, and sTie-2 reflect both extent and time course of compensatory, yet clinically inefficient, angiogenesis in the absence of general hypoxia.     

Cerebrospinal fluid lactate in patients with hepatic encephalopathy

Cerebrospinal fluid (CSF) lactate and pyruvate concentrations were determined in 16 patients with hepatic encephalopathy before and/or after treatment. CSF lactate was significantly increased to 1.92 +/- 0.11 mmol/l in hepatic encephalopathy before the treatment in comparison to 1.40 +/- 0.05 mmol/l in control subjects. In 9 of 11 patients with moderate or stage 2 encephalopathy, CSF lactate levels were below 2 mmol/l. In contrast, in 4 of 5 patients with stage 3-4 encephalopathy, CSF lactate levels were higher than 2 mmol/l. CSF lactate was decreased with the recovery of neurological symptoms by the treatment. These findings indicate that CSF lactate levels reflect the severity of metabolic impairment of the brain. Hypocapnia was frequently observed in these encephalopathic patients, and arterial PCO2 correlated inversely with CSF lactate and linearly with CSF HCO3-, suggesting that CSF lactic acidosis contributes to hyperventilation in hepatic encephalopathy. It is concluded from present results that metabolic disorder of neuronal cells might be one of the important factors for the development of hepatic encephalopathy.     

Intracerebral microdialysis and CSF hydrodynamics in idiopathic adult hydrocephalus syndrome

BACKGROUND: In idiopathic adult hydrocephalus syndrome (IAHS), a pathophysiological model of "chronic ischaemia" caused by an arteriosclerotic process in association with a CSF hydrodynamic disturbance has been proposed. OBJECTIVE: To investigate whether CSF hydrodynamic manipulation has an impact on biochemical markers related to ischaemia, brain tissue oxygen tension (PtiO(2)), and intracranial pressure. METHODS: A microdialysis catheter, a PtiO(2) probe, and an intracerebral pressure catheter were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. A subcutaneous microdialysis probe was used as reference. Intracranial pressure and intracerebral PtiO(2) were recorded continuously. Samples were collected for analysis between 2 and 4 pm on day 1 (baseline) and at the same time on day 2, two to four hours after a lumbar CSF hydrodynamic manipulation. The concentrations of glucose, lactate, pyruvate, and glutamate on day 1 and 2 were compared. RESULTS: After CSF drainage, there was a significant rise in the intracerebral concentration of lactate and pyruvate. The lactate to pyruvate ratio was increased and remained unchanged after drainage. There was a trend towards a lowering of glucose and glutamate. Mean intracerebral PtiO(2) was higher on day 2 than on day 1 in six of eight patients. CONCLUSIONS: There is increased glucose metabolism after CSF drainage, as expected in a situation of postischaemic recovery. These new invasive techniques are promising tools in the future study of the pathophysiological processes in IAHS.     

The metabolic consequences of experimental intraventricular hemorrhage

Experimental intraventricular hemorrhage was produced by injection of autologous fresh blood (0.25 ml/kg) or artificial CSF into the right lateral ventricle of 24 dogs. A transient ventricular fluid acidosis (pH drop to 7.09) was accompanied by increased lactate, pyruvate, ammonia, and Pco2, and decreased bicarbonate and glucose. High lactate/pyruvate ratios were the most persistent abnormality. The control group, which received intraventricular artificial CSF, developed minimal ventricular fluid acidosis (pH 7.26). Lumbar CSF and venous blood acid-base parameters did not change. Simultaneous cisternal samples obtained from some of the animals reflected similar metabolic abnormalities of lesser magnitude. Intraventricular injection of sodium bicarbonate normalized the pH in four animals.     

Intraoperative values of S-100 protein, myelin basic protein, lactate, and albumin in the CSF and serum of neurosurgical patients

