Somatostatin inhibits the ventilatory response to hypoxia in humans

1986 ◽  
Vol 60 (3) ◽  
pp. 997-1002 ◽  
Author(s):  
D. L. Maxwell ◽  
P. Chahal ◽  
K. B. Nolop ◽  
J. M. Hughes
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Open Circuit ◽  
Co2 Production ◽  
Adult Males ◽  
Hypoxic Response ◽  
Ventilatory Responses ◽  
End Tidal ◽  
Hypercapnic Response ◽  
Ventilatory Response To Hypoxia

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.

Diphenhydramine Increases Ventilatory Drive during Alfentanil Infusion

1998 ◽  
Vol 89 (3) ◽  
pp. 642-647. ◽  
Author(s):  
H. Daniel Babenco ◽  
Robert T. Blouin ◽  
Pattilyn F. Conard ◽  
Jeffrey B. Gross
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Blood Levels ◽  
Ventilatory Responses ◽  
Ventilatory Drive ◽  
Before And After ◽  
End Tidal ◽  
Carbon Dioxide Response ◽  
Ventilatory Response To Hypoxia

Background Diphenhydramine is used as an antipruritic and antiemetic in patients receiving opioids. Whether it might exacerbate opioid-induced ventilatory depression has not been determined. Methods The ventilatory response to carbon dioxide during hyperoxia and the ventilatory response to hypoxia during hypercapnia (end-tidal pressure of carbon dioxide [PETCO2] is approximately equal to 54 mmHg) were determined in eight healthy volunteers. Ventilatory responses to carbon dioxide and hypoxia were calculated at baseline and during an alfentanil infusion (estimated blood levels approximately equal to 10 ng/ml) before and after diphenhydramine 0.7 mg/kg. Results The slope of the ventilatory response to carbon dioxide decreased from 1.08+/-0.38 to 0.79+/-0.36 l x min(-1) x mmHg(-1) (x +/- SD, P < 0.05) during alfentanil infusion; after diphenhydramine, the slope increased to 1.17+/-0.28 l x min(-1) x mmHg(-1) (P < 0.05). The minute ventilation (VE) at PETCO2 approximately equal to 46 mmHg (VE46) decreased from 12.1+/-3.7 to 9.7+/-3.6 l/min (P < 0.05) and the VE at 54 mmHg (VE54) decreased from 21.3+/-4.8 to 16.6+/-4.7 l/min during alfentanil (P < 0.05). After diphenhydramine, (VE46 did not change significantly, remaining lower than baseline at 9.9+/-2.9 l/min (P < 0.05), whereas VE54 increased significantly to 20.5+/-3.0 l/min. During hypoxia, VE at SpO2 = 90% (VE90) decreased from 30.5+/-9.7 to 23.1+/-6.9 l/min during alfentanil (P < 0.05). After diphenhydramine, the increase in VE90 to 27.2+/-9.2 l/min was not significant (P = 0.06). Conclusions Diphenhydramine counteracts the alfentanil-induced decrease in the slope of the ventilatory response to carbon dioxide. However, at PETCO2 = 46 mmHg, it does not significantly alter the alfentanil-induced shift in the carbon dioxide response curve. In addition, diphenhydramine does not exacerbate the opioid-induced depression of the hypoxic ventilatory response during moderate hypercarbia.

Sexual influence on the control of breathing

1983 ◽  
Vol 54 (4) ◽  
pp. 874-879 ◽  
Author(s):  
D. P. White ◽  
N. J. Douglas ◽  
C. K. Pickett ◽  
J. V. Weil ◽  
C. W. Zwillich
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Premenopausal Women ◽  
Co2 Production ◽  
Menstrual Phase ◽  
Co2 Partial Pressure ◽  
Ventilatory Responses ◽  
Chemical Stimuli ◽  
Low Levels ◽  
Normal Women

Previous investigation has demonstrated that progesterone, a hormone found in premenopausal women, is a ventilatory stimulant. However, fragmentary data suggest that normal women may have lower ventilatory responses to chemical stimuli than men, in whom progesterone is found at low levels. As male-female differences have not been carefully studied, we undertook a systematic comparison of resting ventilation and ventilatory responses to chemical stimuli in men and women. Resting ventilation was found to correlate closely with CO2 production in all subjects (r = 0.71, P less than 0.001), but women tended to have a greater minute ventilation per milliliter of CO2 produced (P less than 0.05) and consequently a lower CO2 partial pressure (PCO2) (men 35.1 +/- 0.5 Torr, women 33.2 +/- 0.5 Torr; P less than 0.02). Women were also found to have lower tidal volumes, even when corrected from body surface area (BSA), and greater respiratory frequency than comparable males. The hypoxic ventilatory response (HVR) quantitated by the shape parameter A was significantly greater in men [167 +/- 22 (SE)] than in women (109 +/- 13; P less than 0.05). In men this hypoxic response was found to correlate closely with O2 consumption (r = 0.75, P less than 0.001) but with no measure of size or metabolic rate in women. The hypercapnic ventilatory response, expressed as the slope of ventilation vs. PCO2, was also greater in men (2.30 +/- 0.23) than in women (1.58 +/- 0.19, P less than 0.05). Finally women tended to have higher ventilatory responses in the luteal than in the follicular menstrual phase, but this was significant only for HVR (P less than 0.05). Women, with relatively higher resting ventilation, have lower responses to hypoxia and hypercapnia.

