AMERICAN

JOURNAL

OF

Vol. 228, No. 4, April

PHYSIOLOGY

1975.

Printed in U.S.A.

Distribution blood

of H+ and HCO,-

during

respiratory

T. F. HORNBEIN

alkalosis

AND

Anesthesia

Research

Center,

University

of Washington,

E. G. PAVLIN (With of Anesthesiolou Seattle, Washington 9819.5

T.

F.,

AND

E.

HC03- between CSF and blood Am. J. Physiol. 228(4) : 1149-l

acid-base balance; cisternal ion regulation; CSF/plasma

the Technical

Department

G. PAVLIN. Distribution of Hf and during respiratory alkalosis in dogs. 154. 1975.-Anesthetized, paralyzed dogs after a control period at normal pH, were hyperventilated to produce a hypocapnic alkalosis. The pH, Pco~, [HCO 3-1, and [lactate] in cisternal and lumbar CSF and arterial blood were determined at normal conditions (control) shortly after induction of respiratory alkalosis (time 0) and 3, 4.5, and 6 h thereafter. These values along with measurements of the CSF/plasma DC potential (E) allowed calculations of the electrochemical potential difference (~1) between CSF and blood for Hf and HCO3-. After 6 h of hypocapnic alkalosis, pH+ and pnc@had returned to -0.7 and - 1 .O mV of control at the cistern and to - 1 .O and +0.4 mV of control for lumbar CSF. This return of 1-1 is compatible with a passive distribution of these ions though active ion regulation is not ruled out. Assuming passive distribution, differences in AZZ/ApH, between metabolic and respiratory acid-base changes determined the extent of CSF pH homeostasis during compensated acid-base derangements. HORNBEIN,

and lumbar CSF; DC potentials

passive

between

distribution;

THE STUDIES BY SEVERINGHAUS ET AL. (15) on lumbar CSF acid-base balance during ventilatory acclimatization to high altitude represented the initial stimulus toward inquiry concerning the mechanisms regulating brain extracellular fluid pH. These investigators observed that hypoxically induced respiratory alkalosis resulted in a fall in [HCO3%F over the course of 24-48 h sufficient to restore CSF pH essentially to normal in spite of a lowered Pcoz and in spite of continuing alkalosis in blood. Severinghaus calculated that both H+ and HCO3in CSF were not in electrochemical equilibrium with blood and suggested that regulation of CSF pH during hypocapnic alkalosis was by a process of active transport of one or the other of these ions across the blood-brain barrier. As we discussed earlier (10) and as proposed by Siesj ij and Kjallquist (17), the changes observed could be explained qualitatively at least by a process of passive distribution. We have noted that during stable sustained acidosis or alkalosis of metabolic origin (10, 11) and during respiratory acidosis (12), the changes in cisternal and lumbar CSF acid-base status are explicable by a passive process of ion distribution. The purpose of the present study was to determine whether

and

Department

CSF and

in dogs Assistance of Physiolosly

of Mica1 and

Middaugh)

Biobhysics,

during respiratory alkalosis the changes in CSF [H+] and [HCOa-] were quantitatively compatible with a process of passive distribution. The principles and assumptions underlying the approach to this question have been presented in our initial paper (10). This final paper also presents a synthesis and interpretation of results obtained during all four acid-base derangements. METHOD

Six dogs were anesthetized with pentobarbital (25 mg/kg), paralyzed with gallamine, intubated, and mechanically ventilated. The methods of measurement of the CSF/ plasma DC potential difference (E) and acid-base values have been described (10). A control state at pH, of 7.40, achieved in this study by mechanical ventilation at high tidal volumes with CO2 added to inspired gas, was sustained for 1.5-Z h. After control measurements were made, respiratory alkalosis was induced by discontinuing the inspired CO2 without altering the pattern of mechanical ventilation. Pace, was kept constant thereafter by slight adjustments of ventilatory rate. Arterial [HCOS-] decreased about 1 meq/liter with induction of respiratory alkalosis and was maintained constant thereafter by administration of 0.9 N sodium bicarbonate when necessary. Arterial and CSF samples were drawn approximately 1 h after the decrease in Frcoa when PaGO had stabilized at its new level. This sample was defined as time 0. Subsequent samples were obtained 3, 4.5, and 6 h later. Cisternal and lumbar CSF/plasma E was recorded at these times. Calculation of midcapillary values for [H+] and [HCO 3-1 and electrochemical potential differences (p) has been detailed elsewhere (10). RESULTS

