scholarly journals The hypoxic ventilatory response and ventilatory long-term facilitation are altered by time of day and repeated daily exposure to intermittent hypoxia

2011 ◽  
Vol 110 (1) ◽  
pp. 15-28 ◽  
Author(s):  
David G. Gerst ◽  
Sanar S. Yokhana ◽  
Laura M. Carney ◽  
Dorothy S. Lee ◽  
M. Safwan Badr ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Time Of Day ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Daily Exposure ◽  
Long Term Facilitation

This study examined whether time of day and repeated exposure to intermittent hypoxia have an impact on the hypoxic ventilatory response (HVR) and ventilatory long-term facilitation (vLTF). Thirteen participants with sleep apnea were exposed to twelve 4-min episodes of isocapnic hypoxia followed by a 30-min recovery period each day for 10 days. On days 1 (initial day) and 10 (final day) participants completed the protocol in the evening (PM); on the remaining days the protocol was completed in the morning (AM). The HVR was increased in the morning compared with evening on the initial (AM 0.83 ± 0.08 vs. PM 0.64 ± 0.11 l·min−1·%SaO2−1; P ≤ 0.01) and final days (AM 1.0 ± 0.08 vs. PM 0.81 ± 0.09 l·min−1·%SaO2−1; P ≤ 0.01, where %SaO2 refers to percent arterial oxygen saturation). Moreover, the magnitude of the HVR was enhanced following daily exposure to intermittent hypoxia in the morning (initial day 0.83 ± 0.08 vs. final day 1.0 ± 0.08 l·min−1·%SaO2−1; P ≤ 0.03) and evening (initial day 0.64 ± 0.11 vs. final day 0.81 ± 0.09 l·min−1·%SaO2−1; P ≤ 0.03). vLTF was reduced in the morning compared with the evening on the initial (AM 19.03 ± 0.35 vs. PM 22.30 ± 0.49 l/min; P ≤ 0.001) and final (AM 20.54 ± 0.32 vs. PM 23.11 ± 0.54 l/min; P ≤ 0.01) days. Following daily exposure to intermittent hypoxia, vLTF was enhanced in the morning (initial day 19.03 ± 0.35 vs. final day 20.54 ± 0.32 l/min; P ≤ 0.01). We conclude that the HVR is increased while vLTF is decreased in the morning compared with the evening in individuals with sleep apnea and that the magnitudes of these phenomena are enhanced following daily exposure to intermittent hypoxia.

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

2007 ◽  
Vol 103 (6) ◽  
pp. 1973-1978 ◽  
Author(s):  
Michael S. Koehle ◽  
A. William Sheel ◽  
William K. Milsom ◽  
Donald C. McKenzie
Keyword(s):  
Oxygen Saturation ◽  
Intermittent Hypoxia ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Hypoxic Exposure ◽  
Hypoxic Ventilatory Response ◽  
The Third ◽  
Long Duration ◽  
The Mean

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% O2. The short-duration IH (SDIH) protocol comprised twelve 5-min bouts of 12% O2, 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 CO2 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·%SaO2−1 (LDIH and SDIH, respectively), where %SaO2 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 CO2/ventilation plot was unchanged by either intervention, but the CO2/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 CO2 response are not completely concordant and that the changes in CO2 control do not correlate with the increase in the HVR.

Intermittent hypoxia increases ventilation and SaO2 during hypoxic exercise and hypoxic chemosensitivity

2001 ◽  
Vol 90 (4) ◽  
pp. 1431-1440 ◽  
Author(s):  
Keisho Katayama ◽  
Yasutake Sato ◽  
Yoshifumi Morotome ◽  
Norihiro Shima ◽  
Koji Ishida ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Arterial Oxygen Saturation ◽  
Submaximal Exercise ◽  
Arterial Oxygen ◽  
Hypoxic Exposure ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Equivalent ◽  
Hypoxic Exercise

The purpose of this study was 1) to test the hypothesis that ventilation and arterial oxygen saturation (SaO2 ) during acute hypoxia may increase during intermittent hypoxia and remain elevated for a week without hypoxic exposure and 2) to clarify whether the changes in ventilation and SaO2 during hypoxic exercise are correlated with the change in hypoxic chemosensitivity. Six subjects were exposed to a simulated altitude of 4,500 m altitude for 7 days (1 h/day). Oxygen uptake (V˙o 2), expired minute ventilation (V˙e), and SaO2 were measured during maximal and submaximal exercise at 432 Torr before (Pre), after intermittent hypoxia (Post), and again after a week at sea level (De). Hypoxic ventilatory response (HVR) was also determined. At both Post and De, significant increases from Pre were found in HVR at rest and in ventilatory equivalent for O2(V˙e/V˙o 2) and SaO2 during submaximal exercise. There were significant correlations among the changes in HVR at rest and inV˙e/V˙o 2 and SaO2 during hypoxic exercise during intermittent hypoxia. We conclude that 1 wk of daily exposure to 1 h of hypoxia significantly improved oxygenation in exercise during subsequent acute hypoxic exposures up to 1 wk after the conditioning, presumably caused by the enhanced hypoxic ventilatory chemosensitivity.

