Postnatal maturation of the respiratory response to O2 in awake newborn lambs

1982 ◽  
Vol 52 (2) ◽  
pp. 428-433 ◽  
Author(s):  
M. A. Bureau ◽  
R. Begin

The present study was designed to analyze maturation of the respiratory response to hypoxia and hyperoxia in 41 newborn lambs aged 2–90 days. The O2 respiratory response was tested by progressive isocarbic hypoxia while minute ventilation (VE), tidal volume (VT), respiratory frequency (f), mean inspiratory flow (VT/TI), were measured. The occlusion pressure (P0.1) was also determined as an index of the neuromuscular output of the drive to breathe. The strength of the peripheral chemoreceptors was evaluated by the transient O2 100% inhalation test and by the early change in VE (delta VE) to cyanide (KCN) infusion. In all of the 2-, 10-, 30-, and 90-day groups of lambs, hypoxia induced a significant increase in P0.1 and in delta VE, delta VT, f, and VT/TI. The 2-day-old lambs showed a significantly lower response to hypoxia than did the older groups. Similarly, during the hyperoxia test and KCN infusion. Delta VE was smaller in the 2-day lambs than in the other lambs. We conclude that the postnatal maturation of the ventilatory response to O2 occurs in the first 10 days of life in newborn lambs and it is largely due to an increase in sensitivity of the O2 chemoreceptors.

1985 ◽  
Vol 59 (3) ◽  
pp. 869-874 ◽  
Author(s):  
M. A. Bureau ◽  
J. Lamarche ◽  
P. Foulon ◽  
D. Dalle

The contribution of the carotid body chemoreceptor to postnatal maturation of breathing was evaluated in lambs from 7 to 70 days of age. The study was conducted by comparing the eupneic ventilation and resting pneumograms in intact conscious lambs with those of lambs that were carotid body chemodenervated (CBD) at birth. In comparison to the 1-wk-old intact lambs, the CBD lambs had significant decreases in minute ventilation (VE, 313 vs. 517 ml/kg), tidal volume (VT, 7.2 vs. 10.5 ml/kg), respiratory rate (f, 44 vs. 51 breaths/min), and occlusion pressure (P0.1, 2.8 vs. 7.2 cmH2O). Arterial PO2's were 59 vs. 75 Torr (P less than 0.05) and arterial PCO2's 47 vs. 36 Torr (P less than 0.05), respectively, in CBD and intact lambs. In intact lambs from 7 to 70 days, resting VE decreased progressively from 517 to 274 ml/kg (P less than 0.01) due to a fall in VT, mean inspiratory flow (VT/TI), and f, whereas the ratio of inspiratory time to total breath duration remained constant. P0.1 decreased from 7.2 to 3.9 cmH2O from 7 to 42 days. In contrast the CBD lambs experienced only minimal changes in VE, VT, VT/TI, and f during the same period. VE only decreased from 313 to 218 and P0.1 from 2.8 to 2.4 cmH2O. In contrast to that of intact lambs the resting pneumogram of CBD lambs remained relatively fixed from 7 to 70 days. Three CBD lambs died unexpectedly, without apparent cause, in the 4th and 5th wk of life.


1988 ◽  
Vol 64 (6) ◽  
pp. 2544-2551 ◽  
Author(s):  
H. Rigatto ◽  
C. Wiebe ◽  
C. Rigatto ◽  
D. S. Lee ◽  
D. Cates

We studied the ventilatory response to hypoxia in 11 unanesthetized newborn kittens (n = 54) between 2 and 36 days of age by use of a flow-through system. During quiet sleep, with a decrease in inspired O2 fraction from 21 to 10%, minute ventilation increased from 0.828 +/- 0.029 to 1.166 +/- 0.047 l.min-1.kg-1 (P less than 0.001) and then decreased to 0.929 +/- 0.043 by 10 min of hypoxia. The late decrease in ventilation during hypoxia was related to a decrease in tidal volume (P less than 0.001). Respiratory frequency increased from 47 +/- 1 to 56 +/- 2 breaths/min, and integrated diaphragmatic activity increased from 14.9 +/- 0.9 to 20.2 +/- 1.4 arbitrary units; both remained elevated during hypoxia (P less than 0.001). Younger kittens (less than 10 days) had a greater decrease in ventilation than older kittens. These results suggest that the late decrease in ventilation during hypoxia in the newborn kitten is not central but is due to a peripheral mechanism located in the lungs or respiratory pump and affecting tidal volume primarily. We speculate that either pulmonary bronchoconstriction or mechanical uncoupling of diaphragm and chest wall may be involved.


