Comparison of chemoreflex gains obtained with two different methods in cats

This study investigates the correspondence between results of the ventilatory response to CO2 obtained using the technique of dynamic end-tidal CO2 forcing (DEF) and results obtained using the technique of artificial brain stem perfusion (ABP). The DEF technique separates the dynamic ventilatory response into a slow and fast component with gains g1 and g2 as well as the extrapolated CO2 tension at zero ventilation (Bk). The ABP technique results in steady-state central (Sc) and peripheral (Sp) chemoreflex gains and extrapolated CO2 tension at zero ventilation (B). Experiments were performed on 14 alpha-chloralose-urethan anesthetized cats. A wide range of relative peripheral chemosensitivities was obtained by subjecting eight cats to normoxic and three cats to hypoxic CO2 challenges and three cats to both conditions. Statistical analysis of the experimental data showed that the vectors (g1, g2, Bk) and (Sc, Sp, B) for each cat did not differ significantly (P = 0.56). This was also the case for the vectors [g2/(g1 + g2), Bk] and [Sp/(Sc + Sp), B] (P = 0.21). We conclude that in the DEF experiments the slow ventilatory response to isoxic changes in end-tidal CO2 can be equated with the central chemoreflex loop and the faster ventilatory response to the peripheral chemoreflex loop. The agreement between the two techniques is good.     

Effects of CO2 breathing on ventilatory response to sustained hypoxia in normal adults

The relationship between CO2 and ventilatory response to sustained hypoxia was examined in nine normal young adults. At three different levels of end-tidal partial pressure of CO2 (PETCO2, approximately 35, 41.8, and 44.3 Torr), isocapnic hypoxia was induced for 25 min and after 7 min of breathing 21% O2, isocapnic hypoxia was reinduced for 5 min. Regardless of PETCO2 levels, the ventilatory response to sustained hypoxia was biphasic, characterized by an initial increase (acute hypoxic response, AHR), followed by a decline (hypoxic depression). The biphasic response pattern was due to alteration in tidal volume, which at all CO2 levels decreased significantly (P less than 0.05), without a significant change in breathing frequency. The magnitude of the hypoxic depression, independent of CO2, correlated significantly (r = 0.78, P less than 0.001) with the AHR, but not with the ventilatory response to CO2. The decline of minute ventilation was not significantly affected by PETCO2 [averaged 2.3 +/- 0.6, 3.8 +/- 1.3, and 4.5 +/- 2.2 (SE) 1/min for PETCO2 35, 41.8, and 44.3 Torr, respectively]. This decay was significant for PETCO2 35 and 41.8 Torr but not for 44.3 Torr. The second exposure to hypoxia failed to elicit the same AHR as the first exposure; at all CO2 levels the AHR was significantly greater (P less than 0.05) during the first hypoxic exposure than during the second. We conclude that hypoxia exhibits a long-lasting inhibitory effect on ventilation that is independent of CO2, at least in the range of PETCO2 studied, but is related to hypoxic ventilatory sensitivity.     

Evidence for hypoxic depression of CO2-ventilation response in carotid body-resected humans

Steady-state CO2-ventilation response curves with hyperoxia (end-tidal PO2 greater than 200 Torr) and mild hypoxia (end-tidal PO2 approximately equal to 60 Torr) were compared in five carotid body-resected (BR) patients and five control patients. The data were analyzed by fitting a linear equation, V = S(PETCO2-B), where V is minute ventilation S is the response curve slope. PETCO2 is end-tidal PCO2, and B is the response curve threshold. S slightly increased from hyperoxia to hypoxia in both BR and control groups. On the other hand, B moderately increased with hypoxia in BR patients, whereas it slightly decreased in controls. These changes were all not significant. However, in accordance with the change in B, the response curve to hypoxia at V of 10 1/min was significantly shifted in opposite directions in the two groups, i.e., rightward and leftward shift in BR and control groups, respectively. Thus the average magnitude of V calculated at PETCO2 of 40 Torr in hypoxia was significantly lower in BR patients than in controls (P less than 0.01). We conclude that this hypoxic depression of the CO2-ventilation response found in BR patients may have resulted, at least in part, from modulation of the brain stem neural mechanisms that were elicited by loss of afferent discharges from the carotid body.     

