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Biomedical subjects

F R Poulain

Publications and source records attributed to F R Poulain.

5 recordsLinked to original sources

Effects of surfactant apolipoproteins on liposome structure: implications for tubular myelin formation.

Tubular myelin is one of several forms of lung surfactant and may play an important role in its surface activity. To determine possible mechanisms of tubular myelin formation, we studied the effects of purified surfactant proteins (SP-A, SP-B, and SP-C) on large unilamellar dipalmitoylphosphatidylcholine-egg phosphatidylglycerol (7/3; wt/wt) liposomes. We studied different types of membrane interaction induced by the apolipoproteins and correlated these with the observed changes in ultrastructure. Aggregation was assessed by measurement of light absorbance, lysis, and fusion by measurement of the fluorescence emitted by water-soluble and lipid-soluble probes, respectively. Mixtures of the apolipoproteins and liposomes were examined in ultrastructural studies by negative staining and by thin sectioning. We found that each protein had a pronounced and distinct effect on liposome structure. SP-A caused aggregation, whereas SP-B and SP-C also caused extensive leakage of liposome contents (lysis) and some degree of lipid mixing (fusion). The disruptive effects of SP-B and to a lesser extent those of SP-C were correlated by negative staining with the appearance of bilayer disks, which tended to aggregate into large sheets. There was a marked synergy between SP-A and SP-B in the process of membrane fusion in the presence of calcium, which correlated with an early (10 min) and extensive rearrangement of the structures seen by electron microscopy followed by a delayed (24 h) appearance of small amounts of tubular myelin.

Animals

Increased pulmonary vascular filtration pressure does not alter lung liquid secretion in fetal sheep.

The purpose of this study was to determine whether an increase in pulmonary vascular filtration pressure affects net production of liquid within the lumen of the fetal lung. We studied 14 chronically catheterized fetal lambs [130 +/- 3 (SD) days gestation] before, during, and after a 4-h rapid (500 ml/h) intravenous infusion of isotonic saline. In seven fetuses we measured pulmonary arterial and left atrial pressures, lung lymph flow, and protein osmotic pressures in plasma and lymph. In eight lambs with a chronically implanted tracheal loop cannula, we measured the change in luminal lung liquid volume over time by progressive dilution of tracheally instilled 125I-albumin, which stays within the lung lumen. Saline infusion increased pulmonary vascular pressures by 2-3 mmHg and decreased the plasma-lymph difference in protein osmotic pressure by 1 mmHg. Lung lymph flow increased from 1.9 +/- 0.6 to 3.9 +/- 1.2 (SD) ml/h; net production of luminal lung liquid did not change (12 +/- 5 to 12 +/- 6 ml/h). Thus an increase in net fluid filtration pressure in the pulmonary circulation, which was sufficient to double lung lymph flow, had no significant effect on luminal lung liquid secretion in fetal sheep.

Animals

Ion transport regulation of lung liquid secretion in foetal lambs.

To test the hypothesis that liquid formation in the foetal lung reflects the balance between Cl- secretion and Na+ absorption by the respiratory tract epithelium, we studied the independent and combined effects of selective ion transport inhibitors on basal production of lung liquid in foetal lambs. We prepared 19 foetal lambs (gestation 125 +/- 4, term = 147 days) with chronic indwelling catheters for subsequent measurement of luminal liquid production over time (JV). Using an impermeant tracer technique, we measured JV before and after tracheal instillation of 2 different inhibitors of ion transport: bumetanide, a Na(+)-K(+)-2Cl- co-transport inhibitor, and amiloride, a Na+ transport inhibitor. In 7 foetuses we sequentially added bumetanide (10(-4) M) and 2 different concentrations of amiloride (10(-6) M, 10(-4) M) to the liquid within the lung lumen. After we gave bumetanide, JV decreased from 12 +/- 4 ml/h to 0 +/- 5 ml/h and subsequently increased during the 2 periods of amiloride exposure (10(-6) M: 6 +/- 5 ml/h; 10(-4) M: 7 +/- 7 ml/h). In 5 control studies we gave bumetanide, followed by only amiloride vehicle. JV for all time periods in the control studies was similar to the experimental group, demonstrating no effect of amiloride. In 5 foetuses we administered the 2 concentrations of amiloride before bumetanide. There was no change in JV with either concentration of amiloride (baseline: 13 +/- 2 ml/h; 10(-6) M amiloride: 15 +/- 5 ml/h; 10(-4) M amiloride: 13 +/- 6 ml/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride

Intrapulmonary terbutaline and aminophylline decrease lung liquid in fetal lambs.

To see if phosphodiesterase inhibition might enhance the effect of beta-adrenergic stimulation on fetal lung liquid secretion, we studied the independent and combined effects of intrapulmonary terbutaline and aminophylline on net production of lung luminal liquid over time (Jv) in fetal lambs with chronically placed tracheal loop catheters. We calculated Jv during baseline and experimental periods (90-120 min each) by measuring serial concentrations of 125I-albumin, an impermeant tracer that was well mixed in the luminal liquid. In 21 experiments, tracheal instillation of terbutaline (10(-5) M) decreased Jv from 11 +/- 1 (mean +/- SEM) to -3 +/- 2 mL/h. In six other studies, aminophylline (10(-3) M) alone had no significant effect on Jv. In 12 experiments, we gave the two drugs sequentially: terbutaline decreased Jv from 11 +/- 2 to -3 +/- 2 mL/h and aminophylline further decreased Jv to -8 +/- 2 mL/h. Amiloride (10(-4) M), an inhibitor of epithelial Na+ transport, reversed the combined effect of terbutaline and aminophylline, increasing Jv to 8 +/- 1 mL/h. Thus, phosphodiesterase inhibition enhances the beta-adrenergic effect of terbutaline on Na(+)-dependent absorption of liquid from the lung lumen of fetal lambs.

Amiloride

Lung overexpansion increases pulmonary microvascular protein permeability in young lambs.

To study the effects of inflation pressure and tidal volume (VT) on protein permeability in the neonatal pulmonary microcirculation, we measured lung vascular pressures, blood flow, lymph flow (QL), and concentrations of protein in lymph (L) and plasma (P) of 22 chronically catheterized lambs that received mechanical ventilation at various peak inflation pressures (PIP) and VT. Nine lambs were ventilated initially with a PIP of 19 +/- 1 cmH2O and a VT of 10 +/- 1 ml/kg for 2-4 h (base line), after which we overexpanded their lungs with a PIP of 58 +/- 3 cmH2O and a VT of 48 +/- 4 ml/kg for 4-8 h. QL increased from 2.1 +/- 0.4 to 13.9 +/- 5.0 ml/h. L/P did not change, but the ratio of albumin to globulin in lymph relative to the same ratio in plasma decreased, indicating altered protein sieving in the pulmonary microcirculation. Seven other lambs were mechanically ventilated for 2-4 h at a PIP of 34 +/- 1 cmH2O and a VT of 23 +/- 2 ml/kg (base line), after which their chest and abdomen were bound so that PIP increased to 54 +/- 1 cmH2O for 4-6 h without a change in VT. QL decreased on average from 2.8 +/- 0.6 to 1.9 +/- 0.3 ml/h (P = 0.08), and L/P was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals