Possible mechanisms of periodic breathing during sleep

To determine the effect of respiratory control system loop gain on periodic breathing during sleep, 10 volunteers were studied during stage 1-2 non-rapid-eye-movement (NREM) sleep while breathing room air (room air control), while hypoxic (hypoxia control), and while wearing a tight-fitting mask that augmented control system gain by mechanically increasing the effect of ventilation on arterial O2 saturation (SaO2) (hypoxia increased gain). Ventilatory responses to progressive hypoxia at two steady-state end-tidal PCO2 levels and to progressive hypercapnia at two levels of oxygenation were measured during wakefulness as indexes of controller gain. Under increased gain conditions, five male subjects developed periodic breathing with recurrent cycles of hyperventilation and apnea; the remaining subjects had nonperiodic patterns of hyperventilation. Periodic breathers had greater ventilatory response slopes to hypercapnia under either hyperoxic or hypoxic conditions than nonperiodic breathers (2.98 +/- 0.72 vs. 1.50 +/- 0.39 l.min-1.Torr-1; 4.39 +/- 2.05 vs. 1.72 +/- 0.86 l.min-1.Torr-1; for both, P less than 0.04) and greater ventilatory responsiveness to hypoxia at a PCO2 of 46.5 Torr (2.07 +/- 0.91 vs. 0.87 +/- 0.38 l.min-1.% fall in SaO2(-1); P less than 0.04). To assess whether spontaneous oscillations in ventilation contributed to periodic breathing, power spectrum analysis was used to detect significant cyclic patterns in ventilation during NREM sleep. Oscillations occurred more frequently in periodic breathers, and hypercapnic responses were higher in subjects with oscillations than those without. The results suggest that spontaneous oscillations in ventilation are common during sleep and can be converted to periodic breathing with apnea when loop gain is increased.     

Occlusion pressure and ventilation during sleep in normal humans

Previous investigation in normal humans has demonstrated reduced ventilation and ventilatory responses to chemical stimuli during sleep. Most have interpreted this to be a product of decreasing central nervous system sensitivity to the normal stimuli that maintain ventilation, whereas other factors such as increasing airflow resistance could also contribute to this reduction in respiration. To improve our understanding of these events, we measured ventilation and occlusion pressures (P0.1) during unstimulated ventilation and rebreathing-induced hypercapnia during wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. Eighteen subjects (10 males and 8 females) of whom seven were snorers (5 males and 2 females) were studied. Ventilation was reduced during both NREM and REM sleep (P less than 0.05), but this decrement in minute ventilation tended to be greater in snorers than nonsnorers. Unstimulated P0.1, on the other hand, was maintained or increased during sleep in all groups studied, with males and snorers showing the largest increase. The hypercapnic ventilatory response fell during both NREM and REM sleep and tended to be lower during REM than NREM sleep. However, the P0.1 response to hypercapnia during NREM sleep was well maintained at the waking level although the REM response was statistically reduced. These studies suggest that the mechanism of the reduction in ventilation and the hypercapnic ventilatory response seen during sleep, particularly NREM sleep, is likely to be multifactorial and not totally a product of decreasing central respiratory drive.     

Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans

Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O₂ saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O₂-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease.     

The affinity of hemoglobin for oxygen affects ventilatory responses in mutant mice with Presbyterian hemoglobinopathy

