Effect of a single breath of 100% oxygen on respiration in neonates during sleep

To determine the effect of a single breath of 100% O2 on ventilation, 10 full-term [body wt 3,360 +/- 110 (SE) g, gestational age 39 +/- 0.4 wk, postnatal age 3 +/- 0.6 days] and 10 preterm neonates (body wt 2,020 +/- 60 g, gestational age 34 +/- 2 wk, postnatal age 9 +/- 2 days) were studied during active and quiet sleep states. The single-breath method was used to measure peripheral chemoreceptor response. To enhance response and standardize the control period for all infants, fractional inspired O2 concentration was adjusted to 16 +/- 0.6% for a control O2 saturation of 83 +/- 1%. After 1 min of control in each sleep state, each infant was given a single breath of O2 followed by 21% O2. Minute ventilation (VE), tidal volume (VT), breathing frequency (f), alveolar O2 and CO2 tension, O2 saturation (ear oximeter), and transcutaneous O2 tension were measured. VE always decreased with inhalation of O2 (P less than 0.01). In quiet sleep, the decrease in VE was less in full-term (14%) than in preterm (40%) infants (P less than 0.001). Decrease in VE was due primarily to a drop in VT in full-term infants as opposed to a fall in f and VT in preterm infants (P less than 0.05). Apnea, as part of the response, was more prevalent in preterm than in full-term infants. In active sleep the decrease in VE was similar both among full-term (19%) and preterm (21%) infants (P greater than 0.5). These results suggest greater peripheral chemoreceptor response in preterm than in full-term infants, reflected by a more pronounced decrease in VE with O2. The results are compatible with a more powerful peripheral chemoreceptor contribution to breathing in preterm than in full-term infants.     

A respiratory sensory reflex in response to CO2 inhibits breathing in preterm infants.

Traditionally, the increase in ventilation occurring after approximately 4 s of CO2 inhalation in preterm infants has been attributed to an action at the peripheral chemoreceptors. However, on a few occasions, we have observed a short apnea (2-3 s) in response to 3-5% CO2 in these infants. To test the hypothesis that this apnea reflects a respiratory sensory reflex to CO2, we gave nine preterm infants [birth wt 1.5 +/- 0.1 (SE) kg, gestational age 31 +/- 1 wk] 7-8% CO2 while they breathed 21% O2. To study the dose-response relationship, we also gave 2, 4, 6, and 8% CO2 to another group of seven preterm infants (birth wt 1.5 +/- 0.1 kg, gestational age 31 +/- 1 wk). In the first group of infants, minute ventilation during 21% O2 breathing (0.232 +/- 0.022 l.min-1.kg-1) decreased after CO2 administration (0.140 +/- 0.022, P < 0.01) and increased with CO2 removal (0.380 +/- 0.054, P < 0.05). This decrease in ventilation was related to an apnea (12 +/- 2.6 s) occurring 7.7 +/- 0.8 s after the beginning of CO2 inhalation. There was no significant change in tidal volume. In the second group of infants, minute ventilation increased during administration of 2, 4, and 6% CO2 but decreased during 8% CO2 because of the presence of an apnea. These findings suggest that inhalation of a high concentration of CO2 (> 6%) inhibits breathing through a respiratory sensory reflex, as described in adult cats (H. A. Boushey and P. S. Richardson. J. Physiol. Lond. 228: 181-191, 1973).(ABSTRACT TRUNCATED AT 250 WORDS)     

Inspired CO(2) and O(2) in sleeping infants rebreathing from bedding: relevance for sudden infant death syndrome.

Some infants sleep facedown for long periods with no ill effects, whereas others become hypoxemic. Rebreathing of expired air has been determined by CO(2) measurement; however, O(2) levels under such conditions have not been determined. To evaluate this and other factors influencing inspired gas concentrations, we studied 21 healthy infants during natural sleep while facedown on soft bedding. We measured gas exchange with the environment and bedding, ventilatory response to rebreathing, and concentrations of inspired CO(2) and O(2). Two important factors influencing inspired gas concentrations were 1) a variable seal between bedding and infants' faces and 2) gas gradients in the bedding beneath the infants, with O(2)-poor and CO(2)-rich air nearest to the face, fresher air distal to the face, and larger tidal volumes being associated with fresher inspired air. Minute ventilation increased significantly while rebreathing because of an increase in tidal volume, not frequency. The measured drop in inspired O(2) was significantly greater than the accompanying rise in inspired CO(2). This appears to be due to effects of the respiratory exchange ratio and differential tissue solubilities of CO(2) and O(2) during unsteady conditions.     