Hypoxic Arousal Responses in Normal Infants

PEDIATRICS ◽  
1992 ◽  
Vol 89 (5) ◽  
pp. 860-864 ◽  
Author(s):  
Sally L. Davidson Ward ◽  
Daisy B. Bautista ◽  
Thomas C. Keens
Keyword(s):  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Periodic Breathing ◽  
High Risk Group ◽  
Arterial Oxygen ◽  
Sudden Infant ◽  
Hypoxic Ventilatory Response ◽  
Quiet Sleep ◽  
Term Infants ◽  
Increased Risk

Failure to arouse in response to hypoxia has been described in infants at increased risk for sudden infant death syndrome (SIDS) and has been suggested as a possible mechanism for SIDS. However, most SIDS victims are not in a high-risk group before death. Thus, if a hypoxic arousal disorder is an important contributor to SIDS, normal infants might fail to arouse from sleep in response to hypoxia. To test this hypothesis, the authors studied hypoxic arousal responses in 18 healthy term infants younger than 7 months of age (age 12.1 ± 1.7 [SEM] weeks; 56% girls). Hypoxic arousal challenges were performed during quiet sleep by rapidly decreasing inspired oxygen tension (Pio2) to 80 mm Hg for 3 minutes or until arousal (eye opening, agitation, and crying) occurred. Tests were performed in duplicate when possible. Only 8 infants (44%) aroused in response to one or more hypoxic challenges; arousal occurred during 8 (32%) of 25 trials. There were no significant differences in lowest Pio2 or arterial oxygen saturation during hypoxia between those infants who aroused and those who failed to arouse. All 18 infants had a fall in their end-tidal carbon dioxide tension during hypoxia, suggesting that each had a hypoxic ventilatory response despite failure to arouse in the majority. Periodic breathing occurred following hypoxia in only 1 (13%) of the 8 trials that resulted in arousal, compared with 16 (94%) of 17 trials without arousal (P < .005). It is concluded that the majority of normal infants younger than 7 months of age fail to arouse from quiet sleep in response to hypoxia, despite the apparent presence of a hypoxic ventilatory response.

scholarly journals Effect of episodic hypoxia on the susceptibility to hypocapnic central apnea during NREM sleep

2010 ◽  
Vol 108 (2) ◽  
pp. 369-377 ◽  
Author(s):  
Susmita Chowdhuri ◽  
Irina Shanidze ◽  
Lisa Pierchala ◽  
Daniel Belen ◽  
Jason H. Mateika ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Ventilatory Response ◽  
Recovery Period ◽  
Positive Pressure ◽  
Central Apnea ◽  
Hypoxic Ventilatory Response ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Long Term Facilitation

We hypothesized that episodic hypoxia (EH) leads to alterations in chemoreflex characteristics that might promote the development of central apnea in sleeping humans. We used nasal noninvasive positive pressure mechanical ventilation to induce hypocapnic central apnea in 11 healthy participants during stable nonrapid eye movement sleep before and after an exposure to EH, which consisted of fifteen 1-min episodes of isocapnic hypoxia (mean O2 saturation/episode: 87.0 ± 0.5%). The apneic threshold (AT) was defined as the absolute measured end-tidal Pco2 (PetCO2) demarcating the central apnea. The difference between the AT and baseline PetCO2 measured immediately before the onset of mechanical ventilation was defined as the CO2 reserve. The change in minute ventilation (V̇I) for a change in PetCO2 (ΔV̇I/ ΔPetCO2) was defined as the hypocapnic ventilatory response. We studied the eupneic PetCO2, AT PetCO2, CO2 reserve, and hypocapnic ventilatory response before and after the exposure to EH. We also measured the hypoxic ventilatory response, defined as the change in V̇I for a corresponding change in arterial O2 saturation (ΔV̇I/ΔSaO2) during the EH trials. V̇I increased from 6.2 ± 0.4 l/min during the pre-EH control to 7.9 ± 0.5 l/min during EH and remained elevated at 6.7 ± 0.4 l/min the during post-EH recovery period ( P < 0.05), indicative of long-term facilitation. The AT was unchanged after EH, but the CO2 reserve declined significantly from −3.1 ± 0.5 mmHg pre-EH to −2.3 ± 0.4 mmHg post-EH ( P < 0.001). In the post-EH recovery period, ΔV̇I/ΔPetCO2 was higher compared with the baseline (3.3 ± 0.6 vs. 1.8 ± 0.3 l·min−1·mmHg−1, P < 0.001), indicative of an increased hypocapnic ventilatory response. However, there was no significant change in the hypoxic ventilatory response (ΔV̇I/ΔSaO2) during the EH period itself. In conclusion, despite the presence of ventilatory long-term facilitation, the increase in the hypocapnic ventilatory response after the exposure to EH induced a significant decrease in the CO2 reserve. This form of respiratory plasticity may destabilize breathing and promote central apneas.

