Ventilatory acclimatization to moderate hypoxemia in man. The role of spinal fluid (H+).

This study has assessed the regulation of arterial blood and cerebrospinal fluid (CSF) pH and thereby their contribution to the control of breathing in normal man during various stages of ventilatory acclimatization to 3,100 m altitude. CSF acid-base status was determined: (a) from measurements of lumbar spinal fluid during steady-state conditions of chronic normoxia (250 m altitude) and at + 8 h and + 3-4 wk of hypobaric hypoxia; and (b) from changes in cerebral venous P(CO2) at + 1 h hypoxic exposure. After 3-4 wk at 3,100 m, CSF [H(+)] remained significantly alkaline to values obtained in either chronic normoxia or with 1 h hypoxic exposure and was compensated to the same extent ( approximately 66%) as was arterial blood [H(+)]. Ventilatory acclimatization to 3,100 m bore no positive relationship to accompanying changes in arterial P(O2) and pH and CSF pH: (a) CSF pH either increased or remained constant at 8 h and at 3-4 wk hypoxic exposure, respectively, coincident with significant, progressive reductions in Pa(CO2); (b) arterial P(O2) and pH increased progressively with time of exposure; and (c) in the steady-state of acclimatization to 3,100 m the combination of chemical stimuli present, i.e. Pa(O2) = 60 mm Hg, pHa and pH(CSF) = + 0.03-0.04 > control, was insufficient to produce the observed hyperventilation (Pa(CO2) = 32 mm Hg). It was postulated that ventilatory acclimatization to 3,100 m altitude was mediated by factors other than CSF [H(+)] and that the combination of chronic hypoxemia and hypocapnia of moderate degrees provided no mechanisms for the specific regulation of CSF [H(CO3) (-)] and hence for homeostasis of CSF [H(+)].

Hyperventilation in severe diabetic ketoacidosis.

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.

Effects of sodium lactate infusion on cisternal lactate and carbon dioxide levels in nonhuman primates.

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.

Prolonged cerebrospinal fluid acidosis in recently abstinent chronic alcoholics.

Significant cerebrospinal fluid (CSF) acidosis was evident in 80 chronic alcoholics (mean pH, 7.25 +/- 0.06) who were compared with 14 neurologic controls (mean pH, 7.31 +/- 0.02). Acidosis persisted for many weeks after the last drink, and there was no associated systemic acidosis. CSF pH correlated significantly with CSF anion gap, suggesting a primary cerebral metabolic abnormality. Even though one-quarter of the alcoholic patients had a CSF pH less than 7.21, mental impairment was less than expected for the degree of CSF acidosis noted.

Cerebrospinal fluid changes in experimental cardiopulmonary bypass using hemodilution with glucose water.

Cardiopulmonary bypass using hemodilution with isotonic glucose water was performed on seven dogs. Intense systemic metabolic acidosis, hyponatremia, hypochloremia, and hyperglycemia were accompanied by only comparatively small changes in the corresponding cerebrospinal fluid values. The data suggested that in the present study, cardiopulmonary bypass was not associated with gross disruptions of the barriers for bicarbonate, sodium, chloride, and glucose between blood and cerebrospinal fluid.

Effects of acetazolamide on cerebrospinal fluid ions in metabolic alkalosis in dogs.

We hypothesized that inhibition of carbonic anhydrase in the central nervous system by acetazolamide should limit the rise in cisternal cerebrospinal fluid (CSF) [HCO3-] observed in metabolic alkalosis. To test this hypothesis, isosmotic isonatremic metabolic alkalosis was produced in two groups of anesthetized, paralyzed, and mechanically ventilated dogs (8 in each group). Group II animals received 50 mg/kg of acetazolamide intravenously 1 h before induction of metabolic alkalosis of 5-h duration. Renal effects of acetazolamide were eliminated by ligation of renal pedicles. In both groups cisternal CSF [Na+] remained relatively constant during metabolic alkalosis. In group I CSF [Cl-] decreased 3.6 and 8.2 meq/l, respectively, 2.5 and 5 h after induction of metabolic alkalosis. Respective increments in CSF [HCO3-] were 3.4 and 6.0 meq/l. In acetazolamide-treated dogs, during metabolic alkalosis, increments in CSF [HCO3-] (4.8 and 7.2 meq/l, respectively, at 2.5 and 5 h) and decrements in CSF [Cl-] (9.1 and 13.3 meq/l) were greater than those observed in group I. We conclude that, in dogs with metabolic alkalosis and bilateral ligation of renal pedicles, acetazolamide impairs CSF regulation of HCO3- and Cl- ions; acetazolamide not only failed to impede HCO3- rise but actually appeared to increase it. The mechanisms for these observations are discussed.

