Extrapulmonary gas exchange enhances brain oxygen in pigeons.

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

Alterations in cerebrospinal fluid PO(2), PCO(2), and pH measurements during and after experimental thoracic aortic cross-clamping.

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

Physiological mechanisms of hyperventilation during human pregnancy.

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

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.

Intraoperative Changes in Cerebrospinal Fluid Gas Tensions Reflect Paraplegia During Thoracoabdominal Aortic Surgery: A Proof-of-Principle Study.

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

Central nervous system effects of lactate infusion in primates.

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

Brain acidosis in experimental pneumococcal meningitis.

Purulent meningitis is a serious disease that often has a lethal outcome or gives lasting complications due to brain damage. The processes causing brain dysfunction or damage are still not uncovered nor are the reasons for the characteristic increase of CSF lactate, or the decrease of glucose levels and of pH. We studied rabbits with experimentally induced purulent meningitis (Streptococcus pneumoniae). Ten hours after the inoculation into cisterna magna the rabbits developed symptoms of meningitis, with stiffness of the neck, tachypnea, and fever. The CSF level of lactate and the number of leukocytes were significantly increased and the glucose level was decreased. Brain interstitial pH, as measured by ion selective microelectrodes, was significantly decreased from the normal level of 7.4 to 6.9. The levels of energy metabolites in brain cortex, including glucose, were not different between controls and infected animals, and the lactate level was not elevated more than could have been explained by passive diffusion from the CSF. This shows that the brain tissue is not the source of CSF lactate nor the sink for glucose in CSF. The marked acidification of brain interstitial space and CSF demonstrates that purulent meningitis causes a significant disturbance of brain ion homeostasis that could be, at least in part, responsible for the brain dysfunction. We suggest that activated leukocytes consume CSF glucose and produce lactic acid and secrete protons, which causes the CSF and interstitial acidosis.

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.

Monitoring of intrathecal oxygen tension during experimental aortic occlusion predicts ultrastructural changes in the spinal cord.

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

The continuous measurement of cerebrospinal fluid gas tensions in critically ill neurosurgical patients: a prospective observational study.

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

Identification of a subsurface area in the ventral medulla sensitive to local changes in PCO2.

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

Vagal input enhances responsiveness of respiratory discharge to central changes in pH/CO2 in bullfrogs.

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

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)

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.

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.