Mechanics of the ventilatory system in sedated infants: forced oscillations versus single-breath method.

The real--Re(Z)--and imaginary--Im(Z)--parts of the ventilatory system impedance were measured between 6 and 30 Hz in 18 normal infants and in 19 with airway obstruction. The intercept (R0) and slope (S) of the Re(Z)-frequency function, as well as inertance (I) and compliance (C) estimated from Im(Z), were compared with ventilatory system resistance (Rrs) and compliance (Crs) (single-breath method). R0 correlated significantly with Rrs (r = 0.86), although the slope of the regression equation was significantly lower than 1 (P less than 0.01). Negative frequency dependence of Re(Z) was observed in all subjects and a significant correlation was found between S and Rrs (r = -0.80). "Inertance" was negative in 20 subjects and correlated negatively with Rrs (r = -0.61). C correlated with Crs (r = 0.64) and with 1/Rrs (r = 0.85). The ratio of C to Crs (mean +/- SD = 0.168 +/- 0.082) also correlated with 1/Rrs (r = 0.51). The main characteristics of the total impedance/frequency function could be simulated with a model featuring the upper airway wall (Zuaw) in parallel with the ventilatory system (Zrs). It is suggested that the differential change in Zuaw and Zrs with growth accounts for the marked frequency dependence of Re(Z) as well as the inaccurate estimation of both I and C in this population.

Measurement of ventilatory mechanical impedance in infants using a head pressure generator.

Two methods of measuring ventilatory mechanical impedance (Z) by forced oscillations between 6 and 20 Hz were compared in 24 infants aged 2 to 49 months: 1) the application of pressure oscillations at the airway opening (Z1); and 2) the application of pressure oscillations around the head (Z2). The latter has been recently proposed to minimize the influence of compliant upper airway walls (Peslin et al., J Appl Physiol. 1985, 59:1790-1795). Ventilatory resistance and compliance (Rsb, Csb) were also obtained with the single breath method. The real part of Z1 (R1) was markedly lower than that of the corresponding Z2 (R2), at any frequency. R1 exhibited a systematic negative frequency dependence, in contrast with R2. At any frequency, the slope of the regression equation on Rsb was closer to unity for R2 than for R1. The imaginary part of Z1 (X1) was negative over the whole frequency interval, and negative values of inertance were derived from X1. X2 was negative at low and positive at high frequencies. Resonant frequency (mean +/- SD = 10.5 +/- 3.5 Hz) was always reached with Z2 and correlated negatively with body weight (r = -0.61). Inertance estimated from X2 was positive and correlated negatively with body height (r = -0.66). The compliance derived from Z1 (C1 = 3.35 +/- 2.32 10(-3) L.cm H2O-1) was not significantly different from that derived from Z2 (C2 = 2.99 +/- 2.02 10(-3) L.cm H2O-1). The marked difference observed between Z1 and Z2 is related to the importance of the upper airway shunt and may be explained by inaccuracies of both methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of ventilatory system compliance in infants and young children.

Ventilatory system compliance (Crs) was measured in 32 sedated sleeping infants and young children aged 3-54 months breathing spontaneously through a face mask. Airways were occluded during expiration at different lung volumes above FRC and the corresponding airway pressure was measured. A pressure-volume relationship was then calculated by the least square method. To ensure the presence of the Breuer-Hering inspiratory inhibitory reflex, the percent increase of occluded expiratory time relative to the preceding unoccluded breath was calculated in 28 subjects where several end inspiratory occlusions had been maintained up to the next inspiratory effort. This index ranged from 4 to 100% and correlated negatively with age (r = -0.50, P less than 0.01). Crs ranged from 4.5 to 21.8 ml/cm H2O and correlated best with height (H) (Crs = 5.36 X 10(-4) H2.27, r = 0.94).

Ventilatory and waking responses to laryngeal stimulation in sleeping mature lambs.

