Ionic mechanisms of cerebrospinal fluid acid-base regulation

This review emphasizes the importance of strong ions in the regulation of cerebrospinal fluid (CSF) acid-base balance. In a solution like CSF that is devoid of nonbicarbonate buffers. [H+] and [HCO-3] are dependent variables, the independent variables being the CO2 partial pressure (PCO2) and the strong ion difference. Any measureable changes in CSF [HCO-3] and any change in [H+] that occur independent of changes in PCO2 must be accompanied by, if not caused by, changes in strong ions. The role of H+ and HCO-3 vs. strong ions in the ionic mechanisms of CSF acid-base regulation is unknown. For example, these mechanisms could depend only on changes in strong ions that accompany acid-base disorders, or they could be triggered by changes in [H+] or PCO2. These ideas are presented within the context of current concepts concerning the relationship of CSF to brain interstitial fluid (ISF) and the importance of choroid plexus and blood-brain barrier mechanisms in determining CSF and ISF ionic composition. Studies concerning CSF strong ions in normal and abnormal acid-base states are reviewed.     

Hypoxemia lowers cerebrovascular resistance without changing brain and blood [H+]

We designed the present study to see whether, during acute moderate isocapnic hypoxemia, changes in cerebral vascular resistance (CVR) and brain extracellular fluid (ECF) [H+] can or cannot be dissociated from each other. In seven anesthetized and paralyzed dogs we measured brain ECF pH with surface electrodes (n = 4) or double-barreled microelectrodes (n = 3) with tip diameters of less than 30 micron inserted 5 mm below the surface. Cerebral blood flow (CBF) was measured by radioactive microspheres during normoxemia and moderate hypoxemia, whereas brain ECF pH was measured continuously. In six of the seven dogs brain pH did not change during moderate hypoxemia of 4-20 min duration. In these six animals the mean arterial O2 partial pressure decreased from 84.8 +/- 12.9 (SD) to 46.7 +/- 10.2 Torr during hypoxic gas breathing, resulting in a significant drop in CVR from 3.88 +/- 1.88 to 3.27 +/- 1.97 Torr X ml-1 X min X 100 g and a rise in CBF from 31.7 +/- 12.7 to 47.8 +/- 31.5 ml X min-1 X 100 g-1. The mean brain ECF [H+] was 57.4 +/- 8.2 nmol/l (pH = 7.24) during normoxemia and did not change significantly during hypoxic gas breathing [56.6 +/- 7.7 nmol/l (pH = 7.25)]. Furthermore, arterial and sagittal venous blood and cisternal cerebrospinal fluid (CSF) pH did not change significantly during hypoxic gas breathing. We conclude that during acute moderate hypoxemia reduction in CVR can occur independently from increases in brain ECF, cisternal CSF, and arterial and sagittal venous blood [H+] and PCO2.     

大耳白兔动脉血和脑脊液酸碱电解质值及其相互关系

３０只正常大耳白兔,经股动脉穿刺插管和枕骨下经皮穿刺入枕骨下池,在严格隔绝空气情况下,分别取得动脉血和脑脊液（ＣＳＦ）标本,用ＡＢＬ３型血气分析仪及ＣＮ６４４型生化分析仪检测主要酸碱变量及电解质值。经统计学处理结果表明：ＣＳＦｐＨｅｙ ｋ＾＋、Ｃａ＾２＋、Ｍｇ＾２＋浓度〈动脉血,ＣＳＦＰＣＯ２及ＨＣＯ３＾－、Ｃｌ＾－Ｎａ＾＿、Ｈ＾＋〉动脉血。另外,ＣＳＦＰＨ与ｐＨａ,ＣＳＦＰＣＯ２与ＰａＣＯ２、Ｃ     

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.     

Alkaline shift in lumbar and intracranial CSF in man after 5 days at high altitude.