The purpose of this study was to test whether chronically enhanced O2 delivery to tissues, without arterial hyperoxia, can change acute ventilatory responses to hypercapnia and hypoxia. The effects of decreased hemoglobin (Hb)-O2 affinity on ventilatory responses during hypercapnia (0, 5, 7, and 9% CO2 in O2) and hypoxia (10 and 15% O2 in N2) were assessed in mutant mice expressing Hb Presbyterian (mutation in the beta-globin gene, beta108 Asn --> Lys). O2 consumption during normoxia, measured via open-circuit methods, was significantly higher in the mutant mice than in wild-type mice. Respiratory measurements were conducted with a whole body, unrestrained, single-chamber plethysmograph under conscious conditions. During hypercapnia, there was no difference between the slopes of the hypercapnic ventilatory responses, whereas minute ventilation at the same levels of arterial PCO2 was lower in the Presbyterian mice than in the wild-type mice. During both hypoxic exposures, ventilatory responses were blunted in the mutant mice compared with responses in the wild-type mice. The effects of brief hyperoxia exposure (100% O2) after 10% hypoxia on ventilation were examined in anesthetized, spontaneously breathing mice with a double-chamber plethysmograph. No significant difference was found in ventilatory responses to brief hypoxia between both groups of mice, indicating possible involvement of central mechanisms in blunted ventilatory responses to hypoxia in Presbyterian mice. We conclude that chronically enhanced O2 delivery to peripheral tissues can reduce ventilation during acute hypercapnic and hypoxic exposures.     

Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats

During ventilatory acclimatization to hypoxia (VAH), time-dependent increases in ventilation lower Pco(2) levels, and this persists on return to normoxia. We hypothesized that plasticity in the caudal nucleus tractus solitarii (NTS) contributes to VAH, as the NTS receives the first synapse from the carotid body chemoreceptor afferents and also contains CO(2)-sensitive neurons. We lesioned cells in the caudal NTS containing the neurokinin-1 receptor by microinjecting the neurotoxin saporin conjugated to substance P and measured ventilatory responses in awake, unrestrained rats 18 days later. Lesions did not affect hypoxic or hypercapnic ventilatory responses in normoxic control rats, in contrast to published reports for similar lesions in other central chemosensitive areas. Also, lesions did not affect the hypercapnic ventilatory response in chronically hypoxic rats (inspired Po(2) = 90 Torr for 7 days). These results suggest functional differences between central chemoreceptor sites. However, lesions significantly increased ventilation in normoxia or acute hypoxia in chronically hypoxic rats. Hence, chronic hypoxia increases an inhibitory effect of neurokinin-1 receptor neurons in the NTS on ventilatory drive, indicating that these neurons contribute to plasticity during chronic hypoxia, although such plasticity does not explain VAH.     

Ventilatory chemosensitive adaptations to intermittent hypoxic exposure with endurance training and detraining.

The present study was performed to clarify the effects of intermittent exposure to an altitude of 4,500 m with endurance training and detraining on ventilatory chemosensitivity. Seven subjects (sea-level group) trained at sea level at 70% maximal oxygen uptake (VO2 max) for 30 min/day, 5 days/wk for 2 wk, whereas the other seven subjects (altitude group) trained at the same relative intensity (70% altitude VO2 max) in a hypobaric chamber. VO2 max, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response, as an index of central hypercapnic chemosensitivity (HCVR) and as an index of peripheral chemosensitivity (HCVRSB), were measured. In both groups VO2 max increased significantly after training, and a significant loss of VO2 max occurred during 2 wk of detraining. HVR tended to increase in the altitude group but not significantly, whereas it decreased significantly in the sea-level group after training. HCVR and HCVRSB did not change in each group. After detraining, HVR returned to the pretraining level in both groups. These results suggest that ventilatory chemosensitivity to hypoxia is more variable by endurance training and detraining than that to hypercapnia.     

Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine D(2) receptors.

We used genetically engineered D(2) receptor-deficient [D(2)-(-/-)] and wild-type [D(2)-(+/+)] mice to test the hypothesis that dopamine D(2) receptors modulate the ventilatory response to acute hypoxia [hypoxic ventilatory response (HVR)] and hypercapnia [hypercapnic ventilatory response (HCVR)] and time-dependent changes in ventilation during chronic hypoxia. HVR was independent of gender in D(2)-(+/+) mice and significantly greater in D(2)-(-/-) than in D(2)-(+/+) female mice. HCVR was significantly greater in female D(2)-(+/+) mice than in male D(2)-(+/+) and was greater in D(2)-(-/-) male mice than in D(2)-(+/+) male mice. Exposure to hypoxia for 2-8 days was studied in male mice only. D(2)-(+/+) mice showed time-dependent increases in "baseline" ventilation (inspired PO(2) = 214 Torr) and hypoxic stimulated ventilation (inspired PO(2) = 70 Torr) after 8 days of acclimatization to hypoxia, but D(2)-(-/-) mice did not. Hence, dopamine D(2) receptors modulate the acute HVR and HCVR in mice in a gender-specific manner and contribute to time-dependent changes in ventilation and the acute HVR during acclimatization to hypoxia.     