The

changes in cisternal and lumbar CSF/plasma at time 0 (Fig. 2) during respiratory alkalosis agree well with those we observed during respiratory acidosis (12) as well as with the values reported by Held et al. (4). Both cisternal and lumbar E decreased slightly over the next 6 h. The entire lumbar change and about two-thirds of the cisternal one can be explained by a decrease in arterial pH from 7.592 to 7.580 over time, leaving 0.2 mV of the cisternal change unaccounted for. The CSF pH rose initially with the changes in arterial AI?/ApH,

1149 Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (137.154.019.149) on January 11, 2019.

1150

‘I’.

. f ..

3

..

.

..

F.

.

1

i

25

AND

AE

Cistern01

/ ADHO

Lumbar

19.1

mV/pH mV/pti

Lumbor

\ e-

---c-w--\

\

cc

+

-0-a +

t

Cistern0

-I--

i

= - 31.8 =-

G. PAVLJN

E.

....*-•. l+ .*.*....$........*

l

88 l, 8 3 ..2 8 8 8 \ \

8

-8 i

HORNBEIN

I

I

I

1

1

1

1

1

i

\

I 1

1 c

‘iT0 0 II I

I

I’

I’











1



I

I

I/rT \ \ d

Cistern0 \

\

\

\

I-

26 1

I -\ ‘\

-> ‘**...**. Cisterna \ \ -**...* \ --.. I* ...* \ 1 *-*....**- I

.--....--TT '\ ---.-. \ c _--/-. -.-.I 7 -4.---l-----f *......-

ArhrttJl

1

b

1

C

0

1

1

1

2 Time

FIG.

1.

and lumbar tized dogs.

pH, and [HCOs-] CSF vs. time during Vertical bars indicate

hOa,

,

3 (hours)

o f arterial respiratory 4~ 1 SEM.

,

4

1

o

I

1

I

2 Time

i

I

I

c

,

,

5

6

plasma alkalosis

and cisternal in 6 anesthe-

pH (Fig. 1) but returned toward normal in both locations. was held constant after the initial small Arterial [ HCOZ-] decreased from 24.6 decrease (Fig. 1 ), while CSF [HC03-] to 20.5 meq/kg Hz0 in the cistern and from 25.6 to 21 .O meq/kg Hz0 in the lumbar sac. Cisternal and lumbar p for H+ and HCO-, had returned essentially to control by 4.5 h (Fig. 2). DISCUSSION

As with the other three acid-base derangements that we have studied, respiratory alkalosis was associated with a return of prr+ and j&co3essentially to normal values. Other work permitting comparison is limited. From Kazemi et al.‘s (5) observations in dogs during respiratory alkalosis of similar duration, we estimate a cisternal &n+ of +2.4

1

I

I

3 (hours)

4

5

1

6

FIG. 2. CSF/plasma DC potential difference (E) and chemical potential differences for H+ (JL~+) and HC03vs. time during respiratory alkalosis in 6 anesthetized dogs. of AE/ApH, were calculated for change in time 0 sample from Values of pH+ and pHCO3are calculated for concentrations and mean capillary plasma water. Vertical bars indicate &l

electrobnco3--) Values control. in CSF SEM.