In six healthy male volunteers at sea level (PB 747-759 Torr), we measured pH and PCO2 in cerebrospinal fluid (CSF), and in arterial and jugular bulb blood; from these data we estimated PCO2 (12) and pH for the intracranial portion of CSF. The measurements were repeated after 5 days in a hypobaric chamber (PB 447 Torr). Both lumbar and intracranial CSF were significantly more alkaline at simulated altitude than at sea level. Decrease in [HCO3-] IN lumbar CSF at altitude was similar to that in blood plasma. Both at sea level and at high altitude, PCO2 measured in the lumbar CSF was higher than that estimated for the intracranial CSF. At altitude, hyperoxia, in comparison with breathing room air, resulted in an increase in intracranial PCO2, and a decrease in the estimated pH in intracranial CSF. With hyperoxia at altitude, alveolar ventilation was significantly higher than during sea-level hyperoxia or normoxia, confirming that a degree of acclimatization had occurred. Changes in cerebral arteriovenous differences in CO2, measured in three subjects, suggest that cerebral blood flow may have been elevated after 5 days at altitude.     

Effects of acetazolamide on cerebral acid-base balance

Acetazolamide (AZ) inhibition of brain and blood carbonic anhydrase increases cerebral blood flow by acidifying cerebral extracellular fluid (ECF). This ECF acidosis was studied to determine whether it results from high PCO2, carbonic acidosis (accumulation of H2CO3), or lactic acidosis. Twenty rabbits were anesthetized with pentobarbital sodium, paralyzed, and mechanically ventilated with 100% O2. The cerebral cortex was exposed and fitted with thermostatted flat-surfaced pH and PCO2 electrodes. Control values (n = 14) for cortex ECF were pH 7.10 +/- 0.11 (SD), PCO2 42.2 +/- 4.1 Torr, PO2 107 +/- 17 Torr, HCO3- 13.8 +/- 3.0 mM. Control values (n = 14) for arterial blood were arterial pH (pHa) 7.46 +/- 0.03 (SD), arterial PCO2 (PaCO2) 32.0 +/- 4.1 Torr, arterial PO2 (PaO2) 425 +/- 6 Torr, HCO3- 21.0 +/- 2.0 mM. After intravenous infusion of AZ (25 mg/kg), end-tidal PCO2 and brain ECF pH immediately fell and cortex PCO2 rose. Ventilation was increased in nine rabbits to bring ECF PCO2 back to control. The changes in ECF PCO2 then were as follows: pHa + 0.04 +/- 0.09, PaCO2 -8.0 +/- 5.9 Torr, HCO3(-)-2.7 +/- 2.3 mM, PaO2 +49 +/- 62 Torr, and changes in cortex ECF were as follows: pH -0.08 +/- 0.04, PCO2 -0.2 +/- 1.6 Torr, HCO3(-)-1.7 +/- 1.3 mM, PO2 +9 +/- 4 Torr. Thus excess acidity remained in ECF after ECF PCO2 was returned to control values. The response of intracellular pH, high-energy phosphate compounds, and lactic acid to AZ administration was followed in vivo in five other rabbits with 31P and 1H nuclear magnetic resonance spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of SITS, an anion transport blocker, on CSF ionic composition in metabolic alkalosis