Ventilatory and waking responses to laryngeal stimulation were studied in six chronically tracheostomized lambs breathing through an endotracheal tube. A balloon catheter inserted in the rostral tracheal segment allowed application of distilled water onto the larynx. Apnea, the main primary ventilatory response, was shorter in wakefulness (7.9 sec) than in quiet (10.7 sec) or active sleep (10.6 sec, residual variance = 3.29), where the response to laryngeal stimulation was poorly reproducible. Arousal delay measured from the neck muscle EMG was longer in active (21.1 sec) than in quiet sleep (5.4 sec, residual variance = 9.05). Arousal preceded apnea termination more often in quiet than in active sleep. When breathing resumed a sigh frequently occurred following prolonged apneas. We conclude that laryngeal stimulation elicits apnea in all states in mature lambs. The termination of apnea is related to waking up in quiet but not in active sleep, where arousal is depressed. A comparison of our results with data from preterm and adult mammals strongly suggests that the ventilatory response to laryngeal stimulation during active sleep is unaffected by maturation.

Measurement of ventilatory system resistance in infants and young children.

The mechanics of the ventilatory system were studied in 29 sleeping infants and young children by the analysis of a passive expiration following an end-inspiratory airway occlusion ('single breath' method). The ventilatory system time constant (tau rs) to compliance ratio yielded the value of ventilatory system resistance (Rrs). The calculated ventilatory system compliance correlated well with the slope of the quasi static pressure-volume curve (r = 0.97). The allometric relationship between Rrs and height (Rrs = 81.9.10(3).Ht (cm)-1.76, r = -0.82) is in agreement with forced oscillation measurements during the first year of life (Wohl et al., 1969). tau rs was found to increase significantly over the first months of life (P less than 0.01).

Thoracic gas volume at functional residual capacity measured with an integrated-flow plethysmograph in infants and young children.

Thoracic gas volume (TGV) was measured with an integrated flow plethysmograph in 15 infants aged 2-34 months. End-expiratory (TGVe) and end-inspiratory (TGVi) airway occlusions were compared, after correction of TGV for the occluded volume above functional residual capacity (FRC). The relationship between pressure at the airway opening (Pao) and volume displaced from the box during airway occlusion (Vg) was studied numerically by: 1) an algorithm including a correction for the drift of Vg and linear regression analysis (LR); and 2) Fourier analysis of the signals (FFT). TGVe was significantly higher than TGVi (256 vs 237 ml, 20.4 (square root of residual variance; p less than 0.002). The correlation coefficient of the Pao-Vg relationship was slightly but significantly higher for TGVi than for TGVe: 0.9968 (0.9937-0.9995) vs 0.9947 (0.9840-0.9990) (means and range). No difference was observed between LR and FFT, although the intra-individual coefficient of variation was lower for LR than FFT: 5.2% (1.6-11.3) vs 7.9% (1.9-21.0) (means and range). Model simulations suggested that the difference between TGVe and TGVi could be mainly attributed to gas compression in the instrumental deadspace and upper airway wall motion and/or to uneven distribution of alveolar and pleural pressure associated with chest wall distortion.

Respiratory mechanics in spontaneously breathing term and preterm neonates.

The compliance (Crs), resistance (Rrs) and passive time constant (tau rs) of the respiratory system were determined by the single-breath method (sb) in 24 healthy term and preterm newborns. In 22 of them, Crssb was compared to the slope of the pressure-volume curve determined by the multiple occlusion technique (mo), which is not dependent on the assumption of a linear flow-volume relationship. Crssb and Rrs correlated significantly with body weight (kg): Crssb = 0.56 x kg + 1.22 (r = 0.67); Rrs = -20.1 x kg + 134.6 (r = -0.68). No difference in Crs and Rrs between prone and supine positions was found. tau rs was not significantly different between premature (0.21 +/- 0.06 s) and full-term infants (0.21 +/- 0.05 s). Crssb was significantly higher than Crsmo in premature babies (2.27 +/- 0.41 ml.cm H2O-1 vs. 1.98 +/- 0.47 ml.cm H2O-1. This difference may be explained by a continuous braking of expiratory airflow after release of the occlusion, or more likely, by a difference in the lung volume at which Crssb and Crsmo are measured. However, the difference between Crssb and Crsmo (approximately 15%) is in the same range as the intrasubject variability, and is meaningless compared to the alterations of respiratory mechanics observed during neonatal ventilatory disorders. Therefore, the single-breath method appears to be a suitable and noninvasive method to measure respiratory mechanics in nonintubated prematures.

