Hypercapnia and response of cerebral blood flow to hypoxia in newborn lambs

Individual effects of hypoxic hypoxia and hypercapnia on the cerebral circulation are well described, but data on their combined effects are conflicting. We measured the effect of hypoxic hypoxia on cerebral blood flow (CBF) and cerebral O2 consumption during normocapnia (arterial PCO2 = 33 +/- 2 Torr) and during hypercapnia (60 +/- 2 Torr) in seven pentobarbital-anesthetized lambs. Analysis of variance showed that neither the magnitude of the hypoxic CBF response nor cerebral O2 consumption was significantly related to the level of arterial PCO2. To determine whether hypoxic cerebral vasodilation during hypercapnia was restricted by reflex sympathetic stimulation we studied an additional six hypercapnic anesthetized lambs before and after bilateral removal of the superior cervical ganglion. Sympathectomy had no effect on base-line CBF during hypercapnia or on the CBF response to hypoxic hypoxia. We conclude that the effects of hypoxic hypoxia on CBF and cerebral O2 consumption are not significantly altered by moderate hypercapnia in the anesthetized lamb. Furthermore, we found no evidence that hypercapnia results in a reflex increase in sympathetic tone that interferes with the ability of cerebral vessels to dilate during hypoxic hypoxia.     

Hypercapnic hypoxia compromises bactericidal activity of fish anterior kidney cells against opportunistic environmental pathogens

Acute hypoxia can cause massive fish and shellfish mortality. Less clear is the role that chronic sublethal hypoxia might play in aquatic animal health. This study tested whether production of reactive oxygen species (ROS) and bactericidal activity of fish phagocytic cells are suppressed under the conditions of decreased oxygen and pH and increased carbon dioxide which occur in the blood and tissue of animals exposed to sublethal hypoxia. Anterior head kidney (AHK) cells of the mummichog, Fundulus heteroclitus, were exposed in parallel to normoxic (pO2=45 torr, pCO2=3.8 torr, pH=7.6) or hypoxic (pO2=15 torr, pCO2=8.0 torr, pH=7.0) conditions and stimulated with a yeast cell wall extract, zymosan. or live Vibrio parahaemolyticus. Hypercapnic hypoxia suppressed zymosan-stimulated ROS production by 76.0% as measured in the chemiluminescence assay and by 58.5% in the nitroblue tetrazolium (NBT) assay. The low O2, high CO2 and low pH conditions also suppressed superoxide production by 75.0 and 47.3% as measured by the NBT assay at two different challenge ratios of cells:bacteria (1:1 and 1:10, respectively). In addition to its effects on ROS production, hypercapnic hypoxia also reduced bactericidal activity by 23.6 and 72.5% at the 1:1 and 1:10 challenge ratios, respectively. Low oxygen levels alone (pO2=15 torr, pCO2=0.76 torr, pH=7.6) did not significantly compromise the killing activity of cells challenged with equal numbers of V. parahaemolyticus. At the higher 1:10 AHK:bacteria challenge ratio, low oxygen caused a small (26.3%) but significant suppression of bactericidal activity as compared to aerial conditions (pO2=155 torr, pCO2=0.76 torr, pH=7.6). This study demonstrates that while hypoxia alone has detrimental effects on immune function, suppression of phagocytic cell activity is compounded by naturally occurring conditions of hypercapnia and low pH, creating conditions that might be exploited by opportunistic pathogens. These results indicate that the adverse health effects of chronic hypercapnic hypoxia might greatly exceed the effects of low oxygen alone.     

Changes of P50 in hypoxaemia, hypercapnia and polycythaemia: multivariate analysis

Multivariate analysis of P50 changes in hypoxia, hypercapnia and polycythaemia was performed in an heterogeneous group of forty three patients: hypoxic subjects with or without hypercapnia, with or without polycythaemia and polycythaemic subjects without hypoxia. A statistical analysis was undertaken using comparison of the means, study of the correlations, principal component analysis, multiple regression and correspondence analysis. In the patients studied, P50 changes were not wholly explained by those of 2-3 DPG and pH; PaCO2, per se, did not play an important part. Haemoglobin concentration and P50 value would represent an adaptative mechanism to hypoxia: when hypoxia is moderate (80 greater than PaO2 greater than or equal to 65 torr) and isolated, oxygen haemoglobin affinity decreases (P50 increases); when hypoxia is severe (PaO2 less than 65 torr) and combined with hypercapnia and disturbed acid-base equilibrium, P50 comes back to normal range but haemoglobin increases, restoring thus, the normal blood oxygen content.     