mV and Apneo3of -0.8 mV, compared to -0.7 and + 1.0 mV in the present study. Though Leusen and Demeester (8) studied two dogs for similar periods, a control arterial pH more acid than that in CSF differs from all other reports in the literature and makes estimation of Ap suspect. We know of no other published data on respiratory alkalosis in dogs from which 1-1 might be estimated and from which conclusions concerning compatibility with a process of passive distribution might be made. During respiratory alkalosis, [lactate& was observed to rise, more so in lumbar than cisternal CSF (Table 1). This change occurred in the face of a slight decrease in [lactate],. Leusen and Demeester (8), Kazemi et al. (6), and Plum et al. (13) h ave also observed increases in [lactate]csr with hyperventilation. In all these studies the increase in [lactate] cSF accounted for only a part of the decrease in [HC03]esF from control. In the present study, the A[lactate] was 15 % of the A[HCO,-] in cisternal CSF and 30 % in lumbar CSF. The increase in [lactate]esF

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CSF-BLOOD

H+ AND

HC03-

WITH

RESPIRATORY

ALKALOSIS

1151

1. Values for acid-base parameters in arterial plasma, cisternal and lumbar and calculated electrochemical potential dtfferences (p> for H+ and HCOZ- in six dogs during resfiiratory alkalosis with constant plasma [HCO~-] TABLE

Time,

h

[HCOa-1 , meq/kg SO

PH

CSF, CSFlplasma

[Lactate) meq/kg Hz0

Pco2, torr

E,

E, mV

bH+, mV

PHc’O3--,

mV

-

Control

0

3

4.5

6

Values in

METHODS

,4rterial CSF-cistern CSF-lumbar

7.402 7.347 7.350

#I 0.004 It 0.008 & 0.008

21.3 24.6 25.6

* 0.7 It 0.3 zt 0.6

31.8 46.2 48.5

zt 0.7 zt 0.8 zt 0.7

1.4 1.5 1.7

* 0.3 & 0.1 zt 0.2

3.6 5.9

Arterial CSF-cistern CSF-lumbar

7.592 7.478 7.467

It 0.007 zt 0.019 zk 0.013

20.5 23.5 24.3

zt 0.8 zk 0.6 zt 0.8

19.1 32.8 34.8

It 0.5 zk 0.8 A 0.8

1.9 1.8 2.0

zt 0.3 zt 0.1 * 0.2

Arterial CSF-cistern CSF-lumbar

7.587 7.430 7.423

+ zt zt

0.007 0.008 0.008

20.0 20.3 21.2

dz 1.6 zt 0.5 h 0.6

18.8 32.1 34.0

zk 0.5 zt 1.2 AZ 0.7

1.1 2.1 2.9

Arterial CSF-cistern CSF-lumbar

7.581 7.417 7.418

zt 0.006 It 0.004 & 0.005

20.3 20.4 20.8

zt 1.3 zt 0.2 + 0.5

19.6 33.3 33.5

3t 0.5 & 0.5 & 0.7

Arterial CSF-cistern CSF-lumbar

7.580 7.420 7.417

zt 0.003 zt 0.006 zk 0.010

20.3 20.5 21.0

rt 0.7 xk 0.3 & 0.4

19.5 32.9 33.9

* 0.3 zk 0.6 & 0.8

are

means & of ref. 10.

SE.

The

p for

H+

and

HCO3-

are

calculated

could be due either to hypoxia secondary to decreased cerebral blood flow or due to alkalosis (13). Alkalosis enhances lactate production through increased glycolysis related to stimulation of phosphofructokinase (1). During acidosis, either metabolic (ref. 10, Table 1) or respiratory (ref. 12, Table 1) [lactate& did not increase, but during metabolic alkalosis (ref. 11, Table 1) increases in [lactate]osF were like those seen during respiratory alkalosis. This similarity is at first surprising but may be explained by two factors: I) the CSF pH after 6 h of metabolic alkalosis, though less alkaline than with respiratory alkalosis, is nevertheless distinctly more alkaline than control, facilitating some increase in glycolysis; 2) for unknown reasons blood flow after 6 h, estimated from CSF-arterial PCO~ differences, is lower during metabolic than respiratory alkalosis permitting a greater hypoxic contribution to lactic acid production. The relationship between oxygenation and CSF lactate levels has been clearly demonstrated by Plum et al. (13). Data recently reported by Mines and Bledsoe (9) show that hypoxia increased the & for HC03-, as would be expected if hypoxia increases lactic acid production by brain cells while not concomitantly altering ion permeability of the blood-brain barrier. The increase in [Iactate& in the present study (Table 1) may indicate an increased H+ production. One can estimate what pH+ and &reo3might have been if H+ production had not increased, assuming a stoichiometric exchange of lactatefor HC03at the measured CSF Pcoz. After 6 h, pnco3- would have been + 1.7 instead of + 1 .O mV at the cistern and + 1.0 instead of -0.4 at the lumbar region. Similarly, pH+ would be - 1.3 compared to -0.7 mV and 0.5 instead of + 1.2 in the cisternal and lumbar CSF. Even with these calculations, the 6-h values for p have returned close to control. Severinghaus et al.? (15) initial proposal that CSF acidbase balance was regulated by an active transport mecha-