Effects of altered CSF [H+] on ventilatory responses to exercise in the awake goat.

We investigated the effects of selective large changes in the acid-base environment of medullary chemoreceptors on the control of exercise hyperpnea in unanesthetized goats. Four intact and two carotid body-denervated goats underwent cisternal perfusion with mock cerebrospinal fluid (CSF) of markedly varying [HCO-3] (CSF [H+] = 21-95 neq/l; pH 7.68-7.02) until a new steady state of alveolar hypo- or hyperventilation was reached [arterial PCO2 (PaCO2) = 31-54 Torr]. Perfusion continued as the goats completed two levels of steady-state treadmill walking [2 to 4-fold increase in CO2 production (VCO2)]. With normal acid-base status in CSF, goats usually hyperventilated slightly from rest through exercise (-3 Torr PaCO2, rest to VCO2 = 1.1 l/min). Changing CSF perfusate [H+] changed the level of resting PaCO2 (+6 and -4 Torr), but with few exceptions, the regulation of PaCO2 during exercise (delta PaCO2/delta VCO2) remained similar regardless of the new ventilatory steady state imposed by changing CSF [H+]. Thus the gain (slope) of the ventilatory response to exercise (ratio of change in alveolar ventilation to change in VCO2) must have increased approximately 15% with decreased resting PaCO2 (acidic CSF) and decreased approximately 9% with increased resting PaCO2 (alkaline CSF). A similar effect of CSF [H+] on resting PaCO2 and on delta PaCO2/VCO2 during exercise also occurred in two carotid body-denervated goats. Our results show that alteration of the gain of the ventilatory response to exercise occurs on acute alterations in resting PaCO2 set point (via changing CSF [H+]) and that the primary stimuli to exercise hyperpnea can operate independently of central or peripheral chemoreception.

DIDS decreases CSF HCO3- and increases breathing in response to CO2 in awake rabbits.

An inhibitor of the HCO3-/Cl- exchange carrier protein, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or vehicle was infused in mock cerebrospinal fluid (CSF) via the cisterna magna in conscious rabbits at 10 mumol/l for 40 min at 10 microliter/min. Neither treatment had any effect over 2-5 h on the non-CO2-stimulated CSF ion values or blood gases. With CO2 stimulation such that arterial PCO2 (PaCO2) was increased 25 Torr over 3 h, DIDS treatment significantly decreased the stoichiometrically opposite changes in CSF [HCO3-] and [Cl-] that normally accompany hypercapnia and reflect ionic mechanisms of CSF pH regulation. Expressed as delta CSF [HCO3-]/delta PaCO2, DIDS treatment decreased the CSF ionic response by 35%. In a separate paired study design DIDS administration via the same protocol had no effect on resting ventilation but significantly increased the ventilation and tidal volume responses to a 28-Torr increase in PaCO2. Expressed as change in minute ventilation divided by delta PaCO2, DIDS treatment produced a 39.6% increase. The results support the concept of a DIDS-inhibitable anion exchange carrier being involved in CSF pH regulation in hypercapnia and suggest a DIDS-related effect on the ventilatory response to CO2.

Central vs. peripheral chemoreceptors in ventilatory stimulation by Hacetate.