Ventilatory response to exercise in aged runners breathing He-O2 or inspired CO2.

The ventilatory response to exercise below ventilatory threshold (VTh) increases with aging, whereas above VTh the ventilatory response declines only slightly. We wondered whether this same ventilatory response would be observed in older runners. We also wondered whether their ventilatory response to exercise while breathing He-O(2) or inspired CO(2) would be different. To investigate, we studied 12 seniors (63 +/- 4 yr; 10 men, 2 women) who exercised regularly (5 +/- 1 days/wk, 29 +/- 11 mi/wk, 16 +/- 6 yr). Each subject performed graded cycle ergometry to exhaustion on 3 separate days, breathing either room air, 3% inspired CO(2), or a heliox mixture (79% He and 21% O(2)). The ventilatory response to exercise below VTh was 0.35 +/- 0.06 l x min(-1) x W(-1) and above VTh was 0.66 +/- 0.10 l x min(-1) x W(-1). He-O(2) breathing increased (P < 0.05) the ventilatory response to exercise both below (0.40 +/- 0.12 l x min(-1) x W(-1)) and above VTh (0.81 +/- 0.10 l x min(-1) x W(-1)). Inspired CO(2) increased (P < 0.001) the ventilatory response to exercise only below VTh (0.44 +/- 0.10 l x min(-1) x W(-1)). The ventilatory responses to exercise with room air, He-O(2), and CO(2) breathing of these fit runners were similar to those observed earlier in older sedentary individuals. These data suggest that the ventilatory response to exercise of these senior runners is adequate to support their greater exercise capacity and that exercise training does not alter the ventilatory response to exercise with He-O(2) or inspired CO(2) breathing.     

Postnatal developmental changes in CO2 sensitivity in rats.

Ventilatory sensitivity to CO(2) in awake adult Brown Norway (BN) rats is 50-75% lower than in adult Sprague-Dawley (SD) and salt-sensitive Dahl S (SS) rats. The purpose of the present study was to test the hypothesis that this difference would be apparent during the development of CO(2) sensitivity. Four litters of each strain were divided into four groups such that rats were exposed to 7% inspired CO(2) for 5 min in a plethysmograph every third day from postnatal day (P) 0 to P21 and again on P29 and P30. From P0 to P14, CO(2) exposure increased pulmonary ventilation (Ve) by 25-50% in the BN and SD strains and between 25 to over 200% in the SS strain. In all strains beginning around P15, the response to CO(2) increased progressively reaching a peak at P19-21 when Ve during hypercapnia was 175-225% above eucapnia. There were minimal changes in CO(2) sensitivity between P21 and P30, and at both ages there were minimal between-strain differences. At P30, the response to CO(2) in the SS and SD strains was near the adult response, but the response in the BN rats was 100% greater at P30 than in adults. We conclude that 1) CO(2)-sensing mechanisms, and/or mechanisms downstream from the chemoreceptors, change dramatically at the age in rats when other physiological systems are also maturing ( approximately P15), and 2) there is a high degree of age-dependent plasticity in CO(2) sensitivity in rats, which differs between strains.     

Effects of CO2 rebreathing on pulmonary mechanics in premature infants

The effects of hypercapnia produced by CO2 rebreathing on total pulmonary, supraglottic, and lower airway (larynx and lungs) resistance were determined in eight premature infants [gestational age at birth 32 +/- 3 (SE) wk, weight at study 1,950 +/- 150 g]. Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a fluid-filled or 5-Fr Millar pressure catheter. Trials of hyperoxic (40% inspired O2 fraction) CO2 rebreathing were performed during quiet sleep. Total pulmonary resistance decreased progressively as end-tidal PCO2 (PETCO2) increased from 63 +/- 23 to 23 +/- 15 cmH2O.l-1.s in inspiration and from 115 +/- 82 to 42 +/- 27 cmH2O.l-1.s in expiration between room air (PETCO2 37 Torr) and PETCO2 of 55 Torr (P less than 0.05). Lower airway resistance (larynx and lungs) also decreased from 52 +/- 22 to 18 +/- 14 cmH2O.l-1.s in inspiration and from 88 +/- 45 to 30 +/- 22 cmH2O.l-1.s in expiration between PETCO2 of 37 and 55 Torr, respectively (P less than 0.05). Resistance of the supraglottic airway also decreased during inspiration from 7.2 +/- 2.5 to 3.6 +/- 2.5 cmH2O.l-1.s and in expiration from 7.6 +/- 3.3 to 5.3 +/- 4.7 cmH2O.l-1.s at PETCO2 of 37 and 55 Torr (P less than 0.05). The decrease in resistance that occurs within the airway in response to inhaled CO2 may permit greater airflow at any level of respiratory drive, thereby improving the infant's response to CO2.     

Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep.

To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired P(O2). We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O2 saturation = 78-80%), and hyperoxia (inspired O2 fraction = 50-52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sigh-like breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 +/- 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 +/- 0.8 s; P < 0.05), whereas hyperoxia prolonged it (71.5 +/- 13.8 s; P < 0.01). The apneic threshold end-tidal P(CO2) (Pet(CO2)) was defined as the Pet(CO2)) at the onset of apnea. During hypoxia, the apneic threshold Pet(CO2) was higher (38.9 +/- 1.7 Torr; P < 0.01) compared with normoxia (35.8 +/- 1.1; Torr); during hyperoxia, it was lower (33.0 +/- 0.8 Torr; P < 0.05). Furthermore, the difference between the eupneic Pet(CO2) and apneic threshold Pet(CO2) was smaller during hypoxia (3.0 +/- 1.0 Torr P < 001) and greater during hyperoxia (10.6 +/- 0.8 Torr; P < 0.05) compared with normoxia (8.0 +/- 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO2 below the eupneic Pet(CO2) was increased by hypoxia (3.44 +/- 0.63 l.min(-1).Torr(-1); P < 0.05) and decreased by hyperoxia (0.63 +/- 0.04 l.min(-1).Torr(-1); P < 0.05) compared with normoxia (0.79 +/- 0.05 l.min(-1).Torr(-1)). These findings indicate that posthyperventilation apnea is initiated by the peripheral chemoreceptors and that the varying susceptibility to apnea during hypoxia vs. hyperoxia is influenced by the relative activity of these receptors.     

Blood osmolality during in vivo changes of CO2 pressure

In 16 experiments male subjects, age 22.4 +/- 0.5 (SE) yr, inspired CO2 for 15 min (8% end-tidal CO2) or hyperventilated for 30 min (2.5% end-tidal CO2). Osmolality (Osm) and acid-base status of arterialized venous blood were determined at short intervals until 30 min after hypo- and hypercapnia, respectively. During hypocapnia [CO2 partial pressure (PCO2) -2.31 +/- 0.32 kPa (-17.4 Torr), pH + 0.19 units], Osm decreased by 3.9 +/- 0.3 mosmol/kg H2O; during hypercapnia [PCO2 + 2.10 +/- 0.28 kPa (+15.8 Torr), pH -0.12 units], Osm increased by 5.8 +/- 0.7 mosmol/kg H2O. Presentation of the data in Osm-PCO2 or Osm-pH diagrams yields hysteresis loops probably caused by exchange between blood and tissues. The dependence of Osm on PCO2 must result mainly from CO2 buffering and therefore from the formation of bicarbonate. In spite of the different buffer capacities in various body compartments, water exchange allows rapid restoration of osmotic equilibrium throughout the organism. Thus delta Osm/delta pH during a PCO2 jump largely depends on the mean buffer capacity of the whole body. The high estimated buffer value during hypercapnia (38 mmol/kg H2O) compared with hypocapnia (19 mmol/kg H2O) seems to result from very strong muscle buffering during moderate acidosis.     

Changes in Ethylene Production and 1-Aminocyclopropane-l-carboxylic acid Levels in Climacteric Apple Fruits Ralls under Low O2 and High CO2