PEDIATRICS ◽  
1984 ◽  
Vol 73 (5) ◽  
pp. 652-655
Author(s):  
Jonathan M. Couriel ◽  
Anthony Olinsky

The ventilatory response to acute hypercapnia was studied in 68 parents of victims of sudden infant death syndrome and 56 control subjects. Tidal volume, inspiratory time, and total respiratory cycle time were measured before and immediately after a vital capacity breath of 13% CO2 in oxygen. Instantaneous minute ventilation, mean inspiratory flow (tidal volume/inspiratory time), and respiratory timing (inspiratory time/total respiratory cycle time) were calculated. Both groups of subjects showed a marked increase in tidal volume (48.4% ± 26.5%), instantaneous minute ventilation (56% ± 35%), and tidal volume/inspiratory time (56.8% ± 33.5%) after inhalation of the test gas, with little change in inspiratory time/total respiratory cycle time. There were no significant differences between the two groups for ventilation before or after inhalation of the test gas. The ventilatory response to acute hypercapnia is mediated by the peripheral chemoreceptors. These results suggest that an inherited abnormality of peripheral chemoreceptor function is unlikely to be a factor leading to sudden infant death syndrome.


1985 ◽  
Vol 59 (1) ◽  
pp. 18-23 ◽  
Author(s):  
H. B. McCooke ◽  
M. A. Hanson

Respiration was measured noninvasively in conscious kittens at an ambient temperature of 28–32 degrees C. Inspired O2 fraction (FIO2) was reduced abruptly from 0.21 to 0.12, 0.10, or 0.08 for 5 min on the day of birth and then on days 4, 7, 14, and 28. The ventilatory response to hypoxia was biphasic, as reported previously in anesthetized kittens, with minute ventilation (VE) increasing in the first minute and then falling towards control over the next 4 min. The fall in VE was due to a consistent fall in tidal volume, the changes in frequency during the second phase being more variable. The size of the first phase of the response increased up to 14 days, but the time at which the peak increase in VE occurred was not correlated with age. The degree of the secondary fall in VE was similar at each age and at each FIO2 studied. The degree of the biphasic response was significantly reduced after administration of almitrine (2 mg/kg ip) on days 1 and 4, but almitrine did not affect the response in older kittens.


PEDIATRICS ◽  
1983 ◽  
Vol 71 (4) ◽  
pp. 634-638
Author(s):  
Manuel Durand ◽  
Ellen McCann ◽  
June P. Brady

The effect of continuous positive airway pressure (CPAP) on the ventilatory response to CO2 in newborn infants is unknown. The CO2 response to 4% CO2 in air was studied in nine preterm infants without lung disease before and during administration of CPAP (4 to 5 cm H2O) delivered by face mask. Minute ventilation, tidal volume, respiratory frequency, and end-tidal Pco2 were measured, and the slope and intercept of the CO2 response were calculated. Respiratory pattern and changes in oxygenation were also analyzed by measuring inspiratory and expiratory time, mean inspiratory flow, mean expiratory flow, effective respiratory timing, endtidal Po2, and transcutaneous Po2. CPAP significantly decreased minute ventilation from 278.7 to 197.6 mL/mm/kg (P < .001). Tidal volume and respiratory frequency were also significantly decreased. The slope of the CO2 response during CPAP was not significantly different from the slope before CPAP (36 v 33 mL/min/kg/mm Hg, P > .1), but the intercept was shifted to the right (P < .001). The decrease in respiratory frequency was primarily due to a prolongation of expiratory time (P < .05). In addition, transcutaneous Po2 increased during administration of CPAP (P < .001). These findings indicate that: (1) CPAP significantly decreases ventilation in preterm infants without lung disease, affecting both tidal volume and respiratory frequency; (2) CPAP does not appreciably alter the ventilatory response to CO2; (3) the changes in respiratory frequency are primarily accounted for by a prolongation of expiratory time; (4) CPAP improves oxygenation.


