Aminophylline effects on ventilatory response to hypoxia and hyperoxia in normal adults

1989 ◽  
Vol 67 (3) ◽  
pp. 1150-1156 ◽  
Author(s):  
D. Georgopoulos ◽  
S. G. Holtby ◽  
D. Berezanski ◽  
N. R. Anthonisen
Keyword(s):  
Moving Average ◽  
Minute Ventilation ◽  
Base Line ◽  
Breathing Patterns ◽  
Average Technique ◽  
Carotid Bodies ◽  
Before And After ◽  
Arterial O2 Saturation ◽  
Hyperoxic Ventilation ◽  
Breathing Room

In 10 normal young adults, ventilation was evaluated with and without pretreatment with aminophylline, an adenosine blocker, while they breathed pure O2 1) after breathing room air and 2) after 25 min of isocapnic hypoxia (arterial O2 saturation 80%). With and without aminophylline, 5 min of hyperoxia significantly increased inspiratory minute ventilation (VI) from the normoxic base line. In control experiments, with hypoxia, VI initially increased and then declined to levels that were slightly above the normoxic base line. Pretreatment with aminophylline significantly attenuated the hypoxic ventilatory decline. During transitions to pure O2 (cessation of carotid bodies' output), VI and breathing patterns were analyzed breath by breath with a moving-average technique, searching for nadirs before and after hyperoxia. On placebo days, at the end of hypoxia, hyperoxia produced nadirs that were significantly lower than those observed with room-air breathing and also significantly lower than when hyperoxia followed normoxia, averaging, respectively, 6.41 +/- 0.52, 8.07 +/- 0.32, and 8.04 +/- 0.39 (SE) l/min. This hypoxic depression was due to significant decrease in tidal volume and prolongation of expiratory time. Aminophylline partly prevented these alterations in breathing pattern; significant posthypoxic ventilatory depression was not observed. We conclude that aminophylline attenuated hypoxic central depression of ventilation, although it does not affect hyperoxic steady-state hyperventilation. Adenosine may play a modulatory role in hypoxic but not in hyperoxic ventilation.

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)

Effect of 100% O2 on hypoxic eucapnic ventilation

1988 ◽  
Vol 65 (3) ◽  
pp. 1157-1162 ◽  
Author(s):  
S. G. Holtby ◽  
D. J. Berezanski ◽  
N. R. Anthonisen
Keyword(s):  
Young Adults ◽  
Ventilatory Response ◽  
Moving Average ◽  
Average Technique ◽  
Peripheral Chemoreceptors ◽  
Air Breathing ◽  
Central Origin ◽  
Before And After ◽  
Arterial O2 Saturation ◽  
Breathing Room

We measured ventilation in nine young adults while they breathed pure O2 after breathing room air and after 5 and 25 min of hypoxia. With isocapnic hypoxia (arterial O2 saturation 80 +/- 2%) mean ventilation increased at 5 min and then declined, so that at 25 min values did not differ from those on room air. After 3 min of O2 breathing, ventilation was greater than that on room air or after 25 min of isocapnic hypoxia, whether the hyperoxia had been preceded by hypoxia or normoxia. During transitions to pure O2 breathing, ventilation was analyzed breath by breath with a moving average technique, searching for nadirs before and after increases in PO2. After both 5 and 25 min of hypoxia, O2 breathing was associated with transient depressions of ventilation, which were greater after 25 min than after 5 min. Significant depressions were not observed when hyperoxia followed room air breathing, and O2-induced nadirs after hypoxia were lower than those observed during room air breathing. O2 transiently depressed ventilation after hypoxia but not after room air breathing. These results suggest that the normal ventilatory response to isocapnic hypoxia has two components, an excitatory one from peripheral chemoreceptors, which is turned off by O2 breathing, and a slower inhibitory one, probably of central origin, which is affected less promptly by O2 breathing.

