Ventilatory sensitivity to carbon dioxide before and after episodic hypoxia in women treated with testosterone

2007 ◽  
Vol 102 (5) ◽  
pp. 1832-1838 ◽  
Author(s):  
Deepti Ahuja ◽  
Jason H. Mateika ◽  
Michael P. Diamond ◽  
M. Safwan Badr
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Threshold ◽  
Minute Ventilation ◽  
Premenopausal Women ◽  
Oxygen Levels ◽  
Carbon Dioxide Rebreathing ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Testosterone Administration ◽  
Sustained Hypoxia

We hypothesized that the ventilatory threshold and sensitivity to carbon dioxide in the presence of hypoxia and hyperoxia during wakefulness would be increased following testosterone administration in premenopausal women. Additionally, we hypothesized that the sensitivity to carbon dioxide increases following episodic hypoxia and that this increase is enhanced after testosterone administration. Eleven women completed four modified carbon dioxide rebreathing trials before and after episodic hypoxia. Two rebreathing trials before and after episodic hypoxia were completed with oxygen levels sustained at 150 Torr, the remaining trials were repeated while oxygen was maintained at 50 Torr. The protocol was completed following 8–10 days of treatment with testosterone or placebo skin patches. Resting minute ventilation was greater following treatment with testosterone compared with placebo (testosterone 11.38 ± 0.43 vs. placebo 10.07 ± 0.36 l/min; P < 0.01). This increase was accompanied by an increase in the ventilatory sensitivity to carbon dioxide in the presence of sustained hyperoxia (VSco2hyperoxia) compared with placebo (3.6 ± 0.5 vs. 2.9 ± 0.3; P < 0.03). No change in the ventilatory sensitivity to carbon dioxide in the presence of sustained hypoxia (VSco2 hypoxia) following treatment with testosterone was observed. However, the VSco2 hypoxia was increased after episodic hypoxia. This increase was similar following treatment with placebo or testosterone patches. We conclude that treatment with testosterone leads to increases in the VSco2hyperoxia, indicative of increased central chemoreflex responsiveness. We also conclude that exposure to episodic hypoxia enhances the VSco2 hypoxia, but that this enhancement is unaffected by treatment with testosterone.

Ventilatory responses to carbon dioxide at low and high levels of oxygen are elevated after episodic hypoxia in men compared with women

2004 ◽  
Vol 97 (5) ◽  
pp. 1673-1680 ◽  
Author(s):  
Chris Morelli ◽  
M. Safwan Badr ◽  
Jason H. Mateika
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
High Oxygen ◽  
Set Point ◽  
Ventilatory Responses ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Oxygen Gas ◽  
End Tidal

We hypothesized that the acute ventilatory response to carbon dioxide in the presence of low and high levels of oxygen would increase to a greater extent in men compared with women after exposure to episodic hypoxia. Eleven healthy men and women of similar race, age, and body mass index completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the end-tidal partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr), or high oxygen gas mixture (150 Torr). During the trials, PetCO2 increased while the selected level of oxygen was maintained. The point at which minute ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the carbon dioxide set point. The ventilatory response below and above this point was determined. The results showed that the ventilatory response to carbon dioxide above the set point was increased in men compared with women before exposure to episodic hypoxia, independent of the oxygen level that was maintained during the rebreathing trials (50 Torr: men, 5.19 ± 0.82 vs. women, 4.70 ± 0.77 l·min−1·Torr−1; 150 Torr: men, 4.33 ± 1.15 vs. women, 3.21 ± 0.58 l·min−1·Torr−1). Moreover, relative to baseline measures, the ventilatory response to carbon dioxide in the presence of low and high oxygen levels increased to a greater extent in men compared with women after exposure to episodic hypoxia (50 Torr: men, 9.52 ± 1.40 vs. women, 5.97 ± 0.71 l·min−1·Torr−1; 150 Torr: men, 5.73 ± 0.81 vs. women, 3.83 ± 0.56 l·min−1·Torr−1). Thus we conclude that enhancement of the acute ventilatory response to carbon dioxide after episodic hypoxia is sex dependent.

