Ventilatory effects of 8 h of isocapnic hypoxia with and without beta-blockade in humans.

This study investigated whether changing sympathetic activity, acting via beta-receptors, might induce the progressive ventilatory changes observed in response to prolonged hypoxia. The responses of 10 human subjects to four 8-h protocols were compared: 1) isocapnic hypoxia (end-tidal PO2 = 50 Torr) plus 80-mg doses of oral propranolol; 2) isocapnic hypoxia, as in protocol 1, with oral placebo; 3) air breathing with propranolol; and 4) air breathing with placebo. Exposures were conducted in a chamber designed to maintain end-tidal gases constant by computer control. Ventilation (VE) was measured at regular intervals throughout. Additionally, the subjects' ventilatory hypoxic sensitivity and their residual VE during hyperoxia (5 min) were assessed at 0, 4, and 8 h by using a dynamic end-tidal forcing technique. beta-Blockade did not significantly alter either the rise in VE seen during 8 h of isocapnic hypoxia or the changes observed in the acute hypoxic ventilatory response and residual VE in hyperoxia over that period. The results do not provide evidence that changes in sympathetic activity acting via beta-receptors play a role in the mediation of ventilatory changes observed during 8 h of isocapnic hypoxia.     

Ventilatory responses to chemoreceptor stimulation after hypoxic acclimatization in awake goats

Our objective was to test the hypothesis that exposure to prolonged hypoxia results in altered responsiveness to chemoreceptor stimulation. Acclimatization to hypoxia occurs rapidly in the awake goat relative to other species. We tested the sensitivity of the central and peripheral chemoreceptors to chemical stimuli before and after 4 h of either isocapnic or poikilocapnic hypoxia (arterial PO2 40 Torr). We confirmed that arterial PCO2 decreased progressively, reaching a stable value after 4 h of hypoxic exposure (poikilocapnic group). In the isocapnic group, inspired minute ventilation increased over the same time course. Thus, acclimatization occurred in both groups. In goats, isocapnic hypoxia did not result in hyperventilation on return to normoxia, whereas poikilocapnic hypoxia did cause hyperventilation, indicating a different mechanism for acclimatization and the persistent hyperventilation on return to normoxia. Goats exposed to isocapnic hypoxia exhibited an increased slope of the CO2 response curve. Goats exposed to poikilocapnic hypoxia had no increase in slope but did exhibit a parallel leftward shift of the CO2 response curve. Neither group exhibited a significant change in response to bolus NaCN injections or dopamine infusions after prolonged hypoxia. However, both groups demonstrated a similar significant increase in the ventilatory response to subsequent acute exposure to isocapnic hypoxia. The increase in hypoxic ventilatory sensitivity, which was not dependent on the modality of hypoxic exposure (isocapnic vs. poikilocapnic), reinforces the key role of the carotid chemoreceptors in ventilatory acclimatization to hypoxia.     

Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness

Persons with acute altitude sickness hypoventilate at high altitude compared with persons without symptoms. We hypothesized that their hypoventilation was due to low initial hypoxic ventilatory responsiveness, combined with subsequent blunting of ventilation by hypocapnia and/or prolonged hypoxia. To test this hypothesis, we compared eight subjects with histories of acute altitude sickness with four subjects who had been asymptomatic during prior altitude exposure. At a simulated altitude of 4,800 m, the eight susceptible subjects developed symptoms of altitude sickness and had lower minute ventilations and higher end-tidal PCO2's than the four asymptomatic subjects. In measurements made prior to altitude exposure, ventilatory responsiveness to acute hypoxia was reduced in symptomatic compared to asymptomatic subjects, both when measured under isocapnic and poikolocapnic (no added CO2) conditions. Diminution of the poikilocapnic relative to the isocapnic hypoxic response was similar in the two groups. Ventilation fell, and end-tidal PCO2 rose in both groups during 30 min of steady-state hypoxia relative to values observed acutely. After 4.5 h at 4,800 m, ventilation was lower than values observed acutely at the same arterial O2 saturation. The reduction in ventilation in relation to the hypoxemia present was greater in symptomatic than in asymptomatic persons. Thus the hypoventilation in symptomatic compared to asymptomatic subjects was attributable both to a lower acute hypoxic response and a subsequent greater blunting of ventilation at high altitude.     

