Vagal denervation inhibits the increase in pulmonary blood flow during partial lung aeration at birth.

KEY POINTS: Lung aeration at birth significantly increases pulmonary blood flow, which is unrelated to increased oxygenation or other spatial relationships that match ventilation to perfusion. Using simultaneous X-ray imaging and angiography in near-term rabbits, we investigated the relative contributions of the vagus nerve and oxygenation to the increase in pulmonary blood flow at birth. Vagal denervation inhibited the global increase in pulmonary blood flow induced by partial lung aeration, although high inspired oxygen concentrations can partially mitigate this effect. The results of the present study indicate that a vagal reflex may mediate a rapid global increase in pulmonary blood flow in response to partial lung aeration. ABSTRACT: Air entry into the lungs at birth triggers major cardiovascular changes, including a large increase in pulmonary blood flow (PBF) that is not spatially related to regional lung aeration. To investigate the possible underlying role of a vagally-mediated stimulus, we used simultaneous phase-contrast X-ray imaging and angiography in near-term (30 days of gestation) vagotomized (n = 15) or sham-operated (n = 15) rabbit kittens. Rabbits were imaged before ventilation, when one lung was ventilated (unilateral) with 100% nitrogen (N2 ), air or 100% oxygen (O2 ), and after all kittens were switched to unilateral ventilation in air and then ventilation of both lungs using air. Compared to control kittens, vagotomized kittens had little or no increase in PBF in both lungs following unilateral ventilation when ventilation occurred with 100% N2 or with air. However, relative PBF did increase in vagotomized animals ventilated with 100% O2 , indicating the independent stimulatory effects of local oxygen concentration and autonomic innervation on the changes in PBF at birth. These findings demonstrate that vagal denervation inhibits the previously observed increase in PBF with partial lung aeration, although high inspired oxygen concentrations can partially mitigate this effect.

The cardiovascular response to birth asphyxia is altered by the surrounding environment.

BACKGROUND: A sustained bradycardia is used as a major indicator of severe perinatal asphyxia. However, lambs asphyxiated ex utero do not exhibit the same bradycardic response as lambs asphyxiated in utero. It is possible that the local in utero environment may influence the initial cardiovascular response to asphyxia. We assessed the effect of facial immersion in water on the cardiovascular response to birth asphyxia. METHODS: Pregnant ewes (138±1 days gestation) were anaesthetised and fetuses were exteriorised and instrumented for measurement of cardiopulmonary haemodynamics. The lamb's head either remained in air (n=5) or was placed in water that was either warm (40±1°C; n=5) or at room temperature (21±1°C; n=5) before the umbilical cord was clamped to induce asphyxia. RESULTS: Heart rate after bradycardia onset was reduced in lambs asphyxiated with their head in cool water (-34±2%) and warm water (-25±4%) compared with those in air (-11±5%; p<0.05). Similarly, the decrease in blood pressure was faster in lambs with water around the face compared with those in air. From 75 s after asphyxia onset, mean and end-diastolic carotid blood flow was higher in the group asphyxiated in air (25±4 mL/kg/min), compared with the groups in water (13±3 mL/kg/min, warm water; 16±2 mL/kg/min, cool water; p<0.05). CONCLUSIONS: The cardiovascular response to birth asphyxia is altered by the presence and temperature of water surrounding the head. The previous understanding of the vagally mediated bradycardia associated with birth asphyxia may include components of the diving reflex.

Increase in pulmonary blood flow at birth: role of oxygen and lung aeration.