Ethylene production was severely inhibited in climacteric applefruits treated with either low O2(O2 :1–3%, CO2: 0%)or high CO2(O2:15–21%, CO2:10–20%) for 4, 10, and 15 days, respectively. In treatment with low O2 for 10 or 15days, 1-aminocyclopropane-1-carboxylic acid (ACC) was accumulated in large quantity,but in the fruit treated with high CO2, the content of ACC was slightly lower than thatin control fruit. When the fruit was turned to air after 4-days treatment with low O2, ethylene production and ACC content were able to recover to control level. But in the fruits withlow O2 for 10 or 15 days ethylene production was 100 times lower, and ACC contentwas much higher than those in control even 30-35 days after they were turned to air. It appears that inhibitory effect of the low O2 treatment for longer than 10 days on theconversion of ACC to ethylene was irreversible. In the case of high CO2 treatment fordifferent periods ethylene production obviously decreased at first, then followed by arapid increase. When the fruits were turned to air ethylene production in the treat-ment for 4 days was able to recover to control level, but it remained much lower in tre-atment for 10 or 15 days than that in control throughout the period of recovery. However, ACC contents in both treatments were slightly lower than those in control during a few days after the removal of treatment, but increased slightly after 2-3 weeks.Furthemore, the ability of flesh discs to convert exogenous ACC to ethylene was redu-ced remarkably by the treatment of fruits with either low O2 or high CO2 for longerthan 10 days.     

Ventilatory response of the sleeping newborn to CO2 during normoxic rebreathing

The ventilatory response of the newborn to CO2 was studied using a rebreathing method that minimized changes in arterial PO2 during the test. The aim was to study the variability of the ventilatory response to CO2 and take this into account to assess the relative magnitude of the response to CO2 during rapid-eye-movement (REM) sleep and quiet sleep (QS). Five full-term babies aged 4-6 days were given 5% CO2 in air to rebreathe for 1.5-3 min. O2 was added to the rebreathing circuit to maintain arterial O2 saturation and transcutaneous PO2 (Ptco2) at prerebreathing levels. Tests were repeated four to five times in REM sleep and QS. Mean Ptco2 levels varied between individuals but were similar during REM sleep and QS tests for each subject. The mean coefficient of variability of the ventilatory response was 35% (range 15-77%) during QS and 120% (range 32-220%) during REM sleep. PtcO2 fluctuations during tests [6.0 +/- 3.0 (SD) Torr, range 1-13 Torr] were not correlated with ventilatory response. Overall the ventilatory response was significantly lower in REM sleep than in QS (12.2 +/- 3.0 vs. 38.7 +/- 3.0 ml.min-1.Torr-1.kg-1, P less than 0.001; 2-way analysis of variance) due to a small (nonsignificant) fall in the tidal volume response and a significant fall in breathing rate. In 12 REM sleep tests there was no significant ventilatory response; mean inspiratory flow increased significantly during 8 of these 12 tests. We conclude that there is a significant decrease in the ventilatory response of the newborn to CO2 rebreathing during REM sleep compared with QS.     

Effects of inhaled oxygen (up to 40%) on periodic breathing and apnea in preterm infants.

To discover whether increases in inhaled O2 fraction (FIO2; up to 40%) decrease apnea via an increase in minute ventilation (VE) or a change in respiratory pattern, 15 preterm infants (birth weight 1,300 +/- 354 g, gestational age 29 +/- 2 wk, postnatal age 20 +/- 9 days) breathed 21, 25, 30, 35, and 40% O2 for 10 min in quiet sleep. A nosepiece and a flow-through system were used to measure ventilation. Alveolar PCO2, transcutaneous PO2, and sleep states were also assessed. All infants had periodic breathing with apneas greater than or equal to 3 s. With an increase in FIO2 breathing became more regular and apneas decreased (P less than 0.001). This regularization in breathing was not associated with significant changes in VE. However, the variability of VE, tidal volume, and expiratory and inspiratory times decreased significantly. The results indicate that the more regular breathing observed with small increases in FIO2 was not associated with significant changes in ventilation. The findings suggest that the increased oxygenation decreases apnea and periodicity in preterm infants, not via an increase in ventilation, but through a decrease in breath-to-breath variability of VE.     

Bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

We demonstrated spontaneous self-limited bronchoconstriction after eucapnic dry gas hyperpnea in 22 anesthetized, mechanically ventilated guinea pigs pretreated with propranolol (1 mg/kg iv). Eucapnic hyperpnea "challenges" of room temperature dry or humidified gas (5% CO2-95% O2) were performed by mechanically ventilating animals (150 breaths/min, 3-6 ml tidal volume) for 5 min. During a "recovery" period after hyperpnea, animals were returned to standard ventilation conditions (6 ml/kg, 60 breaths/min, 50% O2 in air, fully saturated at room temperature). After dry gas hyperpnea (5 ml, 150 breaths/min), respiratory system resistance (Rrs) increased in the recovery period by 7.7-fold and dynamic compliance (Cdyn) decreased by 79.7%; changes were maximal at approximately 3 min posthyperpnea and spontaneously returned to base line in 10-40 min. This response was markedly attenuated by humidification of inspired air. Four consecutive identical dry air challenges resulted in similar posthyperpnea responses in four animals. Increasing the minute ventilation during hyperpnea (by varying tidal volume from 3 to 6 ml) caused increased bronchoconstriction in a dose-dependent fashion in six animals. Neither vagotomy nor atropine altered the airway response to dry gas hyperpnea. We conclude that dry gas hyperpnea in anesthetized guinea pigs results in a bronchoconstrictor response that shares five similar features with hyperpnea-induced bronchoconstriction in human asthma: 1) time course of onset and spontaneous resolution, 2) diminution with humidification of inspired gas, 3) reproducibility on consecutive identical challenges, 4) stimulus-response relationship with minute ventilation during hyperpnea, and 5) independence of parasympathetic neurotransmission.     

Ventilatory and carotid body chemoreceptor responses to purinergic P2X receptor antagonists in newborn rats

Adenosine triphosphate, acting through purinergic P2X receptors, has been shown to stimulate ventilation and increase carotid body chemoreceptor activity in adult rats. However, its role during postnatal development of the ventilatory response to hypoxia is yet unknown. Using whole body plethysmography, we measured ventilation in normoxia and in moderate hypoxia (12% fraction of inspired O?, 20 min) before and after intraperitoneal injection of suramin (P2X? and P2X? receptor antagonist, 40 mg/kg) in 4-, 7-, 12-, and 21-day-old rats. Suramin reduced baseline breathing (～20%) and the response to hypoxia (～30%) in all rats, with a relatively constant effect across ages. We then tested the effect of the specific P2X? antagonist, A-317491 (150 mg/kg), in rats aged 4, 7, and 21 days. As with suramin, A-317491 reduced baseline ventilation (～55%) and the hypoxic response (～40%) at all ages studied. Single-unit carotid body chemoreceptor activity was recorded in vitro in 4-, 7-, and 21-day-old rats. Suramin (100 μM) and A-317491 (10 μM) significantly depressed the sinus nerve chemosensory discharge rate (～80%) in normoxia (Po? ～150 Torr) and hypoxia (Po? ～60 Torr), and this decrease was constant across ages. We conclude that, in newborn rats, P2X purinergic receptors are involved in the regulation of breathing under basal and hypoxic condition, and P2X?-containing receptors play a major role in carotid body function. However, these effects are not age dependent within the age range studied.     

Hyperbaric hyperoxia reduces exercising forearm blood flow in humans

Hypoxia during exercise augments blood flow in active muscles to maintain the delivery of O(2) at normoxic levels. However, the impact of hyperoxia on skeletal muscle blood flow during exercise is not completely understood. Therefore, we tested the hypothesis that the hyperemic response to forearm exercise during hyperbaric hyperoxia would be blunted compared with exercise during normoxia. Seven subjects (6 men/1 woman; 25 ± 1 yr) performed forearm exercise (20% of maximum) under normoxic and hyperoxic conditions. Forearm blood flow (FBF; in ml/min) was measured using Doppler ultrasound. Forearm vascular conductance (FVC; in ml·min(-1)·100 mmHg(-1)) was calculated from FBF and blood pressure (in mmHg; brachial arterial catheter). Studies were performed in a hyperbaric chamber with the subjects supine at 1 atmospheres absolute (ATA) (sea level) while breathing normoxic gas [21% O(2), 1 ATA; inspired Po(2) (Pi(O(2))) ≈ 150 mmHg] and at 2.82 ATA while breathing hyperbaric normoxic (7.4% O(2), 2.82 ATA, Pi(O(2)) ≈ 150 mmHg) and hyperoxic (100% O(2), 2.82 ATA, Pi(O(2)) ≈ 2,100 mmHg) gas. Resting FBF and FVC were less during hyperbaric hyperoxia compared with hyperbaric normoxia (P < 0.05). The change in FBF and FVC (Δ from rest) during exercise under normoxia (204 ± 29 ml/min and 229 ± 37 ml·min(-1)·100 mmHg(-1), respectively) and hyperbaric normoxia (203 ± 28 ml/min and 217 ± 35 ml·min(-1)·100 mmHg(-1), respectively) did not differ (P = 0.66-0.99). However, the ΔFBF (166 ± 21 ml/min) and ΔFVC (163 ± 23 ml·min(-1)·100 mmHg(-1)) during hyperbaric hyperoxia were substantially attenuated compared with other conditions (P < 0.01). Our data suggest that exercise hyperemia in skeletal muscle is highly dependent on oxygen availability during hyperoxia.     