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.     

Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep.

To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired P(O2). We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O2 saturation = 78-80%), and hyperoxia (inspired O2 fraction = 50-52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sigh-like breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 +/- 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 +/- 0.8 s; P < 0.05), whereas hyperoxia prolonged it (71.5 +/- 13.8 s; P < 0.01). The apneic threshold end-tidal P(CO2) (Pet(CO2)) was defined as the Pet(CO2)) at the onset of apnea. During hypoxia, the apneic threshold Pet(CO2) was higher (38.9 +/- 1.7 Torr; P < 0.01) compared with normoxia (35.8 +/- 1.1; Torr); during hyperoxia, it was lower (33.0 +/- 0.8 Torr; P < 0.05). Furthermore, the difference between the eupneic Pet(CO2) and apneic threshold Pet(CO2) was smaller during hypoxia (3.0 +/- 1.0 Torr P < 001) and greater during hyperoxia (10.6 +/- 0.8 Torr; P < 0.05) compared with normoxia (8.0 +/- 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO2 below the eupneic Pet(CO2) was increased by hypoxia (3.44 +/- 0.63 l.min(-1).Torr(-1); P < 0.05) and decreased by hyperoxia (0.63 +/- 0.04 l.min(-1).Torr(-1); P < 0.05) compared with normoxia (0.79 +/- 0.05 l.min(-1).Torr(-1)). These findings indicate that posthyperventilation apnea is initiated by the peripheral chemoreceptors and that the varying susceptibility to apnea during hypoxia vs. hyperoxia is influenced by the relative activity of these receptors.     

Long-lasting ventilatory response of humans to a single breath of hypercapnia in hyperoxia.

It has often been assumed that under normoxia, closed-loop ventilatory responses to transient CO2 stimulation (i.e., lasting for 1-3 breaths) are less likely to be mediated by the slow-responding central (medullary) chemoreflex. This assumption, however, has not been quantitatively examined in humans. We hypothesized that in the closed-loop respiratory chemical feedback system [in which the centrally mediated ventilatory response to transient changes in the arterial PCO2 levels (PaCO2) will in turn affect the pulmonary CO2 and hence PaCO2], the contribution of the central chemoreflex pathways to brief disturbances in blood gases may be more important than considered previously. Using the technique of pseudorandom binary CO2 stimulation, we quantified the ventilatory response of normal humans to brief disturbances in arterial CO2 during hyperoxia. Tidal volume (VI), inspiratory ventilation (VI), inspiratory time (TI), expiratory time (TE), and end-tidal CO2 fraction (FETCO2) were measured in subjects who inhaled a mixture that was pseudorandomly switched between 95% O2-5% CO2 and 100% O2 (63 breath sequences). From these data, we calculated the responses of VI, VI, TI, TE, and FETCO2 to a single-breath inhalation of 1% CO2 in O2. Our results showed that in response to a brief increase of 0.75 Torr in alveolar CO2, VI showed a transient increase (average peak response of 0.12 1/min) that persisted for greater than or equal to 80 s in every subject. The response of VI was similar to that of VI, whereas TI and TE showed no consistent changes. Using these results we calculated that central chemoreflex pathways may contribute significantly to typical transient CO2 stimulation tests in hyperoxic and normoxic humans.     

Time course of air hunger mirrors the biphasic ventilatory response to hypoxia.