Lung aeration stimulates the increase in pulmonary blood flow (PBF) at birth, but the spatial relationships between PBF and lung aeration and the role of increased oxygenation remain unclear. Using simultaneous phase-contrast X-ray imaging and angiography, we have investigated the separate roles of lung aeration and increased oxygenation in PBF changes at birth using near-term (30 days of gestation) rabbit kits (n = 18). Rabbits were imaged before ventilation, then the right lung was ventilated with 100% nitrogen (N2), air or 100% O2 (oxygen), before all kits were switched to ventilation in air, followed by ventilation of both lungs using air. Unilateral ventilation of the right lung with 100% N2 significantly increased heart rate (from 69.4 ± 4.9 to 93.0 ± 15.0 bpm), the diameters of both left and right pulmonary axial arteries, number of visible vessels in both left and right lungs, relative PBF index in both pulmonary arteries, and reduced bolus transit time for both left and right axial arteries (from 1.34 ± 0.39 and 1.81 ± 0.43 s to 0.52 ± 0.17 and 0.89 ± 0.21 s in the left and right axial arteries, respectively). Similar changes were observed with 100% oxygen, but increases in visible vessel number and vessel diameter of the axial arteries were greater in the ventilated right lung during unilateral ventilation. These findings confirm that PBF increase at birth is not spatially related to lung aeration and that the increase in PBF to unventilated regions is unrelated to oxygenation, although oxygen can potentiate this increase.

Very Preterm Infants Failing CPAP Show Signs of Fatigue Immediately after Birth.

OBJECTIVE: To investigate the differences in breathing pattern and effort in infants at birth who failed or succeeded on continuous positive airway pressure (CPAP) during the first 48 hours after birth. METHODS: Respiratory function recordings of 32 preterm infants were reviewed of which 15 infants with a gestational age of 28.6 (0.7) weeks failed CPAP and 17 infants with a GA of 30.1 (0.4) weeks did not fail CPAP. Frequency, duration and tidal volumes (VT) of expiratory holds (EHs), peak inspiratory flows, CPAP-level and FiO2-levels were analysed. RESULTS: EH incidence increased <6 minutes after birth and remained stable thereafter. EH peak inspiratory flows and VT were similar between CPAP-fail and CPAP-success infants. At 9-12 minutes, CPAP-fail infants more frequently used smaller VTs, 0-9 ml/kg and required higher peak inspiratory flows. However, CPAP-success infants often used large VTs (>9 ml/kg) with higher peak inspiratory flows than CPAP-fail infants (71.8 ± 15.8 vs. 15.5 ± 5.2 ml/kg.s, p <0.05). CPAP-fail infants required higher FiO2 (0.31 ± 0.03 vs. 0.21 ± 0.01), higher CPAP pressures (6.62 ± 0.3 vs. 5.67 ± 0.26 cmH2O) and more positive pressure-delivered breaths (45 ± 12 vs. 19 ± 9%) (p <0.05). CONCLUSION: At 9-12 minutes after birth, CPAP-fail infants more commonly used lower VTs and required higher peak inspiratory flow rates while receiving greater respiratory support. VT was less variable and larger VT was infrequently used reflecting early signs of fatigue.

Monitoring tidal volumes in preterm infants at birth: mask versus endotracheal ventilation.

OBJECTIVE: Upper airway distention during mask ventilation could reduce gas volumes entering the lung compared with ventilation via an endotracheal tube. Therefore, respiratory tract volumes were measured in lambs and tidal volumes were compared in preterm infants before and after intubation. DESIGN: In seven preterm lambs, volumes of the airways (oropharynx, trachea, lungs) were assessed. In 10 preterm infants, delta pressures, tidal volumes and leak were measured during ventilation 2 min before (mask ventilation) and 2 min after intubation (endotracheal ventilation). Inflations coinciding with breaths were excluded. OUTCOME MEASURES: Amount of upper airway distention in lambs and differences in inspiratory and expiratory tidal volume before and after intubation. RESULTS: In lambs, the combined trachea and oropharynx contributed to 14 (12-21) % (median (IQR), whereas the oropharynx contributed to 9 (7-10) % of the total tidal volume measured at the mouth. In preterm infants, inspiratory (11.1 (7.9-22.6) mL/kg vs 5.8 (3.9-9.6) mL/kg (p=0.01)) and expiratory (8.3 (6.8-15.4) mL/kg vs 4.9 (3.9-9.6) mL/kg (p=0.02)) tidal volumes were significantly larger during mask ventilation compared with endotracheal ventilation. Leak was 18.7 (3.3-28.7) % before versus 0 (0-2.3) % after intubation (p<0.0001). Delta pressure was 23.7 (20.8-25.6) cm H2O before versus 24.8 (20.8-26.0) cm H2O after intubation (p>0.05). During mask ventilation, expiratory tidal volume increased from 10.0 (5.4-15.6) mL/kg to 11.3 (7.6-17.0) mL/kg (p=0.01), but remained unchanged during endotracheal ventilation. CONCLUSIONS: During neonatal mask ventilation, distention of the upper respiratory tract contributes to the tidal volumes measured and should be taken into account when targeting tidal volumes during mask ventilation.