Cardiorespiratory response to exercise in men repeatedly exposed to extreme altitude

The ventilatory and heart rate responses to exercise were studied in four experienced high-altitude climbers at sea level and during a 6-wk period above 4,500 m to discover whether their responses to hypoxia were similar to those of high-altitude natives. Comparison was made with results from four scientists who lacked their frequent exposure to extreme altitude. The climbers had greater Vo2max at sea level and altitude but similar ventilatory responses to increasing exercise. On acute hypoxia at sea level their ventilatory response was less than that of scientists. Their heart rate response did not differ from that of scientists at sea level, but with acclimatization the reduction in response was significantly greater. Alveolar gas concentrations were similar after acclimatization, but climbers achieved these changes more rapidly. The increase in hematocrit was similar in the two groups. It is concluded that these climbers, unlike high-altitude residents, have cardiorespiratory responses to exercise similar to those of other lowlanders except that their ventilatory response was lower and the reduction in their heart rate response was greater.     

Hypercapnic and hypoxic ventilatory responses in long-term streptozotocin-diabetic rats during conscious and pentobarbital-induced anesthetic states

To clarify the diabetes mellitus (DM)-associated changes in the respiratory neuronal control system, acute ventilatory responses to progressively increasing hypercapnia (6%) and hypoxia (10%) were compared between normal (N) and streptozotocin (60 mg/kg, i.v.) -DM rats for a long period up to 28 weeks. The same comparison was conducted during the anesthetic state induced with pentobarbital (35 mg/kg, i.p.). During the conscious state, basic ventilatory parameters, such as respiratory rate, tidal volume and minute ventilation, were not impaired in DM rats, but ventilatory responses to hypercapnia and hypoxia were reduced significantly at 16 weeks and later after streptozotocin injection. The reduced responses in DM rats were not recovered by insulin treatment (5-6 U/body, s.c., daily). During the anesthetic state, both hypoxic and hypercapnic responses were depressed more intensely in N rats than in DM rats, resulting in an equivalent level of the response in the two groups. The present study demonstrated that ventilatory responses to hypercapnia and hypoxia were reduced in a long-term DM condition. This may be derived from the impairment of the peripheral and central chemosensitivity. The reduction in ventilatory responses was exaggerated during the anesthetic state.     

Impact of interrupted leptin pathways on ventilatory control.

Leptin deficiency in ob/ob mice produces marked depression of the hypercapnic ventilatory response, particularly during sleep. We now extend our previous findings to determine whether 1) leptin deficiency affects the hypoxic ventilatory response and 2) blockade of the downstream excitatory actions of leptin on melanocortin 4 receptors or inhibitory actions on neuropeptide Y (NPY) pathways has an impact on hypercapnic and hypoxic sensitivity. We have found that leptin-deficient ob/ob mice have the same hypoxic ventilatory response as weight-matched wild-type obese mice. There were no differences in the hypoxic sensitivity between agouti yellow mice and weight-matched controls, or NPY-deficient mice and wild-type littermates. Agouti yellow mice, with blocked melanocortin pathways, exhibited a significant depression of the hypercapnic sensitivity compared with weight-matched wild-type controls during non-rapid eye movement sleep (5.8 +/- 0.7 vs. 8.9 +/- 0.7 ml x min(-1) x %CO(2)(-1), P < 0.01), but not during wakefulness. NPY-deficient transgenic mice exhibited a small increase in the hypercapnic ventilatory response compared with wild-type littermates, but this was only present during wakefulness. We conclude that interruption of leptin pathways does not affect hypoxic sensitivity during sleep and wakefulness but that melanocortin 4 blockade is associated with depressed hypercapnic sensitivity in non-rapid eye movement sleep.     

