The purpose of this study was to see if lung vascular protein permeability is greater in preterm lambs with respiratory distress than it is in lambs without lung disease. We measured pulmonary vascular pressures, lung lymph flow, and concentrations of protein in lymph and plasma of 10 chronically catheterized preterm lambs (gestation 133 +/- 1 d) for 2-4 h before and for 4-8 h after delivery by cesarean section. All lambs were treated with mechanical ventilation after birth and received a constant intravenous infusion of glucose-saline solution at an hourly rate of 10 ml/kg. Respiratory failure developed in six lambs, in which there was a sustained threefold postnatal increase in lung lymph flow and lymph protein flow, with an even greater increase in pleural liquid drainage. Concentrations of protein in lymph and pleural liquid were almost identical, averaging approximately 75% of the plasma protein concentration. In the four preterm lambs without lung disease, lymph flow and lymph protein flow were either near or below fetal values by 6-8 h after birth, and there was little or no pleural liquid drainage. Extravascular lung water averaged 7.3 +/- .8 g/g dry lung in lambs with respiratory failure compared to 4.8 +/- .5 g/g dry lung in lambs without lung disease. Thus, pulmonary edema with abnormal leakage of protein-rich liquid from the lung microcirculation into the interstitium is an important pathological feature of the respiratory disease that often occurs after premature birth.
Background. The standard therapy of dialysis catheter-related bacteraemia involves both systemic antibiotics and catheter replacement. We reported recently that instillation of an antibiotic lock (highly concentrated antibiotic solution) into the catheter lumen after dialysis sessions, in conjunction with systemic antibiotics, can successfully treat many episodes of catheter-related bacteraemia without requiring catheter removal. The present study evaluated whether the likelihood of achieving a cure with this protocol depends on the type of pathogen. Methods. This was a historically controlled interventional study of an antibiotic lock protocol for the treatment of catheter-related bacteraemia. We analysed prospectively the likelihood of clinical cure (fever resolution and negative surveillance cultures) with an antibiotic lock protocol among patients with dialysis catheter-related bacteraemia. In addition, infection-free catheter survival was evaluated for up to 150 days, and compared with that observed among patients managed with routine catheter replacement. Results. Overall, the antibiotic lock protocol was successful in 33 of 47 infected patients (70%) with catheter-related bacteraemia. The likelihood of a clinical cure was 87% for Gram-negative infections, 75% for Staphylococcus epidermidis infections, and only 40% for Staphylococcus aureus infections (P = 0.04). The median infection-free catheter survival with the antibiotic lock protocol was longer than that observed among patients with routine catheter replacement (154 vs 71 days, P = 0.02). Conclusions. The clinical success of an antibiotic lock protocol in eradicating catheter-related bacteraemia while salvaging the catheter is highly dependent on the bacterial pathogen. Thus, the overall success rate in an individual dialysis programme will depend on the relative frequencies of different bacterial pathogens.
Prolonged mechanical ventilation of premature neonates is often associated with abnormal morphological development of the lung and chronic lung disease, sometimes called bronchopulmonary dysplasia (BPD). Impaired alveolar development is a hallmark of this disease. To better understand the effects of mechanical ventilation on lung elastin expression, we studied lung tissue from 10 preterm lambs (gestation = 125 days; term = 148 days) mechanically ventilated for 3-4 wk at a respirator rate of 20 breaths/min and tidal volume of 15 +/- 5 ml/kg (n = 5) or 60 breaths/min and tidal volume of 5 +/- 2 ml/kg (n = 5). Histopathology showed increased elastin accumulation and abnormal morphological development in the ventilated groups. Postmortem lung desmosine content was increased significantly in the 20 breaths/min group. Tropoelastin mRNA expression was increased in both ventilated groups. In situ hybridization localized increased tropoelastin mRNA expression to sites of accumulated elastin in extended alveolar walls with scant, attenuated secondary crests. Lung collagen content, as assessed by the amount of hydroxyproline in lung tissue, was similar to controls. These data suggest that excessive production and accumulation of elastin is associated with chronic lung injury from prolonged mechanical ventilation after premature birth.
To determine whether hypoproteinemia slows the rate at which liquid is cleared from the lung lumen, we studied 36 lambs, 18 of which underwent repeated plasmapheresis, reducing plasma protein concentration by 37% and plasma protein osmotic pressure by 39%. We killed 29 lambs (14 hypoproteinemic and 15 normoproteinemic) and removed their lungs 1, 2, or 6 h after intratracheal instillation of isotonic saline (6 ml/kg body wt). We measured extravascular lung water and determined the percentage of tracheally instilled liquid that was cleared from the lungs by comparison with control lambs that did not receive saline into their airways. The percent liquid cleared from the lungs after 1 and 2 h was significantly less in hypoproteinemic than in normoproteinemic lambs (37 vs. 65% at 1 h, 58 vs. 75% at 2 h, respectively). By 6 h nearly all the liquid (> 92%) was cleared from the lungs of all lambs. Thus hypoproteinemia slows the initial rate of clearance of liquid from the lungs of lambs. To determine whether reduced plasma protein osmotic pressure might redirect this liquid into lung lymphatics, we measured lung lymph flow (Q1) in five lambs (7.7 +/- 1.4 kg, 19 +/- 4 days old) for > or = 2 h before and 6 h after tracheal instillation of saline. In each lamb, paired studies were done 3–6 days apart; between studies the lambs underwent plasmapheresis.(ABSTRACT TRUNCATED AT 250 WORDS)
The goals of this study were 1) to examine changes in lung liquid formation and composition during spontaneous labor in fetal lambs and 2) to determine the importance of beta-adrenergic stimulation and transepithelial Na+ flux in removing liquid from the lung lumen near birth. We measured net production of lung liquid (Jv), lung liquid composition, and transpulmonary electrical potential difference (PD) before and during labor in fetal sheep with chronically implanted tracheal and vascular catheters. We determined Jv by measuring rate of change in lung liquid concentration of 125I-albumin, an impermeant tracer that was mixed in lung liquid at the start of each study. In 17 paired experiments, Jv decreased from 11 +/- 2 ml/h (Jv > 0 = secretion) before labor to -1 +/- 2 ml/h (Jv < 0 = absorption) during labor; in 5 paired experiments, PD changed from -7 +/- 1 mV (lumen negative) before labor to -12 +/- 1 mV during labor. To determine whether absorption of lung liquid during labor is the result of beta-adrenergic stimulation, we studied the effect of propranolol on Jv during labor. When propranolol (40 microM) was added to lung liquid during active labor, Jv decreased from -2 +/- 2 to -8 +/- 3 ml/h (n = 9). Thus, propranolol did not inhibit lung liquid absorption during labor. To determine whether transepithelial Na+ movement provides the driving force for lung liquid clearance during labor, we tested the effects of amiloride, an Na+ transport inhibitor, on Jv and PD.(ABSTRACT TRUNCATED AT 250 WORDS)
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