Ventilation/perfusion mismatch during lung aeration at birth.

At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large increase in pulmonary blood flow (PBF). Current theories predict that the increase in PBF is spatially related to ventilated lung regions as they aerate after birth. Using simultaneous phase-contrast X-ray imaging and angiography we investigated the spatial relationships between lung aeration and the increase in PBF after birth. Six near-term (30-day gestation) rabbits were delivered by caesarean section, intubated and an intravenous catheter inserted, before they were positioned for X-ray imaging. During imaging, iodine was injected before ventilation onset, after ventilation of the right lung only, and after ventilation of both lungs. Unilateral ventilation increased iodine levels entering both left and right pulmonary arteries (PAs) and significantly increased heart rate, iodine ejection per beat, diameters of both left and right PAs, and number of visible vessels in both lungs. Within the 6th intercostal space, the mean gray level (relative measure of iodine level) increased from 68.3 ± 11.6 and 70.3 ± 7.5%·s to 136.3 ± 22.6 and 136.3 ± 23.7%·s in the left and right PAs, respectively. No differences were observed between vessels in the left and right lungs, despite the left lung not initially being ventilated. The increase in PBF at birth is not spatially related to lung aeration allowing a large ventilation/perfusion mismatch, or pulmonary shunting, to occur in the partially aerated lung at birth.

Changes in positive end-expiratory pressure alter the distribution of ventilation within the lung immediately after birth in newborn rabbits.

Current recommendations suggest the use of positive end-expiratory pressures (PEEP) to assist very preterm infants to develop a functional residual capacity (FRC) and establish gas exchange at birth. However, maintaining a consistent PEEP is difficult and so the lungs are exposed to changing distending pressures after birth, which can affect respiratory function. Our aim was to determine how changing PEEP levels alters the distribution of ventilation within the lung. Preterm rabbit pups (28 days gestation) were delivered and mechanically ventilated with one of three strategies, whereby PEEP was changed in sequence; 0-5-10-5-0 cmH2O, 5-10-0-5-0 cmH2O or 10-5-0-10-0 cmH2O. Phase contrast X-ray imaging was used to analyse the distribution of ventilation in the upper left (UL), upper right (UR), lower left (LL) and lower right (LR) quadrants of the lung. Initiating ventilation with 10PEEP resulted in a uniform increase in FRC throughout the lung whereas initiating ventilation with 5PEEP or 0PEEP preferentially aerated the UR than both lower quadrants (p<0.05). Consequently, the relative distribution of incoming VT was preferentially directed into the lower lobes at low PEEP, primarily due to the loss of FRC in those lobes. Following ventilation at 10PEEP, the distribution of air at end-inflation was uniform across all quadrants and remained so regardless of the PEEP level. Uniform distribution of ventilation can be achieved by initiating ventilation with a high PEEP. After the lungs have aerated, small and stepped reductions in PEEP result in more uniform changes in ventilation.

Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and injury in preterm lambs.