Effect of a synthetic progestin on ventilatory response to hypoxia in anesthetized rats

Effects on ventilatory responses to progressive isocapnic hypoxia of a synthetic potent progestin, chlormadinone acetate (CMA), were determined in the halothane-anesthetized male rat. Ventilation during the breathing of hyperoxic gas was largely unaffected by treatment with CMA when carotid chemoreceptor afferents were kept intact. The sensitivity to hypoxia evaluated by hyperbolic regression analysis of the response curve did not differ between the control and CMA groups. The reduction of ventilation after bilateral section of the carotid sinus nerve (CSN) in hyperoxia was less severe in CMA-treated than in untreated animals. Furthermore, the CMA-treated rats showed a larger increase in ventilation during the hypoxia test and a lower PO2 break point for ventilatory depression. Inhibition of hypoxic ventilatory depression by CMA persisted even after the denervation of CSN. We conclude that exogenous progestin likely protects regulatory mechanism(s) for respiration against hypoxic depression through a stimulating action independent of carotid chemoreceptor afferents and without a change in the sensitivity of the ventilatory response to hypoxia.     

Changes in respiratory control in humans induced by 8 h of hyperoxia.

In humans, 8 h of isocapnic hypoxia causes a progressive rise in ventilation associated with increases in the acute ventilatory responses to hypoxia (AHVR) and hypercapnia (AHCVR). To determine whether 8 h of hyperoxia causes the converse of these effects, three 8-h protocols were compared in 14 subjects: 1) poikilocapnic hyperoxia, with end-tidal PO(2) (PET(O(2))) = 300 Torr and end-tidal PCO(2) (PET(CO(2))) uncontrolled; 2) isocapnic hyperoxia, with PET(O(2)) = 300 Torr and PET(CO(2)) maintained at the subject's normal air-breathing level; and 3) control. Ventilation was measured hourly. AHVR and AHCVR were determined before and 0.5 h after each exposure. During isocapnic hyperoxia, after an initial increase, ventilation progressively declined (P < 0.01, ANOVA). After exposure to hyperoxia, 1) AHVR declined (P < 0.05); 2) ventilation at fixed PET(CO(2)) decreased (P < 0.05); and 3) air-breathing PET(CO(2)) increased (P < 0.05); but 4) no significant changes in AHCVR or intercept were demonstrated. In conclusion, 8 h of hyperoxia have some effects opposite to those found with 8 h of hypoxia, indicating that there may be some "acclimatization to hypoxia" at normal sea-level values of PO(2).     

Carotid chemoreceptor activity during acute and sustained hypoxia in goats

The role of carotid body chemoreceptors in ventilatory acclimatization to hypoxia, i.e., the progressive, time-dependent increase in ventilation during the first several hours or days of hypoxic exposure, is not well understood. The purpose of this investigation was to characterize the effects of acute and prolonged (up to 4 h) hypoxia on carotid body chemoreceptor discharge frequency in anesthetized goats. The goat was chosen for study because of its well-documented and rapid acclimatization to hypoxia. The response of the goat carotid body to acute progressive isocapnic hypoxia was similar to other species, i.e., a hyperbolic increase in discharge as arterial PO2 (PaO2) decreased. The response of 35 single chemoreceptor fibers to an isocapnic [arterial PCO2 (PaCO2) 38-40 Torr)] decrease in PaO2 of from 100 +/- 1.7 to 40.7 +/- 0.5 (SE) Torr was an increase in mean discharge frequency from 1.7 +/- 0.2 to 5.8 +/- 0.4 impulses. During sustained isocapnic steady-state hypoxia (PaO2 39.8 +/- 0.5 Torr, PaCO2, 38.4 +/- 0.4 Torr) chemoreceptor afferent discharge frequency remained constant for the first hour of hypoxic exposure. Thereafter, single-fiber chemoreceptor afferents exhibited a progressive, time-related increase in discharge (1.3 +/- 0.2 impulses.s-1.h-1, P less than 0.01) during sustained hypoxia of up to 4-h duration. These data suggest that increased carotid chemoreceptor activity contributes to ventilatory acclimatization to hypoxia.     