Effects of doxapram on carotid chemoreceptor activity in newborn kittens.

Doxapram is a respiratory stimulant which acts on peripheral chemoreceptors and central respiratory neurons in a dose-dependent fashion in the adult cat. In the newborn, the mechanisms of action of doxapram are still unclear. To evaluate the effects of doxapram on the carotid chemosensory discharge and its relationship with dopaminergic mechanisms in the carotid body, two groups of kittens less than 13 days old, anesthetized, artificially ventilated and paralyzed, were prepared for the recording of a single or a few chemosensory afferents of the carotid sinus nerve. The chemosensory activity was recorded under five conditions of inspired gas mixtures (21 and 8% O2 in N2, 100% O2, 5 and 10% CO2 in O2). Group 1 (n = 9) received only doxapram and group 2 (n = 8) was pretreated with haloperidol (1 mg/kg), a dopamine D2-receptor blocker, before receiving doxapram. Doxapram significantly stimulated the discharge rate of the carotid chemoafferents under all conditions of inspired gas. The chemosensory discharge was increased by haloperidol, and was raised further after doxapram by an amount similar to group 1. For instance, in normoxia, the activity increased from 2.9 +/- 0.4 to 7.5 +/- 0.9 impulse/s (mean +/- SEM, p < 0.01) in group 1 and from 3.8 +/- 0.6 to 9.1 +/- 1.0 impulse/s (p < 0.01) in group 2. These results indicate that the mechanisms of response of carotid chemoreceptor to doxapram are developed in the newborn kitten and doxapram acts independent of the dopaminergic mechanisms in the carotid body.

Ventilatory dynamics in children and adults during sinusoidal exercise.

The ventilatory response to sinusoidally varying exercise was studied in five adults and seven prepubertal children to determine whether the faster kinetics of ventilation observed in children during abrupt changes in exercise intensity remained more rapid when exercise intensity varied continuously. Each subject exercised on a cycle ergometer first against a constant load and then against a load fluctuating over six different periods ranging from 0.75 to 10 min. The pedal rate was kept constant for all loads. The inspiratory minute ventilation was determined breath-by-breath. Amplitude (A) and phase angle (phi) of the fundamental component and the first harmonics of the ventilatory response were calculated by Fourier analysis for an integer number of waves for each period. From the relationship between A, phi and frequency, dynamic parameters of a first order model with and without delay were compared between adults and children. Firstly we found that the ventilatory time constant was significantly faster in children: 49.7 (SD 9.1) s vs 74.6 (SD 11.1) s (P less than 0.01). Secondly, the change in A and phi with the frequency was not however characteristic of a first order system without delay in most of the subjects (phi greater than 90 degrees for the shorter periods). Thirdly, even when the ventilatory control system was described as a first order model with a positive delay, time constants remained significantly shorter in children: 45.6 (SD 5.7) s vs 67.4 (SD 13) s (P less than 0.01). The ability to increase ventilation faster in children appeared to be a characteristic of the ventilatory control system during exercise independent of the type of drive used.

Assessment of thoracic gas volume by low-frequency ambient pressure changes in children.