Ventilation-induced lung injury (VILI) of preterm neonates probably contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). Erythropoietin (EPO) has been suggested as a therapy for BPD. The aim of this study was to determine whether prophylactic administration of EPO reduces VILI in preterm newborn lambs. Lambs at 126 days of gestation (term is 147 days) were delivered and ventilated with a high tidal volume strategy for 15 min to cause lung injury, then received gentle ventilation until 2 h of age. Lambs were randomized to receive intravenous EPO (5000 IU kg(-1): Vent+EPO; n = 6) or phosphate-buffered saline (Vent; n = 7) soon after birth: unventilated controls (UVC; n = 8) did not receive ventilation or any treatment. Physiological parameters were recorded throughout the experimental procedure. Samples of lung were collected for histological and molecular assessment of inflammation and injury. Samples of liver were collected to assess the systemic acute phase response. Vent+EPO lambs received higher F IO 2, P aO 2 and oxygenation during the first 10 min than Vent lambs. There were no differences in physiological indices beyond this time. Total lung injury score, airway wall thickness, inflammation and haemorrhage were higher in Vent+EPO lambs than in Vent lambs. Lung inflammation and early markers of lung and systemic injury were elevated in ventilated lambs relative to unventilated lambs; EPO administration further increased lung inflammation and markers of lung and systemic injury. Prophylactic EPO exacerbates VILI, which may increase the incidence and severity of long-term respiratory disease. More studies are required before EPO can be used for lung protection in preterm infants.

Measuring physiological changes during the transition to life after birth.

The transition to life after birth is characterized by major physiological changes in respiratory and hemodynamic function, which are predominantly initiated by breathing at birth and clamping of the umbilical cord. Lung aeration leads to the establishment of functional residual capacity, allowing pulmonary gas exchange to commence. This triggers a significant decrease in pulmonary vascular resistance, consequently increasing pulmonary blood flow and cardiac venous return. Clamping the umbilical cord also contributes to these hemodynamic changes by altering the cardiac preload and increasing peripheral systemic vascular resistance. The resulting changes in systemic and pulmonary circulation influence blood flow through both the oval foramen and ductus arteriosus. This eventually leads to closure of these structures and the separation of the pulmonary and systemic circulations. Most of our knowledge on human neonatal transition is based on human (fetal) data from the 1970s and extrapolation from animal studies. However, there is renewed interest in performing measurements directly at birth. By using less cumbersome techniques (and probably more accurate), our previous understanding of the physiological transition at birth is challenged, as well as the causes and consequences for when this transition fails to progress. This review will provide an overview of physiological measurements of the respiratory and hemodynamic transition at birth. Also, it will give a perspective on some of the upcoming technological advances in physiological measurements of neonatal transition in infants who are unable to make the transition without support.

Noninvasive measurements of hemodynamic transition directly after birth.

BACKGROUND: Cardiac output depends on stroke volume and heart rate (HR). Only HR is used to monitor hemodynamic transition. METHODS: In 24 term newborns born via cesarean section, HR and preductal blood pressure (BP) were measured. Also, using echocardiography, left ventricular dimensions and (Doppler derived) left ventricular output (LVO) were examined at 2, 5, and 10 min after birth. RESULTS: Mean (SD) HR and BP did not change with time (mean HR: 157 (21) bpm at 2 min, 154 (17) bpm at 5 min, and 155 (14) bpm at 10 min; mean BP: 51.2 (15.4) mm Hg at 2 min, 50.5 (11.7) mm Hg at 5 min, and 49.6 (9.5) mm Hg at 10 min). Left ventricular end-diastolic diameter increased from 2 to 5 min (14.3 (1.3) vs. 16.3 (1.7) mm; P < 0.001) and stabilized at 10 min (16.7 (1.4) mm). LVO increased between 2 and 5 min (151 (47) vs. 203 (55) ml/kg/min; P < 0.001) and stabilized at 10 min (201 (45) ml/kg/min). LVO increase was associated with rise in left ventricular stroke volume (r = 0.94; P < 0.001), not with rise in HR (r = 0.37; P value not significant). CONCLUSION: Left ventricular dimensions and LVO significantly increased the first 5 min after birth and stabilized at 10 min, whereas BP remained stable. LVO and left ventricular dimension increase are presumably due to increasing left ventricular preload resulting from pulmonary blood flow and ductal shunting increase.

The administration of 100% oxygen and respiratory drive in very preterm infants at birth.

