Ventilatory Response to Hypercapnia in Normal Subjects after Propranolol, Metoprolol and Oxprenolol

The time course of ventilatory adaptation to medroxyprogesterone acetate (MPA) and potential mediators of this response in plasma and lumbar CSF were determined in five healthy adult males. A significant decrease in arterial PCO2 (PACO2) at rest and exercise was noted within 48 h of drug administration with the maximum effect reached within 7 days and amounting to a 5-Torr decrement in PACO2. Blood and lumbar cerebrospinal fluid pH because significantly alkaline to control as soon as the ventilatory resporse was noted and remained alkaline during the treatment period. The ventilatory and dP/dt max response to exogenous CO2 was unchanged but their response to moderate exercise was increased after MPA. MPA-rlated materials were detected in both the plasma and CSF as soon as the ventilatory response was noted. The increase in CSF MPA-related materials approximated the unbound fraction determined in plasma. We conclude that [H+] in plasma and CSF is a function rather than a cause of ventilator acclimatization to MPA. MPA-related materials are capable of crossing the blood-brain barrier and could potentially exert their ventilatory stimulant effect by some central mechanism.

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Control of breathing at the start of exercise as influenced by posture

Journal of Applied Physiology ◽

10.1152/jappl.1983.55.5.1460 ◽

1983 ◽

Vol 55 (5) ◽

pp. 1460-1466 ◽

Cited By ~ 34

Author(s):

D. Weiler-Ravell ◽

D. M. Cooper ◽

B. J. Whipp ◽

K. Wasserman

Keyword(s):

Stroke Volume ◽

Phase I ◽

Ventilatory Response ◽

Normal Subjects ◽

Initial Increase ◽

Base Line ◽

Co2 Output ◽

End Tidal ◽

Response To Exercise ◽

Initial Change

It has been suggested that the initial phase of the ventilatory response to exercise is governed by a mechanism which responds to the increase in pulmonary blood flow (Q)--cardiodynamic hyperpnea. Because the initial change in stroke volume and Q is less in the supine (S) than in the upright (U) position at the start of exercise, we hypothesized that the increase in ventilation would also be less in the first 20 s (phase I) of S exercise. Ten normal subjects performed cycle ergometry in the U and S positions. Inspired ventilation (VI), O2 uptake (VO2), CO2 output (VCO2), corrected for changes in lung gas stores, and end-tidal O2 and CO2 tensions were measured breath by breath. Heart rate (HR) was determined beat by beat. The phase I ventilatory response was markedly different in the two positions. In the U position, VI increased abruptly by 81 +/- 8% (mean +/- SE) above base line. In the S position, the phase I response was significantly attenuated (P less than 0.001), the increase in VI being 50 +/- 6%. Similarly, the phase I VO2 and VO2/HR responses reflecting the initial increase in Q and stroke volume, were attenuated (P less than 0.001) in the S posture, compared with that for U; VO2 increased 49 +/- 5.3 and 113 +/- 14.7% in S and U, respectively, and VO2/HR increased 16 +/- 3.0 and 76 +/- 7.1% in the S and U, respectively. The increase in VI correlated well with the increase in VO2, (r = 0.80, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Ventilatory response to transient hyperoxia in head injury hyperventilation

Journal of Applied Physiology ◽

10.1152/jappl.1980.49.1.52 ◽

1980 ◽

Vol 49 (1) ◽

pp. 52-58 ◽

Cited By ~ 5

Author(s):

A. G. Leitch ◽

J. E. McLennan ◽

S. Balkenhol ◽

R. L. McLaurin ◽

R. G. Loudon

Keyword(s):