Determining response dynamics of hypoxic air hunger may provide information of use in clinical practice and will improve understanding of basic dyspnea mechanisms. It is hypothesized that air hunger arises from projection of reflex brain stem ventilatory drive ("corollary discharge") to forebrain centers. If perceptual response dynamics are unmodified by events between brain stem and cortical awareness, this hypothesis predicts that air hunger will exactly track ventilatory response. Thus, during sustained hypoxia, initial increase in air hunger would be followed by a progressive decline reflecting biphasic reflex ventilatory drive. To test this prediction, we applied a sharp-onset 20-min step of normocapnic hypoxia and compared dynamic response characteristics of air hunger with that of ventilation in 10 healthy subjects. Air hunger was measured during mechanical ventilation (minute ventilation = 9 +/- 1.4 l/min; end-tidal Pco(2) = 37 +/- 2 Torr; end-tidal Po(2) = 45 +/- 7 Torr); ventilatory response was measured during separate free-breathing trials in the same subjects. Discomfort caused by "urge to breathe" was rated every 30 s on a visual analog scale. Both ventilatory and air hunger responses were modeled as delayed double exponentials corresponding to a simple linear first-order response but with a separate first-order adaptation. These models provided adequate fits to both ventilatory and air hunger data (r(2) = 0.88 and 0.66). Mean time constant and time-to-peak response for the average perceptual response (0.36 min(-1) and 3.3 min, respectively) closely matched corresponding values for the average ventilatory response (0.39 min(-1) and 3.1 min). Air hunger response to sustained hypoxia tracked ventilatory drive with a delay of approximately 30 s. Our data provide further support for the corollary discharge hypothesis for air hunger.     

Chronic intermittent hypoxia increases the CO2 reserve in sleeping dogs.

We hypothesized that chronic intermittent hypoxia (CIH) would induce a predisposition to apnea in response to induced hypocapnia. To test this, we used pressure support ventilation to quantify the difference in end-tidal partial pressure of CO(2) (Pet(CO(2))) between eupnea and the apneic threshold ("CO(2) reserve") as an index of the propensity for apnea and unstable breathing during sleep, both before and following up to 3-wk exposure to chronic intermittent hypoxia in dogs. CIH consisted of 25 s of Pet(O(2)) = 35-40 Torr followed by 35 s of normoxia, and this pattern was repeated 60 times/h, 7-8 h/day for 3 wk. The CO(2) reserve was determined during non-rapid eye movement sleep in normoxia 14-16 h after the most recent hypoxic exposure. Contrary to our hypothesis, the slope of the ventilatory response to CO(2) below eupnea progressively decreased during CIH (control, 1.36 +/- 0.18; week 2, 0.94 +/- 0.12; week 3, 0.73 +/- 0.05 l.min(-1).Torr(-1), P < 0.05). This resulted in a significant increase in the CO(2) reserve relative to control (P < 0.05) following both 2 and 3 wk of CIH (control, 2.6 +/- 0.6; week 2, 3.7 +/- 0.8; week 3, 4.5 +/- 0.9 Torr). CIH also 1) caused no change in eupneic, air breathing Pa(CO(2)); 2) increased the slope of the ventilatory response to hypercapnia after 2 wk but not after 3 wk compared with control; and 3) had no effect on the ventilatory response to hypoxia. We conclude that 3-wk CIH reduced the sensitivity of the ventilatory response to transient hypocapnia and thereby increased the CO(2) reserve, i.e., the propensity for apnea was reduced.     

Almitrine bismesylate and the central and peripheral ventilatory response to CO2

Effects of almitrine bismesylate on the peripheral and central chemoreflex to a CO2 challenge during normoxia were studied in nine alpha-chloralose-urethan anesthetized cats. With the dynamic end-tidal CO2 forcing technique the ventilatory response after a square-wave change in end-tidal PCO2 (PETCO2) was partitioned into a central and a peripheral part using a two-compartment model. With almitrine administered intravenously (0.6 mg/kg followed by a maintenance dose of 0.4 mg.kg-1 X h-1) the CO2 sensitivity of the peripheral chemoreflex increased on the average from 0.315 to 0.564 l.min-1 X kPa-1 (P less than 0.001, 6 cats, 73 runs), whereas the CO2 sensitivity of the central chemoreflex remained the same (P = 0.87). The extrapolated PETCO2 at zero ventilation (apneic threshold) of the (total) steady-state response curve decreased on the average from 3.50 to 2.36 kPa (P less than 0.001). With the artificial brain stem perfusion technique it was confirmed that almitrine did not affect ventilation by administering it to the blood perfusing the brain stem. We conclude that almitrine bismesylate during normoxia enhances the CO2 sensitivity of the peripheral chemoreflex loop and decreases the apneic threshold due to an action located outside the brain stem.     

Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans

After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing.     

Influences of gender and sex hormones on hypoxic ventilatory response in cats.

Hypoxic ventilatory response (HVR) is known to be increased by female as well as male sex hormones, but whether there are differences in HVR between men and women remains unclear. To determine whether gender differences exist in HVR, we undertook systematic comparisons of resting ventilation and HVR in awake male and female cats. Furthermore to explore the potential contribution of sex hormones to gender differences observed, we compared neutered and intact cats of both sexes. Resting ventilation differed among the four groups, but differences disappeared with correction for body weight. Intact females had a lower end-tidal PCO2 than intact male cats (females: 31.6 +/- 0.4 Torr vs. males: 33.6 +/- 0.4 Torr, P less than 0.05), indicating an increased alveolar ventilation per unit CO2 production. HVR expressed as the shape parameter A was similar among the four groups of animals. However, baseline (hyperoxic; end-tidal PO2 greater than 200 Torr) minute ventilation [VI(PO2 greater than 200)] differed among the groups. Therefore we normalized HVR by dividing the shape parameter A by VI(PO2 greater than 200) to compare the relative hypoxic chemosensitivity among the various groups of animals. In addition, we further normalized HVR for body weight, because body size influences ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does cerebral oxygen delivery limit incremental exercise performance?

Previous studies have suggested that a reduction in cerebral oxygen delivery may limit motor drive, particularly in hypoxic conditions, where oxygen transport is impaired. We hypothesized that raising end-tidal Pco(2) (Pet(CO(2))) during incremental exercise would increase cerebral blood flow (CBF) and oxygen delivery, thereby improving peak power output (W(peak)). Amateur cyclists performed two ramped exercise tests (25 W/min) in a counterbalanced order to compare the normal, poikilocapnic response against a clamped condition, in which Pet(CO(2)) was held at 50 Torr throughout exercise. Tests were performed in normoxia (barometric pressure = 630 mmHg, 1,650 m) and hypoxia (barometric pressure = 425 mmHg, 4,875 m) in a hypobaric chamber. An additional trial in hypoxia investigated effects of clamping at a lower Pet(CO(2)) (40 Torr) from ～75 to 100% W(peak) to reduce potential influences of respiratory acidosis and muscle fatigue imposed by clamping Pet(CO(2)) at 50 Torr. Metabolic gases, ventilation, middle cerebral artery CBF velocity (transcranial Doppler), forehead pulse oximetry, and cerebral (prefrontal) and muscle (vastus lateralis) hemoglobin oxygenation (near infrared spectroscopy) were monitored across trials. Clamping Pet(CO(2)) at 50 Torr in both normoxia (n = 9) and hypoxia (n = 11) elevated CBF velocity (～40%) and improved cerebral hemoglobin oxygenation (～15%), but decreased W(peak) (6%) and peak oxygen consumption (11%). Clamping at 40 Torr near maximal effort in hypoxia (n = 6) also improved cerebral oxygenation (～15%), but again limited W(peak) (5%). These findings demonstrate that increasing mass cerebral oxygen delivery via CO(2)-mediated vasodilation does not improve incremental exercise performance, at least when accompanied by respiratory acidosis.     

Influence of pregnancy on ventilatory and carotid body neural output responsiveness to hypoxia in cats

Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats.     

Respiratory control in humans after 8 h of lowered arterial PO2, hemodilution, or carboxyhemoglobinemia.