The effects of acute hypoxia and hypercapnia on oxygen consumption of the freshwater European eel

When exposed to hypoxia, eels Anguilla anguilla were able to regulate and maintain Vo₂ down to a water oxygen tension ( Pwo₂ ) of about 25 mmHg, a value far below those reported in other studies. When exposed to hypercapnia, eels showed a depression in Vo₂ as water carbon dioxide tension ( Pwco₂ ) increased. Faced with combined hypoxia-hypercapnia, eels showed an increase in their sensitivity to hypoxia, and the critical oxygen tension increased to 40–45 mmHg. The possible mechanisms underlying these responses were discussed, and the implications of such findings for extensive culture of eels were highlighted.     

Naloxone accelerates the rate of ventilatory acclimatization to hypoxia in awake rats

During ventilatory acclimatization to hypoxia in rats, PaCO2 progressively falls from about 40 torr in normoxia (PIO2 approximately equal to 150 torr) to a new steady-state at about 23 torr in chronic hypoxia (24 or more hours at PIO2 approximately equal to 90 torr). In acute (20 or 60 minutes) hypoxia naloxone treatment caused a hyperventilation greater than that caused by acute hypoxia alone. Following 20 minutes hypoxia, naloxone treated rats had a PaCO2 = 28.6 +/- 0.7 torr (mean +/- 95% confidence limits) which was significantly lower (P less than .001) than the saline treated PaCO2 = 31.0 +/- 0.6 torr. In contrast, in normoxia and at 24 hour hypoxia and at 20 minute return to normoxia following 24 hours hypoxia, naloxone treatment had no effect on PaCO2. We conclude that in the rat about one third of the ventilatory acclimatization to hypoxia is due to a progressively decreasing endogenous opioid-like inhibition of ventilation.     

Effects of hypercapnia and hypoxia on abdominal expiratory nerve activity

We examined the effects of progressive hypercapnia and hypoxia on the efferent neural activity in a whole abdominal expiratory nerve (medial branch of the cranial iliohypogastric nerve (L1) in anesthetized, paralyzed dogs. To eliminate effects of phasic lung and chest-wall movements on expiratory activity, studies were performed in the absence of breathing movements. Progressive hyperoxic hypercapnia and isocapnic hypoxia were produced in the paralyzed animals by allowing 3-5 min of apnea to follow mechanical ventilation with 100% O2 or 35% O2 in N2, respectively; during hypoxia, isocapnia was maintained by intravenous infusion of tris(hydroxymethyl)aminomethane buffer at a predetermined rate. To quantify abdominal expiratory activity, mean abdominal nerve activity in a nerve burst was computed by integrating the abdominal neurogram and dividing by the duration of the nerve burst. Hypercapnia and hypoxia both increased mean abdominal nerve activity and decreased expiratory duration. In contrast to the ramplike phrenic neurogram, the abdominal neurogram consisted of three phases: an initial rising phase, a plateau phase in which abdominal nerve activity was approximately constant, and a terminal declining phase in which the activity returned to the base-line level. The height of this plateau phase and the rates of rise and decline of abdominal nerve activity all increased with increasing hypercapnia and hypoxia. We conclude that, with proprioceptive inputs constant, both hypercapnia and hypoxia are excitatory to abdominal expiratory neural activity.     

衰老大鼠脑血管反应性研究

实验在麻醉及人工呼吸的7只衰老与7只成年SD大鼠上进行。观察脑血管对高、低血碳酸和高、低血氧的脑血液反应,探索衰老动物脑血流反应最为敏感的因素。结果表明,衰老动物对高血碳酸的反应最为敏感,对其余化学因素的反应均不明显。由此提示,对高血碳酸的脑血流反应的测定似可作为诊断衰老脑血管机能状态的一项有参考价值的生理学方法。     

Are the carotid bodies of the guinea-pig functional?