Effect of upper airway CO2 on breathing in awake ponies

We determined whether the [CO2] in the upper airways (UA) can influence breathing in ponies and whether UA [CO2] contributes to the attenuation of a thermal tachypnea during periods of elevated inspired CO2. Six ponies were studied 1 mo after chronic tracheostomies were created. For one protocol the ponies were breathing room air through a cuffed endotracheal tube. Another smaller tube was placed in the tracheostomy and directed up the airway. By use of this tube, a pump, and prepared gas mixtures, UA [CO2] was altered without affecting alveolar or arterial PCO2. When the ponies were at a neutral environmental temperature (TA) and breathing frequency (f) was 8 breaths X min-1, increasing UA [CO2] up to 18-20% had no effect on f. However, when TA was increased 20 degrees C to increase f to 50 breaths X min-1, then increasing UA [CO2] to 6% or to 18-20% reduced f by 5 +/- 1.7 (SE) and 12 +/- 1.6 breaths X min-1, respectively (t = 3.3, P less than 0.01). These data suggest that in the pony there exists a UA CO2-H+ sensory mechanism. For a second protocol the ponies were breathing a 6% CO2 gas mixture for 15 min in the normal fashion over the entire airway (nares breathing, NBr) or they were breathing this gas mixture for 15 min through the cuffed endotracheal tube (TBr). At a neutral TA, increasing inspired [CO2] to 6% resulted in a 6-breaths X min-1 increase in f during both NBr and TBr.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of a dopamine antagonist on ventilation during sustained hypoxia in mice

To test the hypothesis that dopamine accumulated in the carotid body limits hyperventilation during acclimatization to sustained hypoxia, we administered the dopamine antagonist droperidol to mice undergoing acclimatization to an inspired O2 fraction (FIo2) of 0.1. Twelve mice were exposed to hypoxia for 10 days and ventilation in 10% O2 and in 7% CO2 in air were measured daily by a plethysmographic method. Under both conditions ventilation increased during acclimatization to hypoxia: ventilation in 10% O2 increased from 39.4 +/- 3.8 (mean +/- SE) ml/min before exposure to sustained hypoxia to 72.2 +/- 4.2 ml/min after 3 days of continuous hypoxia, and ventilation in 7% CO2 in air at the same time increased from 113.2 +/- 5.4 ml/min to 140.0 +/- 5.6 ml/min. Twelve mice were exposed to FIo2 of 0.1 for 10 days and received droperidol (300 micrograms/kg intraperitoneally) before exposure to sustained hypoxia and on the 2nd, 4th, and 8th days of continuous hypoxia. Before exposure to sustained hypoxia, droperidol increased ventilation in 10% O2 from 40.1 +/- 2.5 ml/min to 72.5 +/- 5.2 ml/min, but after 2, 4, and 8 days of continuous hypoxia droperidol caused an acute fall in ventilation (ventilation in 10% O2 after droperidol on day 2: 49.1 +/- 3.1 ml/min, on day 4: 44.4 +/- 3.7 ml/min, and on day 8: 27.8 +/- 3.4 ml/min). Two days after the animals were returned to room air, ventilation in 10% O2 again increased in response to droperidol. We conclude that dopamine in the carotid body does not limit ventilatory responses to hypoxia during acclimatization to sustained hypoxia.     

Dynamic ventilatory responses to CO2 in the awake lamb: role of the carotid chemoreceptors.

In awake lambs we investigated the role of the peripheral chemoreceptors in producing dynamic ventilatory (VE) responses to CO2. The immediate VE response, within 15 s, to transient CO2 inhalation was studied in two groups: 1) five lambs before carotid denervation and 2) the same lambs after carotid denervation. The time course of VE responses during the first 60 s after a step change to 8% inspired CO2 was also studied in lambs after carotid denervation and in a group of six carotid body-intact lambs 10-11 days of age. Acute CO2 responses were assessed using step changes to various concentrations of CO2 + air and CO2 + O2, while VE was recorded breath by breath. Intact lambs exhibited a brisk VE response to step changes in CO2, beginning after 3-5 s. Hyperoxia altered but did not suppress the dynamic VE CO2 response when the carotid chemoreceptors were intact. Carotid denervation markedly reduced the VE response during the first 25 s after a CO2 step change, revealing the time delay required for the central chemoreceptors to produce an effective VE response. The residual VE response remaining after CD was thought to be mediated by the remaining aortic body chemoreceptors and was eliminated by adding O2 to the CO2 challenges. However, after carotid denervation, even with CO2 + hyperoxia, the onset of a small tidal volume response was apparent by 10-12 s.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breathing pattern of kittens during hypoxia