from

0.3 0.7

3.4 5.4

zt 0.7 * 0.4

-1.2 -3.0

zt 0.8 =I= 0.8

-2.3 2.3

zt 0.4 zt 0.7

-1.2 3.8

* 1.4 zk 0.9

3.9 -0.1

* *

1 .o 1.0

* 0.2 zk 0.1 zt 0.3

-2.0 2.6

* 0.5 zt 0.7

2.0 6.4

zk 0.8 zt 0.7

0.6 -3.2

+ h

0.8 1.0

1.0 2.1 3.0

* 0.1 zk 0.1 AZ 0.4

-1.5 2.3

It 0.5 z.t 0.6

2.9 6.6

* 0.6 zk 0.9

-0.4 -3.7

zt 0.9 * 1.3

1.0 2.1 3.1

zk 0.2 =t 0.2 r+ 0.4

-1.7 2.0

It *

2.7 6.6

=t 0.4 zt 0.8

-0.2 zt 0.6 -3.4 It 1.0 -as described

CSF-mean

capillary

rt *

0.4 0.7 concentration

differences

nism designed to restore brain extracellular fluid pH to normal was derived from studies during the respiratory alkalosis occurring in man at high altitude. Recently Forster et al. (3) and Dempsey et al. (2) have presented more extensive measurements of lumbar CSF acid-base status in man and ponies undergoing a high-altitude exposure similar to that in the original study of Severinghaus et al. (15). *Though the experiment appears similar, the results are not similar. These recent observations show a continuing and significant alkalosis of CSF, actually exceeding that in blood, even as ventilation increases and PCO~ falls. The conclusion that ventilation is being driven by a stimulus other than central [H+] is intriguing, but of major relevance to the present work is the lingering alkalosis of CSF. At present, the CSF/plasma E and its sensitivity to changes of pH, in man and ponies are unknown. Therefore, even assuming passive ion distribution, species comparison is hazardous but almost too tempting to avoid. In the dog at least, assuming a passive distribution of H+ and HC03-, we have gained the ability to predict the acid-base status of CSF from that in blood. Figure 3 illustrates the changes in E and cisternal pHos* that would be associated with an acute change in pH, from normal to 7.20 followed by complete compensation to a pH, of 7.4. The difference in AE/Ap& between metabolic and respiratory acid-base derangements (Fig. 3A) results in different values for pH CSF at a given arterial pH. For example, assuming a steady state and constant production of metabolic H+ by brain, a pH, of 7.6 would be associated with a CSF pH of 7.422 during respiratory alkalosis and of 7.390 during metabolic alkalosis (Fig. 3B). During respiratory alkalosis, the lower value of AE/ApH, affords less protection of the CSF against change in pH of blood (Fig. 3A); as shown by the iso-pH lines, a AE/ApH, of - 6 1.5 mV would be required to render CSF pH immune from changes in pH of the blood. The greater pro-

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T.