We have previously observed that the guinea-pig appears to have a relatively poor ventilatory (V (E)) response to hypoxia, compared to other mammals. Therefore, in this study, we questioned the ability of the carotid bodies (primary peripheral chemoreceptors) in the guinea-pig to detect hypoxia. The ventilatory responses to poikilocapnic hypoxia (8% O(2)), poikilooxic hypercapnia (8% CO(2)), hyperoxia (100% O(2)) and cyanide (NaCN - 200 mug/kg, i.v.) were assessed before and after carotid body denervation (CBD) in anaesthetized guinea-pigs. Although CBD attenuated the V (E) responses to hypercapnia and cyanide, it had no effect on normoxic breathing or the V (E) responses to hypoxia or hyperoxia. In a separate group of guinea-pigs, nerve activity was recorded from single or few-fibre preparations of the carotid sinus nerve (CSN). Basal chemoreceptor activity could not be detected from any of the nerve preparations. NaCN and hypercapnia consistently provoked an increase in neural activity. In contrast, hypoxia never clearly increased activity in any of the single or few-fibre preparations isolated from the CSN. In conclusion, although the carotid bodies of the guinea-pig, like those of other mammals, are able to detect hypercapnia and histotoxic hypoxia and elicit a reflex increase in V (E), they are essentially hypoxia-insensitive. The latter may explain, at least in part, the relatively poor V (E) response to hypoxia shown by the guinea-pig.     

Hypothermic effect on mice of a 1-10 kD fraction of the small intestine of the hibernating suslik Citellus undulatus during hypoxia and hypercapnia

Studies have been made on a possibility of inducing a prolonged hypothermia by injections to albino mice of a fraction with a molecular mass 1-10 KD isolated from the small intestine of hibernating ground squirrels. Specific conditions for the onset of hibernation (hypoxia, hypercapnia, temperature) were simulated. Exposure of mice to hypoxia and hypercapnia for 2 hours in combination with injection of the mentioned fraction extended hypothermic condition in animals up to 24-36 hours as compared to 2-3 hours after sole injection of the fraction. After the injection of 5-OT under the same conditions, the prolonged hypothermia was less stable.     

低氧适应对家兔脑血流调节的影响

本实验用电磁血流量法观察了低氧适应对家兔脑血流(CBF)调节的影响。结果表明,高CO_2和低O_2高CO_2时,适应组CBF改变不明显,对照组CBF明显增加(p<0.01)。两组脑脊液pH(pH_(CSF))均明显降低(p<0.05和p<0.01)。对照组低O_2高CO_2时的CBF比单独高CO_2增加更多。低CO_2、低O_2低CO_2及低O_2时,CBF和pH_(CSF)均接近于安静值。以低pH值脑脊液(CSF)脑内灌注,对照组CBF趋于增加,适应组不增加。将CO_2饱和的人工CSF用于局部脑表面,适应组脑膜微血管无明显扩张,对照组明显扩张(p<0.01)。该结果提示,低氧适应家兔脑血管和CBF对脑细胞外液H~ 和/或对低O_2的反应降低。     

Functional Body Capacities under the Conditions of Various Concentrations of Carbon Dioxide and Oxygen

We determined a permissible ratio between carbon dioxide and oxygen concentrations during accidental situations. The experiments (n = 138, 10 h each) on the effect of various concentrations of carbon dioxide and oxygen in the inhaled air were conducted on male volunteers aged 20–40 years subjected to a special medical examination. All experiments were divided into five series: hypercapnia + normoxia, hypercapnia + hyperoxia, hypercapnia + hypoxia, normocapnia + hypoxia, and ambient air (control). The results showed that functional capacities of the body are less impaired under the conditions of hypercapnia combined with hyperoxia. Thus, in accidental situations associated with rapid accumulation of carbon dioxide in the atmosphere of airtight chambers, a synchronous increase in pO₂ to 220–230 torr can provide for the highest work capacity.     

Ventilatory chemosensitivity of the 1-day-old chicken hatchling after embryonic hypoxia

