Effects of dexamethasone on meconium aspiration syndrome in newborn piglets.

We examined the effects of dexamethasone on lung function in a piglet model of meconium aspiration syndrome. We induced lung injury in 10 newborn piglets (age 5 +/- 0.2 d) with 4 mL/kg body weight of 20% sterile human meconium in normal saline given via tracheostomy. Ventilator management was aimed at maintaining comparable values of end tidal carbon dioxide, Hb saturation, and arterial blood gases. Lung function was assessed using a BICORE CP100 neonatal monitor. Five piglets received 0.5 mg/kg of dexamethasone 2 and 8 h after meconium administration, whereas control piglets received normal saline at similar times. Ventilator settings, oxygen requirements, and lung compliance were similar between groups at the start of the study. Two hours after the instillation of meconium, there was marked lung dysfunction in both groups as evidenced by increased oxygen requirements [fraction of inspired oxygen (FiO2) 0.98 +/- 0.01 versus FiO2 0.21 +/- 0, p < 0.0001] and reduced lung compliance (0.35 +/- 0.03 versus 0.8 +/- 0.03 mL x kg(-1) x cm(-1) H2O, p < 0.0001). Administration of dexamethasone resulted in lower oxygen requirements (FiO2 0.27 +/- 0.01 versus FiO2 1.0 +/- 0.0, p < 0.00001), lower oxygenation index (2.17 +/- 0.17 versus 22.64 +/- 3.39, p < 0.0001), ventilatory efficiency index (0.30 +/- 0.01 versus 0.07 +/- 0.01, p < 0.0001), and improved lung compliance (0.68 +/- 0.04 versus 0.34 +/- 0.05 mL x kg(-1) x cm(-1) H2O, p < 0.001) compared with the control group. In summary, a two-dose course of 0.5 mg/kg of dexamethasone improved blood gases and lung function in a piglet model of meconium aspiration syndrome.

Utility of daily head ultrasonography for infants on extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: Intracranial hemorrhage (ICH) is a major concern during extracorporeal membrane oxygenation (ECMO). Daily cranial ultrasonography has been used by many ECMO centers as a diagnostic tool for both detecting and following ICH while infants are on bypass. The purpose of this patient review was to look at the usefulness of performing daily cranial ultrasonography (HUS) in infants on ECMO in detecting intraventricular hemorrhage of a magnitude sufficient to alter patient treatment. METHODS: The authors reviewed retrospectively all of the records of all neonates treated with ECMO at the Hermann Children's Hospital, Wilford Hall USAF Medical Center, Cincinnati Children's Hospital, The University of Texas Medical Branch at Galveston, and Texas Children's Hospital between February 1986 to March 1995. Two hundred ninety-eight patients were placed on ECMO during this period. All patients had HUS before, and daily while on ECMO, and all were reviewed by the staff radiologists. A total of 2,518 HUS examinations were performed. RESULTS: Fifty-two of 298 patients (17.5%) had an intraventricular hemorrhage seen on ultrasound scan. Nine of 52 patients (17.3%) had an ICH seen on the initial HUS examination before ECMO, all of which were grade I, and 43 of 52 patients (82.7%) had ICH while on ECMO. Of these ICH, 15 were grade I, 10 were grade II, 10 were grade III, and eight were grade IV. Forty of these ICH (93%) were diagnosed by HUS during the first 5 days of the ECMO course. Seven hundred eighty-six HUS were performed after day 5, at an estimated cost of $300,000 to $450,000 (charges), demonstrating three new intraventricular hemorrhages, one grade I, and one grade IV on day 7 and one grade I on day 8. Eight patients were taken off ECMO because of ICH diagnosed within the first 5 days. One patient was taken off ECMO because of ICH diagnosed after 5 days. This patient had clinical symptoms suggestive of ICH. CONCLUSIONS: Almost all ICH occur during the first 5 days of an ECMO course. Unless there is a clinical suspicion, it is not cost effective to perform HUS after the fifth day on ECMO, because subsequent HUS examinations are unlikely to yield information significant enough to alter management.