1990 ◽  
Vol 68 (2) ◽  
pp. 693-699 ◽  
Author(s):  
Z. B. Chen ◽  
J. Hedner ◽  
T. Hedner

The effect of substance P (SP) and the SP antagonist [D-Pro2,D-Trp7,9]-SP on basal ventilation was investigated in halothane-anesthetized rats. Microinjections of SP (0.4-1.5 nmol) into the ventrolateral medulla oblongata (VLM), (nuclei gigantocellularis, facialis, ambiguus, and reticularis lateralis) or into the dorsomedial medulla oblongata (DM, nucleus tractus solitarius) and its ventral surroundings dose dependently increased tidal volume (VT) and/or minute ventilation. In sensitive areas, the ventilatory stimulation was initiated within minutes, peaked around 8-10 min, and slowly returned to normal over 30-45 min after the injection. In the VLM sites, the increase in VT was generally accompanied by a decrease in respiratory frequency (f), whereas in the DM, f increased in parallel with VT. Furthermore, within the VLM, the respiratory response patterns differed with the definite location of the SP injection. A shortening of inspiratory time was observed in the ventromedial part, the ventrolateral portion of the nucleus paragigantocellularis and ventral to the nucleus facialis. In contrast, a lengthening of expiratory time was seen when SP was injected or applied more laterally along the ventral portion of nucleus facialis and near or directly on the ventral medullary surface. Application of [D-Pro2, D-Trp7,9]SP before or after SP completely antagonized the excitatory effects of SP on ventilation. The SP antagonist administered into the VLM decreased the ventilatory response to hypoxic breathing but caused no change during hyperoxic conditions.


1984 ◽  
Vol 56 (1) ◽  
pp. 84-90 ◽  
Author(s):  
M. A. Bureau ◽  
R. Zinman ◽  
P. Foulon ◽  
R. Begin

The ventilatory response of newborn lambs to hypoxemia was evaluated in two groups of seven awake lambs studied at 2 and 7 days of life. Minute ventilation (VE) and airway occlusion pressure (P0.1) were monitored as the animals were exposed in sequence to room air, 12% O2 (15 min), 7% O2 (15 min), and room air. On 12 and 7% O2, 2-day-old lambs experienced a brisk hyperventilation followed by a VE depression, previously described in newborns of other species (diphasic response). The 7-day-old lambs had a clear diphasic VE response only on 7% O2 breathing. In the 2-day-old lambs, at the time of the relative VE depression to 12% O2, the respiratory centers showed a persisting responsiveness to further hypoxia; switching to 7% O2 caused a brisk increase in VE and P0.1 of 70 and 130%, respectively, which was followed again by a VE depression. The magnitude of the immediate VE response to hypoxia, taken as an index of the chemoreceptor strength, was inversely related to the magnitude of the VE depression (R = 0.81, P less than 0.001). It was concluded that 1) lambs as well as other neonates have an age-related diphasic VE response to hypoxia; 2) at the time of the VE depression, the respiratory centers maintain their responsiveness to further acute hypoxia; and 3) the weakness of the chemoreceptors in the newborn is a major determinant of the diphasic response.


1995 ◽  
Vol 79 (4) ◽  
pp. 1181-1189 ◽  
Author(s):  
F. Xu ◽  
J. Owen ◽  
D. T. Frazier