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 elastic loading on ventilatory response to hypoxia in conscious man

1975 ◽  
Vol 39 (4) ◽  
pp. 548-551 ◽  
Author(s):  
A. S. Rebuck ◽  
M. Betts ◽  
N. A. Saunders
Keyword(s):  
Ventilatory Response ◽  
Variable Speed ◽  
Ventilatory Responses ◽  
Elastic Load ◽  
Resistive Loading ◽  
Elastic Loading ◽  
Progressive Hypoxia ◽  
End Tidal ◽  
Linear Regressions ◽  
Ventilatory Response To Hypoxia

Ventilatory responses to isocapnic hypoxia, with and without an inspiratory elastic load (12.1 cmH2O/l), were measured in seven healthy subjects using a rebreathing technique. During each experiment, the end-tidal PCO2 was held constant using a variable-speed pump to draw gas from the rebreathing bag through a CO2 absorbing bypass. Studies with and without the load were performed in a formally randomized order for each subject. Linear regressions for rise in ventilation against fall in SaO2 were calculated. The range of unloaded responses was 0.74–1.38 1/min per 1% fall in SaO2 and loaded responses 0.71–1.56 1/min per 1% fall in SaO2. Elastic loading did not significantly alter the ventilatory response to progressive hypoxia (P greater than 0.2). In all subjects there was, however, a change in breathing pattern during loading, whereby increments in ventilation were attained by smaller tidal volumes and higher frequencies than in the control experiments. These results support the hypothesis previously proposed in our studies of resistive loading during progressive hypoxia, that a similar control pathway appears to be involved in response to the application of loads to breathing, whether ventilation is stimulated by hypoxia or hypercapnia.

The Ventilatory Effects of Doxapram in Normal Man

1983 ◽  
Vol 65 (1) ◽  
pp. 65-69 ◽  
Author(s):  
P. M. A. Calverley ◽  
R. H. Robson ◽  
P. K. Wraith ◽  
L. F. Prescott ◽  
D. C. Flenley
Keyword(s):  
Oxygen Uptake ◽  
Ventilatory Response ◽  
Co2 Production ◽  
Central Action ◽  
Ventilatory Responses ◽  
Ventilatory Effects ◽  
Normal Man ◽  
End Tidal ◽  
End Tidal Co2 ◽  
Ventilatory Response To Co2

1. To determine the mode of action of doxapram in man we have measured ventilation, oxygen uptake, CO2 production, hypoxic and hypercapnic ventilatory responses in six healthy men before and during intravenous infusion to maintain a constant plasma level. 2. Doxapram changed neither resting oxygen uptake nor CO2 production but produced a substantial increase in resting ventilation at both levels of end-tidal CO2 studied. 3. Doxapram increased the ventilatory response to isocapnic hypoxia from − 0.8 ± 0.4 litre min−1 (%Sao2)−1 to −1.63 ± 0.9 litres min−1 (%Sao2)−1. This was similar to the increase in hypoxic sensitivity which resulted from raising the end-tidal CO2 by 0.5 kPa without adding doxapram. 4. The slope of the ventilatory response to rebreathing CO2 rose from 11.6 ± 5.3 litres min−1 kPa−1 to 20,4 ± 9.8 litres min−1 kPa−1 during doxapram infusion. 5. The marked increase in the ventilatory response to CO2 implies that doxapram has a central action, but the potentiation of the hypoxic drive also suggests that the drug acts on peripheral chemoreceptors, or upon their central connections, at therapeutic concentrations in normal unanaesthetized subjects.