Metabolic Adaptations May Counteract Ventilatory Adaptations of Intermittent Hypoxic Exposure during Submaximal Exercise at Altitudes up to 4000 m

Intermittent hypoxic exposure (IHE) has been shown to induce aspects of altitude acclimatization which affect ventilatory, cardiovascular and metabolic responses during exercise in normoxia and hypoxia. However, knowledge on altitude-dependent effects and possible interactions remains scarce. Therefore, we determined the effects of IHE on cardiorespiratory and metabolic responses at different simulated altitudes in the same healthy subjects. Eight healthy male volunteers participated in the study and were tested before and 1 to 2 days after IHE (7×1 hour at 4500 m). The participants cycled at 2 submaximal workloads (corresponding to 40% and 60% of peak oxygen uptake at low altitude) at simulated altitudes of 2000 m, 3000 m, and 4000 m in a randomized order. Gas analysis was performed and arterial oxygen saturation, blood lactate concentrations, and blood gases were determined during exercise. Additionally baroreflex sensitivity, hypoxic and hypercapnic ventilatory response were determined before and after IHE. Hypoxic ventilatory response was increased after IHE (p<0.05). There were no altitude-dependent changes by IHE in any of the determined parameters. However, blood lactate concentrations and carbon dioxide output were reduced; minute ventilation and arterial oxygen saturation were unchanged, and ventilatory equivalent for carbon dioxide was increased after IHE irrespective of altitude. Changes in hypoxic ventilatory response were associated with changes in blood lactate (r = −0.72, p<0.05). Changes in blood lactate correlated with changes in carbon dioxide output (r = 0.61, p<0.01) and minute ventilation (r = 0.54, p<0.01). Based on the present results it seems that the reductions in blood lactate and carbon dioxide output have counteracted the increased hypoxic ventilatory response. As a result minute ventilation and arterial oxygen saturation did not increase during submaximal exercise at simulated altitudes between 2000 m and 4000 m.     

Ventilatory responses to hypoxia and hypercapnia in awake rats pretreated with capsaicin.

Ventilatory responses to hypoxia and hypercapnia were measured by indirect plethysmography in unanesthetized unrestrained adult rats injected neonatally with capsaicin (50 mg/kg) or vehicle. Such capsaicin treatment ablates a subpopulation of primary afferent fibers containing substance P and various other neuropeptides. Ventilation was measured while the rats breathed air, 12% O2 in N2, 8% O2 in N2, 5% CO2 in O2, or 8% CO2 in O2. Neonatal treatment with capsaicin caused marked alterations in both the magnitude and composition of the hypoxic but not hypercapnic ventilatory response. The increase in minute ventilation evoked by hypoxia in the vehicle-treated rats resulted entirely from an increase in respiratory frequency. In the capsaicin-treated rats the hypoxic ventilatory response was significantly reduced owing to an attenuation of the frequency response. Although both groups responded to hypoxia with a shortening in inspiratory and expiratory times, rats treated with capsaicin displayed less shortening of both respiratory phases. By contrast, hypercapnia induced a brisk ventilatory response in the capsaicin-treated group that was similar in magnitude and pattern to that observed in the vehicle-treated group. Analysis of the components of the hypercapnic ventilatory responses revealed no significant differences between the two groups. We, therefore, conclude that neuropeptide-containing C-fibers are essential for the tachypnic component of the ventilatory response to hypoxia but not hypercapnia.     

