Comparison of recruitment manoeuvres in ventilated sheep with acute respiratory distress syndrome.

BACKGROUND: Recruitment manoeuvres are widely used in clinical practice to open the lung and prevent lung injury by derecruitment, although the evidence is still discussed. In this study two different recruitment manoeuvres were compared to no recruitment manoeuvres (control) in ventilated sheep with acute respiratory distress syndrome (ARDS), induced by lung lavage. METHODS: We performed a prospective, randomised study in 26 ventilated sheep with ARDS, to evaluate the effect of two different recruitment manoeuvres on gas exchange, blood pressure and lung injury. The two different recruitment manoeuvres, the high pressure recruitment manoeuvre (HPRM), with high peak pressure, and the smooth and moderate recruitment manoeuvre (SMRM), with lower peak pressure, were compared to controls (no recruitment) after disconnection. Oxygenation index and ventilation efficacy index were calculated to evaluate gas exchange. Lung injury was assessed by inflammatory response in broncho-alveolar lavage fluid (BALF) and blood and histology of the lung. RESULTS: Oxygenation index improved significantly after both recruitment manoeuvres compared with controls, but no significant difference was found between the recruitment manoeuvres. Blood pressure decreased after HPRM but not after SMRM. HPRM induced a higher number of total cells and more neutrophils in the BALF. In the histology of the lung, mean alveolar size was increased in the dorsocranial region of the lung of SMRM compared to controls. CONCLUSION: Recruitment manoeuvres improved oxygenation, but SMRM was superior, with respect to hemodynamics and pulmonary inflammation, in ventilated sheep suffering from ARDS induced by lung lavage.

Sex differences in lung gas volumes after lipopolysaccharide-induced chorioamnionitis in fetal sheep.

BACKGROUND: Preterm female infants have a survival advantage and enhanced lung development, which is an important determinant of preterm survival. OBJECTIVE: Given the modulation of lung development by fetal exposure to infection/inflammation, we hypothesized that female fetuses have enhanced lung maturational responses to chorioamnionitis compared with male fetuses. METHODS: Time-pregnant ewes received intra-amniotic injections with saline (n = 60) or lipopolysaccharide (LPS) at 2 days (n = 30) or 7 days (n = 45) before surgical delivery at 123 to 125 days of gestation (term: ∼147 days). We assessed inflammatory responses in bronchoalveolar lavage fluid and cord blood, lung maturation with pressure-volume curves, and lung structure. RESULTS: Lung gas volume showed differences between the sexes after 2 days LPS (male 4.6 [1.2] mL/kg, female 7.7 [4.4] mL/kg; P = 0.02) and 7 days LPS (male 20.5 [9.3] mL/kg, female 27.0 [7.0] mL/kg; P = 0.01). The control group was not different by sex (male 8.0 [3.6] mL/kg, female 8.9 [3.9] mL/kg; P > 0.05). No difference in lung structure and in pulmonary and systemic inflammatory response was evident by sex. CONCLUSION: Preterm female sheep fetuses had increased lung gas volumes after exposure to LPS, without any detectable differences in fetal inflammatory responses.

Lipopolysaccharide-induced chorioamnionitis is confined to one amniotic compartment in twin pregnant sheep.

BACKGROUND: Chorioamnionitis is a major risk factor for preterm birth in multifetal pregnancies. However, there is little clinical data whether chorioamnionitis is restricted to one amniotic compartment in multifetal pregnancies. OBJECTIVE: To explore whether chorioamnionitis is confined to the exposed compartment and does not cross to the unaffected fetus in twin pregnancy. METHODS: In twin pregnant sheep, one of the twins was exposed to either 2 or 14 days of intra-amniotic lipopolysaccharide (LPS) while the co-twin was exposed to either 2 or 14 days of intra-amniotic saline (n = 3 for each exposure). Singletons were included in this study to compare the grade of inflammation with twins. All fetuses were delivered at 125 days of gestation (term = 150 days). Chorioamnionitis was confirmed by histological examination. Lung inflammation was assessed by cell count in bronchoalveolar lavage. Lung compliance was assessed at 40 cm H(2)O. Results were compared using analysis of variance (ANOVA) with a post-hoc Tukey analysis. RESULTS: Inflammation in placenta, membranes and lung of LPS-exposed twins was significantly higher after 2 and 14 days of exposure when compared to the saline-exposed co-twins. Lung compliance in LPS-exposed twins was significantly increased after 14 days when compared to saline-exposed co-twins. Intrauterine LPS exposure increased lung compliance and inflammation in the membranes, placenta and lung to the same extent in twins as in singletons. CONCLUSION: In twin pregnant sheep, inflammation of the membranes, placenta and fetal lung was strictly limited to the exposed fetus in the amniotic compartment in which the LPS was injected.

Fetal responses to lipopolysaccharide-induced chorioamnionitis alter immune and airway responses in 7-week-old sheep.

OBJECTIVE: We hypothesized that fetal innate immune responses to lipopolysaccharide-induced chorioamnionitis would alter postnatal systemic immune and airway responsiveness. STUDY DESIGN: Ewes received intraamniotic injections with saline or lipopolysaccharide at 90, 100, and 110 days of gestation. Immune status and airway responsiveness were evaluated at term and at 7 weeks of age. RESULTS: At term, lymphocytes, monocytes, and neutrophils were significantly increased (respectively, 24-fold, 127-fold, and 31,000-fold) in lungs and blood monocytes became Toll-like receptor 2 responsive after lipopolysaccharide exposures. Furthermore, CD4 and CD4/CD25 lymphocytes were increased in thymus and lymph nodes. At 7 weeks, airway reactivity decreased and concentrations of CD8 cytotoxic T lymphocytes changed in the lungs and thymus relative to controls. CONCLUSION: Early gestational lipopolysaccharide exposure increased leukocyte responsiveness at term. Decreased airway reactivity and changes in lymphocytes at 7 weeks postnatal demonstrate persistent effects of fetal exposure to LPS.