Head Injury ◽

Ventilatory Response ◽

Minute Ventilation ◽

Respiratory Control ◽

Normal Subjects ◽

Respiratory Alkalosis ◽

Cerebral Injury ◽

Peripheral Chemoreceptor ◽

Male Patients ◽

Almost All

We have measured breath-by-breath instantaneous minute ventilation (VIinst) before, during, and after the administration of 10 breaths of 100% oxygen to seven male patients with head injury hyperventilation. The patients were hypoxemic (PaO2 61.2 ± 6.3) and hypocapnic (PaCO2 26.6 ± 5.9) with a respiratory alkalosis (pH 7.53 ± 0.06) while breathing air. Following the oxygen VIinst fell on the average by 40 ± 12.7% from 16.06 ± 3.75 1.min-1 to a minimum of 9.73 ± 3.20 1.min-1 at 20.4 ± 2.9 s after the first breath of oxygen. In the majority of our hyperventilating patients, almost all of the resting hyperventilation could be abolished transiently by 100% oxygen. This fall in ventilation represents the peripheral chemoreceptor contribution to resting ventilation and is increased in the head injury patients in comparison with normal subjects breathing air or hypoxic gas mixtures, altitude-acclimatized subjects and patients who are hypoxic because of chronic bronchitis or interstitial lung disease. We suggest that the increased reflex hypoxic drive to ventilation found in our patients is secondary to their cerebral injury, resulting in a reduction of descending cortical inhibitory influences on the medullary respiratory control centers.

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The effect of Airway Anaesthesia on the Control of Breathing and the Sensation of Breathlessness in Man

Clinical Science ◽

10.1042/cs0680215 ◽

1985 ◽

Vol 68 (2) ◽

pp. 215-225 ◽

Cited By ~ 47

Author(s):

A. J. Winning ◽

R. D. Hamilton ◽

S. A. Shea ◽

C. Knott ◽

A. Guz

Keyword(s):

Tidal Volume ◽

Ventilatory Response ◽

Normal Subjects ◽

Cough Reflex ◽

Before And After ◽

Median Diameter ◽

Receptor Block ◽

Normal Man ◽

End Tidal ◽

Ventilatory Response To Co2

1. The effect on ventilation of airway anaesthesia, produced by the inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter = 4.77 μm), was studied in 12 normal subjects. 2. The dose and distribution of the aerosol were determined from lung scans after the addition to bupivacaine of 99mTc. Bupivacaine labelled in this way was deposited primarily in the central airways. The effectiveness and duration of airway anaesthesia were assessed by the absence of the cough reflex to the inhalation of three breaths of a 5% citric acid aerosol. Airway anaesthesia always lasted more than 20 min. 3. Resting ventilation was measured, by respiratory inductance plethysmography, before and after inhalation of saline and bupivacaine aerosols. The ventilatory response to maximal incremental exercise and, separately, to CO2 inhalation was studied after the inhalation of saline and bupivacaine aerosols. Breathlessness was quantified by using a visual analogue scale (VAS) during a study and by questioning on its completion. 4. At rest, airway anaesthesia had no effect on mean tidal volume (VT), inspiratory time (Ti), expiratory time (Te) or end-tidal Pco2, although the variability of tidal volume was increased. On exercise, slower deeper breathing was produced and breathlessness was reduced. The ventilatory response to CO2 was increased. 5. The results suggest that stretch receptors in the airways modulate the pattern of breathing in normal man when ventilation is stimulated by exercise; their activation may also be involved in the genesis of the associated breathlessness. 6. A hypothesis in terms of a differential airway/alveolar receptor block, is proposed to explain the exaggerated ventilatory response to CO2.

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The Rate of Isometric Inspiratory Pressure Development as a Measure of Responsiveness to Carbon Dioxide in Man

Clinical Science ◽

10.1042/cs0490057 ◽

1975 ◽

Vol 49 (1) ◽

pp. 57-68 ◽

Cited By ~ 5

Author(s):

A. W. Matthews ◽

J. B. L. Howell

Keyword(s):

Initial Rate ◽

Ventilatory Response ◽

Pressure Change ◽

Normal Subjects ◽

Inspiratory Pressure ◽

Pulmonary Mechanics ◽

Inspiratory Muscles ◽

Pressure Development ◽

Respiratory Centre ◽

Very High

1. A technique has been developed for assessing CO2 responsiveness by measuring the maximum rate of isometric inspiratory pressure change at the mouth [(dP/dt)max.]. 2. By use of a rebreathing technique, the (dP/dt)max. response to CO2 was shown to correlate well with the ventilatory response in thirty-two normal subjects. 3. The addition of an external flow resistance sufficient to reduce the ventilatory response by a mean of 33.4% produced no significant mean change in the (dP/dt)max. response in thirty subjects. 4. In six patients recovering from bronchial asthma, reduction of airways obstruction led to a mean increase in the ventilatory response of 109% without any significant mean change in the (dP/dt)max. response. 5. An increase in lung volume did not reduce the (dP/dt)max. response in five normal subjects. 6. At very high lung volumes, six normal subjects were able to develop a higher (dP/dt)max. during voluntary inspiratory efforts than has been recorded during spontaneous breathing response to CO2. 7. It is believed that (dP/dt)max. represents the initial rate of development of force by the inspiratory muscles before this can be modified by mechanical loading, proprioceptive feedback mechanisms or conscious response and can therefore be used to study changes in the motor output of the respiratory centre in response to ventilatory stimuli independently of pulmonary mechanics.