Influences of Morphine on the Ventilatory Response to Isocapnic Hypoxia 

1997 ◽  
Vol 86 (6) ◽  
pp. 1342-1349 ◽  
Author(s):  
Aad Berkenbosch ◽  
Luc J. Teppema ◽  
Cees N. Olievier ◽  
Albert Dahan
Keyword(s):  
Carbon Dioxide ◽  
Steady State ◽  
Shape Parameter ◽  
Ventilatory Response ◽  
Depressant Effect ◽  
Ventilatory Responses ◽  
Before And After ◽  
End Tidal ◽  
Ventilatory Response To Hypoxia ◽  
Carbon Dioxide Sensitivity

Background The ventilatory response to hypoxia is composed of the stimulatory activity from peripheral chemoreceptors and a depressant effect from within the central nervous system. Morphine induces respiratory depression by affecting the peripheral and central carbon dioxide chemoreflex loops. There are only few reports on its effect on the hypoxic response. Thus the authors assessed the effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide sensitivities of the central and peripheral chemoreflex loops. Methods The steady-state ventilatory responses to six levels of end-tidal oxygen tension (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon dioxide tension (P[ET]CO2, 41 mmHg) before and after intravenous administration of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an exponential function characterized by the hypoxic sensitivity and a shape parameter. The hypercapnic ventilatory responses, determined before and after administration of morphine hydrochloride, were separated into a slow central and a fast peripheral component characterized by a carbon dioxide sensitivity and a single offset B (apneic threshold). Results At constant P(ET)CO2, morphine decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110 ml/ min (P < 0.01). The hypoxic sensitivity and shape parameter did not differ from control. The ventilatory response to carbon dioxide was displaced to higher P(ET)CO2 levels, and the apneic threshold increased by 6 mmHg (P < 0.01). The central and peripheral carbon dioxide sensitivities decreased by about 30% (P < 0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105; morphine = 0.161 +/- 0.084). Conclusions Morphine depresses ventilation at hyperoxia but does not depress the steady-state increase in ventilation due to hypoxia. The authors speculate that morphine reduces the central depressant effect of hypoxia and the peripheral carbon dioxide sensitivity at hyperoxia.

Low chemoresponsiveness and inadequate hyperventilation contribute to exercise-induced hypoxemia

1995 ◽  
Vol 79 (2) ◽  
pp. 575-580 ◽  
Author(s):  
C. A. Harms ◽  
J. M. Stager
Keyword(s):  
Oxygen Consumption ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Arterial Oxygen Saturation ◽  
Maximal Oxygen Consumption ◽  
Co2 Production ◽  
Arterial Oxygen ◽  
Ventilatory Parameters ◽  
Exercise Induced ◽  
End Tidal

Is inadequate hyperventilation a cause of the exercise-induced hypoxemia observed in some athletes during intense exercise? If so, is this related to low chemoresponsiveness? To test the hypothesis that exercise-induced hypoxemia, inadequate hyperventilation, and chemoresponsiveness are related, 36 nonsmoking healthy men were divided into hypoxemic (Hyp; n = 13) or normoxemic (Nor; n = 15) groups based on arterial oxygen saturation (SaO2; Hyp < or = 90%, Nor > 92%) observed during maximum O2 uptake (VO2max). Men with intermediate SaO2 values (n = 8) were only included in correlation analysis. Ventilatory parameters were collected at rest, during a treadmill maximal oxygen consumption (VO2max) test, and during a 5-min run at 90% VO2max. Chemoresponsiveness at rest was assessed via hypoxic ventilatory response (HVR) and hypercapnic ventilatory response (HCVR). VO2max was not significantly different between Nor and Hyp. SaO2 was 93.8 +/- 0.9% (Nor) and 87.7 +/- 2.0% (Hyp) at VO2max. End-tidal PO2 and the ratio of minute ventilation to oxygen consumption (VE/VO2) were lower while PETCO2 was higher for Hyp (P < or = 0.01). End-tidal PO2, end-tidal PCO2, and VE/VO2 correlated (P < or = 0.05) to SaO2 (r = 0.84, r = -0.70, r = 0.72, respectively), suggesting that differences in oxygenation were due to differences in ventilation. HVR and HCVR were significantly lower for Hyp. HVR was related to VE/VO2 (r = 0.43), and HCVR was related to the ratio of VE to CO2 production at VO2max (r = 0.61)

Ventilatory Response to Hypercapnia as Experimental Model to Study Effects of Oxycodone on Respiratory Depression

2021 ◽  
Vol 16 ◽  
Author(s):  
Lynn R. Webster ◽  
Erik Hansen ◽  
Gregory J. Stoddard ◽  
Austin Rynders ◽  
David Ostler ◽  
...  
Keyword(s):  
Respiratory Depression ◽  
Ventilatory Response ◽  
Volume Flow Rate ◽  
Minute Ventilation ◽  
Statistical Significance ◽  
Adult Males ◽  
Post Dose ◽  
Double Blind ◽  
End Tidal ◽  
End Tidal Co2