We investigated the effects of sustained embryonic hypoxia on the neonatal ventilatory chemosensitivity. White Leghorn chicken eggs were incubated at 38 degrees C either in 21% O(2) throughout incubation (normoxia, Nx) or in 15% O(2) from embryonic day 5 (hypoxia, Hx), hatching time included. Hx embryos hatched approximately 11 h later than Nx, with similar body weights. Measurements of gaseous metabolism (oxygen consumption, Vo(2)) and pulmonary ventilation (Ve) were conducted either within the first 8 h (early) or later hours (late) of the first posthatching day. In resting conditions, Hx had similar Vo(2) and body temperature (Tb) and slightly higher Ve and ventilatory equivalent (Ve/Vo(2)) than Nx. Ventilatory chemosensitivity was evaluated from the degree of hyperpnea (increase in Ve) and of hyperventilation (increase in Ve/Vo(2)) during acute hypoxia (15 and 10% O(2), 20 min each) and acute hypercapnia (2 and 4% CO(2), 20 min each). The chemosensitivity differed between the early and late hours, and at either time the responses to hypoxia and hypercapnia were less in Hx than in Nx because of a lower increase in Ve and a lower hypoxic hypometabolism. In a second group of Nx and Hx hatchlings, the Ve response to 10% O(2) was tested in the same hatchlings at the early and late hours. The results confirmed the lower hypoxic chemosensitivity of Hx. We conclude that hypoxic incubation affected the development of respiratory control, resulting in a blunted ventilatory chemosensitivity.     

The role of prostacyclin in the hypercapnic and hypoxic cerebrovascular dilations

The cerebral blood flow (CBF H/A) and the production of a stable prostacyclin metabolite, 6-Keto PGF 1 alpha ( 6KPGF ) was studied in 5 baboons in control, hypercapnic and hypoxic conditions. In steady-state conditions CBF H/A was measured by the clearance of an intra-arterial bolus injection of 133xenon and arterial and cerebral venous blood was sampled for assay of 6KPGF by radioimmunoassay. Both hypercapnia and hypoxia significantly increased CBF H/A and both increments were abolished by indomethacin. However, only hypoxia showed an increased 6KPGF production. Thus, hypoxia, but not hypercapnia, appears to produce cerebral vasodilation by increasing prostacyclin production.     

Oxygen and carbon dioxide sensitivity of ventilation in amphibious crabs, Cardisoma guanhumi, breathing air and water

Amphibious crabs, Cardisoma guanhumi, were acclimated to breathing either air or water and exposed to altered levels of oxygen and/or carbon dioxide in the medium. Hypercapnia (22, 36 and 73 torr CO(2)) stimulated a significant hypercapnic ventilatory response (HCVR) in both groups of crabs, with a much greater effect on scaphognathite frequency (Deltaf(SC)=+700%) in air-breathing crabs than water-breathing crabs (Deltaf(SC)=+100%). In contrast, hyperoxia induced significant hypoventilation in both sets of crabs. However, simultaneous hyperoxia and hypercapnia triggered a greater than 10-fold increase in f(SC) in air-breathing crabs but no change in water-breathing crabs. For water-breathing crabs hypoxia simultaneous with hypercapnia triggered the same response as hypoxia alone-bradycardia (-50%), and a significant increase in f(SC) at moderate exposures but not at the more extreme levels. The response of air-breathing crabs to hypoxia concurrent with hypercapnia was proportionally closer to the response to hypercapnia alone than to hypoxia. Thus, C. guanhumi were more sensitive to ambient CO(2) than O(2) when breathing air, characteristic of fully terrestrial species, and more sensitive to ambient O(2) when breathing water, characteristic of fully aquatic species. C. guanhumi possesses both an O(2)- and a CO(2)-based ventilatory drive whether breathing air or water, but the relative importance switches when the respiratory medium is altered.     

High-Field MRI Reveals a Drastic Increase of Hypoxia-Induced Microhemorrhages upon Tissue Reoxygenation in the Mouse Brain with Strong Predominance in the Olfactory Bulb

Human pathophysiology of high altitude hypoxic brain injury is not well understood and research on the underlying mechanisms is hampered by the lack of well-characterized animal models. In this study, we explored the evolution of brain injury by magnetic resonance imaging (MRI) and histological methods in mice exposed to normobaric hypoxia at 8% oxygen for 48 hours followed by rapid reoxygenation and incubation for further 24 h under normoxic conditions. T2*-, diffusion-weighted and T2-relaxometry MRI was performed before exposure, immediately after 48 hours of hypoxia and 24 hours after reoxygenation. Cerebral microhemorrhages, previously described in humans suffering from severe high altitude cerebral edema, were also detected in mice upon hypoxia-reoxygenation with a strong region-specific clustering in the olfactory bulb, and to a lesser extent, in the basal ganglia and cerebral white matter. The number of microhemorrhages determined immediately after hypoxia was low, but strongly increased 24 hours upon onset of reoxygenation. Histologically verified microhemorrhages were exclusively located around cerebral microvessels with disrupted interendothelial tight junction protein ZO-1. In contrast, quantitative T2 and apparent-diffusion-coefficient values immediately after hypoxia and after 24 hours of reoxygenation did not show any region-specific alteration, consistent with subtle multifocal but not with regional or global brain edema.     