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Depression of hypoxic ventilatory response in humans by somatostatin

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.3.1050 ◽

1988 ◽

Vol 65 (3) ◽

pp. 1050-1054 ◽

Cited By ~ 34

Author(s):

R. B. Filuk ◽

D. J. Berezanski ◽

N. R. Anthonisen

Keyword(s):

Intravenous Infusion ◽

Ventilatory Response ◽

Normal Subjects ◽

Small Decrease ◽

Hypoxic Ventilatory Response ◽

Arterial O2 Saturation ◽

Ventilatory Response To Hypoxia

In nine normal subjects we measured the ventilatory response to isocapnic hypoxia with and without an intravenous infusion of 1 mg of somatostatin. Arterial O2 saturation was rapidly lowered to 80 +/- 2% in 2 min and maintained for 30 min. During control experiments, ventilation increased immediately (3-5 min) and then declined so that at 25 min of hypoxia ventilation was little above that in room air. Somatostatin was associated with a small decrease in ventilation while the subjects breathed room air. With hypoxia there was no immediate increase in ventilation for the group as a whole, although an increase was observed in one subject. With somatostatin, after 25 min of hypoxia, mean ventilation was lower than at any other time in the study; as hypoxia was discontinued ventilation increased slightly. Somatostatin causes profound depression of the ventilatory response to hypoxia by a mechanism that is not known but may be central. With somatostatin hypoxia of 25-min duration tends to depress ventilation.

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Peripheral muscle ergoreceptors and ventilatory response during exercise recovery in heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.3.h913 ◽

1999 ◽

Vol 276 (3) ◽

pp. H913-H917 ◽

Cited By ~ 4

Author(s):

Noelle Francis ◽

Alain Cohen-Solal ◽

Damien Logeart

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ventilatory Response ◽

Normal Subjects ◽

Exercise Recovery ◽

Cuff Inflation ◽

Half Time ◽

Peripheral Muscle ◽

Patients With Heart Failure ◽

Kinetics Of

Recent studies have suggested that the increased ventilatory response during exercise in patients with chronic heart failure was related to the activation of muscle metaboreceptors. To address this issue, 23 patients with heart failure and 7 normal subjects performed arm and leg bicycle exercises with and without cuff inflation around the arms or the thighs during recovery. Obstruction slightly reduced ventilation and gas exchange variables at recovery but did not change the kinetics of recovery of these parameters compared with nonobstructed recovery: half-time of ventilation recovery was 175 ± 54 to 176 ± 40 s in patients and 155 ± 66 to 127 ± 13 s in controls ( P < 0.05, patients vs. controls, not significant within each group from baseline to obstructed recovery). We conclude that muscle metaboreceptor activation does not seem to play a role in the exertion hyperventilation of patients with heart failure.

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Intravenous adenosine and dyspnea in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00913.2004 ◽

2005 ◽

Vol 98 (1) ◽

pp. 180-185 ◽

Cited By ~ 61

Author(s):

Nausherwan K. Burki ◽

Wheeler J. Dale ◽

Lu-Yuan Lee

Keyword(s):

Heart Rate ◽

Heart Rate Response ◽

Ventilatory Response ◽

Normal Subjects ◽

Peripheral Chemoreceptor ◽

C Fibers ◽

Group Data ◽

Lung Resistance ◽

Time Latency ◽

Stimulation Of

Intravenous adenosine for the treatment of supraventricular tachycardia is reported to cause bronchospasm and dyspnea and to increase ventilation in humans, but these effects have not been systematically studied. We therefore compared the effects of 10 mg of intravenous adenosine with placebo in 21 normal subjects under normoxic conditions and evaluated the temporal sequence of the effects of adenosine on ventilation, dyspnea, and heart rate. The study was repeated in 11 of these subjects during hyperoxia. In all subjects, adenosine resulted in the development of dyspnea, assessed by handgrip dynamometry, without any significant change ( P > 0.1) in lung resistance as measured by the interrupter technique. There were significant increases ( P < 0.05) in ventilation and heart rate in response to adenosine. The dyspneic response occurred slightly before the ventilatory or heart rate responses in every subject, but the timing of the dyspneic, ventilatory, and heart rate responses was not significantly different when the group data were analyzed (18.9 ± 5.8, 20.3 ± 5.5, and 19.7 ± 4.5 s, respectively). During hyperoxia, adenosine resulted in similar effects, with no significant differences in the magnitude of the ventilatory response; however, compared with the normoxic state, the intensity of the dyspneic response was significantly ( P < 0.05) reduced, whereas the heart rate response increased significantly ( P < 0.05). These data indicate that intravenous adenosine-induced dyspnea is not associated with bronchospasm in normal subjects. The time latency of the response indicates that the dyspnea is probably not a consequence of peripheral chemoreceptor or brain stem respiratory center stimulation, suggesting that it is most likely secondary to stimulation of receptors in the lungs, most likely vagal C fibers.

