Blunted hypoxic ventilatory drive in subjects susceptible to high-altitude pulmonary edema

It has been proposed that subjects susceptible to high-altitude pulmonary edema (HAPE) show exaggerated hypoxemia with relative hypoventilation during the early period of high-altitude exposure. Some previous studies suggest the relationship between the blunted hypoxic ventilatory response (HVR) and HAPE. To examine whether all the HAPE-susceptible subjects consistently show blunted HVR at low altitude, we evaluated the conventional pulmonary function test, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response (HCVR) in ten lowlanders who had a previous history of HAPE and compared these results with those of eight control lowlanders who had no history of HAPE. HVR was measured by the progressive isocapnic hypoxic method and was evaluated by the slope relating minute ventilation to arterial O2 saturation (delta VE/delta SaO2). HCVR was measured by the rebreathing method of Read. All measurements were done at Matsumoto, Japan (610 m). All the HAPE-susceptible subjects showed normal values in the pulmonary function test. In HCVR, HAPE-susceptible subjects showed relatively lower S value, but there was no significant difference between the two groups (1.74 +/- 1.16 vs. 2.19 +/- 0.4, P = NS). On the other hand, HAPE-susceptible subjects showed significantly lower HVR than control subjects (-0.42 +/- 0.23 vs. -0.87 +/- 0.29, P less than 0.01). These results suggest that HAPE-susceptible subjects more frequently show low HVR at low altitude. However, values for HVR were within the normal range in 2 of 10 HAPE-susceptible subjects. It would seem therefore that low HVR alone need not be a critical factor for HAPE. This could be one of several contributing factors.     

Relationship between resting ventilatory chemosensitivity and maximal oxygen uptake in moderate hypobaric hypoxia.

This study tested the hypothesis that the extent of the decrement in (.)Vo(2max) and the respiratory response seen during maximal exercise in moderate hypobaric hypoxia (H; simulated 2,500 m) is affected by the hypoxia ventilatory and hypercapnia ventilatory responses (HVR and HCVR, respectively). Twenty men (5 untrained subjects, 7 long distance runners, 8 middle distance runners) performed incremental exhaustive running tests in H and normobaric normoxia (N) condition. During the running test, (.)Vo(2), pulmonary ventilation (Ve) and arterial oxyhemoglobin saturation (Sa(O(2))) were measured, and in two ventilatory response tests performed during N, a rebreathing method was used to evaluate HVR and HCVR. Mean HVR and HCVR were 0.36 +/- 0.04 and 2.11 +/- 0.2 l.min(-1).mmHg(-1), respectively. HVR correlated significantly with the percent decrements in (.)Vo(2max) (%d(.)Vo(2max)), Sa(O(2)) [%dSa(O(2)) = (N-H).N(-1).100], and (.)Ve/(.)Vo(2) seen during H condition. By contrast, HCVR did not correlate with any of the variables tested. The increment in maximal Ve between H and N significantly correlated with %d(.)Vo(2max). Our findings suggest that O(2) chemosensitivity plays a significant role in determining the level of exercise hyperventilation during moderate hypoxia; thus, a higher O(2) chemosensitivity was associated with a smaller drop in (.)Vo(2max) and Sa(O(2)) under those conditions.     

Augmented hypoxic ventilatory response in men at altitude.

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Control of ventilation and aerobic work capacity in elite climbers

Hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR), and maximal oxygen uptake (VO2max) were measured in elite male climbers (Clim.: n = 4) and physically active controls (Con.: n = 8). Although mean value of S, an index of HCVR, showed almost the same values in both groups (Clim.: 2.26 +/- 0.62 vs. Con.: 1.85 +/- 0.58 l.min-1.Torr-1), mean value of A, an index of HVR, was significantly higher in climbers than controls (Clim.: 237.8 +/- 109.2 vs. Con.: 111.3 +/- 62.0 l.min-1.Torr-1). Mean value of VO2max in climbers was not different from that in controls (Clim.: 49.3 +/- 2.9 vs. Con.: 47.5 +/- 5.7 ml.kg-1.min-1). These results demonstrate that elite climbers are characterized by their enhanced ventilatory response to hypoxia rather than prominency in aerobic work capacity. It is speculated that enhanced HVR in climbers makes compensation for decreased VO2max at high altitude. The enhanced HVR in elite climbers who have ordinary values in VO2max may be one of factors in their successful performance at extreme altitude.     

Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity.

Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250-300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15 s of 5% O(2) + 5 min of 21% O(2), 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory response to graded isocapnic hypoxia was examined in both groups of animals under anesthetized conditions. Hypoxic sensory response was significantly enhanced in SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the effects were not secondary to cardiovascular changes. SDIH, however, had no significant effect on the hypercapnic sensory response. The effects of SDIH on the hypoxic sensory response completely reversed after SDIH animals were placed in a normoxic environment for an additional 10 days. Previous treatment with systemic administration of O(2)(-)* radical scavenger prevented SDIH-induced augmentation of the hypoxic sensory response. These results demonstrate that SDIH but not LDIH results in selective augmentation of the hypoxic response of the carotid body and O(2)(-)* radicals play an important role in SDIH-induced sensitization of the carotid body.     

Effect of caffeine on ventilatory responses to hypercapnia, hypoxia, and exercise in humans

The effect of oral caffeine on resting ventilation (VE), ventilatory responsiveness to progressive hyperoxic hypercapnia (HCVR), isocapnic hypoxia (HVR), and moderate exercise (EVR) below the anaerobic threshold (AT) was examined in seven healthy adults. Ventilatory responses were measured under three conditions: control (C) and after ingestion of either 650 mg caffeine (CF) or placebo (P) in a double-blind randomized manner. None of the physiological variables of interest differed significantly for C and P conditions (P greater than 0.05). Caffeine levels during HCVR, HVR, and EVR were 69.5 +/- 11.8, 67.8 +/- 10.8, and 67.8 +/- 10.9 (SD) mumol/l, respectively (P greater than 0.05). Metabolic rate at rest and during exercise was significantly elevated during CF compared with P. An increase in VE from 7.4 +/- 2.5 (P) to 10.5 +/- 2.1 l/min (CF) (P less than 0.05) was associated with a decrease in end-tidal PCO2 from 39.1 +/- 2.7 (P) to 35.1 +/- 1.3 Torr (CF) (P less than 0.05). Caffeine increased the HCVR, HVR, and EVR slopes (mean increase: 28 +/- 8, 135 +/- 28, 14 +/- 5%, respectively) compared with P; P less than 0.05 for each response. Increases in resting ventilation, HCVR, and HVR slopes were associated with increases in tidal volume (VT), whereas the increase in EVR slope was accompanied by increases in both VT and respiratory frequency. Our results indicate that caffeine increases VE and chemosensitivity to CO2 inhalation, hypoxia, and CO2 production during exercise below the AT.     

Human hypoxic ventilatory response with blood dopamine content under intermittent hypoxic training

Adaptation to intermittent hypoxia can enhance a hypoxic ventilatory response (HVR) in healthy humans. Naturally occurring oscillations in blood dopamine (DA) level may modulate these responses. We have measured ventilatory response to hypoxia relative to blood DA concentration and its precursor DOPA before and after a 2-week course of intermittent hypoxic training (IHT). Eighteen healthy male subjects (mean 22.8+/-2.1 years old) participated in the study. HVRs to isocapnic, progressive, hypoxic rebreathing were recorded and analyzed using piecewise linear approximation. Rebreathing lasted for 5-6 min until inspired O2 reached 8 to 7%. IHT consisted of three identical daily rebreathing sessions separated by 5-min breaks for 14 consecutive days. Before and after the 2-week course of IHT, blood was sampled from the antecubital vein to measure DA and DOPA content. The investigation associated pretraining high blood DA and DOPA values with low HVR (r = -0.66 and -0.75, respectively), elevated tidal volume (r = 0.58 and 0.37) and vital capacity (r = 0.69 and 0.58), and reduced respiratory frequency (r = -0.89 and -0.82). IHT produced no significant change in ventilatory responses to mild hypoxic challenge (Peto2 from 110 to 70-80 mm Hg; 1 mm Hg = 133.3 Pa) but elicited a 96% increase in ventilatory response to severe hypoxia (from 70-80 to 45 mm Hg). Changes in HVRs were not accompanied by statistically significant shifts in blood DA content (24% change), although a twofold increase in DOPA concentration was observed. Individual subject's changes in DA and DOPA content were not correlated with HVR changes when these two parameters were evaluated in relation to the IHT. We hypothesize that DA flowing to the carotid body through the blood may provoke DA autoreceptor-mediated inhibition of endogenous DA synthesis-release, as shown in our baseline data.     