Dopamine and carotid body function in the newborn lamb

1983 ◽  
Vol 54 (3) ◽  
pp. 814-820 ◽  
Author(s):  
D. E. Mayock ◽  
T. A. Standaert ◽  
R. D. Guthrie ◽  
D. E. Woodrum
Keyword(s):  
Carotid Body ◽  
Bolus Injection ◽  
Carotid Sinus ◽  
Minute Ventilation ◽  
Saline Control ◽  
Postnatal Life ◽  
Before And After ◽  
Breathing Room ◽  
Age Studies ◽  
Ventilatory Response To Hypoxia

The effect of dopamine on the acute ventilatory response to hypoxia was investigated in four newborn lambs studied on the 1st day of postnatal life and eight lambs studied between 7 and 12 days of age. Studies were accomplished during nonrapid-eye-movement sleep in unanesthetized tracheotomized animals. Changes in minute ventilation (VE/kg), tidal volume, and frequency induced by intravenous bolus injection of dopamine (10 micrograms/kg) or saline control were assessed while animals were breathing room air or N2, before and after carotid body denervation (CBD). Dopamine depressed resting ventilation at both postnatal ages. This effect was greater in the older animals. Dopamine blunted the hypoxia-induced increase in VE/kg at both ages. The magnitude of this depression did not vary with postnatal age. Dopamine induced cessation of respiratory effort at end expiration (apnea) during room air and N2 breathing significantly more often in the older animals. The effect of dopamine was mediated at the carotid body. CBD decreased ventilation by an increase in breath-to-breath interval in older animals, suggesting carotid sinus nerve afferent activity is more important during eucapnic respiration in older animals than in the immediate newborn period.

Respiratory effects of brief baroreceptor stimuli in the anesthetized dog

1985 ◽  
Vol 59 (4) ◽  
pp. 1258-1265 ◽  
Author(s):  
E. L. Dove ◽  
P. G. Katona
Keyword(s):  
Stimulus Onset ◽  
Base Line ◽  
Stimulus Magnitude ◽  
Carotid Bodies ◽  
Baroreceptor Stimulation ◽  
Before And After ◽  
Anesthetized Dogs ◽  
Line Pressure ◽  
Alpha Chloralose ◽  
Cardiovascular Variables

To quantify the immediate isocapnic respiratory response to baroreceptor stimulation, pressure in the isolated externally perfused carotid sinuses (CS) of 24 vagotomized alpha-chloralose-anesthetized dogs was increased selectively during either inspiration or expiration as a step (from time of onset to end of respiratory phase) or a pulse (500 ms). The rise time (150 ms), base-line pressure (80 mmHg), and stimulus magnitude (40 mmHg) were similar for the two stimuli. The time of stimulus onset (delay), expressed as a percent of control time of inspiration (TI) or expiration (TE), was varied. TI, TE, and tidal volume (VT) were expressed as percent changes from control. Stimuli delivered early in inspiration lengthened TI [23.5 +/- 6.4% (SE) for step and 11.7 +/- 6.3% for pulse stimuli at 5% delay] more effectively than late stimuli. VT was essentially unaltered. In contrast, step stimuli delivered during expiration caused a lengthening of TE (32.7 +/- 6.3% at 5% delay) that did not depend on the delay (up to 75%). Very late (85%) pulse stimuli lengthened TE (15.2 +/- 5.7%) more effectively than early stimuli. For both stimuli, the expiratory VT was unaltered. When the responses are compared before and after separation of the blood supply of the carotid bodies from the CS region and when they are compared before and after inhibition of reflex systemic hypotension by ganglionic blockade, the observed responses were shown to be due solely to CS baroreceptor stimulation and not to alterations in carotid body blood flow or reflex changes in systemic cardiovascular variables.

