Breathing response of the fetal sheep to CO2.
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Animals↗
Biomedical subjects
H Rigatto
Publications and source records attributed to H Rigatto.
Effect of antenatal dexamethasone on neonatal leukocyte count.
The leukocyte count and differential white blood cell count during the first hour of life was determined in 164 neonates born of mothers receiving antenatal steroids and compared to 171 neonates of mothers randomly assigned to a placebo group. A leukemoid reaction (greater than 40,000 WBC/mm3) was seen only once each in the neonates born of placebo or steroid treated mothers. In addition, maternal steroid treatment had no general effect, except in a small subgroup of neonates born 3 to 7 days after the mother had been treated with 20 mg dexamethasone, where the total leukocyte and the absolute neutrophil counts were higher than the placebo group and other subgroups.
Analysis of Variance↗
A developmental study on types and frequency distribution of short apneas (3 to 15 seconds) in term and preterm infants.
We measured the frequency distribution and the ventilatory correlates of the various types of apneas 3 to 15 s long during sleep in eight term infants (birth weight 3.65 +/- 0.16 kg; gestational age 39.5 +/- 0.3 wk) and eight preterm infants (birth weight 2.07 +/- 0.18 kg; gestational age 34.3 +/- 0.4 wk). Each infant was studied on five to seven occasions from birth to 56 wk of postconceptual age using a modified flow-through system. Sixty-six paired epochs of quiet sleep (1163 min) and rapid eye movement sleep (829 min) were analyzed in term infants and 85 paired epochs of quiet sleep (1553 min) and rapid eye movement sleep (1328 min) in preterm infants. Of the 783 apneas recorded in term infants 82% were central, 1.5% obstructive, 0.5% mixed, and 16% were of the breath-holding type; the corresponding figures for the 4086 apneas recorded in preterm infants were 93, 0.5, 1.0, and 5.5%. This distribution was similar in the two sleep states but term infants had a higher percentage of breath-holding apneas than preterm infants (p less than 0.01). In preterm infants the rate of central apneas decreased with postnatal age (p less than 0.01); in term infants the rate did not change significantly. The duration of apneas showed a modal distribution for central apneas at about 8 s for both groups during the 1st month of life (p less than 0.05). The findings suggest: 1) apneas in the newborn and early infancy are primarily central and are more frequent in preterm than in term infants.(ABSTRACT TRUNCATED AT 250 WORDS)
Apnea↗
Neonatal blood pressure at birth by the Doppler method.
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Blood Pressure↗
Fetal breathing and behavior measured through a double-wall Plexiglas window in sheep.
The inability to see the fetus makes the assessment of fetal behavior difficult. To circumvent this problem we implanted a Plexiglas window in the left flank of the ewe. Fetuses were instrumented for measurements of sleep, breathing, and swallowing. Ten fetal sheep were studied on 32 occasions. Six fetuses were delivered through the window at term, and postnatal behavior was compared with intrauterine behavior. Fetuses observed during resting conditions alternated between periods of quiet sleep [high-voltage electrocortical activity (ECoG)] and active or rapid-eye-movement sleep (low-voltage ECoG). In quiet sleep, movements were absent except for periodic generalized electromyographic discharges. Eye and breathing movements were rare or absent. Swallowing was also absent. In active sleep, movements were increased with powerful breathing and swallowing activity. Fetal wakefulness defined by open eyes and purposeful movements of the head was never seen in utero but was clearly observed after delivery. We conclude that fetal wakefulness as defined postnatally was not able to be demonstrated in utero.
Animals↗
The effect of rebreathing CO2 on ventilation and diaphragmatic electromyography in newborn infants.
We tested the hypothesis of whether the reduced ventilatory response to CO2 in preterm as compared to term infants is related to primary central unresponsiveness, or to mechanical impairment of the respiratory pump. Eleven preterm (n = 19; gestational age 32 +/- 0.4 wk) and 14 term (n = 24; GA 40 +/- 0.3 wk) infants were studied. Minute integrated diaphragmatic activity EMGDi X f), and mean inspiratory diaphragmatic activity (EMGDi/TI), were used as indices of central output. After 3 min breathing 21% O2 (control), infants rebreathed from a bag containing 5% CO2 in 40% O2 for 2 to 3 minutes. We measured VE, VT, f, VT/TI. Sleep states were monitored. Preterm infants had a decreased ventilatory response to CO2 both in quiet sleep (QS) (0.0379 +/- 0.067 vs 0.505 +/- 0.032 L . (min . kg . kPa PACO2)-1; P less than 0.04) and in active sleep (AS) (0.210 +/- 0.032 vs 0.331 +/- 0.048 L . (min . kg . kPa PACO2)-1; P less than 0.04). The decrease in response primarily was a function of a lack of increase in tidal volume with CO2 in QS and a lack of increase in f in AS. Parallel to these changes there were significant correlations between the increases in EMGDi X f and VE with inhaled CO2 (r = 0.75; P less than 0.001); VT and EMGDi (r = 0.63; P less than 0.01); and between the increases in EMGDi/TI and VT/TI with inhaled CO2 (r = 0.64; P less than 0.001). The results suggest that ventilatory response to CO2 is (1) correlated highly with diaphragmatic indices of central output; (2) less in active than in quiet sleep; (3) less in preterm than in term infants. We conclude that despite their increased chest wall compliance, preterm infant respond less to CO2 because of central unresponsiveness.