Influence of testosterone on ventilation and chemosensitivity in male subjects

There is increasing evidence that men have higher ventilatory responses to chemical stimuli than age-matched women and that certain disorders of respiratory rhythmicity, particularly sleep apnea, occur more commonly in men. Accordingly, we studied the influence of the male hormone, testosterone, on the control of breathing. Twelve hypogonadal males were studied at least 30 (mean +/- SE: 69.7 +/- 8.9) days after discontinuing testosterone replacement and again following hormone administration. In each subject plasma testosterone concentration, metabolic rate [O2 consumption (VO2) and CO2 production (VCO2)], minute ventilation (VE), and chemosensitivity [hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses] were determined on and off hormone replacement. With testosterone administration VO2 increased from 248 +/- 15 to 276 +/- 18 ml/min (P less than 0.05), with VCO2 showing a similar but nonsignificant trend. This was associated with an increase in VE from 8.41 +/- 0.78 to 9.91 +/- 0.75 l/min (P less than 0.05) but no change in PCO2. The HVR, expressed as A, increased 44% with hormone replacement from a value of 122 +/- 23 to 176 +/- 28 (P less than 0.01), whereas the HCVR was minimally affected by testosterone administration. These findings may in part explain the previously described differences between male and female subjects in hypoxic sensitivity.     

Ventilatory response of the sleeping newborn to CO2 during normoxic rebreathing

The ventilatory response of the newborn to CO2 was studied using a rebreathing method that minimized changes in arterial PO2 during the test. The aim was to study the variability of the ventilatory response to CO2 and take this into account to assess the relative magnitude of the response to CO2 during rapid-eye-movement (REM) sleep and quiet sleep (QS). Five full-term babies aged 4-6 days were given 5% CO2 in air to rebreathe for 1.5-3 min. O2 was added to the rebreathing circuit to maintain arterial O2 saturation and transcutaneous PO2 (Ptco2) at prerebreathing levels. Tests were repeated four to five times in REM sleep and QS. Mean Ptco2 levels varied between individuals but were similar during REM sleep and QS tests for each subject. The mean coefficient of variability of the ventilatory response was 35% (range 15-77%) during QS and 120% (range 32-220%) during REM sleep. PtcO2 fluctuations during tests [6.0 +/- 3.0 (SD) Torr, range 1-13 Torr] were not correlated with ventilatory response. Overall the ventilatory response was significantly lower in REM sleep than in QS (12.2 +/- 3.0 vs. 38.7 +/- 3.0 ml.min-1.Torr-1.kg-1, P less than 0.001; 2-way analysis of variance) due to a small (nonsignificant) fall in the tidal volume response and a significant fall in breathing rate. In 12 REM sleep tests there was no significant ventilatory response; mean inspiratory flow increased significantly during 8 of these 12 tests. We conclude that there is a significant decrease in the ventilatory response of the newborn to CO2 rebreathing during REM sleep compared with QS.     

Abdominal muscle activity during CO2 rebreathing in sleeping neonates

Comparison of the abdominal muscle response to CO2 rebreathing in rapid-eye-movement (REM) and non-REM (NREM) sleep was performed in healthy premature infants near full term. Eight subjects were studied at a postconceptional age of 40 +/- 1.6 (SD) wk (range 38-43 wk) during spontaneous sleep. Sleep stages were defined on the basis of electrophysiological and behavioral criteria, and diaphragmatic and abdominal muscle electromyographic activity was recorded by cutaneous electrodes. The responses to CO2 were measured by a modified Read rebreathing technique. The minute ventilation and diaphragmatic and abdominal muscle electromyographic activities were calculated and plotted against end-tidal CO2 partial pressure. Both the ventilatory and diaphragmatic muscle responses to CO2 decreased from NREM to REM sleep (P less than 0.05). Abdominal muscles were forcefully recruited in response to CO2 rebreathing during NREM sleep. In REM sleep, abdominal muscle response to CO2 was virtually absent or decreased compared with NREM sleep (P less than 0.05). We conclude that 1) the abdominal muscles are recruited during NREM sleep in response to CO2 rebreathing in healthy premature infants near full term and 2) the abdominal muscle recruitment is inhibited during REM sleep compared with NREM sleep, and this REM sleep-related inhibition probably contributes to the decrease in the ventilatory response to CO2 rebreathing in REM sleep.     