Role of the carotid bodies in chemosensory ventilatory responses in the anesthetized mouse

2004 ◽  
Vol 97 (4) ◽  
pp. 1401-1407 ◽  
Author(s):  
Masahiko Izumizaki ◽  
Mieczyslaw Pokorski ◽  
Ikuo Homma
Keyword(s):  
Tidal Volume ◽  
Carotid Body ◽  
Minute Ventilation ◽  
Respiratory Frequency ◽  
Whole Body ◽  
Sudden Increase ◽  
Ventilatory Responses ◽  
Carotid Bodies ◽  
Before And After ◽  
Carotid Body Denervation

We examined the effects of carotid body denervation on ventilatory responses to normoxia (21% O2 in N2 for 240 s), hypoxic hypoxia (10 and 15% O2 in N2 for 90 and 120 s, respectively), and hyperoxic hypercapnia (5% CO2 in O2 for 240 s) in the spontaneously breathing urethane-anesthetized mouse. Respiratory measurements were made with a whole body, single-chamber plethysmograph before and after cutting both carotid sinus nerves. Baseline measurements in air showed that carotid body denervation was accompanied by lower minute ventilation with a reduction in respiratory frequency. On the basis of measurements with an open-circuit system, no significant differences in O2 consumption or CO2 production before and after chemodenervation were found. During both levels of hypoxia, animals with intact sinus nerves had increased respiratory frequency, tidal volume, and minute ventilation; however, after chemodenervation, animals experienced a drop in respiratory frequency and ventilatory depression. Tidal volume responses during 15% hypoxia were similar before and after carotid body denervation; during 10% hypoxia in chemodenervated animals, there was a sudden increase in tidal volume with an increase in the rate of inspiration, suggesting that gasping occurred. During hyperoxic hypercapnia, ventilatory responses were lower with a smaller tidal volume after chemodenervation than before. We conclude that the carotid bodies are essential for maintaining ventilation during eupnea, hypoxia, and hypercapnia in the anesthetized mouse.

Ventilatory response to oxygen after eucapnic hypoxia in conscious dogs

1993 ◽  
Vol 74 (4) ◽  
pp. 1916-1920 ◽  
Author(s):  
K. Y. Cao ◽  
M. Berthon-Jones ◽  
C. E. Sullivan ◽  
C. W. Zwillich
Keyword(s):  
Ventilatory Response ◽  
Moving Average ◽  
Minute Ventilation ◽  
Conscious Dogs ◽  
Ventilatory Drive ◽  
Adult Humans ◽  
The Difference ◽  
Arterial O2 Saturation ◽  
Sustained Hypoxia ◽  
Ventilatory Response To Hypoxia

In humans the ventilatory [minute ventilation (VI)] response to sustained hypoxia is biphasic: an initial brisk increase followed by a decline is usually seen. However, in adult dogs, the ventilatory response to a similar stimulus shows no decline. To evaluate if central ventilatory drive is altered by sustained hypoxia, we measured the lowest ventilation (nadir) as the lowest moving average of seven sequential breaths within 200 s after transition to hyperoxia (100% O2) after 3 different exposures: room air, 4-min (brief) eucapnic hypoxia (arterial O2 saturation = approximately 80%), and 12-min (prolonged) eucapnic hypoxia. The nadir hyperoxic VI after brief hypoxia (2.7 +/- 0.2 l/min) was similar to that after room air (2.6 +/- 0.2 l/min; P > 0.05), with both less than prior room air mean VI (P < 0.05). The nadir after prolonged hypoxia (3.5 +/- 0.3 l/min) was significantly greater than that after brief hypoxia (P < 0.05). This suggests that central ventilatory drive increases in conscious dogs after sustained eucapnic hypoxia. The reason for the difference in central ventilatory response to hypoxia between conscious dogs and adult humans is unexplained.

Mechanisms of improved arterial oxygenation after peripheral chemoreceptor stimulation during hypoxic exercise

1993 ◽  
Vol 74 (4) ◽  
pp. 1666-1671 ◽  
Author(s):  
R. Naeije ◽  
C. Melot ◽  
G. Niset ◽  
M. Delcroix ◽  
P. D. Wagner
Keyword(s):  
Minute Ventilation ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Peripheral Chemoreceptor ◽  
Pulmonary Hemodynamics ◽  
Arterial Pco2 ◽  
Fractional Concentration ◽  
Before And After ◽  
Arterial O2 Saturation ◽  
Hypoxic Exercise