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.     

Two patterns of daily hypoxic exposure and their effects on measures of chemosensitivity in humans.

The purpose of this study was to compare chemoresponses following two different intermittent hypoxia (IH) protocols in humans. Ten men underwent two 7-day courses of poikilocapnic IH. The long-duration IH (LDIH) protocol consisted of daily 60-min exposures to normobaric 12% O(2). The short-duration IH (SDIH) protocol comprised twelve 5-min bouts of 12% O(2), separated by 5-min bouts of room air, daily. Isocapnic hypoxic ventilatory response (HVR) was measured daily during the protocol and 1 and 7 days following. Hypercapnic ventilatory response (HCVR) and CO(2) threshold and sensitivity (by the modified Read rebreathing technique) were measured on days 1, 8, and 14. Following 7 days of IH, the mean HVR was significantly increased from 0.47 +/- 0.07 and 0.47 +/- 0.08 to 0.70 +/- 0.06 and 0.79 +/- 0.06 l.min(-1).%Sa(O(2))(-1) (LDIH and SDIH, respectively), where %Sa(O(2)) is percent arterial oxygen saturation. The increase in HVR reached a plateau after the third day. One week post-IH, HVR values were unchanged from baseline. HCVR increased from 3.0 +/- 0.4 to 4.0 +/- 0.5 l.min(-1).mmHg(-1). In both the hyperoxic and hypoxic modified Read rebreathing tests, the slope of the CO(2)/ventilation plot was unchanged by either intervention, but the CO(2)/ventilation curve shifted to the left following IH. There were no correlations between the changes in response to hypoxia and hypercapnia. There were no significant differences between the two IH protocols for any measures, indicating that comparable changes in chemoreflex control occur with either protocol. These results also suggest that the two methods of measuring CO(2) response are not completely concordant and that the changes in CO(2) control do not correlate with the increase in the HVR.     

Ventilatory, hemodynamic, sympathetic nervous system, and vascular reactivity changes after recurrent nocturnal sustained hypoxia in humans

Recurrent and intermittent nocturnal hypoxia is characteristic of several diseases including chronic obstructive pulmonary disease, congestive heart failure, obesity-hypoventilation syndrome, and obstructive sleep apnea. The contribution of hypoxia to cardiovascular morbidity and mortality in these disease states is unclear, however. To investigate the impact of recurrent nocturnal hypoxia on hemodynamics, sympathetic activity, and vascular tone we evaluated 10 normal volunteers before and after 14 nights of nocturnal sustained hypoxia (mean oxygen saturation 84.2%, 9 h/night). Over the exposure, subjects exhibited ventilatory acclimatization to hypoxia as evidenced by an increase in resting ventilation (arterial Pco(2) 41.8 +/- 1.5 vs. 37.5 +/- 1.3 mmHg, mean +/- SD; P < 0.05) and in the isocapnic hypoxic ventilatory response (slope 0.49 +/- 0.1 vs. 1.32 +/- 0.2 l/min per 1% fall in saturation; P < 0.05). Subjects exhibited a significant increase in mean arterial pressure (86.7 +/- 6.1 vs. 90.5 +/- 7.6 mmHg; P < 0.001), muscle sympathetic nerve activity (20.8 +/- 2.8 vs. 28.2 +/- 3.3 bursts/min; P < 0.01), and forearm vascular resistance (39.6 +/- 3.5 vs. 47.5 +/- 4.8 mmHg.ml(-1).100 g tissue.min; P < 0.05). Forearm blood flow during acute isocapnic hypoxia was increased after exposure but during selective brachial intra-arterial vascular infusion of the alpha-blocker phentolamine it was unchanged after exposure. Finally, there was a decrease in reactive hyperemia to 15 min of forearm ischemia after the hypoxic exposure. Recurrent nocturnal hypoxia thus increases sympathetic activity and alters peripheral vascular tone. These changes may contribute to the increased cardiovascular and cerebrovascular risk associated with clinical diseases that are associated with chronic recurrent hypoxia.     