Disulfonic stilbenes combine with the carrier protein involved in anion transport and inhibit the exchange of Cl- for HCO3- in a variety of biomembranes. Our aim was to determine whether such a mechanism is operative in the regulation of cerebrospinal fluid (CSF) [HCO3-] in metabolic alkalosis. In anesthetized, curarized, and artificially ventilated dogs either mock CSF (group I, 9 dogs) or mock CSF containing SITS, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (group II, 7 dogs) was periodically injected into both lateral cerebral ventricles. During 6 h of isocapnic metabolic alkalosis, produced by intravenous infusion of Na2CO3 solution, plasma [HCO3-] was increased by approximately 14 meq/l in both groups. In SITS-treated animals the mean cisternal CSF [HCO3-] increased by 7.7 meq/l after 6 h, and this was significantly higher than the respective increment, 3.5 meq/l, noted in the control group. Increments in CSF [HCO3-] in both groups were reciprocated by decrements in CSF [Cl-] with CSF [Na+] remaining unchanged. Cisternal CSF PCO2 and lactate concentrations showed similar increments in both groups. It is hypothesized that in metabolic alkalosis a carrier transports HCO3- out of cerebral fluid in exchange for Cl- and that SITS inhibits this mechanism. The efflux of HCO3- out of CSF in metabolic alkalosis would minimize the rise in CSF [HCO3-] brought about by HCO3-] influx from blood into CSF and therefore contributes to the CSF [H+] homeostasis.     

Ventral medullary extracellular fluid pH and PCO2 during hypoxemia

We designed experiments to study changes in ventral medullary extracellular fluid (ECF) PCO2 and pH during hypoxemia. Measurements were made in chloralose-urethan-anesthetized spontaneously breathing cats (n = 12) with peripherial chemodenervation. Steady-state measurements were made during normoxemia [arterial PO2 (PaO2) = 106 Torr], hypoxemia (PaO2 = 46 Torr), and recovery (PaO2 = 105 Torr), with relatively constant arterial PCO2 (approximately 44 Torr). Mean values of ventilation were 945, 683, and 1,037 ml/min during normoxemia, hypoxemia, and recovery from hypoxemia, respectively. Ventilatory depression occurred in each cat during hypoxemia. Mean values of medullary ECF PCO2 were 57.7 +/- 7.2 (SD), 59.4 +/- 9.7, and 57.4 +/- 7.2 Torr during normoxemia, hypoxemia, and recovery to normoxemia, respectively; respective values for ECF [H+] were 60.9 +/- 8.0, 64.4 +/- 11.6, and 62.9 +/- 9.2 neq/l. Mean values of calculated ECF [HCO3-] were 22.8 +/- 3.0, 21.7 +/- 3.3, and 21.4 +/- 3.1 meq/l during normoxemia, hypoxemia, and recovery, respectively. Changes in medullary ECF PCO2 and [H+] were not statistically significant. Therefore hypoxemia caused ventilatory depression independent of changes in ECF acid-base variables. Furthermore, on return to normoxemia, ventilation rose considerably, still independent of changes in ECF PCO2, [H+], and [HCO3-].     

Oxygen uptake, acid-base status, and performance with varied inspired oxygen fractions

Six subjects rode a bicycle ergometer on three occasions breathing 17, 21, or 60% oxygen. In addition to rest and recovery periods, each subject worked for 10 min at 55% of maximal oxygen uptake (VO2 max) and then to exhaustion at approximately 90% VO2 max. Performance time, inspired and expired gas fractions, ventilation, and arterialized venous oxygen tension (PO2), carbon dioxide tension (PCO2), lactate, and pH were measured. VO2, carbon dioxide output, [H+]a, and [HCO3-]a were calculated. Performance times were longer in hyperoxia than in normoxia or hypoxia. However, VO2 was not different at exhaustion in normoxia compared with hypoxia or hyperoxia. During exercise, hypoxia was associated with increased lactate levels and decreased [H+]a, PCO2, and [HCO3-]a. The opposite trends were generally associated with hyperoxia. At exhaustion, [H+]a was not different under any inspired oxygen fraction. These results support the contention that oxygen is not limiting for exercise of this intensity and duration. The results also suggest that [H+] is a possible limiting factor and that the effect of oxygen on performance is perhaps related to control of [H+].     

Acid-base changes in the running greyhound: contributing variables.