Almitrine, a peripheral chemoreceptor agonist, has been reported to increase arterial O2 saturation (SaO2) without changing minute ventilation (VE) during hypoxic exercise (Giesbrecht et al. J. Appl. Physiol. 70: 1770–1774, 1991). To explain this finding, we studied pulmonary hemodynamics (right heart catheterization) and gas exchange (multiple inert gas elimination technique) in six healthy volunteers at rest and during heavy exercise in normobaric normoxia (fractional concentration of O2 in inspired air 0.21) or hypoxia (fractional concentration of O2 in inspired air 0.125), before and after 75 mg of almitrine taken orally. During normoxic exercise, at a mean O2 uptake (VO2) of 4.0 l/min, almitrine increased arterial PO2 (PaO2) (P < 0.05), SaO2 (P < 0.01), and VE (P < 0.05) and decreased arterial PCO2 (P < 0.01), without affecting pulmonary hemodynamics or ventilation-perfusion distributions. During hypoxic exercise, at a mean VO2 of 3.0 l/min, almitrine increased SaO2 (P < 0.01) and VE (P < 0.01) and decreased arterial PCO2 (P < 0.05), with no effect on PaO2 or on ventilation-perfusion distributions and with a slight pulmonary vasoconstriction (P < 0.01). Almitrine during hypoxia did not affect cardiac output or calculated O2 diffusing capacity, but it did increase the slope of the VE/VO2 relationship (P < 0.01). We conclude that during hypoxic exercise, a pharmacological stimulation of the peripheral chemoreceptors improves SaO2 but not PaO2 by means of increased ventilation and an associated leftward shift of the oxyhemoglobin dissociation curve.

Attenuation of hypoxic ventilation by hyperbaric O2: effects of pressure and exposure time

1989 ◽  
Vol 66 (2) ◽  
pp. 851-856 ◽  
Author(s):  
I. Liberzon ◽  
R. Arieli ◽  
D. Kerem
Keyword(s):  
Exposure Time ◽  
Minute Ventilation ◽  
Quantitative Description ◽  
Time Duration ◽  
Reduced Frequency ◽  
Carotid Bodies ◽  
Scale Of Effect ◽  
Before And After ◽  
Control Response ◽  
Hyperbaric O2

Hyperoxia affects O2 chemoreception in the highly perfused carotid bodies and causes a reduction of the ventilatory hypoxic drive (HD) as was shown for anesthetized cats and awake rats. We looked for a quantitative description of such an effect on HD as a function of both O2 pressure and exposure duration. Ventilation of rats was measured using the barometric method before and after hyperbaric O2 (HBO) exposure, at either air, 80% O2, or 4% O2. We used three exposure durations: 180, 550 and 900 min. The O2 pressure ranged between 1.2 and 3.0 ATA. At each time duration we used four to five groups of rats at a range of O2 pressures that yielded the full scale of effect on HD but avoided obvious lasting difficulties in breathing. HBO caused a reduction of breathing frequency and elevation of tidal volume in both air and 80% O2 but almost no change in minute ventilation. Hypoxic minute ventilation (4% O2) decreased after HBO, mainly through reduced frequency. HD was described by a power function of O2 pressure for each HBO duration. HD did not decline below 20% of the full control response. Ventilatory HD diminution is pictured as a function of both O2 pressure and HBO duration. The dependency of HD on exposure time and on pressure is similar to other known toxic effects of HBO.

Breathing Pattern during and after Smoking Cigarettes

1982 ◽  
Vol 63 (5) ◽  
pp. 473-483 ◽  
Author(s):  
Martin J. Tobin ◽  
Anne W. Schneider ◽  
Marvin A. Sackner
Keyword(s):  
Breathing Pattern ◽  
Minute Ventilation ◽  
Systematic Difference ◽  
Breathing Patterns ◽  
Inspiratory Time ◽  
Stimulant Effect ◽  
Respiratory Inductive Plethysmography ◽  
Before And After ◽  
Respiratory Centre ◽  
Airway Conductance