1152

7.42-

7.2

7.3

7.4

7.5

7.6

P&i FIG. 3. Predicted relationship between CSF/plasma E, pHc& and pH, during acute and compensated acid-base derangements, assuming passive distribution of H+ and HC03-. Thus in steady an acute derangement of 0.20 pH, state Apn+ = 0. In this example, from normal is illustrated. AE/ApH. = -40 mV during metabolic and - 30 mV during respiratory derangements. In deriving pHcs~ from Nernst equation, we have ignored effects of change in flow or acid-base state on mean capillary pH, assuming arterial-mean capillary pH difference to be constant. A: E vs. pH,. Lines of iso-pHcsF have a slope of - 61.5 mV/pH,,. B: pHcs~ versus pH,. Lines of isopotential have a slope of 1. See text for interpretation.

tection of CSF pH observed during metabolic acid-base derangements than during those of respiratory origin has been noted by several investigators (7, 16) but has not been previously explained. With complete compensation, the difference in Ai?/ ApH, between metabolic and respiratory acid-base changes dictates that CSF pH will not return to its original value. For example, with renal compensation for a respiratory alkalosis (Fig. 3) the pH of CSF will return toward normal but even with complete compensation to pH, = 7.40, pHcsF would remain about .03 U more alkaline than

F.

HORNBEIN

AND

E.

G.

PAVLIN

normal. Qualitatively at least, these predictions are in agreement with the observations of Forster et al. (3) and Dempsey et al. (2). In a similar way, during respiratory acidosis systemic compensation should leave the CSF somewhat acid (pHcsF = 7.287, Fig. 3). This prediction also agrees with clinical reports of CSF pH in patients with chronic hypercapnia, although the hypoxemia seen in these patients might also contribute to the acidity of CSF (7) Although an acute metabolic acid-base change will be associated with a similar though lesser change in CSF pH, Fig. 3 shows that respiratory compensation, if complete, would be associated with a CSF pH on the opposite side of normal. For example, with a fully compensated metabolic acidosis we would predict a pHcsF of 7.353 (Fig. 3B). The observation that ventilatory compensation for a metabolic acid-base derangement never completely returns pH, to 7.40 has been ascribed to the fact that to do so would require a system with a gain, A’V’ApH, approaching infinity. From our observations an additional factor, namely the lesser change in E during respiratory compensation, would contribute to the failure of complete compensation. Even assuming that ventilatory compensation for a metabolic acidosis could restore the pH of CSF to 7.32 (distinctly an oversimplification), the associated arterial pH would be about 7.33 and not 7.40 (Fig. 3B). Similarly, a compensated metabolic alkalosis would yield a pH, of 7.48 when pHcsF had returned to normal. Assuming passive distribution, variations from these predicted values might result from absence of a steady state for ion distribution between brain extracellular fluid and blood or from alterations in the rate of production of metabolic H+ by brain tissue. The differences in pH+ and j&Co3between 6 h and control for all acid-base states studied are summarized in Table 2. In general, values returned to within 1 mV of control. Physiologically a difference of 1 mV would represent a pH difference of 0.016 or a [HC03-] difference of 0.5-1.2 meq/kg H20 (depending on plasma [HCO3-]) between CSF and blood. It is likely, though, that a portion of the remaining Ap for H+ or HCO, is not physiological but is a consequence of experimental imprecision (e.g., imperfect control of blood acid-base status, alterations in with variations in metabolism or brain Hf production temperature or anesthetic depth, precision of sampling and analytical procedures). In addition, one other factor will demand that either TABLE 2. Changes in 1-1for H+ and HCOS- (Ap> betzueen 6 h and control in normal dogs and during sustained acid-base derangements of metabolic or respiratory origin

tiH+, mv Cistern

L\c(HCO3-

Lumbar

Cistern

P n-iv

Lumbar I

Control Metabolic Metabolic Respiratory Respiratory Numbers

(10) acidosis (10) alkalosis (11) acidosis (12) alkalosis in parentheses

-0.2 0.0 +0.1 +0.7 -0.7 are

reference

+0.1

+0.5 +0.6 +1.3 +1.2

+o.s +0.7

+0.9 -0.4

+0.9

-0.4

-0.7 +1 .o

-0.6

-0.4

numbers.