In humans exposed to 8 h of isocapnic hypoxia, there is a progressive increase in ventilation that is associated with an increase in the ventilatory sensitivity to acute hypoxia. To determine the relative roles of lowered arterial PO2 and oxygen content in generating these changes, the acute hypoxic ventilatory response was determined in 11 subjects after four 8-h exposures: 1) protocol IH (isocapnic hypoxia), in which end-tidal PO2 was held at 55 Torr and end-tidal PCO2 was maintained at the preexposure value; 2) protocol PB (phlebotomy), in which 500 ml of venous blood were withdrawn; 3) protocol CO, in which carboxyhemoglobin was maintained at 10% by controlled carbon monoxide inhalation; and 4) protocol C as a control. Both hypoxic sensitivity and ventilation in the absence of hypoxia increased significantly after protocol IH (P < 0.001 and P < 0.005, respectively, ANOVA) but not after the other three protocols. This indicates that it is the reduction in arterial PO2 that is primarily important in generating the increase in the acute hypoxic ventilatory response in prolonged hypoxia. The associated reduction in arterial oxygen content is unlikely to play an important role.     

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.     

Maximum oxygen uptake and arterial blood oxygenation during hypoxic exercise in rats.

The objectives of these experiments were 1) to describe the effect of maximum treadmill exercise on gas exchange, arterial blood gases, and arterial blood oxygenation in rats acclimated for 3 wk to simulated altitude (SA, barometric pressure 370-380 Torr) and 2) to determine the contribution of acid-base changes to the changes in arterial blood oxygenation of hypoxic exercise. Maximum O2 uptake (VO2max) was measured in four groups of rats: 1) normoxic controls run in normoxia (Nx), 2) normoxic controls run in acute hypoxia [AHx inspiratory PO2 (PIO2) approximately 70 Torr], 3) SA rats run in hypoxia (3WHx, PIO2 approximately 70 Torr), and 4) SA rats run in normoxia (ANx). VO2max (ml STPD.min-1.kg-1) was 70.8 +/- 0.9 in Nx, 46.4 +/- 1.9 in AHx, 52.6 +/- 1.1 in 3WHx, and 70.0 +/- 2.4 in ANx. Exercise resulted in acidosis, hypocapnia, and elevated blood lactate in all groups. Although blood lactate increased less in 3WHx and ANx, pH was the same or lower than in Nx and AHx, reflecting the low buffer capacity of SA. In AHx and 3WHx, arterial PO2 increased with exercise; however, O2 saturation of hemoglobin in arterial blood (SaO2) decreased. In vitro measurements of the Bohr shift suggest that SaO2 decreased as a result of a decrease in hemoglobin O2 affinity. The data indicate that several features of hypoxic exercise in this model are similar to those seen in humans, with the exception of the mechanism of decrease in SaO2, which, in humans, appears to be due to incomplete alveolar-capillary equilibration.     

Ventilatory acclimatization to hypoxia is not dependent on arterial hypoxemia

Goats were prepared so that one carotid body (CB) could be perfused with blood in which the gas tensions could be controlled independently from the blood perfusing the systemic arterial system, including the brain. Since one CB is functionally adequate, the nonperfused CB was excised. To determine whether systemic arterial hypoxemia is necessary for ventilatory acclimatization to hypoxia (VAH), the CB was perfused with hypoxic normocapnic blood for 6 h [means +/- SE: partial pressure of carotid body O2 (PcbO2), 40.6 +/- 0.3 Torr; partial pressure of carotid body CO2 (PcbCO2), 38.8 +/- 0.2 Torr] while the awake goat breathed room air to maintain systemic arterial normoxia. In control periods before and after CB hypoxia the CB was perfused with hyperoxic normocapnic blood. Changes in arterial PCO2 (PaCO2) were used as an index of changes in ventilation. Acute hypoxia (0.5 h of hypoxic perfusion) resulted in hyperventilation sufficient to reduce average PaCO2 by 6.7 Torr from control (P less than 0.05). Over the subsequent 5.5 h of hypoxic perfusion, average PaCO2 decreased further, reaching 4.8 Torr below that observed acutely (P less than 0.05). Acute CB hyperoxic perfusion (20 min) following 6 h of hypoxia resulted in only partial restoration of PaCO2 toward control values; PaCO2 remained 7.9 Torr below control (P less than 0.05). The progressive hyperventilation that occurred during and after 6 h of CB hypoxia with concomitant systemic normoxia is similar to that occurring with total body hypoxia. We conclude that systemic (and probably brain) hypoxia is not a necessary requisite for VAH.     