Intravenous infusion of Hacetate in conscious rabbits induces a greater decrease in cerebrospinal fluid (CSF) [HCO3-] and arterial CO2 partial pressure (PaCO2) than does HCl, HNO3, or Hacetate. To test whether acetate per se can stimulate central chemoreceptors, HCl- or Hacetate-acidified mock CSF was infused via the cisterna magna in conscious rabbits with catheters preimplanted under anesthesia. HCl infusion induced a greater decrease in PaCO2 refuting this hypothesis. To evaluate the role of the carotid body HCl and Hacetate were infused intravenously in an intact (CB+) and a chemodenervated group (CB-). In CB+ rabbits Hacetate infusion produced a greater decrease in PaCO2. In CB- rabbits, the fractional decrease in arterial PaCO2 was less for both acids compared with that of the CB+ rabbits, but it was significantly greater for Hacetate infusion (21.2 +/- 2.5%, mean +/- SE) than for HCl infusion (14.5 +/- 1.8%). Thus the carotid body is not necessary for the greater Hacetate ventilatory stimulation. The working hypothesis is that nonionic diffusion of Hacetate into brain or acetate replacement of HCO3- in CSF production lowers [HCO3-] near central chemoreceptors.

Effects of amiloride and diethyl pyrocarbonate on CSF HCO-3 and ventilation in hypercapnia.

Amiloride (10(-3) M), a Na+-H+ countertransport inhibitor, infused into the cisterna magna (10 microliter/min for 40 min) of ketamine-xylazine-anesthetized rabbits decreased the cerebrospinal fluid (CSF) HCO3- response to 3 h of hypercapnia [arterial PCO2 (PaCO2) = 60 Torr] by 21.6% (mean delta CSF [HCO3-]/delta PaCO2 0.232 vs. 0.296 mmol.l-1.Torr-1, P less than 0.05). Diethyl pyrocarbonate (DEPC, 10(-3) M), a histidine-blocking agent, infused into the cisterna magna decreased the CSF HCO3- response to hypercapnia by 25.3% (mean delta CSF [HCO3-]/delta PaCO2, 0.230 vs. 0.308 mmol.l-1.Torr-1, P less than 0.02). DEPC is known to inhibit the ventilatory response to hypercapnia (E. Nattie. Respir. Physiol. 64: 161-176, 1986) by a direct effect at the ventrolateral medulla (E. Nattie. J. Appl. Physiol. 61: 843-850, 1986). In this study amiloride had no significant effect on the ventilatory response to hypercapnia. The interpretation is that a Na+-H+ countertransport protein, perhaps with a histidine at a key location, is involved in CSF acid-base regulation and that amiloride appears to have no effects on the chemoreception process. DEPC appears to have effects on chemoreception and on CSF acid-base regulation.

CSF acid-base regulation and ventilation in iso- and hypocapnic Hacetate acidosis.

Intravenous infusion in conscious rabbits of Hacetate decreases both arterial CO2 partial pressure PaCO2 and cerebrospinal fluid (CSF) HCO3- more than observed with HCl or HNO3 infusion. These acids did not affect CSF HCO3- in isocapnic conditions, and this study asks whether Hacetate infusion will do so. Arterial, central venous, and cisterna magna catheters were implanted in pentobarbital-anesthetized rabbits and all subsequent measurements were performed in the conscious state. Hacetate was infused intravenously over 6 h to decrease plasma HCO3- the same amount in a group allowed to decrease its PaCO2 in response to the acid (hypocapnic) and one in which PaCO2 was maintained at control levels (isocapnic). CSF HCO3- decreased significantly in isocapnia, although the change was less than in hypocapnia. Stoichiometrically by 6 h the measured CSF HCO3- change was balanced by an increase in acetate in hypocapnia and the sum of an increase in acetate and a decrease in chloride in isocapnia. Mechanistically, net acetate entry into CSF appears to involve an exchange for chloride as proposed for NO3-/Cl- and a process that lowers CSF HCO3-. This process could be competitive replacement of HCO3- by acetate in the CSF production mechanism or nonionic diffusive entry of Hacetate into CSF with subsequent titration of HCO3-. The decreases in CSF HCO3- result from the acetate mechanism and the hypocapnic effect on Cl- and HCO3-. The greater ventilatory response results from the greater CSF acidification or a specific effect of acetate per se.

CSF acidosis augments ventilation through cholinergic mechanisms.