Carbon Dioxide↗
Control of ventilation in the newborn.
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Biomechanical Phenomena↗
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.
Abdominal Muscles↗
Naloxone reduces decrease in ventilation induced by hypoxia in newborn infants.
The mechanism responsible for the decrease in ventilation during breathing of low fractional concentration of inspired O2 in the newborn infant is poorly understood. The present study tested the hypothesis that endogenous opiates account for this ventilatory decrease. Eleven healthy newborn infants breathed 15% O2, balance N2 for 5 min following an injection of saline and following an injection of naloxone. Neither injection caused a change in minute ventilation (VE) or ventilatory pattern when the infants were breathing room air. However, the decreased ventilation during hypoxia following naloxone was significantly less than that following saline. VE dropped about 14% following saline but only about 4% following naloxone. However, the adult ventilatory response to hypoxemia, i.e., a relatively sustained increase in VE, was not attained. Naloxone had no influence on the occurrence of periodic breathing during hypoxemia. Thus in the healthy full-term newborn infant, endogenous opiates account only for a part of the decreased ventilation during hypoxemia.
Humans↗
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.
Humans↗
A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy.
In a large multicentered, collaborative randomized and blinded trial utilizing antenatal corticosteroids, the goals included determining the effectiveness of these agents in accelerating lung maturation, as well as monitoring any short-term or long-term adverse effects of this treatment on the parturient, fetus, and/or infant. More than 100 specific items, pertaining to diagnoses, complications, and outcomes were recorded for the 696 mothers enrolled in the study and their 745 infants. A significantly decreased incidence of necrotizing enterocolitis (P = .002) was found in the infants treated with steroids. The possibility of accelerated intestinal maturation induced by antenatal maternal steroid therapy exists. This treatment regimen is particularly attractive as adverse aspects of steroid therapy at the dosage utilized have not been demonstrated.
Clinical Trials as Topic↗
Ventilatory response to 100% and 15% O2 during wakefulness and sleep in preterm infants.
To examine the ventilatory response to 100% and 15% O2 during wakefulness and sleep, we studied eleven preterm infants birthweight 1770 +/- 102 g; gestational age 32 +/- 1 weeks; postnatal age 31 +/- 5 days) on two occasions each. Wakefulness (W) was present around feeding time and was defined by open eyes for more than 2 min plus presence of purposeful movements. Rapid eye movement (REM) and non-rapid eye movement (N-REM) sleep were defined using electroencephalogram (EEG), electrooculogram (EOG), electrocardiogram (ECG), and body movements. During 100% O2 breathing, immediate (30 s) decreases of 28, 39 and 37% followed by late (5 min) increases in ventilation (Ve) of 42, 49 and 27% were observed during W, REM and N-REM sleep (P greater than 0.05 between states). PaCO2 decreased significantly towards the end of 5 min of breathing 100% O2 in W, REM and N-REM sleep (P greater than 0.05). Average duration of apnea following sudden administration of 100% O2 was 8.5, 11.1 and 8.8 s during W, REM and N-REM sleep (P greater than 0.05 between states). During inhalation of 15% O2, there was a late decrease in ventilation of 19 and 23% during wakefulness and REM sleep, and a sustained increase in Ve of 17% during N-REM sleep (P less than 0.05). PaCO2 at the end of hypoxia (5 min) was significantly decreased in N-REM sleep only (P less than 0.05). We suggest that (i) peripheral chemoreceptor activity is qualitatively intact during W and sleep, as reflected by (a) the immediate changes in Ve during inhalation of high and low O2, and (b) apnea following administration of 100% O2. (ii) The late decrease in ventilation with hypoxia is absent in N-REM sleep.
Electroencephalography↗
The response to stimulation of hindlimb nerves in fetal sheep, in utero, during the different phases of electrocortical activity.
The relationship between the amplitude of electrically evoked responses from nerves of a hindlimb and electrocortical activity has been determined in fetal sheep from 105-141 days gestation. Stimulation of the common sciatic, tibial or peroneal nerves and recording from the two nerves not stimulated revealed an early (4.5 ms) and late (18.6 ms) evoked neural response, probably reflex. These responses were reduced or absent in low voltage compared with high voltage electrocortical activity after 125 days gestation. Spontaneous gastrocnemius activity was more frequent during high voltage activity. The electrocorticogram was undifferentiated before 115 days, and the evoked responses in peripheral nerves were largest when breathing and eye movements were present. After electrocortical differentiation the responses were enhanced when brief episodes of augmented eye and breathing movements occurred during the transition between high and low voltage activity. The possibility that this indicates arousal or wakefulness in utero is discussed.
Animals↗
Tidal volume and respiratory frequency in infants with bronchopulmonary dysplasia (BPD).