Sodium-coupled transport of glucose by plasma membranes of type II pneumocytes.

Sodium-dependent absorption of alveolar fluid promotes efficient gas exchange. In animal models, alveolar glucose stimulates phlorizin-sensitive, Na(+)-dependent fluid absorption. It is hypothesized that Na+/glucose cotransporters are localized to apical membranes of type II pneumocytes. Enriched apical and basolateral plasma membrane vesicles were isolated from adult bovine type II pneumocytes. Uptakes of 22Na+ and [3H]glucose by enriched apical and basolateral vesicles were monitored over time. Following addition of external glucose (75 mM), 22Na+ uptake by mannitol-loaded, apically-enriched vesicles was significantly increased over controls. Substitution of interior-negative charge gradients for internally directed Na+ gradients increased glucose-dependent Na+ uptakes even greater. By contrast, external glucose did not significantly promote 22Na+ uptake by enriched basolateral vesicles. External Na+ (75 mM) significantly increased [3H]glucose uptakes by enriched apical vesicles with evidence of overshoot. Phlorizin (100 microM) inhibited both glucose-coupled 22Na+ uptakes and Na(+)-coupled [3H]glucose uptakes. These observations support localization of electrogenic, Na+/glucose cotransporters to enriched apical membranes of mature type II pneumocytes.

Sodium chloride cotransport at the basolateral membrane of type II pneumocytes.

Current evidence indirectly supports the hypothesis that Na+/Cl- cotransport occurs at basolateral membranes of type II pneumocytes. To test this hypothesis, enriched apical and basolateral plasma membrane vesicles were prepared from adult bovine type II pneumocytes. Uptake of 22Na+ or 36Cl- by these vesicle populations was monitored over time. Using enriched basolateral vesicles, substitution of formate- for Cl- nearly eliminated 22Na+ uptake, and substitution of Tris+ for Na+ significantly reduced 36Cl- uptake. These observations of Cl(-)-dependent 22Na+ uptake and Na(+)-dependent 36Cl- uptake demonstrated coupling between Na+ and Cl- absorption at the basolateral membrane. Na+/Cl- cotransport inhibitors, furosemide (1 mM) and bumetanide (0.1 mM), also reduced 22Na+ and 36Cl- uptakes by enriched basolateral vesicles. By contrast, furosemide and bumetanide did not affect 22Na+ and 36Cl- uptakes by enriched apical vesicles. Collectively, these observations support localization of Na+/Cl- cotransport to the basolateral membranes of mature type II pneumocytes.

Sodium/proton transport by apical membranes of type-II pneumocytes.

Recent studies fail to confirm the coexistence of Na+ channels and Na+/H+ exchange at the apical membranes of lower airway epithelia. Availability of plasma membrane vesicles simplifies the investigation of membrane transport processes. Apical and basolateral plasma membrane vesicles of disrupted type-II pneumocytes were fractionated upon nonlinear, continuous sucrose gradients. To investigate sodium transport, 22Na+ uptake by apical membrane vesicles was assayed in the presence and absence of transmembrane sodium diffusion potentials. Interior-negative sodium diffusion potentials promoted 22Na+ uptake 1.5-fold. Internally-directed H+ gradients or NH+4 gradients inhibited 22Na+ uptake 40-50%. Amiloride (1-1000 microM) inhibited uptake 10-79%. To investigate H+ transport, decay of transmembrane pH gradients was monitored with pH probe acridine orange. In the presence or absence of externally-directed H+ gradients, external sodium promoted internal alkalinization, except in the presence of external amiloride. These observations of amiloride-sensitive, electrogenic Na+ uptake and amiloride-sensitive, electroneutral, Na+/H+ coupling indicate coexistence of Na+ channels and Na+/H+ exchange at the apical membrane of type-II pneumocytes.