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CSF-BLOOD

H+

AND

HC03--

WITH

RESPIRATORY

1153

ALKALOSIS

not return to control, namely differences in pH+ or pHCO3the relative permeabilities of the two ions across the bloodbrain barrier. If the permeabilities of these ions differed greatly (e.g., if one were totally impermeable), then the more permeable ion would distribute in response to electrochemical forces, returning close to its control value for JL The concentration of the impermeable ion in CSF would be secondarily determined by the concentration of the permeable ion and the PCO~ as defined quantitatively by the Henderson equation. As a consequence, the value of p for the less permeable ion will be in part a function of differences between CSF and mean-capillary Pcoz. Any changes in this gradient during the course of an experiment, due either to alterations in blood flow relative to metabolism or to displacement along the blood CO2 dissociation curve, will necessarily result in failure. of p for the less permeable ion to return to control, The actual values of p for H+ and HCO,for a given CSF-blood PCO~ difference will be determined by the ratio of permeabilities of the two ions. This relationship has been described quantitatively by Roos (14) in relation to the intracellular distribution of DMO. Examining the values of Ap for H+ and HCOz (Table Z), there is no obvious tendency toward better regulation of one ion than the other. In the control series, though, APE+ changes much less than &&~O~- in association with a rise in CSF-arteria1 Pco2 over the 6 h, implying a greater permeability for H+ than HC03, as suggested recently by Woodbury (18). Nevertheless, our data are unconvincing, perhaps because the permeabilities of the two ions are too similar but more likely because changes in CSF-blood Pco2 differences are too small for changes in Ap to be distinguished from the methodological noise level of the experiments. Although we have thus far chosen to interpret the values for &J summarized in Table 2 as supporting the hypothesis are passively distributed between that H+ and HC03 brain extracellular fluid and blood, the relative constancy in this series of studies lends itself to Of pH+ and PHCOsalternative explanations. If the surfeit of H+ and deficit of HCO, in CSF derives from brain tissue production of metabolic H+, the magnitudes of &+ and pnC03- would reflect the balance between rate of H+ production and permeability of the blood-brain barrier to these ions. Either metabolic H+

production and permeability must not have been significantly altered by the various acid-base derangements or any change in production must have been accompanied by a proportionate change in H+ or HC03 permeability. Whether permeability across the blood-brain barrier for these ions is variable and how such a mechanism might be linked to brain H+ production is not known. Indeed information concerning the permeabilities of H+ and HCOaB is notably sparse (18). Alternatively, H+ (or HC03) might be actively transported across the blood-brain barrier to explain the normal disequilibrium conditions. As with metabolic H+ production, either the rate of pumping and permeability must be fixed and unaltered by changes in systemic acidbase balance, or both must change proportionately to restore the original values for p. Although the biological pumps with which we are familiar are variable within the physiologic range, we cannot exclude either possibility from consideration. Nevertheless, a variable permeability linked to pump rate is distinctly less appealing than a constant pump with constant permeability. A pump with receptor sites possessing high affinity for one of the ions in question would operate in a saturated mode, i.e., at an essentially constant rate, throughout the range of physiologic pH. Why a pump would want to behave so unpurposefully is another question. In summary there is no evidence to exclude any of the four explanations from the realm of credibility. All we can say is that the observed constancy of &- and pnco3- after 6 h of stable acid-base derangements is compatible with a passive distribution for H+ and HCO,-. Intuitively, a a constant metabolic H+ production and constant permeabilities seem most appealing. Emotionally, our need for conceptual tidiness would wish it to be so. Physiologically, we do not know. We thank Ms. Patricia Reynolds and Mary Watson for patience and help. This work was supported by Public Health Service Grant GM 1599 l-05 from the National Institute of General Medical Sciences, National Institutes of Health. T. F. Hornbein is supported by Research Career Development Award Grant 5 K03 HE0961 7-09. Received

for

publication

3 June

1974.