Ventilatory and heart rate responses to hypoxia in well-trained judo athletes

Twenty-four active judo athletes were examined by an isocapnic progressive hypoxia test. The results of ventilatory and heart rate responses to hypoxia were analyzed by the hyperbolic equations, VE = VO + AVE/(PETO2 - CVE) and HR = HRO + AHR/(PETO2 - CHR), respectively, where VE and HR are observed ventilation and heart rate, VO and HRO the horizontal asymptote in ventilation and heart rate for infinite end-tidal PO2 (PETO2), AVE and AHR the slope constant indicating the magnitude of hypoxic sensitivity, and CVE and CHR the vertical asymptote in PETO2 for infinite ventilation and heart rate. AVE was further re-calculated after VE was normalized for a 70 kg body mass, using an allometric coefficient, and was defined as AVEN. 1) AVE and AVEN significantly increased with increasing body weight (BW) as has been reported previously, but no such correlation was found between AHR and BW. 2) VO2 at rest was found to be positively correlated with AVE and AVEN but not with AHR. 3) The relationship between AVE and AHR was not significant. Thus, the characteristic feature seen in hypoxic ventilatory activity was not accompanied by a similar trend in heart rate response.     

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.     

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.     

Hypoxic ventilatory response and arterial desaturation during heavy work

Arterial desaturation in athletes during intense exercise has been reported by several authors, yet the etiology of this phenomenon remains obscure. Inadequate pulmonary ventilation, due to a blunted respiratory drive, has been implicated as a factor. To investigate the relationship between the ventilatory response to hypoxia, exercise ventilation, and arterial desaturation, 12 healthy male subjects [age, 23.8 +/- 3.6 yr; height, 181.6 +/- 5.6 cm; weight, 73.7 +/- 6.2 kg; and maximal O2 uptake (VO2max), 63.0 +/- 2.2 ml.kg-1 min-1] performed a 5-min treadmill test at 100% of VO2max, during which arterial blood samples and ventilatory data were collected every 15 s. Alveolar PO2 (PAO2) was determined using the ideal gas equation. On a separate occasion the ventilatory response to isocapnic hypoxia was measured. Arterial PO2 decreased by an average of 29 Torr during the test, associated with arterial desaturation [arterial O2 saturation (SaO2) 92.0%]. PAO2 was maintained; however, alveolar-arterial gas pressure difference increased progressively to greater than 40 Torr. Minimal hypocapnia was observed, despite marked metabolic acidosis. There was no significant correlation observed between hypoxic drives and ventilation-to-O2 uptake ratio or SaO2 (r = 0.1 and 0.06, respectively, P = NS). These data support the conclusions that hypoxic drives are not related to maximal exercise ventilation or to the development of arterial desaturation during maximal exercise.     

Selected contribution: chemoreflex responses to CO2 before and after an 8-h exposure to hypoxia in humans.

