Time course of ozone-induced changes in breathing pattern in healthy exercising humans

2007 ◽  
Vol 102 (2) ◽  
pp. 688-697 ◽  
Author(s):  
Edward S. Schelegle ◽  
William F. Walby ◽  
William C. Adams

We examined the time course of O3-induced changes in breathing pattern in 97 healthy human subjects (70 men and 27 women). One- to five-minute averages of breathing frequency (fB) and minute ventilation (V̇e) were used to generate plots of cumulative breaths and cumulative exposure volume vs. time and cumulative exposure volume vs. cumulative breaths. Analysis revealed a three-phase response; delay, no response detected; onset, fB began to increase; response, fB stabilized. Regression analysis was used to identify four parameters: time to onset, number of breaths at onset, cumulative inhaled dose of ozone at onset of O3-induced tachypnea, and the percent change in fB. The effect of altering O3 concentration, V̇e, atropine treatment, and indomethacin treatment were examined. We found that the lower the O3 concentration, the greater the number of breaths at onset of tachypnea at a fixed ventilation, whereas number of breaths at onset of tachypnea remains unchanged when V̇e is altered and O3 concentration is fixed. The cumulative inhaled dose of O3 at onset of tachypnea remained constant and showed no relationship with the magnitude of percent change in fB. Atropine did not affect any of the derived parameters, whereas indomethacin did not affect time to onset, number of breaths at onset, or cumulative inhaled dose of O3 at onset of tachypnea but did attenuate percent change in fB. The results are discussed in the context of dose response and intrinsic mechanisms of action.

1995 ◽  
Vol 78 (2) ◽  
pp. 555-561 ◽  
Author(s):  
D. A. Sidney ◽  
C. S. Poon

To investigate how breathing is controlled during CO2 stimulation, steady-state ventilatory responses to rebreathing through a tube (DS) and inspiring a fixed PCO2 (INH) were compared in healthy human subjects. Tests were performed in hyperoxia with (IRL) and without (NL) an inspiratory resistive load (15 cmH2O.l–1.s at 1 l/s). The mean slope of the minute ventilation (VE)-end-tidal PCO2 relationship was significantly higher in DS-IRL than in INH-IRL [1.86 +/- 0.67 (SD) vs. 1.40 +/- 0.32 l.min-1.Torr-1, P < 0.01], and it was significantly different between INH-NL and INH-IRL (1.64 +/- 0.41 vs. 1.40 +/- 0.32 l.min-1.Torr-1, P < 0.05) but not between DS-NL and DS-IRL (1.85 +/- 0.72 vs. 1.86 +/- 0.67 l.min-1.Torr-1). The slope of the VE-tidal volume relationship was significantly lower in DS-NL than in INH-NL (19.6 +/- 3.8 vs. 21.2 +/- 5.1 min-1, P < 0.05), but other comparisons in breathing pattern between NL and IRL and between DS and INH failed to reach significance. We concluded that 1) alterations in alveolar PCO2 temporal profile by DS could induce changes in VE-end-tidal PCO2 sensitivity and ventilatory pattern, 2) these changes may be modified by increased mechanical impairment resulting from IRL, and 3) carotid chemoreceptor mediation is not necessary for the observed effects of DS.


1986 ◽  
Vol 61 (6) ◽  
pp. 2252-2259 ◽  
Author(s):  
E. P. Ingenito ◽  
J. Solway ◽  
E. R. McFadden ◽  
B. M. Pichurko ◽  
E. G. Cravalho ◽  
...  

A numerical computer model of heat and water transfer within the tracheobronchial tree of humans was developed based on an integral formulation of the first law of thermodynamics. Simulation results were compared with directly measured intraluminal airway temperature profiles previously obtained in normal human subjects, and a good correlation was demonstrated. The model was used to study aspects of regional pulmonary heat transfer and to predict the outcomes of experiments not yet performed. The results of these simulations show that a decrease in inspired air temperature and water content at fixed minute ventilation produces a proportionately larger increase in heat loss from extrathoracic airways relative to intrathoracic, whereas an increase in minute ventilation at fixed inspired air conditions produces the opposite pattern, with cold dry air penetrating further into the lung, and that changes in breathing pattern (tidal volume and frequency) at fixed minute ventilation and fixed inspiratory-to-expiratory (I/E) ratio do not affect local air temperature profiles and heat loss, whereas changes in I/E ratio at fixed minute ventilation do cause a significant change.