Hypoventilation after acute phrenicotomy of the urethane anaesthetized rats.

The aim of this study was to explore the mechanism resulting in hypoventilation in rats with denervated diaphragm. Bilateral cervical phrenicotomy (PX) was performed in 15 male rats anaesthetized with urethane (1.3 g/kg i.p.); other 8 rats were sham operated (SX). Ventilation, PaCO2 and the integrated EMG of the external intercostal muscles (iEMG) were measured before and after the surgery, at regular intervals, up to 4 hours postoperatively. During the 4 hours after PX there was a progressive decrease in minute ventilation and an increase in PaCO2 compared with the control values and with that in the SX rats. The increase in PaCO2 was accompanied by an increase in the peak amplitude of the iEMG to 155 +/- 18% of control values after PX and to 228 +/- 33% 4 hours later. Despite the augmented EMG activity tidal volume gradually decreased. The iEMG of the intercostal muscles, however, did not reach a maximum because the shortlasting stimulation of breathing by acute hypercapnia and hypoxia as the result of added dead space (0.5 ml) increased the iEMG still further. These results indicate that both the central and peripheral mechanisms contribute to hypoventilation in anaesthetized rats with denervated diaphragm.     

The effects of acute hypercapnia on cerebral indole amine metabolism.

The effects of 1-h exposure to hypercapnia (PaCO2, 90-110 MMHg) on cerebral indole amine metabolism were studied in rats by measurement of cerebral hemisphere contents of tryptophan, 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA), 5-HIAA content was increased after 1-h exposure to hypercapnia, whereas tryptophan, 5-HTP, and 5-HT remained unchanged from control. The accumulation of 5-HTP after decarboxylase inhibition with 3-hydroxybenzyl hydrazine was increased in hypercapnic rats and indicated an increased activity of tryptophan hydroxylase. During the 1-h exposure to hypercapnia there was increased accumulation of 5-HT after monoamine oxidase inhibition with pargyline and increased accumulation of 5-HIAA arter probenecid. The results indicate an increased synthesis and degradation of indole amines in acute hypercapnia.     

Influence of initial respiratory status on the short-and long-term activity of the trout red blood cell β-adrenergic Na+/H+ exchanger

The effects of ambient O₂ partial pressure and CO₂ partial pressure on the intensity of rainbow trout (Oncorhynchus mykiss) red blood cell -adrenergic Na⁺/H⁺ exchange were investigated. This was accomplished in vitro by continuously monitoring whole blood extracellular pH, partial pressures of O₂ and CO₂ and by measuring red blood cell water content and Na⁺ concentration before and 30 min after the addition of a catecholamine mixture (final nominal concentrations: 250 nmol·l^-1 adrenaline and 20 nmol·l^-1 noradrenaline). The experiments were performed under six different initial conditions combining two ambient partial pressures of CO₂ (1.50 and 6.75 torr) and three ambient partial pressures of O₂ (15, 30 and 150 torr). The activation of red blood cell Na⁺/H⁺ exchange (as indicated by marked reductions of whole blood pH) was followed by transient reductions in blood partial pressures of CO₂ and O₂ (2 min) resulting from the shift of the CO₂/HCO₃ ^- equilibrium within the cell and the subsequent binding of O₂ to the haemoglobin. The initial reduction in blood CO₂ partial pressure was followed by a rise reflecting the titration of plasma HCO₃ ^- by extruded H⁺. At low partial pressure of CO₂ (1.50 torr) there was a pronounced stimulatory effect of hypoxia on the initial intensity of the extracellular acidification (5 min), whereas at high CO₂ partial pressure (6.75 torr) hypoxia actually lowered the extent of the initial acidification. In all cases, Na⁺/H⁺ exchange activation was accompanied by increases in cell water content and red blood cell Na⁺ levles when measured 30 min after addition of catecholamines. Both hypercapnia and hypoxia increased the magnitude of these changes although the largest changes in cell water content and Na⁺ levels were observed under hypercapnic conditions. Thus, the long-term activity (as determined by measuring cell water and Na⁺ levels) of the Na⁺/H⁺ exchanger was enhanced both by hypercapnia and hypoxia regardless of the initial CO₂ partial pressure. The initial activity (5 min), on the other hand, although stimulated by hypercapnia was influenced by hypoxia in opposing directions depending upon the initial CO₂ partial pressure of the blood.Abbreviations RBC red blood cell(s) - Hb haemoglobin - pHe extracellular pH - P _bCO₂ blood partial pressure of CO₂ - P _bO₂ blood partial pressure of O₂     