Effects of pulmonary restriction on hypercapnic responses of heart-lung transplant recipients

Previous studies of hypercapnic ventilatory responses (HCVR) in human heart-lung transplant recipients (HLTX) have yielded conflicting results. We compared the HCVR of restricted transplant recipients (HLTX-R) to recipients with normal pulmonary function (HLTX-N), and normal controls (C). HLTX-R exhibited limited tidal volume responses, whereas their frequency responses were essentially identical to those of other subjects. Accordingly, HCVR of HLTX-R (1.45 +/- 0.59 l.min-1.Torr CO2(-1)) were significantly depressed compared with both HLTX-N and C (2.90 +/- 0.55 vs 3.05 +/- 1.23, respectively) (P less than 0.02). Despite undoubtedly greater ventilatory impedances, airway (mouth) occlusion pressure responses (Pm0.1) during hypercarbia of HLTX-R (0.46 +/- 0.28 cmH2O) were similar to those of C (0.43 +/- 0.20) and paradoxically blunted compared with HLTX-N (0.83 +/- 0.36) (P less than 0.02). We conclude that pulmonary reflexes are superfluous for maintenance of HCVR in HLTX with normal respiratory mechanics, whereas the presence of moderate restriction results in profound depression of CO2 responses among these subjects.     

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.     

Optimization of the method of progressive hypercapnia by determination of the sensitivity threshold

Ventilatory response to CO2 rebreathing is a method which allows to evaluate the reactivity of chemoreceptors. However this method doesn't study the sensibility threshold, i.e. the Pe.t.CO2 value for which the ventilatory response appears clearly. This sensibility threshold was measured in 10 healthy subjects by rebreathing a gas mixture: 7% CO2 and 50% O2 to avoid hypoxy. It was defined as the value of Pe.t.CO2 for which the ventilation was above the tidal ventilation + 2 standard deviations. The sensibility threshold (51 +/- 4.35 mm Hg) was independent of the reactivity slope represented by the slope of the linear relation between minute ventilation (VE) and Pe.t.CO2 (1.34 +/- 0.60 l/min/mm Hg/m2) and consequently appears as an interesting parameter in order to evaluate the ventilatory response to CO2 by rebreathing.     

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.     

Effect of hypercapnia and hypoxia on respiratory muscle activation in humans

We studied the electromyographic activity of the diaphragm (EMGdi) and abdominal external oblique (EMGeo) muscles in response to progressive hypercapnia (HCVR) and hypoxia (HVR) in five normal males. The slopes of the regression lines relating log EMGdi activity to minute volume of ventilation (VE) were steeper during HVR runs than HCVR runs (mean +/- SE, 0.03201 +/- 0.00724 vs. 0.02729 +/- 0.00676, P less than 0.03). Phasic expiratory EMGeo activity was seen in 15 of 15 HCVR runs but in only 6 of 15 HVR runs. Furthermore, the maximum level of VE attained before the onset of EMGeo activity was significantly lower during HCVR runs than during HVR runs (23.1 +/- 2.5 vs. 34.8 +/- 4.01/min, P less than 0.003). We conclude that in awake humans 1) the diaphragm is activated to a greater extent by hypoxia than hypercapnia at a given VE and 2) hypercapnia causes a more consistent recruitment of abdominal expiratory activity at lower VE than does hypoxia.     

Impact of repeated daily exposure to intermittent hypoxia and mild sustained hypercapnia on apnea severity

We examined whether exposure to intermittent hypoxia (IH) during wakefulness impacted on the apnea/hypopnea index (AHI) during sleep in individuals with sleep apnea. Participants were exposed to twelve 4-min episodes of hypoxia in the presence of sustained mild hypercapnia each day for 10 days. A control group was exposed to sustained mild hypercapnia for a similar duration. The intermittent hypoxia protocol was completed in the evening on day 1 and 10 and was followed by a sleep study. During all sleep studies, the change in esophageal pressure (ΔPes) from the beginning to the end of an apnea and the tidal volume immediately following apneic events were used to measure respiratory drive. Following exposure to IH on day 1 and 10, the AHI increased above baseline measures (day 1: 1.95 ± 0.42 fraction of baseline, P ≤ 0.01, vs. day 10: 1.53 ± 0.24 fraction of baseline, P < 0.06). The indexes were correlated to the hypoxic ventilatory response (HVR) measured during the IH protocol but were not correlated to the magnitude of ventilatory long-term facilitation (vLTF). Likewise, ΔPes and tidal volume measures were greater on day 1 and 10 compared with baseline (ΔPes: -8.37 ± 0.84 vs. -5.90 ± 1.30 cmH(2)0, P ≤ 0.04; tidal volume: 1,193.36 ± 101.85 vs. 1,015.14 ± 119.83 ml, P ≤ 0.01). This was not the case in the control group. Interestingly, the AHI on day 10 (0.78 ± 0.13 fraction of baseline, P ≤ 0.01) was significantly less than measures obtained during baseline and day 1 in the mild hypercapnia control group. We conclude that enhancement of the HVR initiated by exposure to IH may lead to increases in the AHI during sleep and that initiation of vLTF did not appear to impact on breathing stability. Lastly, our results suggest that repeated daily exposure to mild sustained hypercapnia may lead to a decrease in breathing events.     