AIM: To retrospectively investigate the changes of SpO2 and respiratory drive in preterm infants at birth after administration of 100% oxygen. METHODS: Respiratory parameters, FiO2 and oximetry of infants <32 weeks gestation before and after receiving FiO2 1.0 were reviewed during continuous positive airway pressure (CPAP) or positive pressure ventilation (PPV). RESULTS: Results are given as median (IQR) or percentages where appropriate. Suitable recordings were made in 50 infants (GA 27 (26-29) weeks), 17 received CPAP and 33 PPV. SpO2 increased rapidly in the first minute after FiO2 1.0 and remained stable. The duration of FiO2 1.0 tended to be shorter in the CPAP group than in the PPV group (CPAP vs. PPV: 65 (33-105) vs. 100 (40-280) s; p = 0.05), SpO2 >95% occurred more often in PPV group (53% vs. 69%) and lasted longer (70(40-95) vs. 120(50-202) s). In CPAP group, minute volume increased from 134 (76-265) mL/kg/min 1 minute before to 240 (157-370) mL/kg/min (p<0.01) 1 minute after start FiO2 1.0 and remained stable at 2 minutes (252 (135-376) mL/kg/min; ns). The rate of rise to maximum tidal volume increased (from 13.8 (8.0-22.4) mL/kg/s to 18.2 (11.0-27.5) mL/kg/s; p<0.0001) to 18.8 (11.8-27.8) mL/kg/s; ns). In the PPV group respiratory rate increased from 0(0-4) to 9(0-20) at 1 minute (p<0.001) to 23 (0-34) breaths per minute at 2 minutes (p<0.01). CONCLUSION: In preterm infants at birth, a rapid increase in oxygenation, resulting from a transient increase to 100% oxygen might improve respiratory drive, but increases the risk for hyperoxia.

Establishing functional residual capacity in the non-breathing infant.

The transition to newborn life critically depends upon lung aeration and the onset of air-breathing, which triggers major cardiovascular changes required for postnatal life, including increases in pulmonary blood flow. Recent imaging studies indicate that lung aeration and functional residual capacity (FRC) recruitment results from inspiratory efforts, which create transpulmonary pressure gradients. During inspiration, these pressure gradients drive airway liquid movement through the conducting and into the distal airways where it crosses the pulmonary epithelium and enters the surrounding tissue. Although this process can occur rapidly (within 3-5 breaths), liquid clearance from lung tissue is much slower, resulting in oedema and increased interstitial tissue pressures, facilitating liquid re-entry into the airways at FRC. Whereas this liquid may be cleared during the next inspiration, liquid re-entry at FRC can be opposed by Na(+) reabsorption, oncotic pressures and expiratory braking manoeuvres. Recognition that transpulmonary pressure gradients mainly drive airway liquid clearance at birth has provided a clearer understanding of how this process may be facilitated in very preterm infants. In particular, it underpins the rationale for providing respiratory support that initially focuses on moving liquid through tubes (airways) rather than air. As the viscosity of liquid is much greater than air, the resistance to moving liquid is ≈ 100 times greater than air, necessitating the use of higher pressures or longer inflation times. Although it is unclear how this strategy could be safely applied clinically, it is clear that end-expiratory pressures are required to create and maintain FRC in preterm infants.

Expired CO2 levels indicate degree of lung aeration at birth.

As neonatal resuscitation critically depends upon lung aeration at birth, knowledge of the progression of this process is required to guide ongoing care. We investigated whether expired CO2 (ECO2) levels indicate the degree of lung aeration immediately after birth in two animal models and in preterm infants. Lambs were delivered by caesarean section and ventilated from birth. In lambs, ECO2 levels were significantly (p<0.0001) related to tidal volumes and CO2 clearance/breath increased exponentially when tidal volumes were greater than 6 mL/kg. Preterm (28 days of gestation; term = 32 days) rabbits were also delivered by caesarean section and lung aeration was measured using phase contrast X-ray imaging. In rabbit kittens, ECO2 levels were closely related (p<0.001) to lung volumes at end-inflation and were first detected when ∼7% of the distal lung regions were aerated. ECO2 levels in preterm infants at birth also correlated with tidal volumes. In each infant, ECO2 levels increased to >10 mmHg 28 (median) (21-36) seconds before the heart rate increased above 100 beats per minute. These data demonstrate that ECO2 levels can indicate the relative degree of lung aeration after birth and can be used to clinically assess ventilation in the immediate newborn period.