1983 ◽  
Vol 55 (4) ◽  
pp. 1311-1320 ◽  
Author(s):  
G. G. Haddad ◽  
M. R. Gandhi ◽  
G. M. Hochwald ◽  
T. L. Lai

We studied the changes in ventilation induced by intracisternal administration of enkephalins in four unanesthetized adult dogs. Instantaneous minute ventilation (VT/TT) decreased markedly after D-Ala-Met-enkephalinamide (DAME). Mean VT/TT decreased maximally by 20-50 min after DAME and lasted an additional 15-60 min; by 2 h, VT/TT had returned to base line. Four doses (5, 25, 60, and 125 micrograms/kg) of DAME were used, and the ventilatory response depended on the dose. Mean inspiratory time decreased but mean expiratory time and mean TT showed a marked prolongation. Periodic breathing (2-3 breaths separated by long apneic pauses) occurred in every study and the frequency of sighs increased considerably. All these ventilatory changes were reversed by low doses of naloxone or naltrexone; in addition, VT/TT increased well above base line after the administration of these antagonists. However, naloxone did not increase VT/TT when injected without prior administration of DAME. We conclude that 1) the decrease in VT/TT is due to a decrease in respiratory duty cycle; 2) periodic breathing and increased frequency of sighs constitute part of the changes in the ventilatory pattern induced by DAME; 3) a ventilatory withdrawal reaction may occur after a receptor-agonist interaction of short duration; and 4) although enkephalins can modulate ventilation and the breathing pattern in a major way, these data provide no evidence suggesting that this modulation is tonic.


2002 ◽  
Vol 93 (6) ◽  
pp. 2129-2136 ◽  
Author(s):  
A. S. Jordan ◽  
P. G. Catcheside ◽  
F. J. O'Donoghue ◽  
R. D. McEvoy

Obstructive sleep apnea (OSA) is more common in men than in women for reasons that are unclear. The stability of the respiratory controller has been proposed to be important in OSA pathogenesis and may be involved in the gender difference in prevalence. Repetitive hypoxia elicits a progressive rise in ventilation in animals [long-term facilitation (LTF)]. There is uncertainty whether LTF occurs in humans, but if present it may stabilize respiration and possibly also the upper airway. This study was conducted to determine 1) whether LTF exists during wakefulness in healthy human subjects and, if so, whether it is more pronounced in women than men and 2) whether inspiratory pump and upper airway dilator muscle activities are affected differently by repetitive hypoxia. Twelve healthy young men and ten women in the luteal menstrual phase were fitted with a nasal mask and intramuscular genioglossal EMG (EMGgg) recording electrodes. After 5 min of rest, subjects were exposed to ten 2-min isocapnic hypoxic periods (∼9% O2 in N2, arterial O2 saturation ∼80%) separated by 2 min of room air. Inspired minute ventilation (V˙i) and peak inspiratory EMGgg activity were averaged over 30-s intervals, and respiratory data were compared between genders during and after repetitive hypoxia by using ANOVA for repeated measures. V˙i during recovery from repetitive hypoxia was not different from the resting level and not different between genders. There was no facilitation of EMGgg activity during or after repetitive hypoxia. EMGgg activity was reduced below baseline during recovery from repetitive hypoxia in women. In conclusion, we have found no evidence of LTF of ventilation or upper airway dilator muscle activity in healthy subjects during wakefulness.


1992 ◽  
Vol 73 (3) ◽  
pp. 837-840 ◽  
Author(s):  
W. Knaupp ◽  
S. Khilnani ◽  
J. Sherwood ◽  
S. Scharf ◽  
H. Steinberg

Hypoxia causes an increased production of erythropoietin (EPO), but the time course of the EPO response in humans has not been well characterized. This study examines the relationship between the duration of normobaric hypoxic exposure and plasma EPO levels in healthy human subjects. Six volunteers breathed a gas mixture of 10.5% O2–89.5% N2 continuously for 5, 60, and 120 or intermittently for 240 min. O2 saturations were maintained between 75 and 85% during the exposure. Arterial pH was 7.467 +/- 0.019, PO2 37.05 +/- 2.43 Torr, and PCO2 36.69 +/- 2.05 Torr. O2 half-saturation pressures of hemoglobin were normal for all subjects. Plasma EPO was measured every 30 min for 360 min by radioimmunoassay. No increase in EPO was seen after the 5- and 60-min exposures. However, a 50% increase was seen 240 min after the initiation of the 120-min hypoxic exposure (P less than 0.01). Intermittent exposure resulted in an increase of EPO by 52% 360 min after the onset of exposure (P less than 0.05). Therefore, exposing humans continuously to an inspiratory O2 fraction of 0.105 for 120 min or intermittently for 240 min provides a sufficient stimulus to increase production of EPO.


1992 ◽  
Vol 263 (6) ◽  
pp. R1271-R1276 ◽  
Author(s):  
P. Burnier ◽  
L. Tappy ◽  
E. Jequier ◽  
D. Schneeberger ◽  
R. Chiolero