Effect of testosterone on the apneic threshold in women during NREM sleep

2003 ◽  
Vol 94 (1) ◽  
pp. 101-107 ◽  
Author(s):  
X. S. Zhou ◽  
J. A. Rowley ◽  
F. Demirovic ◽  
M. P. Diamond ◽  
M. S. Badr
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Premenopausal Women ◽  
Nrem Sleep ◽  
Central Apnea ◽  
Rapid Eye Movement Sleep ◽  
A Value ◽  
Before And After ◽  
Testosterone Administration ◽  
End Tidal

The hypocapnic apneic threshold (AT) is lower in women relative to men. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during non-rapid eye movement sleep in eight healthy, nonsnoring, premenopausal women before and after 10–12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 min with tidal volumes ranging from 175 to 215% above eupneic tidal volume and respiratory frequency matched to eupneic frequency. Cessation of MV resulted in hypocapnic central apnea or hypopnea depending on the magnitude of hypocapnia. Nadir minute ventilation as a percentage of control (%V˙e) was plotted against the change in end-tidal CO2(Pet CO2 ); %V˙e was given a value of zero during central apnea. The AT was defined as the Pet CO2 at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression V˙e vs. Pet CO2 . Both the AT (39.5 ± 2.9 vs. 42.1 ± 3.0 Torr; P = 0.002) and HPVR (0.20 ± 0.05 vs. 0.33 ± 0.11%V˙e/Torr; P = 0.016) increased with testosterone administration. We conclude that testosterone administration increases AT in premenopausal women, suggesting that the increased breathing instability during sleep in men is related to the presence of testosterone.

Peripheral chemoreflex responsiveness is increased at elevated levels of carbon dioxide after episodic hypoxia in awake humans

2004 ◽  
Vol 96 (3) ◽  
pp. 1197-1205 ◽  
Author(s):  
Jason H. Mateika ◽  
Chris Mendello ◽  
Dany Obeid ◽  
M. Safwan Badr
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
High Oxygen ◽  
Recruitment Threshold ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Carbon Dioxide Levels ◽  
Peripheral Chemoreflex ◽  
Long Term Facilitation ◽  
Ventilatory Response To Hypoxia

We hypothesized that the acute ventilatory response to hypoxia is enhanced after exposure to episodic hypoxia in awake humans. Eleven subjects completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then breathed from a bag containing normocapnic (42 Torr), low (50 Torr), or high oxygen (140 Torr) gas mixtures. During the trials, PetCO2 increased while a constant oxygen level was maintained. The point at which ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the ventilatory recruitment threshold. The ventilatory response below and above the recruitment threshold was determined. Ventilation did not persist above baseline values immediately after exposure to episodic hypoxia; however, PetCO2 levels were reduced compared with baseline. In contrast, compared with baseline, the ventilatory response to progressive increases in carbon dioxide during rebreathing trials in the presence of low but not high oxygen levels was increased after exposure to episodic hypoxia. This increase occurred when carbon dioxide levels were above but not below the ventilatory recruitment threshold. We conclude that long-term facilitation of ventilation (i.e., increases in ventilation that persist when normoxia is restored after episodic hypoxia) is not expressed in awake humans in the presence of hypocapnia. Nevertheless, despite this lack of expression, the acute ventilatory response to hypoxia in the presence of hypercapnia is increased after exposure to episodic hypoxia.

scholarly journals Nasal high flow reduces minute ventilation during sleep through a decrease of carbon dioxide rebreathing

2019 ◽  
Vol 126 (4) ◽  
pp. 863-869 ◽  
Author(s):  
Maximilian Pinkham ◽  
Russel Burgess ◽  
Toby Mündel ◽  
Stanislav Tatkov
Keyword(s):  
Carbon Dioxide ◽  
Gas Exchange ◽  
Tidal Volume ◽  
Respiratory Rate ◽  
Dead Space ◽  
Minute Ventilation ◽  
Control Ventilation ◽  
High Flow ◽  
Carbon Dioxide Rebreathing ◽  
Anatomical Dead Space

Nasal high flow (NHF) is an emerging therapy for respiratory support, but knowledge of the mechanisms and applications is limited. It was previously observed that NHF reduces the tidal volume but does not affect the respiratory rate during sleep. The authors hypothesized that the decrease in tidal volume during NHF is due to a reduction in carbon dioxide (CO2) rebreathing from dead space. In nine healthy males, ventilation was measured during sleep using calibrated respiratory inductance plethysmography (RIP). Carbogen gas mixture was entrained into 30 l/min of NHF to obtain three levels of inspired CO2: 0.04% (room air), 1%, and 3%. NHF with room air reduced tidal volume by 81 ml, SD 25 ( P < 0.0001) from a baseline of 415 ml, SD 114, but did not change respiratory rate; tissue CO2 and O2 remained stable, indicating that gas exchange had been maintained. CO2 entrainment increased tidal volume close to baseline with 1% CO2 and greater than baseline with 3% CO2 by 155 ml, SD 79 ( P = 0.0004), without affecting the respiratory rate. It was calculated that 30 l/min of NHF reduced the rebreathing of CO2 from anatomical dead space by 45%, which is equivalent to the 20% reduction in tidal volume that was observed. The study proves that the reduction in tidal volume in response to NHF during sleep is due to the reduced rebreathing of CO2. Entrainment of CO2 into the NHF can be used to control ventilation during sleep. NEW & NOTEWORTHY The findings in healthy volunteers during sleep show that nasal high flow (NHF) with a rate of 30 l/min reduces the rebreathing of CO2 from anatomical dead space by 45%, resulting in a reduced minute ventilation, while gas exchange is maintained. Entrainment of CO2 into the NHF can be used to control ventilation during sleep.