Increased carotid body hypoxic sensitivity during acclimatization to hypobaric hypoxia

Mechanisms of ventilatory acclimatization to chronic hypoxia remain unclear. To determine whether the sensitivity of peripheral chemoreceptors to hypoxia increases during acclimatization, we measured ventilatory and carotid sinus nerve responses to isocapnic hypoxia in seven cats exposed to simulated altitude of 15,000 ft (barometric pressure = 440 Torr) for 48 h. A control group (n = 7) was selected for hypoxic ventilatory responses matched to the preacclimatized measurements of the experimental group. Exposure to 48 h of hypobaric hypoxia produced acclimatization manifested as decrease in end-tidal PCO2 (PETCO2) in normoxia (34.5 +/- 0.9 Torr before, 28.9 +/- 1.2 after the exposure) as well as in hypoxia (28.1 +/- 1.9 Torr before, 21.8 +/- 1.9 after). Acclimatization produced an increase in hypoxic ventilatory response, measured as the shape parameter A (24.9 +/- 2.6 before, 35.2 +/- 5.6 after; P less than 0.05), whereas values in controls remained unchanged (25.7 +/- 3.2 and 23.1 +/- 2.7; NS). Hypoxic exposure was associated with an increase in the carotid body response to hypoxia, similarly measured as the shape parameter A (24.2 +/- 4.7 in control, 44.5 +/- 8.2 in acclimatized cats). We also found an increased dependency of ventilation on carotid body function (PETCO2 increased after unilateral section of carotid sinus nerve in acclimatized but not in control animals). These results suggest that acclimatization is associated with increased hypoxic ventilatory response accompanied by enhanced peripheral chemoreceptor responsiveness, which may contribute to the attendant rise in ventilation.     

Breathing during sleep with mild hypoxia

To investigate ventilatory response to mild hypoxia during non-rapid-eye-movement sleep, we administered approximately 16% O2 (which corresponds to concentrations found in commercial high altitude air craft) to 12 normal subjects by using a Venturi mask, which did not alter the breathing pattern during this study. Under mild hypoxia, inspiratory minute ventilation during sleep showed an initial rapid increase (P less than 0.001) but then declined significantly (P less than 0.001) and stabilized. Stable levels differed among individuals and, compared with those measured before hypoxia, were significantly lower in some subjects, higher in one, and essentially unchanged in the others. The initial rapid increase in minute ventilation after mild hypoxia during sleep correlated with the respective values of hypoxic ventilatory response during the awake state (P less than 0.01), but the final lowered levels did not. We conclude that the ventilatory response after mild hypoxia during sleep is biphasic and hypoxic depression exerts considerable influence on ventilation under mild hypoxia during sleep. So we should take hypoxic depression into consideration to evaluate the response to hypoxia during sleep.     

Acute inhalation of cigarette smoke augments hypoxic chemosensitivity in humans

Hypoxic and hypercapnic ventilatory responses were measured after two levels of acute inhalation of cigarette smoke, minimum-level nicotine smoke (smoke 1) and nicotine-containing smoke (smoke 2), in 10 normal men. Chemosensitivity to hypoxia and hypercapnia was assessed both in terms of slope factors for ventilation-alveolar PO2 curve (A) and ventilation-alveolar PCO2 line (S) and of absolute levels of minute ventilation (VE) at hypoxia or hypercapnia. Ventilatory response to hypoxia and absolute level of VE at hypoxia significantly increased from 23.5 +/- 22.6 (SD) to 38.6 +/- 31.3 l . min-1 . Torr and from 10.6 +/- 2.5 to 12.6 +/- 3.5 l . min-1, respectively, during inhalation of cigarette smoke 2 (P less than 0.05). Inhalation of cigarette smoke 2 tended to increase the ventilatory response to hypercapnia, and the absolute level of VE at hypercapnia rose from 1.42 +/- 0.75 to 1.65 +/- 0.58 l . min-1 . Torr-1 and from 23.7 +/- 4.9 to 25.5 +/- 5.9 l . min-1, respectively, but these changes did not attain significant levels. Cigarette smoke 2 inhalation induced an increase in heart rate from 64.7 +/- 5.7 to 66.4 +/- 6.3 beats . min-1 (P less than 0.05) during room air breathing, whereas resting ventilation and specific airway conductance did not change significantly. On the other hand, acute inhalation of cigarette smoke 1 changed none of these variables. These results indicate that hypoxic chemosensitivity is augmented after cigarette smoke and that nicotine is presumed to act on peripheral chemoreceptors.     