Ventilation is influenced by the acid-base status of the brain extracellular fluids (ECF). CO2 may affect ventilation independent of changes in H+. Whether the acidic condition directly alters neuronal firing or indirectly alters neuronal firing through changes in endogenous neurotransmitters remains unclear. In this work, ventriculocisternal perfusion (VCP) was used in anesthetized (pentobarbital sodium, 30 mg/kg) spontaneously breathing dogs to study the ventilatory effects of acetylcholine (ACh), eucapnic acidic (pH approximately 7.0) cerebrospinal fluid (CSF), and hypercapnic acidic (pH approximately 7.1) CSF in the absence and presence of atropine (ATR). Each animal served as its own control. Base line was defined during VCP with control mock CSF (pH approximately 7.4). With ATR (4.8 mM) there was an insignificant downward trend in minute ventilation (VE). ACh (6.6 mM) increased VE 53% (n = 12, P less than 0.01), eucapnic acidic CSF increased VE 41% (n = 12, P less than 0.01), and hypercapnic acidic CSF increased VE 47% (n = 6, P less than 0.01). These positive effects on ventilation were not seen in the presence of ATR. This suggests that acidic brain ECF activates ventilatory neurons through muscarinic cholinergic mechanisms. Higher concentrations of ACh increased ventilation in a concentration-dependent manner. Higher concentrations of ATR decreased ventilation progressively, resulting in apnea. The results suggest that ACh plays a significant role in the central augmentation of ventilation when the brain ECF is made acidic by either increasing CSF PCO2 or decreasing CSF bicarbonate.

Blood-brain barrier to hydrogen ion during acute metabolic acidosis in piglets.

The present study investigates the integrity of the blood-brain barrier to H+ or HCO3- during acute plasma acidosis in 35 newborn piglets anesthetized with pentobarbital sodium. Cerebrospinal fluid acid-base balance, cerebral blood flow (CBF), and cerebral oxygenation were measured after infusion of HCl (0.6 N, 0.191-0.388 ml/min) for a period of 1 h at a constant arterial PCO2 of 35-40 Torr. HCl infusion resulted in decreased arterial pH from 7.38 +/- 0.01 to 7.00 +/- 0.02 (P less than 0.01). CBF measured by the tracer microsphere technique was decreased by 12% from 69 +/- 6 to 61 +/- 4 ml.min-1.100 g-1 (P less than 0.05). Infusion of 0.6 N NaCl as a hypertonic control had no effect on CBF. Cerebral metabolic rate for O2 and O2 extraction was not significantly changed from control (3.83 +/- 0.20 ml.min-1.100 g-1 and 5.7 +/- 0.6 ml/100 ml, respectively) during acid infusion. Cerebral venous PO2 was increased from 41.6 +/- 2.1 to 53.8 +/- 4.0 Torr by HCl infusion (P less than 0.02) associated with a shift in O2-hemoglobin affinity of blood in vivo from 38 +/- 2 to 50 +/- 1 Torr. Cisternal cerebrospinal fluid pH decreased from 7.336 +/- 0.014 to 7.226 +/- 0.027 (P less than 0.005), but cerebrospinal fluid HCO3- concentration was not changed from control (25.4 +/- 1.0 meq/l). These data suggest that there is a functional blood-brain barrier in newborn piglets, that is relatively impermeable to HCO3- or H+ and maintains cerebral perivascular pH constant in the face of acute severe arterial acidosis. (ABSTRACT TRUNCATED AT 250 WORDS)

Differential respiratory effects of HCO3- and CO2 applied on ventral medullary surface of rats.

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.

Cl- replacement alters the ventilatory response to central chemoreceptor stimulation.

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.

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.

Effects of insulin-induced hypoglycemia on intracellular pH and impedance in the cerebral cortex of the rat.