In 19 pentobarbital sodium-anesthetized kittens aged 5-34 days, inspired O2 was reduced from 21 to 6-12%. Respiratory frequency (f) and tidal volume (VT) increased within 30 s. Over 5 min f fell to about 60% below control; VT usually fell but remained above control. Arterial pressure fell in 80% of trials, sometimes before f fell. Arterial CO2 was below control, but raising inspired CO2 to keep expired CO2 at control did not prevent the fall in f and VT. The relation between VT and esophageal pressure or diaphragm electromyogram (EMG) did not change consistently, nor was the ratio of high to low frequencies in the diaphragm EMG altered. Carotid chemoreceptor discharge increased within 15 s, and at 5 min it was much above control. We conclude that the change in the breathing pattern in hypoxia is probably due to the activation of a central mechanism.     

Internal carotid flow velocity with exercise before and after acclimatization to 4,300 m.

Cerebral blood flow and O2 delivery during exercise are important for well-being at altitude but have not been studied. We expected flow to increase on arrival at altitude and then to fall as O2 saturation and hemoglobin increased, thereby maintaining cerebral O2 delivery. We used Doppler ultrasound to measure internal carotid artery flow velocity at sea level and on Pikes Peak, CO (4,300 m). In an initial study (1987, n = 7 men) done to determine the effect of brief (5-min) exercises of increasing intensity, we found at sea level that velocity [24.8 +/- 1.4 (SE) cm/s rest] increased by 15 +/- 7, 30 +/- 6, and 22 +/- 8% for cycle exercises at 33, 71, and 96% of maximal O2 uptake, respectively. During acute hypobaric hypoxia in a decompression chamber (inspired PO2 = 83 Torr), velocity (23.2 +/- 1.4 cm/s rest) increased by 33 +/- 6, 20 +/- 5, and 17 +/- 9% for exercises at 45, 72, and 98% of maximal O2 uptake, respectively. After 18 days on Pikes Peak (inspired PO2 = 87 Torr), velocity (26.6 +/- 1.5 cm/s rest) did not increase with exercise. A subsequent study (1988, n = 7 men) of the effect of prolonged exercise (45 min at approximately 100 W) found at sea level that velocity (24.8 +/- 1.7 cm/s rest) increased by 22 +/- 6, 13 +/- 5, 17 +/- 4, and 12 +/- 3% at 5, 15, 30, and 45 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maturation of steady-state CO2 sensitivity in vagotomized anesthetized lambs.

The maturation of the respiratory sensitivity to CO2 was studied in three groups of anesthetized (ketamine, acepromazine) lambs 2-3, 14-16, and 21-22 days old. The lambs were tracheostomized, vagotomized, paralyzed, and ventilated with 100% O2. Phrenic nerve activity served as the measure of respiration. The lambs were hyperventilated to apneic threshold, and end-tidal PCO2 was raised in 0.5% steps for 5-7 min each to a maximum 7-8% and then decreased in similar steps to apneic threshold. The sinus nerves were cut, and the CO2 test procedure was repeated. Phrenic activity during the last 2 min of every step change was analyzed. The CO2 sensitivity before and after sinus nerve section was determined as change in percent minute phrenic output per Torr change in arterial PCO2 from apneic threshold. Mean apneic thresholds (arterial PCO2) were not significantly different among the groups: 34.8 +/- 2.08, 32.7 +/- 2.08, and 34.7 +/- 2.25 (SE) Torr for 2- to 3-, 14- to 16-, and 21- to 22-day-old lambs, respectively. After sinus denervation, apneic thresholds were raised in all groups [39.9 +/- 2.08, 40.9 +/- 2.08, and 45.3 +/- 2.25 (SE) Torr, respectively] but were not different from each other. CO2 response slopes did not change with age before or after sinus nerve section. We conclude that carotid bodies contribute to the CO2 response during hyperoxia by affecting the apneic threshold but do not affect the steady-state CO2 sensitivity and the central chemoreceptors are functionally mature shortly after birth.