The metabolic and respiratory effects of intravenous 0.5 M sodium acetate (at a rate of 2.5 mmol/min during 120 min) were studied in nine normal human subjects. O2 consumption (VO2) and CO2 production (VCO2) were measured continuously by open-circuit indirect calorimetry. VO2 increased from 251 +/- 9 to 281 +/- 9 ml/min (P < 0.001), energy expenditure increased from 4.95 +/- 0.17 kJ/min baseline to 5.58 +/- 0.16 kJ/min (P < 0.001), and VCO2 decreased nonsignificantly (211 +/- 7 ml/min vs. 202 +/- 7 ml/min, NS). The extrapulmonary CO2 loss (i.e., bicarbonate generation and excretion) was estimated at 48 +/- 5 ml/min. This observation is consistent with 1 mol of bicarbonate generated from 1 mol of acetate metabolized. Alveolar ventilation decreased from 3.5 +/- 0.2 l/min basal to 3.1 +/- 0.2 l/min (P < 0.001). The minute ventilation (VE) to VO2 ratio decreased from 22.9 +/- 1.3 to 17.6 +/- 0.9 l/l (P < 0.005), arterial PO2 decreased from 93.2 +/- 1.9 to 78.7 +/- 1.6 mmHg (P < 0.0001), arterial PCO2 increased from 39.2 +/- 0.7 to 42.1 +/- 1.1 mmHg (P < 0.0001), pH from 7.40 +/- 0.005 to 7.50 +/- 0.007 (P < 0.005), and arterial bicarbonate concentration from 24.2 +/- 0.7 to 32.9 +/- 1.1 (P < 0.0001). These observations indicate that sodium acetate infusion results in substantial extrapulmonary CO2 loss, which leads to a relative decrease of total and alveolar ventilation.


1994 ◽  
Vol 76 (3) ◽  
pp. 1082-1087 ◽  
Author(s):  
F. O′Connell ◽  
V. E. Thomas ◽  
R. W. Fuller ◽  
N. B. Pride ◽  
J. A. Karlsson

We examined the effects of the alpha 2-receptor agonist clonidine, administered orally and by inhalation, on citric acid- and capsaicin-induced reflexes in guinea pigs and healthy human subjects. In groups (n = 8-10) of conscious guinea pigs, oral clonidine (10 and 100 micrograms/kg) was without effects, whereas inhaled clonidine (10–1,000 microM) caused a concentration-dependent inhibition of citric acid-induced cough (coughs during 3 min: control, 6.5 +/- 0.9; 1,000 microM clonidine, 1.7 +/- 1.0; P < 0.05) and reflex bronchoconstriction (time to onset of bronchoconstriction: control, 191 +/- 24 s; 1,000 microM clonidine, 317 +/- 33 s; P < 0.05). The inhibitory effect of inhaled clonidine on both reflexes was completely reversed by pretreatment with yohimbine but not with prazosin. In 12 healthy human volunteers, oral clonidine (150 mg) caused a significant fall in supine and erect systolic blood pressure and a significant increase in drowsiness as measured on a visual analogue scale 1 and 2 h after administration. Despite these effects, oral clonidine had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. In contrast to the effects in guinea pigs, inhaled clonidine (281 microM) had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. These data suggest that peripheral alpha 2-receptors exert an inhibitory effect on sensory neurotransmission in the guinea pig but not in the healthy human airway, indicating an important difference between the two species.


1986 ◽  
Vol 120 (1) ◽  
pp. 233-247 ◽  
Author(s):  
W.K. MILSOM ◽  
P. CHAN

Induced changes in resting lung volume (VLR) in the turtle Chrysemys picta (Schneider) had no effect on resting levels of minute ventilation in animals breathing room air but did change their breathing pattern. Increasing VLR caused an increase in the number of breaths in each episode (burst) of breathing but a reduction in the incidence of such breathing bursts and thus an increase in the length of periods of breath-holding. The data indicate that these effects were largely the consequence of changes in lung volume per se rather than changes in lung gas stores. Although both hypoxia and hypercapnia stimulated ventilation via increases in tidal volume and breathing frequency, they produced distinct changes in breathing pattern. While hypoxia (3% O2) caused an increase in the number of bursts of breathing (B/min) and reduced the number of breaths (b) in each burst (b/B), hypercapnia (5% CO2) increased both B/min and b/B. These data suggest that the size and incidence of bursts of breathing must be under separate control. One consequence of the different effects of hypoxia and hypercapnia on breaths per burst (b/B) was that hypoxic-hypercapnic gas mixtures (3% O2+5% CO2) failed to stimulate ventilation as much as hypercapnia alone. Administration of hypoxic, hypercapnic and hypoxic-hypercapnic gas mixtures to elevate respiratory drive eliminated the effects of changes in VLR on breathing pattern. Thus, although changes in VLR are important in the control of breathholding in animals breathing air, their effect decreases as respiratory drive increases.


2001 ◽  
Vol 57 (2) ◽  
pp. 7-10
Author(s):  
S. Narain ◽  
J. Lin ◽  
T. Puckree

This study examined the effects of ankle passive movement on lung function in healthy adults. A pre-test post-test experimental design was used. Passive plantar and dorsiflexion of the ankle were performed at 60 repetitions per minute on 60 healthy subjects in the supine position. Lung function at rest was compared to that during passive movements. The results indicated that all measured parameters including the breathing frequency, tidal volume, minute ventilation, oxygen consumption and carbon dioxide output, increased significantly during passive movements as compared to those at rest. The authors conclude that passive movements elicit a significant ventilatory increase in healthy human subjects. The effect of passive movements in the treatment of unconscious or diseased individuals should be investigated.


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