Measurement of absolute regional lung air volumes from near-field x-ray speckles.

Propagation-based phase contrast x-ray (PBX) imaging yields high contrast images of the lung where airways that overlap in projection coherently scatter the x-rays, giving rise to a speckled intensity due to interference effects. Our previous works have shown that total and regional changes in lung air volumes can be accurately measured from two-dimensional (2D) absorption or phase contrast images when the subject is immersed in a water-filled container. In this paper we demonstrate how the phase contrast speckle patterns can be used to directly measure absolute regional lung air volumes from 2D PBX images without the need for a water-filled container. We justify this technique analytically and via simulation using the transport-of-intensity equation and calibrate the technique using our existing methods for measuring lung air volume. Finally, we show the full capabilities of this technique for measuring regional differences in lung aeration.

Correction: Expired CO2 Levels Indicate Degree of Lung Aeration at Birth.

[This corrects the article DOI: 10.1371/journal.pone.0070895.].

The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits.

BACKGROUND: Recent phase-contrast X-ray imaging studies suggest that inspiration primarily drives lung aeration and airway liquid clearance at birth, which questions the role of adrenaline-induced activation of epithelial sodium channels (ENaCs). We hypothesized that pressures generated by inspiration have a greater role in airway liquid clearance than do ENaCs after birth. METHODS: Rabbit pups (30 d of gestation) were delivered and sedated, and 0.1 ml of saline (S) or amiloride (Am; an ENaC inhibitor) was instilled into the lungs before mechanical ventilation. Two other groups (30 d of gestation) were treated similarly but were also given adrenaline (S/Ad and Am/Ad) before mechanical ventilation. RESULTS: Amiloride and adrenaline did not affect functional residual capacity (FRC) recruitment (P > 0.05). Amiloride increased the rate of FRC loss between inflations (Am: -5.2 ± 0.6 ml/kg/s), whereas adrenaline reduced the rate of FRC loss (S/Ad: -1.9 ± 0.3 ml/kg/s) as compared with saline-treated controls (S: -3.5 ± -0.6 ml/kg/s; P < 0.05). CONCLUSION: These data indicate that inspiration is a major determinant of airway liquid clearance and FRC development during positive pressure ventilation. Although ENaC inhibition and adrenaline administration had no detectable effect on FRC development, ENaC may help to prevent liquid from re-entering the airways during expiration.

Effects of naloxone on the breathing pattern of a newborn exposed to maternal opiates.

AIM: To give new insights into how an infant responded to naloxone, given after acquiring a maternal opiate by recording the breathing pattern directly after birth. METHOD: A respiratory recording is presented of an infant during resuscitation in the delivery room after receiving naloxone for respiratory depression, resulting from maternal remifentanyl use. RESULTS: The infant was born apneic and bradycardic. Normal resuscitation manoeuvres had no effect on the respiratory drive. Directly after administration of naloxone, a tachypneic breathing pattern with sporadic expiratory breaking manoeuvres was observed. CONCLUSION: The immediate tachypnoea is most likely a direct effect of the naloxone causing an immediate 'rebound response' after the release of the opiate-induced inhibition of the respiratory drive.

Auditing resuscitation of preterm infants at birth by recording video and physiological parameters.