Adenosine infusion and periodic breathing during sleep.

Intravenously administered adenosine may increase ventilation (VI) and the ventilatory response to CO2 (HCVR). Inasmuch as we have previously hypothesized that those with higher HCVR may be more prone to periodic breathing during sleep, we measured VI and HCVR and monitored ventilatory pattern in seven healthy subjects before and during an infusion of adenosine (80 micrograms.kg-1.min-1) during uninterrupted sleep. Adenosine increased the mean sleeping VI (7.6 +/- 0.4 vs. 6.5 +/- 0.4 l/min, P less than 0.05) and decreased mean end-tidal CO2 values (42.4 +/- 1.2 vs. 43.7 +/- 1.0 Torr, P = 0.06, paired t test) during stable breathing. In six of seven subjects, periodic breathing occurred during this infusion. The amplitude (maximum VI--mean VI) and period length of this periodic breathing was variable among subjects and not predicted by baseline HCVR [correlation coefficients (r) = 0.64, P = 0.17 and r = -0.1, P = 0.9, respectively]. Attempts to measure HCVR during adenosine infusion were unsuccessful because of frequent arousals and continued periodic breathing despite hyperoxic hypercapnia. We conclude that adenosine infusion increases VI and produces periodic breathing during sleep in most normal subjects studied.     

Effect of endurance exercise training on ventilatory function in older individuals

To evaluate the effect of endurance training on ventilatory function in older individuals, 1) 14 master athletes (MA) [age 63 +/- 2 yr (mean +/- SD); maximum O2 uptake (VO2max) 52.1 +/- 7.9 ml . kg-1 . min-1] were compared with 14 healthy male sedentary controls (CON) (age 63 +/- 3 yr; VO2max of 27.6 +/- 3.4 ml . kg-1 . min-1), and 2) 11 sedentary healthy men and women, age 63 +/- 2 yr, were reevaluated after 12 mo of endurance training that increased their VO2max 25%. MA had a significantly lower ventilatory response to submaximal exercise at the same O2 uptake (VE/VO2) and greater maximal voluntary ventilation (MVV), maximal exercise ventilation (VEmax), and ratio of VEmax to MVV than CON. Except for MVV, all of these parameters improved significantly in the previously sedentary subjects in response to training. Hypercapnic ventilatory response (HCVR) at rest and the ventilatory equivalent for CO2 (VE/VCO2) during submaximal exercise were similar for MA and CON and unaffected by training. We conclude that the increase in VE/VO2 during submaximal exercise observed with aging can be reversed by endurance training, and that after training, previously sedentary older individuals breathe at the same percentage of MVV during maximal exercise as highly trained athletes of similar age.     

Selected contribution: Acute and sustained ventilatory responses to hypoxia in high-altitude natives living at sea level.

High-altitude (HA) natives have blunted ventilatory responses to hypoxia (HVR), but studies differ as to whether this blunting is lost when HA natives migrate to live at sea level (SL), possibly because HVR has been assessed with different durations of hypoxic exposure (acute vs. sustained). To investigate this, 50 HA natives (>3,500 m, for >20 yr) now resident at SL were compared with 50 SL natives as controls. Isocapnic HVR was assessed by using two protocols: protocol 1, progressive stepwise induction of hypoxia over 5-6 min; and protocol 2, sustained (20-min) hypoxia (end-tidal Po(2) = 50 Torr). Acute HVR was assessed from both protocols, and sustained HVR from protocol 2. For HA natives, acute HVR was 79% [95% confidence interval (CI): 52-106%, P = not significant] of SL controls for protocol 1 and 74% (95% CI: 52-96%, P < 0.05) for protocol 2. By contrast, sustained HVR after 20-min hypoxia was only 30% (95% CI: -7-67%, P < 0.001) of SL control values. The persistent blunting of HVR of HA natives resident at SL is substantially less to acute than to sustained hypoxia, when hypoxic ventilatory depression can develop.     

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.