To determine the factors responsible for changes in [H+] during and after sprint exercise in the racing greyhound, Stewart's quantitative acid-base analysis was applied to arterial blood plasma samples taken at rest, at 8-s intervals during exercise, and at various intervals up to 30 min after a 402-m spring (approximately 30 s) on the track. [Na+], [K+], [Cl-], [total Ca], [lactate], [albumin], [Pi], PCO2, and pH were measured, and the [H+] was calculated from Stewart's equations. This short sprint caused all measured variables to change significantly. Maximal changes were strong ion difference decreased from 36.7 meq/l at rest to 16.1 meq/l; [albumin] increased from 3.1 g/dl at rest to 3.7 g/dl; PCO2, after decreasing from 39.6 Torr at rest to 27.9 Torr immediately prerace, increased during exercise to 42.8 Torr and then again decreased to near 20 Torr during most of recovery; and [H+] rose from 36.6 neq/l at rest to a peak of 76.6 neq/l. The [H+] calculated using Stewart's analysis was not significantly different from that directly measured. In addition to the increase in lactate and the change in PCO2, changes in [albumin], [Na+], and [Cl-] also influenced [H+] during and after sprint exercise in the running greyhound.     

Roles of CO2, O2, and acid in arteriovenous [H+] difference during muscle contractions

To determine the origins of the arteriovenous [H+] difference of muscle during contractions, arterial and muscle venous blood sample pairs were taken before and after 0.5, 5.0, and 30.0 min of 4/s isometric twitches of the gastrocnemius-plantaris muscle group of anesthetized dogs. These samples were analyzed for PO2, PCO2, and pH, the concentrations of O2, CO2, K+, Na+, La-, and Cl- in whole blood, and La-, K+, Na+, and Cl- in plasma. Whole blood was hemolyzed and analyzed for PO2, PCO2, and pH. Net O2 uptake, CO2 output, L, K+, Na+, and Cl- were calculated in addition to net output of non-CO2 acid (HA) and strong ion difference ([SID]) and common ion [SID] ([K+] + [Na+] - [Cl-] - [La-]). From these data we partitioned the origins of the arteriovenous [H+] difference via the common PCO2-pH diagram and via a [H+]-PCO2 diagram and determined whether true plasma arteriovenous [H+] differences reflect plasma and cell arteriovenous [H+] differences. The arteriovenous [H+] differences of plasma and hemolyzed blood were the same, showing that true plasma does reflect plasma and cells. K+ showed a small significant but transient output. Na+ was not significant, whereas Cl- showed a significant transient uptake. Lactate output and HA, calculated for dog blood acid-base, showed transient outputs and were the same. At 5.0 min when the arteriovenous difference was largest, CO2 alone would have increased [H+] 15.9 nmol/l whereas desaturation of Hb would have decreased [H+] 4.2 nmol/l and lactate could have raised [H+] 1.0 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)     

Newborn puppy cerebral acid-base regulation in experimental asphyxia and recovery

We hypothesized that part of the newborn tolerance of asphyxia involves strong ion changes that minimize the cerebral acidosis and hasten its correction in recovery. After exposure of newborn puppies to 15 or 30 min experimental asphyxia (inhalation of gas with fractional concentration of CO2 and of O2 in inspired gas = 0.07-0.08 and 0.02-0.03, respectively), blood lactate increased to 13.2 and 23.4 mmol/l, respectively, brain tissue lactate increased to 14.4 and 19.7 mmol/kg, and cerebrospinal fluid (CSF) lactate increased to 7.6 and 14.4 mmol/l. We presume that the tissue lactate increase reflects increases in brain cell and extracellular fluid lactate concentration. The lactate increase, a change that will decrease the strong ion difference (SID), [HCO3-], and pH, was accompanied by increases in Na+ (plasma, CSF, brain), K+ (plasma, CSF), and osmolality without change in Cl-. After 60-min recovery, plasma and brain lactate decreased significantly, but CSF lactate remained unchanged. [H+] recovery was more complete than that of the strong ions due to hyperventilation-induced hypocapnia. We conclude that during asphyxia-induced lactic acidosis, changes in strong ions occur that lessen the decrease in SID and minimize the acidosis in plasma and CSF. To the extent that the increase in brain tissue sodium reflects increases in intra-and extracellular fluid sodium concentration, the decrease in SID will be less in these compartments as well. In recovery, CSF ionic values change little; plasma and brain tissue lactate decrease with a similar time course, and the [H+] is rapidly returned toward normal by hypocapnia even while the SID is below normal.     