The ventilatory sensitivity to CO2, in hyperoxia, is increased after an 8-h exposure to hypoxia. The purpose of the present study was to determine whether this increase arises through an increase in peripheral or central chemosensitivity. Ten healthy volunteers each underwent 8-h exposures to 1) isocapnic hypoxia, with end-tidal PO2 (PET(O2)) = 55 Torr and end-tidal PCO2 (PET(CO2)) = eucapnia; 2) poikilocapnic hypoxia, with PET(O2) = 55 Torr and PET(CO2) = uncontrolled; and 3) air-breathing control. The ventilatory response to CO2 was measured before and after each exposure with the use of a multifrequency binary sequence with two levels of PET(CO2): 1.5 and 10 Torr above the normal resting value. PET(O2) was held at 250 Torr. The peripheral (Gp) and the central (Gc) sensitivities were calculated by fitting the ventilatory data to a two-compartment model. There were increases in combined Gp + Gc (26%, P < 0.05), Gp (33%, P < 0.01), and Gc (23%, P = not significant) after exposure to hypoxia. There were no significant differences between isocapnic and poikilocapnic hypoxia. We conclude that sustained hypoxia induces a significant increase in chemosensitivity to CO2 within the peripheral chemoreflex.     

Depression of ventilation hypoxia in man.

In five normal male subjects, ventilation, PaO2, and PaCO2 were measured during the rapid progressive isocapnic production of hypoxia (5 min) and during the equally rapid isocapnic reversal of hypoxia. At similar PaO2, PaCO2, and pH, ventilation was less at a time when alveolar PO2 was increasing than when alveolar PO2 was decreasing. We interpret these results as showing that human ventilation is depressed by mild-to-moderate hypoxia (40-60 Torr), that such depression is probably central, and that it is ordinarily masked by peripheral chemoreceptor stimulation. We are not able to distinguish whether the ventilatory depression is caused by decreased central chemoreceptor PCO2 due to an increase in cerebral flow, direct hypoxic depressing of the central respiratory mechanism, or both.     

Effect of brain blood flow on hypoxic ventilatory response in humans

To assess the effect of brain blood flow on hypoxic ventilatory response, we measured arterial and internal jugular venous blood gases and ventilation simultaneously and repeatedly in eight healthy male humans in two settings: 1) progressive and subsequent sustained hypoxia, and 2) stepwise and progressive hypercapnia. Ventilatory response to progressive isocapnic hypoxia [arterial O2 partial pressure 155.9 +/- 4.0 (SE) to 46.7 +/- 1.5 Torr] was expressed as change in minute ventilation per change in arterial O2 saturation and varied from -0.16 to -1.88 [0.67 +/- 0.19 (SE)] l/min per % among subjects. In the meanwhile, jugular venous PCO2 (PjCO2) decreased significantly from 51.0 +/- 1.1 to 47.3 +/- 1.0 Torr (P less than 0.01), probably due to the increase in brain blood flow, and stayed at the same level during 15 min of sustained hypoxia. Based on the assumption that PjCO2 reflects the brain tissue PCO2, we evaluated the depressant effect of fall in PjCO2 on hypoxic ventilatory response, using a slope for ventilation-PjCO2 line which was determined in the second set of experiments. Hypoxic ventilatory response corrected with this factor was -1.31 +/- 0.33 l/min per %, indicating that this factor modulated hypoxic ventilatory response in humans. The ventilatory response to progressive isocapnic hypoxia did not correlate with this factor but significantly correlated with the withdrawal test (modified transient O2 test), which was performed on a separate day. Accordingly we conclude that an increase in brain blood flow during exposure to moderate hypoxia may substantially attenuate the ventilatory response but that it is unlikely to be the major factor of the interindividual variation of progressive isocapnic hypoxic ventilatory response in humans.     

Cardiorespiratory and cerebrovascular responses to acute poikilocapnic hypoxia following intermittent and continuous exposure to hypoxia in humans.