Resting and exercise ventilatory chemosensitivity across the menstrual cycle

We hypothesized that resting and exercise ventilatory chemosensitivity would be augmented in women when estrogen and progesterone levels are highest during the luteal phase of the menstrual cycle. Healthy, young females (n = 10; age = 23 ± 5 yrs) were assessed across one complete cycle: during early follicular (EF), late follicular (LF), early luteal, and mid-luteal (ML) phases. We measured urinary conjugates of estrogen and progesterone daily. To compare values of ventilatory chemosensitivity and day-to-day variability of measures between sexes, males (n = 10; age = 26 ± 7 yrs) were assessed on 5 nonconsecutive days during a 1-mo period. Resting ventilation was measured and hypoxic chemosensitivity assessed using an isocapnic hypoxic ventilatory response (iHVR) test. The hypercapnic ventilatory response was assessed using the Read rebreathing protocol and modified rebreathing tests. Participants completed submaximal cycle exercise in normoxia and hypoxia. We observed a significant effect of menstrual-cycle phase on resting minute ventilation, which was elevated in the ML phase relative to the EF and LF phases. Compared with males, resting end-tidal CO(2) was reduced in females during the EF and ML phases but not in the LF phase. We found that iHVR was unaffected by menstrual-cycle phase and was not different between males and females. The sensitivity to chemical stimuli was unaffected by menstrual-cycle phase, meaning that any hormone-mediated effect is of insufficient magnitude to exceed the inherent variation in these chemosensitivity measures. The ventilatory recruitment threshold for CO(2) was generally lower in women, which is suggestive of a hormonally related lowering of the ventilatory recruitment threshold. We detected no effect of menstrual-cycle phase on submaximal exercise ventilation and found that the ventilatory response to normoxic and hypoxic exercise was quantitatively similar between males and females. This suggests that feed-forward and feed-back influences during exercise over-ride the effects of naturally occurring changes in sex hormones.     

Control of ventilation in elite synchronized swimmers

Synchronized swimmers perform strenuous underwater exercise during prolonged breath holds. To investigate the role of the control of ventilation and lung volumes in these athletes, we studied the 10 members of the National Synchronized Swim Team including an olympic gold medalist and 10 age-matched controls. We evaluated static pulmonary function, hypoxic and hypercapnic ventilatory drives, and normoxic and hyperoxic breath holding. Synchronized swimmers had an increased total lung capacity and vital capacity compared with controls (P less than 0.005). The hypoxic ventilatory response (expressed as the hyperbolic shape parameter A) was lower in the synchronized swimmers than controls with a mean value of 29.2 +/- 2.6 (SE) and 65.6 +/- 7.1, respectively (P less than 0.001). The hypercapnic ventilatory response [expressed as S, minute ventilation (1/min)/alveolar CO2 partial pressure (Torr)] was no different between synchronized swimmers and controls. Breath-hold duration during normoxia was greater in the synchronized swimmers, with a mean value of 108.6 +/- 4.8 (SE) vs. 68.03 +/- 8.1 s in the controls (P less than 0.001). No difference was seen in hyperoxic breath-hold times between groups. During breath holding synchronized swimmers demonstrated marked apneic bradycardia expressed as either absolute or heart rate change from basal heart rate as opposed to the controls, in whom heart rate increased during breath holds. Therefore the results show that elite synchronized swimmers have increased lung volumes, blunted hypoxic ventilatory responses, and a marked apneic bradycardia that may provide physiological characteristics that offer a competitive advantage for championship performance.(ABSTRACT TRUNCATED AT 250 WORDS)