In order to evaluate changes in extra- and intracellular pH in the brain during hypoglycemia rats were injected with insulin and pH changes evaluated when the EEG showed a slow-wave-polyspike pattern ('precoma'), or when EEG activity had ceased for 5, 15 or 30 min ('coma'). Extra- and intracellular acid-base changes were evaluated from pCO2 and HCO3-concentrations. In order to allow calculation of intracellular pH ( and HCO3- concentrations) changes in extracellular fluid volume were estimated by measurements of cortical tissue impedance. The main results were as follows. (1) At constant arterial pCO2 and CSF HCO3- concentration either rose (15 min of coma) or remained unchanged (all other groups). However, since the cerebrovenous (and tissue) pCO2 fell, all groups except one (30 min of coma) showed a significant increase in extracellular fluid pH. (2) During severe hypoglycemia, and especially when EEG activity ceased, cortical impedance increased markedly. Calculations with the help of the Rayleigh and Maxwell equations showed that the extracellular fluid volume was reduced to about 50% of control. (3) Intracellular pH increased significantly in precoma and in coma of 15 and 30 min duration. However, pH in the 5 min coma group was significantly lower (but no different from control). (4) In general, the increase in intracellular pH is consistent with previous findings that hypoglycemia is associated with oxidation of endogenous acid metabolites. However, the data suggest that in the initial period of coma acids accumulate by some unidentified mechanism.

Pial arteriolar vessel diameter and CO2 reactivity during prolonged hyperventilation in the rabbit.

Hyperventilation reduces intracranial pressure (ICP) acutely through vasoconstriction, but its long-term effect on vessel diameter is unknown. In seven rabbits with a cranial window implanted 3 weeks earlier, the effect of prolonged hyperventilation on vessel diameter was studied. Anesthesia was maintained for 54 hours with a pentobarbital drip (1 mg/kg/hr). The pH, CO2, and HCO3- levels were measured in arterial blood and cisterna magna cerebrospinal fluid (CSF). The diameter of 31 pial arterioles was measured with an image splitter. After baseline measurements, pCO2 was reduced from 38 to 25 mm Hg and allowed to return to 38 mm Hg for 10 minutes every 4 hours. There was an initial vasoconstriction of 13%, which progressively diminished by 3% every 4 hours. Thus, by the 20th hour, vessel diameters at a pCO2 of 25 mm Hg had returned to slightly above baseline values obtained at a pCO2 of 38 mm Hg. The temporary return of pCO2 to 38 mm Hg every 4 hours caused vasodilation: 12% at 4 hours, gradually increasing to 16% at 52 hours. Thus, at 52 hours, the vessel diameters were 105% of baseline at a pCO2 of 25 mm Hg and increased to 122% at a pCO2 of 38 mm Hg. Arterial pH had returned to baseline at 20 hours, and CSF pH had returned at 24 hours. Bicarbonate in blood and CSF remained decreased throughout the experiments. In three control experiments during which normocapnia was maintained, vessel diameter and pH and bicarbonate levels remained unaltered over the same period. The CO2 reactivity, tested by brief periods of hyperventilation every 4 hours, also did not change. These results indicate that hyperventilation is effective in reducing cerebral blood volume for less than 24 hours and that it should be used only during actual ICP elevations. If used preventively, its effect may have worn off by the time ICP starts to rise for other reasons, and further decreases in pCO2 cannot be obtained. Moreover, the reduction in buffer capacity with lower bicarbonate renders the vessels more sensitive to changes in PaCO2. This could lead to more pronounced elevations in ICP during transient rises in PaCO2, such as during endotracheal suctioning in head-injured patients.

Correlation between acid-base status, concentrations of lactate and of pyruvate in blood and cerebrospinal fluid in patients treated in an intensive care unit.

Results of examinations of 41 patients treated in an intensive care unit are reported. The patients were divided into three groups and examined on the first and twelfth days of treatment. In the first group were 15 patients who had received circulatory resuscitation, the second group was 13 patients with lesions of the central nervous system of traumatic or vascular origin and the third group was 13 patients with acute respiratory insufficiency of toxic or infective origin. The cerebrospinal fluid of patients in the second group showed the lowest pH (mean pH 7.28) and bicarbonate concentration (19.05 mequiv./1); this group also had the lowest PO2 values. Moderate respiratory alkalosis was observed in the arterial blood of patients with lesions of the central nervous system. Concentrations of lactate in the cerebrospinal fluid were increased in all three groups of patients although blood lactate concentrations were normal. The lactate/pyruvate concentration ratio was highest in the resuscitated patients.

Cerebrospinal fluid acid-base status during normocapnia and acute hypercapnia in equine neonates.

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.