We tested the hypothesis that intermittent hypoxia (IH) and/or continuous hypoxia (CH) would enhance the ventilatory response to acute hypoxia (HVR), thereby altering blood pressure (BP) and cerebral perfusion. Seven healthy volunteers were randomly selected to complete 10-12 days of IH (5-min hypoxia to 5-min normoxia repeated for 90 min) before ascending to mild CH (1,560 m) for 12 days. Seven other volunteers did not receive any IH before ascending to CH for the same 12 days. Before the IH and CH, following 12 days of CH and 12-13 days post-CH exposure, all subjects underwent a 20-min acute exposure to poikilocapnic hypoxia (inspired fraction of O(2), 0.12) in which ventilation, end-tidal gases, arterial O(2) saturation, BP, and middle cerebral artery blood flow velocity (MCAV) were measured continuously. Following the IH and CH exposures, the peak HVR was elevated and was related to the increase in BP (r = 0.66 to r = 0.88, respectively; P < 0.05) and to a reciprocal decrease in MCAV (r = 0.73 to r = 0.80 vs. preexposures; P < 0.05) during the hypoxic test. Following both IH and CH exposures, HVR, BP, and MCAV sensitivity to hypoxia were elevated compared with preexposure, with no between-group differences following the IH and/or CH conditions, or persistent effects following 12 days of sea level exposure. Our findings indicate that IH and/or mild CH can equally enhance the HVR, which, by either direct or indirect mechanisms, facilitates alterations in BP and MCAV.     

Cardiovascular and cerebrovascular responses to acute isocapnic and poikilocapnic hypoxia in humans

We examined the cardiovascular and cerebrovascular responses to acute isocapnic (IH) and poikilocapnic hypoxia (PH) in 10 men (25.7 +/- 4.2 yr, mean +/- SD). Heart rate (HR), mean arterial pressure (MAP), and mean peak middle cerebral artery blood flow velocity (Vp) were measured continuously during two randomized protocols of 20 min of step IH and PH (45 Torr). HR was elevated during both IH (P < 0.01) and PH (P < 0.01), with no differences observed between conditions. MAP was modestly elevated across all time points during IH but only became elevated after 5 min during PH. During IH, Vp was elevated from baseline throughout the exposure with a consistent hypoxic sensitivity of approximately 0.34 cm x s(-1).%desaturation(-1) (P < 0.05). The Vp response to PH was biphasic with an initial decrease from baseline occurring at 79 +/- 23 s, followed by a subsequent elevation, becoming equivalent to the IH response by 10 min. The nadir of the PH response exhibited a hypoxic sensitivity of -0.24 cm x s(-1) x % desaturation(-1). When expressed in relation to end-tidal Pco2, a sensitivity of -1.08 cm x s(-1).Torr(-1) was calculated, similar to previously reported sensitivities to euoxic hypocapnia. Cerebrovascular resistance (CVR) was not changed during IH. During PH, an initial increase in CVR was observed. However, CVR returned to baseline by 20 min of PH. These data show the cerebrovascular response to PH consists of an early hypocapnia-mediated response, followed by a secondary increase, mediated predominantly by hypoxia.     

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)     

Changes in respiratory control during and after 48h of isocapnic and poikilocapnic hypoxia in humans

Ventilatory acclimatization tohypoxia is associated with an increase in ventilation under conditionsof acute hyperoxia(E_hyperoxia) and an increase in acute hypoxic ventilatory response (AHVR). Thisstudy compares 48-h exposures to isocapnic hypoxia( protocol I) with 48-hexposures to poikilocapnic hypoxia ( protocolP) in 10 subjects to assess the importance ofhypocapnic alkalosis in generating the changes observed in ventilatoryacclimatization to hypoxia. During both hypoxic exposures,end-tidal PO₂ was maintained at60 Torr, with end-tidal PCO₂ held at the subject's prehypoxic level( protocol I) or uncontrolled( protocol P).E_hyperoxiaand AHVR were assessed regularly throughout the exposures.E_hyperoxia(P < 0.001, ANOVA) and AHVR(P < 0.001) increased during thehypoxic exposures, with no significant differences betweenprotocols I andP. The increase inE_hyperoxiawas associated with an increase in slope of theventilation-end-tidal PCO₂ response(P < 0.001) with no significantchange in intercept. These results suggest that changes in respiratorycontrol early in ventilatory acclimatization to hypoxiaresult from the effects of hypoxia per se and not the alkalosisnormally accompanying hypoxia.