The validity of a new method for measuring thoracic gas volume (TGV) was studied in 69 children, 4-16 yrs old, including twelve normal children and 57 children with an obstructive (n = 38) or restrictive (n = 19) respiratory disease. The method consisted of applying very slow (0.05 Hz) sinusoidal variations of ambient pressure around the body (delta Pam = 40 cmH2O peak to peak) and studying the relationship between delta Pam and the resulting gas displacement at the mouth (Vaw): TGVapc = PB.delta Vaw/delta Pam.cos phi, where PB is barometric minus alveolar water vapour pressure and phi the phase angle between Pam and Vaw. Functional residual capacities derived from TGVapc (FRCapc) were compared to the values obtained by plethysmography (FRCplet) and by helium dilution (FRCdil). FRCapc did not differ significantly from FRCplet in either the entire group (1.75 +/- 0.62 l vs 1.79 +/- 0.45 l) or in the patient subgroups. However, with the new method a trend to slightly lower FRCs was seen in patients with the most obstruction (p less than 0.05). FRCdil was significantly lower than both FRCapc and FRCplet (p less than 0.001), particularly in children with obstruction. Significant correlations were found between the three methods (p less than 0.001). On the other hand, the method investigated requires that the subject breathe very regularly for a period of several minutes. This was rarely achieved, so that the reproducibility of the measurements was unacceptably low. At present, the method cannot be recommended for routine use in 4-16 yr old children.

Dual responses of carotid chemosensory afferents to dopamine in the newborn kitten.

The effects of dopamine and of dopamine D2 receptor blocker haloperidol on the activity of carotid chemoreceptors were studied in 24 anesthetized, paralyzed and artificially ventilated newborn kittens aged 0-17 days. Single or few fiber preparations of chemoreceptors were made from one carotid sinus nerve. The responses of the chemosensory afferents to intravenous injections of dopamine (5-50 micrograms.kg-1) were studied in kittens breathing air and 8% O2 in N2. The effects of haloperidol on the chemosensory activity in air or 100% O2 and on the chemosensory response to hypoxia were studied. Dopamine inhibited the chemosensory discharge in 25/44 studies in normoxia. Of the 9 studies performed in hypoxia, dopamine was excitatory in 5 or had no effect in 4 (P < 0.05 vs normoxia). Inhibition of the chemosensory discharge was observed in 24/37 studies performed in kittens aged more than 3 days and was predominantly excitatory in 6/7 studies in kittens aged 0-3 days (P < 0.01). One minute after haloperidol, the chemosensory discharge had increased significantly in all experiments. The biphasic pattern of chemosensory response to hypoxia (Marchal et al., Respir. Physiol. 87: 183-193, 1992) was not changed by haloperidol. The steady-state chemosensory activity was significantly increased after haloperidol, respectively from 3.9 +/- 0.7 impulses.sec-1 to 9.8 +/- 1.2 impulses.sec-1 in air, and from 13.1 +/- 1.4 impulses.sec-1 to 17.8 +/- 2.4 impulses.sec-1 in hypoxia (mean +/- SEM, P < 0.03). It is concluded that the dopaminergic mechanisms are active in the carotid body of the kitten, and the observed responses to dopamine and haloperidol are qualitatively similar to those reported in the adult cat.

Carotid chemoreceptor response to natural stimuli in the newborn kitten.

The activities of carotid chemoreceptors at three levels of inspired PO2 (55, 145 and 690 Torr) and at two levels of inspired PCO2 (35 and 70 Torr in O2) were studied in 28 anesthetized, mechanically ventilated kittens aged 0-17 days. A biphasic response to hypoxia was found in 46% of them: the chemosensory activity increased to a peak within 30 sec after the initial response to hypoxia and thereafter declined slowly to a stable value. The steady-state single-fiber chemosensory activity at an inspired PO2 of 55 Torr was significantly lower in kittens less than 10 days old (mean +/- SE: 5.8 +/- 0.6 impulses.sec-1) than in the older ones (8.8 +/- 1.3 impulses.sec-1, P less than 0.03). The response curves to arterial PO2 were hyperbolic in both groups but the curve for the younger kittens was displaced to the left of the curve for the older ones. The response to hypercapnia was a progressive increase in chemosensory activity with little evidence of rapid or slow adaptation. The response to hypercapnia was significantly stronger in the older kittens than in the young ones. It is concluded that, in the kitten, the carotid chemoreceptor response to hypoxia may be biphasic. The responses to hypoxia and hypercapnia are already developed but are weak at birth and continue to develop further during the first weeks of postnatal life.