Cerebrospinal fluid acid-base balance during muscular exercise

Ventilation, metabolism, arterial blood gases, and blood and cerebrospinal fluid (CSF) acid-base status were measured in exercise studies on seven ponies during mild, moderate, and near-maximal treadmill exercise. CSF and arterial blood were sampled via indwelling catheters. Generally measurements were made during the 3rd, 6th, and 9th minute of steady-state exercise, with CSF sampled only during the 9th minute. Alveolar ventilation (VA) and metabolic rate (VO2) increased proportionately during exercise below the anaerobic threshold, but above this threshold, VA increased at a faster rate than VO2. The similarity of these response to those observed in man suggests the pony is a suitable animal model for study of exercise hyperpnea. No change in CSF acid-base balance occurred with light-to-moderate work; however, with near-maximal work a fall in CSF carbon dioxide partial pressure due to hyperventilation caused CSF to become alkaline (pH = 7.380) relative to rest (pH = 7.330). CSF lactate increased slightly with exercise but had no effect on CSF [HCO3-], which remained constant from rest to severe exercise. We conclude that it is unlikely the hyperpnea at any intensity of exercise results from an increased H+ stimulation at the medullary chemoreceptor.     

Control of active proton transport in turtle urinary bladder by cell pH

The rate of active H+ secretion (JH) across the luminal cell membrane of the turtle bladder decreases linearly with the chemical (delta pH) or electrical potential gradient (delta psi) against which secretion occurs. To examine the control of JH from the cell side of the pump, acid-base changes were imposed on the cellular compartment by increasing serosal[HCO3-] at constant PCO2 or by varying PCO2 at constant [HCO3-]. When serosal [HCO3-] was increased from 0 to 60 mM, cell [H+] decreased, as estimated by the 5,5-dimethyloxazoladine-2,4- dione method. JH was a saturable function of cell [H+], with an apparent Km of 25 nM. When PCO2 was varied between 1 and 20% at various serosal Km of 25 nM. When PCO2 was varied between 1 and 20% at various serosal [HCO3-], the PCO2 required to reach a maximal JH increased with [HCO3-] so that JH was a function of cell [H+] rather than of cell [HCO3-] or CO2. The proton pump was controlled asymmetrically with respect to the pH component of the electrochemical potential for protons, microH. On the cell side of the pump, a delta pH of < 1 U was required to vary JH between maximal and zero values, whereas on the luminal side a delta pH of 3 U was required. Cell [H+] regulates JH by determining the availability of H+ to the pump in a relationship resembling Michaelis-Menten kinetics. Increasing luminal [H+] generates an energy barrier at a luminal pH near 4.4 that equals the free energy (per H+ translocated) of the metabolic driving reaction.     

Cerebrospinal fluid ions in metabolic acidosis in dogs: effects of acetazolamide

We hypothesized that, during isosmotic isonatremic HCl acidosis with maintained isocapnia in cisternal cerebrospinal fluid (CSF), acetazolamide, by inhibiting carbonic anhydrase (CA) in the central nervous system (CNS), should produce an isonatric hyperchloric metabolic acidosis in CSF. Blood and CSF ions and acid-base variables were measured in two groups of anesthetized and paralyzed dogs with bilateral ligation of renal pedicles during 5 h of HCl acidosis (plasma [HCO3-] = 11 meq/l). Mechanical ventilation was regulated such that arterial PCO2 dropped and CSF Pco2 remained relatively constant. In group I (control group, n = 6), CSF [Na+] remained unchanged, [HCO3-] and strong ions difference (SID) fell, respectively, 6.1 and 5 meq/l, and [Cl-] rose 3.5 meq/l after 5 h of acidosis. In acetazolamide-treated animals, (group II, n = 7), CSF [Na+] remained unchanged, [HCO3-], and SID fell 11 and 7.1 meq/l, respectively, and [Cl-] rose 7.1 meq/l. We conclude that during HCl acidosis inhibition of CNS CA by acetazolamide induces an isonatric hyperchloric metabolic acidosis in CSF, which is more severe than that observed in controls.     