Increased chemoreceptor output and ventilatory response to sustained hypoxia

1989 ◽  
Vol 67 (3) ◽  
pp. 1157-1163 ◽  
Author(s):  
D. Georgopoulos ◽  
S. Walker ◽  
N. R. Anthonisen
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Base Line ◽  
Breathing Patterns ◽  
Peripheral Chemoreceptor ◽  
Depressant Action ◽  
Before And After ◽  
End Tidal ◽  
Arterial O2 Saturation ◽  
Sustained Hypoxia

In adult humans the ventilatory response to sustained hypoxia (VRSH) is biphasic, characterized by an initial brisk increase, due to peripheral chemoreceptor (PC) stimulation, followed by a decline attributed to central depressant action of hypoxia. To study the effects of selective stimulation of PC on the ventilatory response pattern to hypoxia, the VRSH was evaluated after pretreatment with almitrine (A), a PC stimulant. Eight subjects were pretreated with A (75 mg po) or placebo (P) on 2 days in a single-blind manner. Two hours after drug administration, they breathed, in succession, room air (10 min), O2 (5 min), room air (5 min), hypoxia [25 min, arterial O2 saturation (SaO2) = 80%], O2 (5 min), and room air (5 min). End-tidal CO2 was kept constant at the normoxic base-line values. Inspiratory minute ventilation (VI) and breathing patterns were measured over the last 2 min of each period and during minutes 3–5 of hypoxia, and nadirs in VI were assessed just before and after O2 exposure. Independent of the day, the VRSH was biphasic. With P and A pretreatment, early hypoxia increased VI 4.6 +/- 1 and 14.2 +/- 1 (SE) l/min, respectively, from values obtained during the preceding room-air period. On A day the hypoxic ventilatory decline was significantly larger than that on P day, and on both days the decline was a constant fraction of the acute hypoxic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon dioxide effects on the ventilatory response to sustained hypoxia

1988 ◽  
Vol 64 (4) ◽  
pp. 1451-1456 ◽  
Author(s):  
P. A. Easton ◽  
N. R. Anthonisen
Keyword(s):  
Carbon Dioxide ◽  
Young Adults ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Initial Response ◽  
Initial Increase ◽  
Additional Increase ◽  
End Tidal ◽  
End Tidal Co2 ◽  
Sustained Hypoxia

We examined the interrelation between CO2 and the ventilatory response to moderate (80% arterial saturation) sustained hypoxia in normal young adults. On a background of continuous CO2-stimulated hyperventilation, hypoxia was introduced and sustained for 25 min. Initially, with the introduction of hypoxia onto hypercapnia, there was a brisk additional increase in inspiratory minute ventilation (VI) to 284% of resting VI, but the response was not sustained and hypoxic VI declined by 36% to a level intermediate between the initial increase and the preexisting hypercapnic hyperventilation. Through the continuous hypercapnia, the changes in hypoxic ventilation resulted from significant alterations in tidal volume (VT) and mean inspiratory flow (VT/TI) without changes in respiratory timing. In another experiment, sustained hypoxia was introduced on the usual background of room air, either with isocapnia or without maintenance of end-tidal CO2 (ETCO2) (poikilocapnic hypoxia). Regardless of the degree of maintenance of ETCO2, during 25 min of sustained hypoxia, VI showed an initial brisk increase and then declined by 35-40% of resting VI to a level intermediate between the initial response and resting room air VI. For both isocapnia and poikilocapnic conditions, the attenuation of VI was an expression of a diminished VT. Thus the decline in ventilation with sustained hypoxia occurred regardless of the background ETCO2, suggesting that the mechanism underlying the hypoxic decline is independent of CO2.

