Inflammatory cytokines in gastric fluid at birth and the development of bronchopulmonary dysplasia.

AIM: To assess whether the levels of inflammatory and anti-inflammatory proteins in gastric fluid of premature infants shortly after birth are associated with the development of bronchopulmonary dysplasia (BPD). METHODS: Gastric fluid retrieved within 1 h of birth of premature infants (gestational age <29 weeks) was analysed for interleukin (IL)-8, growth-related oncogene (Gro)-α, epithelial cell-derived neutrophil-activating peptide (ENA)-78, IL-1ß and Clara cell secretory protein with ELISA. RESULTS: Of 51 enrolled infants, 86% had BPD. Of these, 54% had mild BPD, 30% had moderate BPD and 16% had severe BPD. Clinical chorioamnionitis was associated with high levels of IL-8, Gro-α, Epithelial cell-derived neutrophil-activating peptide-78 (ENA-78) and IL-1ß in gastric fluid. Gastric fluid levels of IL-8, Gro-α, ENA-78 and IL-1ß were higher in infants with moderate or severe BPD than in those with no or mild BPD. Ligation of the patent ductus arteriosus was associated with the development of moderate or severe BPD. These associations were no longer significant after adjustment for gestational age. CONCLUSION: The levels of inflammatory mediators in gastric fluid samples retrieved soon after birth from intubated or nonintubated infants can be used to assess the infants' perinatal exposure to inflammatory mediators and its association with neonatal outcome.

Postnatal nicotine exposure does not further compromise hypoxia defense mechanisms in prenatally nicotine-exposed lambs.

AIMS: To determine whether combined pre- and postnatal nicotine exposure compared with prenatal exposure alone results in more compromised postnatal hypoxia defense mechanisms and further alteration of the postnatal breathing pattern (reduced tidal volume and increased respiratory rate). METHODS: Seven lambs exposed to nicotine prenatally (pN) (approximate maternal dose: 0.5 mg/kg/d) and seven lambs exposed to nicotine pre- and postnatally (ppN) (postnatal dose: 1.6-2 mg/kg/d) were studied without sedation at an average age of 5 d and 21 d during resting (room air) conditions, during exposure to 10% O2 and during a brief exposure to 100% O2. RESULTS: Resting minute ventilation, occlusion pressure, effective impedance, heart rate and mean arterial blood pressure were similar in the two groups during wakefulness and quiet sleep. Resting tidal volume was significantly higher in ppN than in pN lambs during wakefulness (9.4 +/- 0.7 vs 7.7 +/- 1.4 ml/kg, p < 0.05) and quiet sleep (9.8 +/- 0.6 vs 7.6 +/- 1.5 ml/kg, p < 0.01) at 5 d and also at 21 d during wakefulness (7.7 +/- 1.0 vs 6.2 +/- 1.1 ml/kg, p < 0.05). The ventilatory, heart rate and blood pressure responses to hypoxia were comparable in the two groups during both activity states. Time to arousal from quiet sleep in response to hypoxia was equivalent in the two groups. The ventilatory response to hyperoxia was not significantly different in the two groups during either activity state. CONCLUSION: Continued postnatal nicotine exposure after prenatal exposure did not further compromise hypoxia defense mechanisms after birth.

Nicotine delays arousal during hypoxemia in lambs.

A decreased ability to arouse from sleep in response to arterial hypoxemia may lead to severe asphyxia and has been proposed as a mechanism of sudden infant death syndrome. Based on previous observations that nicotine exposure, a major environmental risk factor for sudden infant death syndrome, may impair hypoxic defense in neonates, we hypothesized that a short-term infusion of nicotine could impair hypoxic arousal through interference with oxygen-sensing mechanisms. Seven chronically instrumented unanesthetized lambs were studied at the age of 4.6 +/- 1.3 d during normoxia and acute hypoxia (0.1 fraction of inspired oxygen) for 5 min. Ventilation, transcutaneous Hb oxygen saturation, blood pressure, heart rate, and time to arousal were compared during a control saline infusion and during a 0.5 microg x kg(-1) x min(-1) nicotine infusion. Activity states, i.e. wakefulness and quiet sleep as well as arousal, were defined by EEG, nuchal electromyogram, and electrooculogram. Each lamb acted as its own control. Arousal from quiet sleep occurred significantly later during nicotine infusion compared with control (177 +/- 93 versus 57 +/- 41 s, p < 0.01) and at a lower transcutaneous Hb oxygen saturation (60 +/- 12 versus 79 +/- 12%, p < 0.01) (paired t test). The ventilatory response to hypoxia in wakefulness was similar during both conditions but was significantly attenuated in quiet sleep during nicotine infusion (p < 0.001, 2-way ANOVA repeated-measures design). Blood pressure and heart rate responses were similar during both conditions. These results suggest that a brief nicotine exposure blunts oxygen sensitivity in young lambs, a finding of potential relevance for sudden infant death syndrome.

Cerebral Doppler blood flow velocimetry and central hemodynamics in the ovine fetus during hypoxemia-acidemia.

The purpose of this study was to assess the effects of hypocapnic hypoxia, acidemia and the combination of hypoxia/acidemia on blood flow velocity variables in the fetal cerebral circulation. Chronically instrumented fetal sheep were used and the ewes were induced to breathe a hypoxic gas mixture for about 90 min. This caused an initial period of hypoxemia followed by a period of mixed hypoxemia/acidemia. When the ewe was reoxygenated, the fetus experienced a period of normoxic acidemia. The fetal cerebral circulation was assessed by recording Doppler blood flow velocity waveform variables in a cerebral vessel and the umbilical artery, using standard ultrasound equipment. External carotid artery blood flow was maintained during hypoxic and hypoxic/acidotic periods despite a fall in cardiac output. In the cerebral vessel, mean maximum velocity (time-averaged maximum velocity), minimum diastolic velocity and maximum systolic velocity manifested increases during hypoxic and hypoxic-acidotic periods, but pulsatility index did not change due to the effect of reduced heart rate on pulsatility index. Umbilical artery pulsatility index increased in the hypoxic and hypoxic-acidotic periods, despite unchanged mean maximum velocity, minimum diastolic velocity and maximum systolic velocity. With acute hemodynamic changes, the measurement of pulsatility index can yield misleading results. For clinical and experimental research on the fetal cerebral circulation, more attention should be paid to the individual Doppler variables, especially to the mean maximum velocity, than to the pulsatility index alone. Changes in mean maximum velocity recorded from the cerebral artery seem to reflect changes in the cerebral arterial flow.