Blood osmolality in vitro: dependence on PCO2, lactic acid concentration, and O2 saturation

Changes of osmolality (Osm) were measured by freezing-point determination in true plasma of 10 healthy subjects. This was done after equilibration with CO2 (0.5-10.0%), after the addition of lactic acid (10 and 20 mmol/l), and after deoxygenation. The graph for the dependence of Osm on CO2 partial pressure (PCO2) in oxygenated blood resembles the classical CO2 absorption curve. The increase of Osm with PCO2 (approximately 0.2 mosmol . kg H2O-1 . Torr-1) is almost as great as the increase in dissolved CO2 plus bicarbonate (HCO-3). Addition of lactic acid shifts the curve upward by only 0.6 mosmol/mmol because of displacement of HCO-3. Deoxygenation has no significant effect at constant PCO2 despite an increase in [HCO-3]. This is probably due to the binding of 2,3-diphosphoglycerate to hemoglobin. It can be seen in the Osm-pH diagram that differences between CO2 and lactic acid titration largely disappear. For each lactic acid concentration there is a linear dependence corresponding to the linear [HCO-3]-pH relation in plasma. At constant pH, Osm increases after deoxygenation. The observed in vitro relation might explain part of the osmolality increase during physical exercise.     

Plasma [H+] regulation and whole blood [CO2] in exercising ponies

The major objective was to determine in ponies whether factors in addition to changes in blood PCO2 contribute to changes in plasma [H+] during submaximal exercise. Measurements were made to establish in vivo plasma [H+] at rest and during submaximal exercise, and CO2 titration of blood was completed for both in vitro and acute in vivo conditions. In 19 ponies arterial plasma [H+] was decreased from rest 4.5 neq/l (P less than 0.05) during the 7th min of treadmill running at 6 mph, 5% grade (P less than 0.5). A 5.6-Torr exercise hypocapnia accounted for approximately 2.9 neq/l of this reduced [H+]. The non-PCO2 component of this alkalosis was approximately neq/l, and it was due presumably to a 1.7-meq/l increase from rest in the plasma strong ion difference (SID). Despite the arterial hypocapnia, mixed venous PCO2 was 2.7 Torr above rest during steady-state exercise. Nevertheless, mixed venous plasma [H+] was 1.2 neq/l above rest during exercise, which was presumably due to the increase in SID. Also studied was the effect of submaximal exercise on whole blood CO2 content (CCO2). In vitro, at a given PCO2 there was minimal difference in CCO2 between rest and exercise blood, but plasma [HCO3-] was greater for exercise blood than for rest blood. In vivo, during steady-state exercise, arterial plasma blood. In vivo, during steady-state exercise, arterial plasma [HCO3-] was unchanged or slightly elevated from rest, but CaCO2 was 4 vol% below rest.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo regulation of plasma [H+] in ponies during acute changes in PCO2