Background: Opioid analgesics used to treat pain can cause respiratory depression. However, this effect has not been extensively studied, and life- threatening, opioid-induced respiratory depression remains difficult to predict. We tested the ventilatory response to hypercapnia for evaluating the pharmacodynamic effect of a drug on respiratory depression. Methods: We conducted a randomized, placebo-controlled, double-blind, crossover, study in 12 healthy adult males. Subjects received 2 treatments (placebo and immediate-release oxycodone 30 mg) separated by a 24-hour washout period. Subjects inhaled a mixture of 7% carbon dioxide, 21% oxygen, and 72% nitrogen for 5 minutes to assess respiratory depression. Minute ventilation, respiratory rate, tidal volume, flow rate, end-tidal CO2, and oxygen saturation were recorded continuously at pre-dose and 30, 60, 120, and 180 minutes post-dose. The primary endpoint was the effect on ventilatory response to hypercapnia at 60 minutes post-dose, as assessed by the slope of the linear relationship between minute ventilation and end-tidal CO2. Results: At 60 minutes post-dose, subjects had a mean slope of 2.4 in the oxycodone crossover period, compared to 0.1 in the placebo period (mean difference, 2.3; 95%CI: 0.2 to 4.5; p = 0.035). Statistical significance was likewise achieved at the secondary time points (30, 120, and 180 minutes post-dose, p <0.05). Conclusions: This model for testing ventilatory response to hypercapnia discriminated the effect of 30 mg of oxycodone vs. placebo for up to 3 hours after a single dose. It may serve as a method to predict the relative effect of a drug on respiratory depression.

Ventilatory response to hypercapnia during sleep and wakefulness in cats

1984 ◽  
Vol 56 (5) ◽  
pp. 1347-1354 ◽  
Author(s):  
A. Netick ◽  
W. J. Dugger ◽  
R. A. Symmons
Keyword(s):  
Eye Movement ◽  
Response Curve ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Ventilatory Responses ◽  
A Value ◽  
The Right ◽  
Hypercapnic Response

Eucapnic breathing and ventilatory responses to hypercapnia were studied in seven cats during sleep and wakefulness. No significant differences were found in minute ventilation (VE), alveolar ventilation (VA), or alveolar PCO2 (PACO2) between wakefulness (W) and non-rapid-eye-movement (NREM) sleep, but VA and VE were less during rapid-eye-movement (REM) sleep than W, and PACO2 declined during REM compared with NREM. To test the hypercapnic response, cats were required to rebreathe from a bag containing 6% CO2 and 94% O2 (to eliminate the hypoxic response). The response curve was displaced to the right during NREM and REM; the slope was reduced only during REM to a value about 75% of W and NREM. Eye movements, quantifying phasic REM, were only slightly correlated (negatively) with the deviation of ventilation from the response curve. The hypercapnic response was diminished, not eliminated, during REM, even during phasic REM. The reduced slope arose principally from the failure of the expiratory time to shorten with hypercapnia as during W and NREM. The cat's hypercapnic response compared with the dog's, measured by others with the same methodology, suggests that differences between species may be more crucial than methodology in explaining earlier contradictory results.

Ventilatory responses to hypercapnia and hypoxia during continuous aspirin ingestion

1977 ◽  
Vol 43 (6) ◽  
pp. 971-976 ◽  
Author(s):  
D. J. Riley ◽  
B. A. Legawiec ◽  
T. V. Santiago ◽  
N. H. Edelman
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Normal Subjects ◽  
Carbon Dioxide Tension ◽  
Base Line ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Responses ◽  
Hypercapnic Ventilatory Response ◽  
The Central Nervous System ◽  
End Tidal

Hypercapnic and hypoxic ventilatory responses were serially measured in nine normal subjects given 3.9 g aspirin (ASA) per day for 9 days. Minute ventilation (VE), end-tidal carbon dioxide tension (PETCO2), venous bicarbonate concentration [HCO3-], oxygen consumption (VO2), hypercapnic ventilatory response (deltaVE/deltaPCO2), and isocapnic hypoxic ventilatory response (A) were determined before, 2 h after the first dose, and at 72-h intervals during the next 14 days. Serum salicylate levels averaged 18.6 +/- 2.0 mg/dl. VE increased (P less than 0.05, PETCO2 decreased (P less than 0.05), and [HCO3-] did not change significantly during drug ingestion. deltaVE/deltaPCO2 increased gradually to a value 37% greater than control by day 3 and remained constant (P less 0.01). A increased by 251% and VO2 by 18% within 2 h and remained constant for the remainder of the ASA period (P less than 0.01). All values returned to base line within 24 h following cessation of ASA. We conclude that during continuous ASA ingestion there is a gradual increase of hypercapnic ventilatory response. This may reflect slow entrance of ASA into the central nervous system. In contrast, there is a rapid rise in hypoxic ventilatory response which may be mechanically linked to changes in metabolic rate.

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