To examine the respiratory pattern in infants with BPD, we compared measurements in 4 infants not retaining CO2 (PACO2 = 40) with those in 4 infants retaining CO2 (PACO2 = 52). We also studied 14 healthy preterm infants, 7 not retaining CO2 (PACO2 = 32) and 7 retaining CO2 (PACO2 = 45). In infants with BPD, minute ventilation (VE) was 0.996 (mean) and 1.0021 l/min with and without CO2 retention (P greater than 0.5). Tidal volume (VT) was 12.6 and 21.1 (P less than 0.001) and total duration of the respiratory cycle (Ttot) 0.77 and 1.33 (P less than 0.005) with and without CO2 retention. VT/Ti were 45.00 and 44.89, respectively (P greater than 0.5). In preterm infants, VE was 0.537 and 0.710 l/min with high and low CO2 (P greater than 0.1). VT was 15.4 and 11.00 (P greater than 0.2) and Ttot 1.63 and 0.99 (P less than 0.002) with high and low CO2. VT/Ti was 32.08 and 30.56 (P greater than 0.5). These findings suggest: (1) in infants with BPD, VT and frequency (f) change in much the same way as in adult subjects with chronic obstructive lung disease, i.e., VT decreases and Ttot shortens (f) in association with high PACO2; (2) mean inspiratory flow is essentially the same in infants with BPD who do and do not retain CO2; and (3) in infants with normal lungs, VT and Ttot increase (f) in association with high PACO2, breathing pattern being entirely controlled via changes in the timing mechanism, the inspiratory drive remaining unaltered.
Carbon Dioxide↗
The effect of 2% CO2, 100% O2, theophylline and 15% O2 on "inspiratory drive" and "effective" timing in preterm infants.
We studied 20 preterm infants (B.W. 1440 +/- 80 g (S.E.); G.A. 33 +/- 1 wk) to determine the effect of respiratory stimulants and depressants on respiratory output as measured by VE = VT . f, and VE = VT/Ti . Ti/Ttot. These 20 infants were divided in four groups of five infants. Each group received a respiratory stimulant (2% CO2, 100% O2 or theophylline) or'a respiratory depressant (15% O2). VT/Ti is mean inspiratory flow and represents a mechanic translation of neuronal output. Ti/Ttot is a dimensionless number and has been defined as effective timing. Each study consisted of 3-5 min while the infant breathed 21% O2, followed by 5 min breathing 2% CO2, 100% O2 or 15% O2. The effect of theophylline was assessed by 48-72 h after the initial dose. The respiratory stimulants caused an increase in VT with little or no change in f; 15% O2 produced a decrease in f primarily. According to the newer approach, 2% CO2, 100% O2 and theophylline produced an increase in "inspiratory drive" with little or no change in "effective" timing; 15% O2 decreased "effective" timing primarily via an increase in Te. These findings suggest that the paradoxical decrease in ventilation during hypoxia in preterm infants may not be solely dependent on the central depressant effects of O2. At least in part, the mechanism may be due to a direct action of low O2 on elements controlling expiratory time.
Carbon Dioxide↗
Effect of lung inflation on ventilation and various phases of the respiratory cycle in preterm infants.
The effect of sudden and sustained lung inflation on inspiratory time (Ti), expiratory time (Te) and duration of apnea, as a translation of the Hering-Breuer reflex, has not been systematically analyzed in preterm infants. To examine such effects, 10 infants (body weight 1,550 +/- 110 g; gestational age 31 +/- 1 weeks) were studied. Lung inflation was obtained by applying negative pressure around the chest using a negative pressure incubator. After a control period, lung volume functional residual capacity was increased by an average of 14, 23, 34 and 53%. During lung inflation, Ti, Te, total respiratory cycle duration, incidence and duration of apnea increased. Minute ventilation decreased due to a decrease in frequency. Tidal volume decreased but not significantly. Inspiratory and expiratory flows decreased. These results (1) confirm the presence of the Hering-Breuer reflex in preterm infants, as reflected by increased Te and appearance of apnea during lung inflation; and (2) show that contrary to expectations, Ti increased significantly with lung inflation.
Apnea↗
Effect of periodic or regular respiratory pattern on the ventilatory response to low inhaled CO2 in preterm infants during sleep.
We wanted to know whether the ventilatory response to low concentrations of CO2 is measurable in the absence of change in alveolar PCO2, is sleep state dependent, and is dictated by the resting respiratory pattern. Therefore, we gave 11 preterm infants (birth weight, 1,565 +/- 122 g; gestational age, 32 +/- 1 wk; postnatal age, 28 +/- 5 days) 0.5 to 1.5% CO2 after a control period of breathing 21% O2. They were studied on 2 or 3 occasions, the aim being to have 5 infants in each of 2 categories, periodic to regular breathing, and regular to regular breathing, after administration of CO2 in both sleep states (n = 20). In both sleep states, when low CO2 increased ventilation, alveolar PCO2 also increased. The increase in ventilation was primarily due to an increase in breathing frequency if breathing was periodic, and to an increase in tidal volume if breathing was regular. This response was not affected by sleep state. We conclude that changes in respiratory pattern with low inhaled CO2 are fundamentally dependent on whether the baseline respiration is periodic or regular.
Carbon Dioxide↗