Sea-level PCO2 relates to ventilatory acclimatization at 4,300 m

1993 ◽  
Vol 75 (3) ◽  
pp. 1117-1122 ◽  
Author(s):  
J. T. Reeves ◽  
R. E. McCullough ◽  
L. G. Moore ◽  
A. Cymerman ◽  
J. V. Weil
Keyword(s):  
Sea Level ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Barometric Pressure ◽  
Interindividual Variation ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Wide Range ◽  
Time Required ◽  
End Tidal

There is considerable variation among individuals in the extent of, and the time required for, ventilatory acclimatization to altitude. Factors related to this variation are unclear. The present study tested whether interindividual variation in preascent ventilation or magnitude of hypoxic ventilatory response related to ventilatory acclimatization to altitude. Measurements in 37 healthy resting male subjects at sea level indicated a wide range (34–48 Torr) of end-tidal PCO2 values. When these subjects were taken to Pikes Peak, CO (4,300 m, barometric pressure 462 mmHg), the end-tidal PCO2 values measured on arrival and repeatedly over 19 days were correlated with the sea-level end-tidal PCO2. At 4,300 m, subjects with high end-tidal PCO2 had low values of arterial oxygen saturation (SaO2). Also, sea-level end-tidal PCO2 related to SaO2 after 19 days at 4,300 m. Twenty-six of the subjects had measurements of isocapnic hypoxic ventilatory response (HVR) at sea level. The end-tidal PCO2 values on arrival and after 19 days residence at 4,300 m were inversely related to the sea-level HVR values. Thus both the PCO2 and the HVR as measured at sea level related to the extent of subsequent ventilatory acclimatization (decrease in end-tidal PCO2) and the level of oxygenation at altitude. The finding in our cohort of subjects that sea-level end-tidal PCO2 was inversely related to HVR raised the possibility that among individuals the magnitude of the hypoxic drive to breathe influenced the amount of ventilation at all altitudes, including sea level.

Control of breathing in Sherpas at low and high altitude

1980 ◽  
Vol 49 (3) ◽  
pp. 374-379 ◽  
Author(s):  
P. H. Hackett ◽  
J. T. Reeves ◽  
C. D. Reeves ◽  
R. F. Grover ◽  
D. Rennie
Keyword(s):  
High Altitude ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Arterial Oxygen Saturation ◽  
Carbon Dioxide Tension ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Oxygen Administration ◽  
End Tidal

Sherpas are well known for their physical performance at extreme altitudes, yet they are reported to have blunted ventilatory responses to acute hypoxia and relative hypoventilation in chronic hypoxia. To examine this paradox, we studied ventilatory control in Sherpas in comparison to that in Westerners at both low and high altitude. At low altitude, 25 Sherpas had higher minute ventilation, higher respiratory frequency, and lower end-tidal carbon dioxide tension than 25 Westerners. The hypoxic ventilatory response of Sherpas was found to be similar to that in Westerners, even though long altitude exposure had blunted the responses of some Sherpas. At high altitude, Sherpas again had higher minute ventilation and a tendency toward higher arterial oxygen saturation than Westerners. Oxygen administration increased ventilation further in Sherpas but decreased ventilation in Westerners. We conclude that Sherpas differ from other high-altitude natives; their hypoxic ventilatory response is not blunted, and they exhibit relative hyperventilation.

scholarly journals Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males

2017 ◽  
Vol 123 (3) ◽  
pp. 534-543 ◽  
Author(s):  
Naomi L. Deacon ◽  
R. Doug McEvoy ◽  
Daniel L. Stadler ◽  
Peter G. Catcheside
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Arousal State ◽  
Obstructive Sleep ◽  
Hypercapnic Hypoxia ◽  
Long Term Facilitation ◽  
Healthy Males ◽  
Gas Exposure

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO2levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO2and 3.0 ± 0.2% O2) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO2, O2saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea.NEW & NOTEWORTHY Both arousal state and concomitant CO2levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity.

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