Vascular distension in muscles contributes to respiratory control in sheep.

It has recently been proposed that afferent fibers from skeletal muscle could sense the state of the microvascular circulation, linking ventilation to the degree of peripheral perfusion or vascular distension (Huszczuk et al., Respir. Physiol., 91:207-226, 1993). Ventilatory and circulatory responses to manipulation of peripheral vascular pressures in the hind limbs of anaesthetized (sodium thiopental) sheep were examined. Inflatable balloons were placed at the caudal ends of the abdominal aorta and the vena cava (Vc). Aortic (Ao) occlusion induced a consistent normocapnic decrease in minute ventilation (VE). In contrast, VE increased significantly during vena cava obstruction, leading to hypocapnia. Small changes in systemic blood pressure were observed (+7 mmHg for Ao occlusion and -12 mmHg during Vc obstruction). Moreover, inflation of the caval balloon superimposed on a previously established Ao occlusion, preventing venous drainage of anastomotic inflow, resulted in a significant rise in distal vascular pressures with trivial changes in systolic blood pressure. This led to a gradual rise of VE, despite further reduction of the CO2 flux to the lungs. The subsequent deflation of the aortic balloon, exposing the hindlimb vasculature to aortic pressure, resulted in an even more profound hypocapnic hyperpnea. The concurrent arterial blood pressure changes were too small to possibly involve the ventilatory component of the arterial baroreflex. We therefore hypothesize, that perfusion-related afferent signals within the muscles could contribute to respiratory homeostasis by maintaining ventilation of the lungs commensurate with the circulatory state of the muscular apparatus.

Papaverine injection into the hindlimb circulation stimulates ventilation in sheep.

To test the hypothesis, previously suggested by Huszczuk et al. (1993), that distention of the peripheral microvascular network could, per se, stimulate ventilation, the ventilatory effects of papaverine-induced muscular vasodilation were studied in ten anaesthetized sheep. Because systemic action of papaverine may involve the arterial baro- and chemoreceptors, the animals were surgically prepared for a reversible isolation of the hindlimb circulation. Papaverine injection (1-2 mg/kg) into the arterial inflow of the isolated limbs provoked a 13 +/- 6 sec-delayed increase in VE by 1.8 +/- 0.2 L min-1 (p < 0.01) with a concomitant decrease in peripheral vascular resistance and no decrease in the systemic arterial blood pressure. Identical control injection into a jugular vein prior to the hindlimb circulatory separation yielded an increase of VE by 4.95 +/- 0.58 L min-1 with a latency of 21 +/- 2 sec and a coinciding moderate decrease of the systemic arterial pressure. The present data suggest that papaverine injection into the hindlimb circulation can stimulate ventilation independently of its possible effects on the arterial baro- or chemoreceptors, supporting the hypothesis that muscular vasodilation could contribute to the control of breathing through a neural link.

[Oculorespiratory reflex]. / Le réflexe oculo-respiratoire (R.O.R.).

The lack of interest about oculorespiratory reflex (ORR) in surgery and experimental studies is obvious. However the authors insist on the importance of its clinical traduction. The purpose of this study is to determinate an experimental model with titration of stimulus (pressure or traction) and therapeutic test. Our first Results prove the clinic entity of O.R.R. In first conclusion, we can insist on the importance of ventilatory assistance during squint surgery and on the monitoring of PE CO2 and Sa O2.