The general contribution of the cerebellum to hypoxic respiratory responses and the special role of the fastigial nucleus (FN) in the hypoxic respiratory reflex mediated via peripheral chemoreceptors were investigated in anesthetized and spontaneously breathing cats. Seven cats were exposed to isocapnic progressive hypoxia before and after cerebellectomy by decreasing the fractional concentration of end-tidal O2 (FETO2) from 15 +/- 0.3% to 7% while maintaining the pressure of end-tidal CO2 at a constant level of approximately 30 mmHg. Five additional cats inhaled five breaths of pure N2 (transient hypoxia) and received sodium cyanide (50 micrograms iv) before and after thermal lesions of the bilateral FN. The results showed that cerebellectomy or FN lesions failed to alter the respiratory variables (minute ventilation, tidal volume, respiratory frequency, and the peak of integrated diaphragm activity) during eupneic breathing. However, cerebellectomy significantly attenuated minute ventilation (FETO2 < or = 13%) and the peak of integrated diaphragm activity (FETO2 < or = 10%) compared with control. During progressive hypoxia, changes in respiratory frequency were noted earlier (FETO2 < or = 13%) than changes in tidal volume (FETO2 < or = 10%). Similarly, bilateral lesions of the FN resulted in a profound reduction in these respiratory responses to transient hypoxia and sodium cyanide. We conclude that the cerebellum can facilitate the respiratory response to hypoxia and that the FN is an important region in the modulation of the hypoxic respiratory responses, presumably via its effects on inputs from peripheral chemoreceptors.


1990 ◽  
Vol 69 (2) ◽  
pp. 490-497 ◽  
Author(s):  
R. D. Ballard ◽  
W. C. Tan ◽  
P. L. Kelly ◽  
J. Pak ◽  
R. Pandey ◽  
...  

To characterize ventilatory responses to bronchoconstriction during sleep and to assess the effect of prior sleep deprivation on ventilatory and arousal responses to bronchoconstriction, bronchoconstriction was induced in eight asthmatic subjects while they were awake, during normal sleep, and during sleep after a 36-h period of sleep deprivation. Each subject was bronchoconstricted with increasing concentrations of aerosolized methacholine while ventilatory patterns and lower airway resistance (Rla) were continually monitored. The asthmatic patients maintained their minute ventilation as Rla increased under all conditions, demonstrating a stable tidal volume with a mild increase in respiratory frequency. Inspiratory drive, as measured by occlusion pressure (P0.1), increased progressively and significantly as Rla increased under all conditions (slopes of P0.1 vs. Rla = 0.249, 0.112, and 0.154 for awake, normal sleep, and sleep after sleep deprivation, respectively, P less than 0.0006). Chemostimuli did not appear to contribute significantly to the observed increases in P0.1. Prior sleep deprivation had no effect on ventilatory and P0.1 responses to bronchoconstriction but did significantly raise the arousal threshold to induced bronchoconstriction. We conclude that ventilatory responses to bronchoconstriction, unlike extrinsic loading, are not imparied by the presence of sleep, nor are they chemically mediated. However, prior sleep deprivation does increase the subsequent arousal threshold.


1986 ◽  
Vol 61 (1) ◽  
pp. 133-137 ◽  
Author(s):  
P. W. Blanchard ◽  
A. Cote ◽  
S. Hobbs ◽  
P. Foulon ◽  
J. V. Aranda ◽  
...  

In this study we have evaluated the role of the peripheral chemoreceptors in the ventilatory response to caffeine at a dose currently used in human infants for treatment of central apneas (10 mg/kg). Twelve lambs were studied; six had carotid body denervation (CBD) and six had a sham denervation (intact). The denervation was done the 2nd wk of life, and the study of the response to caffeine infusion was carried out at a mean age of 82 days. The awake and nonsedated animals received 10 mg/kg of caffeine, and caffeine blood levels were, respectively, 8.8 and 9.0 mg/l in the intact and in the CBD lambs. The intact lambs responded to caffeine by a significant immediate increase in minute ventilation (VE) of 46% from 274 to 400 ml X min-1 X kg-1 (P less than 0.001), 1 min after caffeine infusion. This response rapidly faded, but VE was still increased at 2 h, 314 ml X min-1 X kg-1. The increase in ventilation was brought about by a change in mean inspiratory flow (VT/TI), which increased from 9.9 to 14.0 ml X s-1 X kg-1 within 1 min (P less than 0.01); VT/TI was still increased at 11.2 ml X s-1 X kg-1 2 h later. In contrast, for the CBD lambs there was no response to caffeine infusion as measured by VE or VT/TI. We conclude that bolus caffeine infusion produces a rapid response in VE followed by a fall in VE that remained above base line until at least 2 h postinfusion, and the intact chemoreceptor function appears as an essential mediator for these increases in ventilation, since the peripheral chemodenervation has completely abolished the VE response to this particular dose of caffeine.


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