Cardiopulmonary haemodynamics in lambs during induced capillary leakage immediately after preterm birth.

1. Early postnatal events might play a critical role in the development of cardiorespiratory diseases of prematurity. Although the exact mechanism is unknown, capillary leakage resulting in increased interstitial fluid volume has been postulated to play a critical role. We investigated the effects of capillary leakage, induced by a volume load, on cardiopulmonary and systemic haemodynamics immediately after preterm delivery. 2. Fetal sheep were instrumented at 129 days gestation, delivered and ventilated. After 15 min, lambs in the volume load group received intravenous saline (50 mL/kg) infused over 10 min; control lambs received no infusion. At 30 min, lambs underwent a pulmonary challenge by increasing positive end-expiratory pressure (PEEP) by 2 cmH(2)O every 10 min to 10 cmH(2)O, with similar decrements back to baseline PEEP. Pulmonary blood flow (PBF) and arterial pressures were recorded in real-time and cardiovascular variables were measured by Doppler echocardiography. 3. Total protein concentration in the bronchoalveolar-lavage fluid was higher in volume load lambs compared with controls, and histological interstitial fluid retention was evident in volume load lambs, both indicative of capillary leak. PBF increased immediately after the volume load, but PBF, pulmonary and systemic arterial pressures, and oxygenation all deteriorated during the PEEP challenge compared with controls, coinciding with an increase in downstream pulmonary resistance. Three of six volume load lambs had pulmonary haemorrhage, which was not observed in control lambs. 4. Capillary leakage had moderate effects, but subsequent high levels of PEEP had significant negative effects on cardiopulmonary and respiratory function in preterm lambs. Capillary leakage might contribute to postnatal cardiopulmonary failure in preterm infants.

Pulmonary vascular and alveolar development in preterm lambs chronically colonized with Ureaplasma parvum.

Ureaplasma species, the most commonly isolated microorganisms in women with chorioamnionitis, are associated with preterm delivery. Chorioamnionitis increases the risk and severity of bronchopulmonary dysplasia and persistent pulmonary hypertension in newborns. It is not known whether the timing of exposure to inflammation in utero is an important contributor to the pathogenesis of bronchopulmonary dysplasia. We hypothesized that chronic inflammation would alter the pulmonary air space and vascular development after 70 days of exposure to infection. Pregnant ewes were given intra-amniotic injection of Ureaplasma parvum serovars 3 or 6 at low (2 x 10(4) cfu) or high doses (2 x 10(7) cfu) or media (controls) at 55 days gestational age. Fetuses were delivered at 125 days (term = 150 days). U. parvum was grown from the lungs of all exposed fetuses, and neutrophils and monocytes were increased in the air spaces. Lung mRNA expression of IL-1beta and IL-8, but not IL-6, was modestly increased in U. parvum-exposed fetuses. U. parvum exposure increased surfactant and improved lung gas volumes. The changes in lung inflammation and maturation were independent of serovar or dose. Exposure to U. parvum did not change multiple indices of air space or vascular development. Parenchymal elastin and collagen content were similar between groups. Expression of several endothelial proteins and pulmonary resistance arteriolar media thickness were also not different between groups. We conclude that chronic exposure to U. parvum does not cause sustained effects on air space or vascular development in premature lambs.

Continuous positive airway pressure failure in preterm infants: incidence, predictors and consequences.

BACKGROUND: Preterm infants ≤32 weeks' gestation are increasingly being managed on continuous positive airway pressure (CPAP), without prior intubation and surfactant therapy. Some infants treated in this way ultimately fail on CPAP and require intubation and ventilation. OBJECTIVES: To define the incidence, predictors and consequences of CPAP failure in preterm infants managed with CPAP from the outset. METHODS: Preterm infants 25-32 weeks' gestation were included in the study if inborn and managed with CPAP as the initial respiratory support, with division into two gestation ranges and grouping according to whether they were successfully managed on CPAP (CPAP-S) or failed on CPAP and required intubation <72 h (CPAP-F). Predictors of CPAP failure were sought, and outcomes compared between the groups. RESULTS: 297 infants received CPAP, of which 65 (22%) failed, with CPAP failure being more likely at lower gestational age. Most infants failing CPAP had moderate or severe respiratory distress syndrome radiologically. In multivariate analysis, CPAP failure was found to be predicted by the highest FiO2 in the first hours of life. CPAP-F infants had a prolonged need for respiratory support and oxygen therapy, and a higher risk of death or bronchopulmonary dysplasia at 25-28 weeks' gestation (CPAP-F 53% vs. CPAP-S 14%, relative risk 3.8, 95% CI 1.6, 9.3) and a substantially higher risk of pneumothorax at 29-32 weeks. CONCLUSION: CPAP failure in preterm infants usually occurs because of unremitting respiratory distress syndrome, is predicted by an FiO2 ≥0.3 in the first hours of life, and is associated with adverse outcomes.

Variable ventilation improves ventilation and lung compliance in preterm lambs.

PURPOSE: In adult animals, ventilation with variable tidal volume and rate improves lung mechanics, arterial oxygenation and ventilation compared to a monotonously controlled ventilation pattern. We assessed the physiological consequences of variable ventilation in the immature lung. METHODS: Lambs delivered at 129 days (term = 150 days) were euthanised (n = 9) or anaesthetised, tracheostomised and suctioned prior to prophylactic intra-tracheal surfactant instillation (Curosurf(®), 100 mg/kg) and commencement of controlled ventilation (50 breaths/min, tidal volume 7.7 ± 0.8 mL/kg). Volume history was standardised at 20 min with two sustained (3 s) inflations to 30 cmH(2)O followed immediately by measurement of baseline dynamic lung mechanics (FlexiVent, Scireq, Canada). Ventilation was continued according to prior randomisation (variable or conventional ventilation). For variable ventilation (n = 9), breath-to-breath tidal volume and respiratory rate varied but intra-breath minute volume (MV) and average tidal volume were equivalent to the conventional ventilation group with fixed tidal volume and rate (n = 7). Lung mechanics and gas exchange were measured at intervals. Lambs were euthanised at 2 h. Inflammatory cell counts and protein from bronchoalveolar lavage fluid and lung tissue cytokine mRNA were quantified. RESULTS: At study completion, PaCO(2) (p = 0.026) and mean airway pressure (p = 0.002) were lower and pH (p = 0.047), ventilation efficiency index (p = 0.021) and dynamic compliance were higher (p = 0.003) in lambs on variable rather than conventional ventilation. However, oxygenation indices and post-mortem static compliances were not different between groups. CONCLUSION: Variable ventilation improves ventilation efficiency and in vivo lung compliance in the preterm lung, but unlike adult models, had no effect on arterial oxygenation.