Sex Differences in Morphine-induced Ventilatory Depression Reside within the Peripheral Chemoreflex Loop 

1999 ◽  
Vol 90 (5) ◽  
pp. 1329-1338 ◽  
Author(s):  
Elise Sarton ◽  
Luc Teppema ◽  
Albert Dahan
Keyword(s):  
Carbon Dioxide ◽  
Sex Differences ◽  
Minute Ventilation ◽  
Carbon Dioxide Tension ◽  
Central Component ◽  
Men And Women ◽  
Ventilatory Depression ◽  
End Tidal ◽  
Peripheral Chemoreflex ◽  
Sustained Hypoxia

Background This study gathers information in humans on the sites of sex-related differences in ventilatory depression caused by the mu-opioid receptor agonist morphine. Methods Experiments were performed in healthy young men (n = 9) and women (n = 7). Dynamic ventilatory responses to square-wave changes in end-tidal carbon dioxide tension (7.5-15 mmHg) and step decreases in end-tidal oxygen tension (step from 110 to 50 mmHg, duration of hypoxia 15 min) were obtained before and during morphine infusion (intravenous bolus dose 100 microg/kg, followed by 30 microg x kg(-1) x h(-1)). Each hypercapnic response was separated into a fast peripheral and slow central component, which yield central (Gc) and peripheral (Gp) carbon dioxide sensitivities. Values are mean +/- SD. Results In carbon dioxide studies in men, morphine reduced Gc from 1.61 +/- 0.33 to 1.23 +/- 0.12 l x min(-1) x mmHg(-1) (P &lt; 0.05) without affecting Gp (control, 0.41 +/- 0.16 and morphine, 0.49 +/- 0.12 l x min(-1) x mmHg(-1), not significant). In carbon dioxide studies in women, morphine reduced Gc, from 1.51 +/- 0.74 to 1.17 +/- 0.52 l x min(-1) x mmHg(-1) (P &lt; 0.05), and Gp, from 0.54 +/- 0.19 to 0.39 +/- 0.22 l x min(-1) x mmHg(-1) (P &lt; 0.05). Morphine-induced changes in Gc were equal in men and women; changes in Gp were greater in women. In hypoxic studies, morphine depressed the hyperventilatory response at the initiation of hypoxia more in women than in men (0.54 +/- 0.23 vs. 0.26 +/- 0.34 l x min(-1) x %(-1), respectively; P &lt; 0.05). The ventilatory response to sustained hypoxia (i/e., 15 min) did not differ between men and women. Conclusions The data indicate the existence of sex differences in morphine-induced depression of responses mediated via the peripheral chemoreflex pathway, with more depression in women, but not of responses mediated via the central chemoreflex pathway. In men and women, morphine did not change the translation of the initial hyperventilatory response to short-term hypoxia into the secondary decrease in inspired minute ventilation (Vi) caused by sustained hypoxia.

Long-term facilitation of ventilation and genioglossus muscle activity is evident in the presence of elevated levels of carbon dioxide in awake humans

2006 ◽  
Vol 291 (4) ◽  
pp. R1111-R1119 ◽  
Author(s):  
Daniel P. Harris ◽  
Arvind Balasubramaniam ◽  
M. Safwan Badr ◽  
Jason H. Mateika
Keyword(s):  
Carbon Dioxide ◽  
Muscle Activity ◽  
Control Experiment ◽  
Minute Ventilation ◽  
Recovery Period ◽  
Genioglossus Muscle ◽  
Healthy Humans ◽  
Episodic Hypoxia ◽  
Long Term Facilitation

We hypothesized that long-term facilitation (LTF) of minute ventilation and peak genioglossus muscle activity manifests itself in awake healthy humans when carbon dioxide is sustained at elevated levels. Eleven subjects completed two trials. During trial 1, baseline carbon dioxide levels were maintained during and after exposure to eight 4-min episodes of hypoxia. During trial 2, carbon dioxide was sustained 5 mmHg above baseline levels during exposure to episodic hypoxia. Seven subjects were exposed to sustained elevated levels of carbon dioxide in the absence of episodic hypoxia, which served as a control experiment. Minute ventilation was measured during trial 1, trial 2, and the control experiment. Peak genioglossus muscle activity was measured during trial 2. Minute ventilation during the recovery period of trial 1 was similar to baseline (9.3 ± 0.5 vs. 9.2 ± 0.7 l/min). Likewise, minute ventilation remained unchanged during the control experiment (beginning vs. end of control experiment, 14.4 ± 1.7 vs. 14.7 ± 1.4 l/min). In contrast, minute ventilation and peak genioglossus muscle activity during the recovery period of trial 2 was greater than baseline (minute ventilation: 28.4 ± 1.7 vs. 19.6 ± 1.0 l/min, P < 0.001; peak genioglossus activity: 1.6 ± 0.3 vs. 1.0 fraction of baseline, P < 0.001). We conclude that exposure to episodic hypoxia is necessary to induce LTF of minute ventilation and peak genioglossus muscle activity and that LTF is only evident in awake humans in the presence of sustained elevated levels of carbon dioxide.

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