OBJECTIVES: To assess the concentrations of S-100 protein, myelin basic protein (MBP), and lactate, and the (CSF)/serum albumin ratio (Qalb) during intracranial neurosurgical procedures. METHODS: Samples of CSF from 91 patients with various CNS diseases were obtained by aspiration of cisternal CSF at the beginning of surgery (before starting surgical manipulation of the brain) and concentrations of S-100 protein, MBP, and lactate, and Qalb were determined. At the same time blood was sampled for determination of serum S-100 protein concentration. Patients were divided into three groups according to the aetiology of their CNS disease (intracranial haemorrhage, n=11; benign intracranial mass lesion, n=52; malignant neoplastic disease, n=28). Radiological and intraoperative characteristics were documented. RESULTS: In each of these three groups median values of all four CSF variables measured were raised. The occurrence of brain oedema and a midline shift correlated significantly with raised concentrations of MBP and Qalb. Breaching of the arachnoid layer, documented at surgery for benign lesions, correlated with higher concentrations of MBP, lactate, CSF S-100 protein, and Qalb. CONCLUSIONS: Intraoperative values of S-100 protein, MBP, lactate, and Qalb are increased in patients with intracranial haemorrhage, benign intracranial mass lesion, and malignant neoplastic disease. Breaching of the arachnoid layer and oedema is associated with higher concentrations of some of the aforementioned proteins. These biochemical data can serve as a basis for further research into CSF specific proteins.     

Arterial blood gas changes in panic disorder and lactate-induced panic

Lactate infusions were conducted in 12 male panic patients and 8 male normal controls with arterial catheters in place to reassess previously reported acid-base changes based on venous blood samples. The analysis of arterial pH, carbon dioxide pressure, and bicarbonate concentration confirmed most venous findings. At baseline, before the infusion, venous blood shows evidence of mixed chronic and acute respiratory alkalosis in patients while arterial blood gasses are most consistent with developing acute respiratory alkalosis. During the infusion both bloods are consistent with mixed metabolic and respiratory alkalosis with the patients hyperventilating more than normal controls and panicking patients hyperventilating more than nonpanicking patients. Arterial blood seems more sensitive than venous blood in detecting baseline differences between panicking and nonpanicking patients. A baseline arterial carbon dioxide pressure of 40 mmHg or higher and an arterial pH below 7.40 may predict no subsequent panic to lactate infusion.     

颅脑创伤患者的颅内压相关参数对预后的影响

目的探究颅内压相关参数对颅脑创伤（TBI）患者生存状况的影响。 方法回顾性分析新兴县人民医院神经外科自2016年6月至2018年6月收治的62例TBI患者的临床资料,依据出院时患者预后的GOS评分将其分为预后不良组（死亡、GOSⅠ~Ⅱ级,25例）与预后良好组（GOSⅢ~Ⅳ级,37例）。比较2组患者术后24 h内颅内压、脑组织氧分压、脑灌注压和血流动力学情况,并分析颅内压相关参数与TBI患者不良预后的相关性。 结果预后良好组患者的颅内压、脑组织氧分压水平低于预后不良组,脑灌注压、收缩期血流速度（Vs）、平均血流速度（Vm）和舒张期末血流速度（Vd）水平均高于预后不良组,差异均具有统计学意义（P<0.05）。TBI患者的颅内压、脑组织氧分压水平与不良预后呈现正相关（r=0.618,P=0.000;r=0.514,P=0.000）,脑灌注压水平、Vs、Vm和Vd与不良预后呈负相关（r=-0.571,P=0.000;r=-0.562,P=0.000;r=-0.501,P=0.000;r=-0.575,P=0.000）。 结论颅内压、脑组织氧分压、脑灌注压和血流动力学情况与TBI患者的预后具有相关性,积极控制颅内压和脑组织氧分压升高,促进脑灌注压,密切监测血流动力血指标,可改善患者生存状况。     

Regulation of pH and HCO3 in brain and CSF of the developing mammalian central nervous system

Acute (2-h) metabolic acidosis or alkalosis was induced in immature rats to ascertain the ability of their incompletely-developed CNS to regulate pH when challenged with perturbations in blood [H] and [HCO3]. Brain and cisternal CSF pH were determined from steady-state distribution of [14C]dimethadione, a weak organic acid. By 1 week post partum, there was a remarkable stability of pH in the cerebral cortex of animals subjected to arterial pH extremes of 7.1 and 7.5. However, CSF pH in 1-week-old animals rendered alkalotic remained 0.07-0.08 units above control due to lack of a compensatory increase in pCO2, and to a blood-CSF barrier apparently more permeable to HCO3. As arterial HCO3, i.e. [HCO3]art, was varied from about 10 to 30 mmol/l, the infants maintained [HCO3]csf only half as effectively as adults, i.e. delta [HCO3]art was 0.4 and 0.2 at 1 and greater than 4 weeks, respectively. Throughout postnatal ontogenesis, [HCO3]csf was more resistant to alteration by metabolic acidosis than by alkalosis. Overall, the results indicate that immature rats challenged with systemic acid-base loads are less capable than adults in regulating CSF pH, but they are able to maintain brain pH.