Effects of a 1-yr stay at altitude on ventilation, metabolism, and work capacity.

The hypoxic and hypercapnic ventilatory drive, gas exchange, blood lactate and pyruvate concentrations, acid-base balance, and physical working capacity were determined in three groups of healthy males: 17 residents examined at sea level (group I), 24 sea-level natives residing at 1,680-m altitude for 1 yr and examined there (group II), and 17 sea-level natives residing at 3,650-m altitude for 1 yr and examined there (group III). The piecewise linear approximation technique was used to study the ventilatory response curves, which allowed a separate analysis of slopes during the first phase of slow increase in ventilation and the second phase of sharp increase. The hypoxic ventilatory response for both isocapnic and poikilocapnic conditions was greater in group II and even greater in group III. The first signs of consciousness distortion in sea-level residents appeared at an end-tidal O2 pressure level (4.09 +/- 0.56 kPa) higher than that of temporary residents of middle (3.05 +/- 0.12) and high altitude (2.90 +/- 0.07). The hypercapnic response was also increased, although to a lesser degree. Subjects with the highest hypoxic respiratory sensitivity at high altitude demonstrated greater O2 consumption at rest, greater ventilatory response to exercise, higher physical capacity, and a less pronounced anaerobic glycolytic flux but a lower tolerance to extreme hypoxia. That is, end-tidal O2 pressure that caused a distortion of the consciousness was higher in these subjects than in those with lower hypoxic sensitivity. Two extreme types of adaptation strategy can be distinguished: active, with marked reactions of "struggle for oxygen," and passive, with reduced O2 metabolism, as well as several intermediate types.(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatostatin inhibits the ventilatory response to hypoxia in humans

The effects of a 90-min infusion of somatostatin (1 mg/h) on ventilation and the ventilatory responses to hypoxia and hypercapnia were studied in six normal adult males. Minute ventilation (VE) was measured with inductance plethysmography, arterial 02 saturation (SaO2) was measured with ear oximetry, and arterial PCO2 (Paco2) was estimated with a transcutaneous CO2 electrode. The steady-state ventilatory response to hypoxia (delta VE/delta SaO2) was measured in subjects breathing 10.5% O2 in an open circuit while isocapnia was maintained by the addition of CO2. The hypercapnic response (delta VE/delta PaCO2) was measured in subjects breathing first 5% and then 7.5% CO2 (in 52-55% O2). Somatostatin greatly attenuated the hypoxic response (control mean -790 ml x min-1.%SaO2 -1, somatostatin mean -120 ml x min-1.%SaO2 -1; P less than 0.01), caused a small fall in resting ventilation (mean % fall - 11%), but did not affect the hypercapnic response. In three of the subjects progressive ventilatory responses (using rebreathing techniques, dry gas meter, and end-tidal Pco2 analysis) and overall metabolism were measured. Somatostatin caused similar changes (mean fall in hypoxic response -73%; no change in hypercapnic response) and did not alter overall O2 consumption nor CO2 production. These results show an hitherto-unsuspected inhibitory potential of this neuropeptide on the control of breathing; the sparing of the hypercapnic response is suggestive of an action on the carotid body but does not exclude a central effect.     

Women at altitude: ventilatory acclimatization at 4,300 m.