Effects of hypoxia and hypercapnia on surfactant protein expression proliferation and apoptosis in A549 alveolar epithelial cells

During lung injury alveolar epithelial cells are directly exposed to changes in PO(2) and PCO(2). Integrity of alveolar epithelial type II cells (AECII) is critical in lung injury but the effect of hypoxia and hypercapnia on AECII function, viability and proliferation has not been clearly investigated. Aim of the present work was to determine the direct effect of hypoxia and hypercapnia on surfactant protein expression, proliferation and apoptosis of lung epithelial cells in vitro. A549 alveolar epithelia cells were subjected to hypoxia (1%O(2)-5% CO(2)) or hypercapnia (21% O(2-) 15% CO(2)) and expression of surfactant protein C was measured and compared to normal conditions (21% O(2)- 5% CO(2)). Cell cycle progression and apoptosis were measured by flow cytometric analysis. RESULTS: A549 alveolar epithelial cells produce surfactant proteins, including surfactant protein C, when cultured under normal conditions, which is reduced under hypoxic conditions. Specifically, pro-SpC expression is moderately decreased after 8 h of culture in hypoxia, and is completely attenuated after 48 h. Hypercapnia decreases pro-SpC expression only after 48 h of exposure. Stimulation with TNF-alpha partly reverses pSPC decrease observed under hypoxic and hypercapnic conditions. Hypoxic culture of A549 cells results in progressive arrest of cells in the G1 phase of the cell cycle and increased apoptosis first observed 4 h following exposure and peaking at 24 h. In contrast hypercapnia has no significant effect on alveolar epithelial cell proliferation or apoptosis. CONCLUSIONS: Taken together we can conclude that hypoxia rapidly and severely affects AECII function and viability while hypercapnia has an inhibitory effect on pro-SpC production only after prolonged exposure.     

Morning attenuation in cerebrovascular CO2 reactivity in healthy humans is associated with a lowered cerebral oxygenation and an augmented ventilatory response to CO2.

We hypothesized that, in healthy subjects without pharmacological intervention, an overnight reduction in cerebrovascular CO(2) reactivity would be associated with an elevated hypercapnic ventilatory [ventilation (VE)] responsiveness and a reduction in cerebral oxygenation. In 20 healthy male individuals with no sleep-related disorders, continuous recordings of blood velocity in the middle cerebral artery, arterial blood pressure, VE, end-tidal gases, and frontal cortical oxygenation using near infrared spectroscopy were monitored during hypercapnia (inspired CO(2), 5%), hypoxia [arterial O(2) saturation (Sa(O(2))) approximately 84%], and during a 20-s breath hold to investigate the related responses to hypercapnia, hypoxia, and apnea, respectively. Measurements were conducted in the evening (6-8 PM) and in the early morning (6-8 AM). From evening to morning, the cerebrovascular reactivity to hypercapnia was reduced (5.3 +/- 0.6 vs. 4.6 +/- 1.1%/Torr; P < 0.05) and was associated with a reduced increase in cerebral oxygenation (r = 0.39; P < 0.05) and an elevated morning hypercapnic VE response (r = 0.54; P < 0.05). While there were no overnight changes in cerebrovascular reactivity or VE response to hypoxia, there was greater cerebral desaturation for a given Sa(O(2)) in the morning (AM, -0.45 +/- 0.14 vs. PM, -0.35 +/- 0.14%/Sa(O(2)); P < 0.05). Following the 20-s breath hold, in the morning, there was a smaller surge middle cerebral artery velocity and cerebral oxygenation (P < 0.05 vs. PM). These data indicate that normal diurnal changes in the cerebrovascular response to CO(2) influence the hypercapnic ventilatory response as well as the level of cerebral oxygenation during changes in arterial Pco(2); this may be a contributing factor for diurnal changes in breathing stability and the high incidence of stroke in the morning.