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Relationship between inspiratory drive and perceived inspiratory effort in normal man

Clinical Science ◽

10.1042/cs0780493 ◽

1990 ◽

Vol 78 (5) ◽

pp. 493-496 ◽

Cited By ~ 4

Author(s):

J. E. Clague ◽

J. Carter ◽

M. G. Pearson ◽

P. M. A. Calverley

Keyword(s):

Ventilatory Response ◽

Free Breathing ◽

Normal Subjects ◽

Inspiratory Effort ◽

Respiratory Drive ◽

Occlusion Pressure ◽

Resistive Loading ◽

Mouth Occlusion Pressure ◽

The Individual ◽

Induced Changes

1. To examine the relationship between the inspiratory effort sensation (IES) and respiratory drive as reflected by mouth occlusion pressure (P0.1) we have studied loaded and unloaded ventilatory responses to CO2 in 12 normal subjects. 2. The individual coefficient of variation of the effort sensation response to CO2 (IES/Pco2) between replicate studies was 21% and was similar to the variability of the ventilatory response (VE/Pco2) (18%) and the occlusion pressure response (P0.1/Pco2) (22%). 3. IES was well correlated with P0.1 (r >0.9) for both free-breathing and loaded runs. 4. Resistive loading reduced the ventilatory response to hypercapnia from 19.3 1 min−1 kPa−1 (sd 7.5) to 12.6 1 min−1 kPa−1 (sd 3.9) (P <0.01). IES and P0.1 responses increased with resistive loading from 2.28 (sd 0.9) to 3.15 (sd 1.1) units/kPa and 2.8 (sd 1.2) to 3.73 (sd 1.5) cmH2O/kPa, respectively (P <0.01). 5. Experimentally induced changes in Pco2 and respiratory impedance were accompanied by increases in IES and P0.1. We found no evidence that CO2 increased IES independently of its effect on respiratory drive.

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Effect of resistive loading on ventilatory response to hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1975.38.6.965 ◽

1975 ◽

Vol 38 (6) ◽

pp. 965-968 ◽

Cited By ~ 5

Author(s):

A. S. Rebuck ◽

E. F. Juniper

Keyword(s):

Response Curve ◽

Mechanical Load ◽

Ventilatory Response ◽

Arterial Oxygen Saturation ◽

Normal Subjects ◽

Arterial Oxygen ◽

Resistive Load ◽

O2 Concentration ◽

Resistive Loading ◽

Ventilatory Response To Hypoxia

Ventilatory responses to hypoxia, with and without an inspiratory resistive load, were measured in eight normal subjects, using a rebreathing technique. During the studies, the end-tidal P-CO2 was kept constant at mixed venous level (Pv-CO2) by drawing expired gas through a variable CO2-absorbing bypass. The initial bag O2 concentration was 24% and rebreathing was continued until the O2 concentration in the bag fell to 6% or the subject's arterial oxygen saturation (Sa-O2), monitored continuously by ear oximetry, fell to 70%. 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 Sa-O2 were calculated. The range of unloaded responses was 0.78–3.59 1/min per 1% fall in Sa-O2 and loaded responses 0.37–1.68 1/min per 1% fall in Sa-O2. In each subject, the slope of the response curve during loading fell by an almost constant fraction of the unloaded response, such that the ratio of loaded to unloaded slope in all subjects ranged from 0.41 to 0.48. However, the extrapolated intercept of the response curve on the Sa-O2 axis did not alter significantly indicating that the P-CO2 did not alter between experiments. These results suggest that the change in ventilatory response to hypoxia during inspiratory resistive loading is related to the mechanical load applied, with the loaded slope being directly proportional to the unloaded one.

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