Women living at low altitudes or acclimatized to high altitudes have greater effective ventilation in the luteal (L) compared with follicular (F) menstrual cycle phase and compared with men. We hypothesized that ventilatory acclimatization to high altitude would occur more quickly and to a greater degree in 1) women in their L compared with women in their F menstrual cycle phase, and 2) in women compared with men. Studies were conducted on 22 eumenorrheic, unacclimatized, sea-level (SL) residents. Indexes of ventilatory acclimatization [resting ventilatory parameters, hypoxic ventilatory response, hypercapnic ventilatory response (HCVR)] were measured in 14 women in the F phase and in 8 other women in the L phase of their menstrual cycle, both at SL and again during a 12-day residence at 4,300 m. At SL only, ventilatory studies were also completed in both menstrual cycle phases in 12 subjects (i.e., within-subject comparison). In these subjects, SL alveolar ventilation (expressed as end-tidal PCO(2)) was greater in the L vs. F phase. Yet the comparison between L- and F-phase groups found similar levels of resting end-tidal PCO(2), hypoxic ventilatory response parameter A, HCVR slope, and HCVR parameter B, both at SL and 4,300 m. Moreover, these indexes of ventilatory acclimatization were not significantly different from those previously measured in men. Thus female lowlanders rapidly ascending to 4,300 m in either the L or F menstrual cycle phase have similar levels of alveolar ventilation and a time course for ventilatory acclimatization that is nearly identical to that reported in male lowlanders.     

Respiratory response to chemical stimuli and exercise capacity under conditions of acute hypoxia in elite mountain climbers]

To investigate the factors that modulate exercise performance at extreme altitude, the role of the following variables was analyzed in 16 climbers: 1) ventilatory response to chemical stimuli (hypoxia and hypercapnia); and, 2) maximum exercise performance while breathing room air and during acute hypoxia (F1O2, 0.11). Seven climbers (elite climbers, AE) had previously ascended to 8,000 m or more above sea level, and 9 (A) had never achieved such extreme altitude. Then healthy sedentary subjects (C) of similar age (31.1 +/- 6.0 SD years) were used as control group. Elite climbers showed higher ventilatory responses to both transient hypoxia (-0.49 +/- 0.13 L x min-1 x %-1) (p less than 0.05) and progressive hypoxia (-0.47 +/- 0.13 L x min-1 x %-1) than C (-0.33 +/- 0.14 and -0.30 +/- 0.15 L x min-1 x %-1, respectively). By contrast, no differences were observed between the two groups of climbers. The ventilatory response to hypercapnia was higher in AE (3.04 +/- 1.03 L x min-1 mmHg-1) compared to A (1.85 +/- 0.73 L x min-1 mmHg-1) (p less than 0.05) but similar to that observed in C. Breathing 11% O2, maximum workload and oxyhemoglobin desaturation during maximum exercise were similar in both groups of climbers. Additionally, the ventilatory response to hypoxia did not correlate with maximum workload (F1O2, 0.11), maximal ventilation during exercise (F1O2, 0.11), nor with the altitude score. The present study supports previous reports that inform about the role of the ventilatory response to hypoxia in the exercise performance at high altitude.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intermittent hypoxia increases ventilation and Sa(O2) during hypoxic exercise and hypoxic chemosensitivity.

The purpose of this study was 1) to test the hypothesis that ventilation and arterial oxygen saturation (Sa(O2)) during acute hypoxia may increase during intermittent hypoxia and remain elevated for a week without hypoxic exposure and 2) to clarify whether the changes in ventilation and Sa(O2) during hypoxic exercise are correlated with the change in hypoxic chemosensitivity. Six subjects were exposed to a simulated altitude of 4,500 m altitude for 7 days (1 h/day). Oxygen uptake (VO2), expired minute ventilation (VE), and Sa(O2) were measured during maximal and submaximal exercise at 432 Torr before (Pre), after intermittent hypoxia (Post), and again after a week at sea level (De). Hypoxic ventilatory response (HVR) was also determined. At both Post and De, significant increases from Pre were found in HVR at rest and in ventilatory equivalent for O2 (VE/VO2) and Sa(O2) during submaximal exercise. There were significant correlations among the changes in HVR at rest and in VE/VO2 and Sa(O2) during hypoxic exercise during intermittent hypoxia. We conclude that 1 wk of daily exposure to 1 h of hypoxia significantly improved oxygenation in exercise during subsequent acute hypoxic exposures up to 1 wk after the conditioning, presumably caused by the enhanced hypoxic ventilatory chemosensitivity.