OBJECTIVE: To evaluate compliance with neonatal resuscitation guidelines during resuscitation of preterm infants by video recording of delivery room management and monitoring physiologic parameters. METHODS: The delivery room management of preterm infants at birth was recorded by an independent researcher. Physiological parameters (airway pressures, gas flow, tidal volume, heart rate and oxygen saturation) were measured, use of supplemental oxygen was noted and a video of the resuscitation was recorded. All signals were digitised and recorded using specially designed software. The delivery room management was then evaluated and compared with the local resuscitation guidelines. RESULTS: Thirty-four infants were included with a mean (SD) gestational age of 30.6 (3.2) weeks and birth weight of 1292 (570) g. Time from birth to initial evaluation was longer than recommended (65 (15) s). Respiratory support was started at 70 (23) s. In 7/34 infants (21%), interventions were performed according to guidelines. In 25/34 infants (74%), one or more respiratory interventions were not performed according to guidelines. In 10/34 infants (29%), one or more non-respiratory interventions (mainly related to the prevention of heat loss) were not performed according to guidelines. The presence and adequacy of spontaneous breathing was difficult to judge clinically. In almost all occasions (96%) the information from the respiratory function monitor was not used. CONCLUSIONS: Neonatal caregivers often deviate from resuscitation guidelines. Respiratory function monitoring parameters were often not used during resuscitation. A difficult part of neonatal resuscitation is subjectively assessing spontaneous breathing.

Surfactant increases the uniformity of lung aeration at birth in ventilated preterm rabbits.

Surfactant deficiency is a major cause of respiratory failure in newborns. We have investigated the roles of surfactant and positive end-expiratory pressure (PEEP) in the development of a functional residual capacity (FRC) and the distribution of ventilation at birth. Preterm rabbit pups (28 d GA) were delivered and received either saline or surfactant and then ventilated with (3PEEP) or without (0PEEP) 3 cm H2O PEEP (groups: saline/0PEEP, surfactant/0PEEP, saline/3PEEP, surfactant/3PEEP). Lung gas volumes were measured using plethysmography, and the uniformity of ventilation was analyzed using phase contrast (PC) x-ray imaging. Surfactant/0PEEP pups had greater FRCs and the lungs were more uniformly ventilated than saline/0PEEP pups; FRC at inflation 19-21 was 2.46 ± 0.52 mL/kg versus 0.91 ± 0.95 mL/kg (p < 0.05). Saline/3PEEP pups developed an FRC of 7.54 ± 1.68 mL/kg at inflation 19-21 (p < 0.05), but the distribution of ventilation was initially nonuniform. Surfactant/3PEEP pups had an FRC of 8.50 ± 0.80 mL/kg (at inflation 19-21), and the distribution of ventilation was more uniform than with saline/3PEEP (p < 0.05). In ventilated preterm newborn rabbits, PEEP has a greater effect on FRC than surfactant, although the two are additive. Surfactant, administered at birth, markedly improved the uniformity of ventilation irrespective of whether PEEP was applied.

Inspiration regulates the rate and temporal pattern of lung liquid clearance and lung aeration at birth.

At birth, the initiation of pulmonary gas exchange is dependent on air entry into the lungs, and recent evidence indicates that pressures generated by inspiration may be involved. We have used simultaneous plethysmography and phase-contrast X-ray imaging to investigate the contribution of inspiration and expiratory braking maneuvers (EBMs) to lung aeration and the formation of a functional residual capacity (FRC) after birth. Near-term rabbit pups (n = 26) were delivered by cesarean section, placed in a water plethysmograph, and imaged during the initiation of spontaneous breathing. Breath-by-breath changes in lung gas volumes were measured using plethysmography and visualized using phase-contrast X-ray imaging. Pups rapidly (1-5 breaths) generate a FRC (16.2 +/- 1.2 ml/kg) by inhaling a greater volume than they expire (by 2.9 +/- 0.4 ml.kg(-1).breath(-1) over the first 5 breaths). As a result, 94.8 +/- 1.4% of lung aeration occurred during inspiration over multiple breaths. The incidence of EBMs was rare early during lung aeration, with most (>80%) occurring after >80% of max FRC was achieved. Although EBMs were associated with an overall increase in FRC, 34.8 +/- 5.3% of EBMs were associated with a decrease in FRC. We conclude that lung aeration is predominantly achieved by inspiratory efforts and that EBMs help to maintain FRC following its formation.