1. The breathing patterns of ten habitual smokers were monitored in the semi-recumbent position with respiratory inductive plethysmography before and after smoking cigarettes. The subjects smoked a high-tar-content (HTC) and a low-tar-content (LTC) cigarette. The mean (±sd) values and frequency histograms of minute ventilation , tidal volume (VT), frequency (fR), inspiratory time (TI), fractional inspiratory time (TI/TTOT) and mean inspiratory flow (VT/TI) during baseline were compared with the values during and after smoking. 2. On a separate occasion, specific airway conductance (sGaw) and multiple-breath nitrogen washout were measured before and after smoking in six of the subjects. 3. One group of smokers (n = 4) had a greatly increased mean (±sd) baseline VT/TI (390 ± 39 ml/s) compared with normal non-smokers and another group (n = 6) a near normal VT/TI (246 ± 36 ml/s). The first group (‘deep inhalers’) had a significantly higher mean inhalation fraction (volume of inhaled smoke and air/vital capacity; 0·25 ± 0·05). The second group had a lower mean inhalation fraction of 0·14 ± 003 (‘moderate inhalers’). 4. VT/TI decreased to 323 ± 33 ml/s in the post-smoking period in the deep inhalers, whereas it increased to 345 ± 65 ml/s in the moderate inhalers during smoking. No systematic difference in VT/TI was noted between smoking high- and low-tar cigarettes, although the high-tar brand tended to have a greater effect on VT/TI. Deep inhalers showed a fall in VT during and after smoking. Moderate inhalers showed a decrease in TI/TTOT during and after smoking. 5. sGaw, measured in four moderate inhalers and two deep inhalers, fell in all subjects after smoking HTC (19 ± 8·7%; P < 0·01) and LTC (13·9 ± 10%) cigarettes. 6. ‘Sham’ smoking with an unlit cigarette produced no change in breathing pattern. 7. In moderate inhalers, the increase in respiratory output (as reflected by increased VT/TI) combined with a reduction in TI/TTOT appears to reflect the respiratory-centre stimulant effect of nicotine directly or indirectly through broncho-constriction. This contrasts with the reduced neural drive in deep inhalers, which may relate to some overriding satiating effect of the smoking.

Naloxone reduces ventilatory depression of brain hypoxia

1987 ◽  
Vol 63 (2) ◽  
pp. 699-706 ◽  
Author(s):  
J. A. Neubauer ◽  
M. A. Posner ◽  
T. V. Santiago ◽  
N. H. Edelman
Keyword(s):  
Minute Ventilation ◽  
Linear Increase ◽  
Endogenous Opioids ◽  
Base Line ◽  
Endogenous Opioid ◽  
Brain Hypoxia ◽  
Ph Response ◽  
Before And After ◽  
Ventral Medullary Surface ◽  
Ventilatory Depression

To assess whether endogenous opioids participate in respiratory depression due to brain hypoxia, we determined the ventilatory response to progressive carboxyhemoglobinemia (1% CO, 40% O2) before and after administration of naloxone (NLX, 0.1 mg/kg iv). Minute ventilation (VI) and ventral medullary surface pH (Vm pH) were measured in six anesthetized, peripherally chemodenervated cats. NLX consistently increased base-line hyperoxic VI from 618 +/- 99 to 729 +/- 126 ml/min (P less than 0.05). Although NLX did not alter the Vm pH response to CO [initial alkalosis, Vm pH +0.011 +/- 0.003 pH units, followed by acidosis, Vm pH -0.082 +/- 0.036 at carboxyhemoglobin (HbCO) 55%], NLX attenuated the amount of ventilatory depression; increasing HbCO to 55% decreased VI to 66 +/- 6% of base line before NLX and to 81 +/- 9% of base line after NLX (P less than 0.05). The difference in response after NLX was primarily the result of a linear increase in tidal volume (VT) with decreasing Vm pH (delta VT = 60.3 ml/-pH unit) which was absent before NLX. To assess whether the site of action of the endogenous opioid effect was the central chemosensors, the ventilatory and Vm pH response to progressive HbCO was determined in three additional cats before and after topical application of NLX (3 X 10(-4) M) to the ventral medullary surface. The effect of topical NLX was similar to systemic NLX; significant attenuation of the reduction in VI with increasing HbCO. We conclude that 1) endogenous opioids mediate a portion of the depression of ventilation due to acute brain hypoxia, and 2) this effect is probably at the central chemosensitive regions.

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