The major objective of this study was to test the hypothesis that in ponies the change in plasma [H+] resulting from a change in PCO2 (delta H+/delta PCO2) is less under acute in vivo conditions than under in vitro conditions. Elevation of inspired CO2 and lowering of inspired O2 (causing hyperventilation) were used to respectively increase and decrease arterial PCO2 (Paco2) by 5-8 Torr from normal. Arterial and mixed venous blood were simultaneously sampled in 12 ponies during eucapnia and 5-60 min after Paco2 had changed. In vitro data were obtained by equilibrating blood in a tonometer at five different levels of PCO2. The in vitro slopes of the H+ vs. PCO2 relationships were 0.73 +/- 0.01 and 0.69 +/- 0.01 neq.1-1.Torr-1 for oxygenated and partially deoxygenated blood, respectively. These slopes were greater (P less than 0.001) than the in vivo H+ vs. PCO2 slopes of 0.61 +/- 0.03 and 0.57 +/- 0.03 for arterial and mixed venous blood, respectively. The delta HCO3-/delta pH (Slykes) was 15.4 +/- 1.1 and 17.0 +/- 1.1 for in vitro oxygenated and partially deoxygenated blood, respectively. These values were lower (P less than 0.001) than the in vivo values of 23.3 +/- 2.7 and 25.2 +/- 4.7 Slykes for arterial and mixed venous blood, respectively. In vitro, plasma strong ion difference (SID) increased 4.5 +/- 0.2 meq/l (P less than 0.001) when Pco2 was increased from 25 to 55 Torr. A 3.5-meq/l decrease in [Cl-] (P less than 0.001) and a 1.3 +/- 0.1 meq/l increase in [Na+] (P less than 0.001) accounted for the SID change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypobaric hypoxia (380 Torr) decreases intracellular and total body water in goats

The effects of prolonged hypoxia on body water distribution was studied in four unanesthetized adult goats (Capra lircus) at sea level and after 16 days in a hypobaric chamber [(380 Torr, 5,500 m, 24 +/- 1 degrees C); arterial PO2 = 27 +/- 2 (SE) Torr]. Total body water (TBW), extracellular fluid volume (ECF), and plasma volume (PV) were determined with 3H2O, [14C]inulin, and indocyanine green dye, respectively. Blood volume (BV) [BV = 100PV/(100 - hematocrit)], erythrocyte volume (RCV) (RCV = BV - PV), and intracellular fluid (ICF) (ICF = TBW - ECF) and interstitial fluid (ISF) (ISF = ECF - PV) volumes were calculated. Hypoxia resulted in increased pulmonary ventilation and arterial pH and decreased arterial PCO2 and PO2 (P less than 0.05). In addition, body mass (-7.1%), TBW (-9.1%), and ICF volume (-14.4%) all decreased, whereas ECF (+11.7%) and ISF (+27.7%) volumes increased (P less than 0.05). The decrease in TBW accounted for 89% of the loss of body mass. Although PV decreased significantly (-15.3%), BV was unchanged because of an offsetting increase in RCV (+39.5%; P less than 0.05). We conclude that, in adult goats, prolonged hypobaric hypoxia results in decreases in TBW volume, ICF volume, and PV, with concomitant increases in ECF and ISF volumes.     

Effect of plasma [K+] on the DC potential and on ion distributions between CSF and blood.

Keeping the arterial pH at 7.4 and PaCO2 at 40 mmHg in eight anesthetized dogs, we acutely raised plasma potassium concentration from 3.4 to 8.2 meq/1, then allowed it to decay back to control levels. The cerebrospinal fluid (CSF)-blood electrical potential difference (pd) increased 13.2 mV per 10-fold increase in plasma [K+]. Again keeping arterial pH at 7.4 and PaCO2 at 40 mmHg, we elevated plasma [K+] in four dogs from 3.3 to 8.0 meq/1 and maintained this level for 6 h. We found 1) that the PD increased from a control value of +1.3 to +8.9mV, showing no tendency to decay over the 6 h; and 2) that the change in PD did not affect the distribution of Na+, K+, H+, Cl-, or HCO3- between blood and CSF over the 6 h. These results suggest that under these conditions the PD between CSF and blood may play no effective role in determining the distributions of these charged species by 6 h. These results are contrasted with recent findings which suggest that H+ and HCO3- are distributed according to passive forces between CSF and blood.