REFERENCES 1. COHEN, P. J. The metabolic functions of oxygen and biochemical lesions of hypoxia. Anesthesiology 37 : 148-I 77, 1972. 2. DEMPSEY, J. A., N. 0. GLEDHILL, AND G. A. DE PICO. Independent effects of moderate hypoxemia on the regulation of CSF and blood H+ and ventilation in man. Federation Proc. 32 : 385, 1974. AND J. WILL. Effect of altitude 3. FORSTER, H., L. HAMILTON, sojourn on ventilation and cerebrospinal fluid and arterial acidbase status. Federation Proc. 32 : 387, 1974. 4. HELD, D., V. FENCL, AND J. R. PAPPENHEIMER. Electrical potential of cerebrospinal fluid. J. Neurophysiol. 27 : 942-959, 1964. 5. KAZEMI, H., D. C. SHANNON, AND E. CARVALLO-GIL. Brain CO2 buffering capacity in respiratoryacidosis and alkalosis. J. AppZ. Physiol. 22: 241-246, 1967. 6. KAZEMI, H., L. M. VALENCA, AND D. C. SHANNON. Brain and cerebrospinal fluid lactate concentration in respiratory acidosis and alkalosis. Resf. Physiol. 6 : 178-l 86, 1969.

7. LEUSEN, I. Regulation of cerebrospinal fluid composition with reference to breathing. Physiol. Rev. 52: l-56, 1972. 8. LEUSEN, I., AND G. DEMEESTER. Acid-base balance in cerebrospinal fluid during prolonged artificial hyperventilation. Arch. Intern. Physiol. Biochem. 72 : 72 1-724, 9. MINES, A. H., AND S. W. BLEDSOE.

normoxic distribution 1974.

acid-base between

change CSF

1964.

Effect of chronic hypoxic and on the D.C. voltage and HCOsand blood. Federation Proc. 33: 454,

10. PAVLIN, E. G., AND T. F. HORNBEIN. Distribution HCOsbetween CSF and blood during metabolic dogs. Am. J. Physiol. 228: 1134-l 140, 1975. 11. PAVLIN, E. G., AND T. F. HORNBEIN. Distribution HCOsbetween CSF and blood during metabolic dogs. Am. J. Physiol. 228: 1141-l 144, 1975. 12. PAVLIN, E. G., AND T. F. HORNBEIN. Distribution

of H+ and acidosis in of H+ and alkalosis in of Hf

and

Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (137.154.019.149) on January 11, 2019.

1154 rHC03in dogs.

T.

between CSF and blood during respiratory acidosis J. Physiol. 228: 1145-1148, 1975. 13. PLUM, F., J. B. POSNER, AND W. W. SMITH. Effect of hyperbarichyperoxic hyperventilation on blood, brain, and CSF lactate. Am. J. Physiol. 2 15 : 1240-1244, 1968. 14. Roos, A. Intracellular pH and intracellular buffering power of the cat brain. Am. J. Physiol. 209: 1233-1246, 1965. 15. SEVERINGHAUS, J. W., R. A. MITCHELL, B. W. RICHARDSON, AND M. M. SINGER. Respiratory control at high altitude suggesting Am.

F.

HORNBEIN

AND

E.

G.

PAVLIN

active 1155-l

transport regulation of CSF pH. J. A@. Physiol. 18: 166, 1963. 16. SIESJ~, B. K. The regulation of cerebrospinal fluid. pH. Kidney Intern. 1: 360-374, 1972. 17. SIESJ~, B. K., AND A. KJ~~LLQUIST. A new theory for the regulation of the extracellular pH in the brain. &and. J. C&n. Lab. Invest. 24 : l-9, 1969. 18. WOODBURY, J. W. Alfred Benson Symp. Ion Homeostasis of the Brain, 3rd, Copenhagen, 1971, p. 275-289.

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Distribution of H+ and HCO3 minus between CSF and blood during respiratory alkalosis in dogs.

AMERICAN JOURNAL OF Vol. 228, No. 4, April PHYSIOLOGY 1975. Printed in U.S.A. Distribution blood of H+ and HCO,- during respiratory T. F. H...
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