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Biomedical subjects

G Saumon

Publications and source records attributed to G Saumon.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effect of changes in paracellular permeability on airspace liquid clearance: role of glucose transport.

The role of the pulmonary sodium-glucose cotransport is unknown. We hypothesized that altering glucose balance (the level of passive vs. active transport) across the airspace epithelium might affect luminal liquid clearance (Jw). A mathematical model was developed to calculate Jw from the rate of epithelial glucose uptake and paracellular permeability. The model predicted that steady-state luminal glucose concentration in fluid-filled lungs should be very low (< 0.5 mM, plasma concentration being 10 mM) and that selective changes in paracellular permeability might affect Jw. Protamine was used to increase paracellular permeability in fluid-filled isolated rat lungs. Protamine modified the glucose equilibrium across the epithelium and increased Jw (P < 0.001) in lungs instilled with fluid that contained no glucose. This increase was accurately described by the model (R2 = 0.92). Jw increased because the entry into airspaces of one glucose molecule and its reuptake results in the net absorption of four osmolytes as long as the cotransport has Na-to-glucose stoichiometry of 2:1, operates below saturation, and the barrier selectivity is preserved. Thus modulating paracellular permeability to small solutes might aid in the removal of edema fluid and participate in the regulation of epithelial lining fluid volume and composition.

Absorption↗
PubMed1996

Comparison of the effects of heat and moisture exchangers and heated humidifiers on ventilation and gas exchange during weaning trials from mechanical ventilation.

Heat and moisture exchangers (HME) are increasingly used to warm and humidify inspired gases in intubated ventilated patients. But these devices add dead space that may alter the alveolar ventilation. This could impair the efficiency of spontaneous ventilation (SV) during weaning trials from mechanical ventilation. Fifteen patients were tested with an HME (Hygrobac-DAR) and a heated humidifier (HH) (Fischer-Paykel MR 450) in a random order during weaning trials in SV with inspiratory pressure support. Minute ventilation VE, tidal volume), and respiratory rate were recorded and arterial blood was sampled for blood gas analysis with each device. The HME gave a significantly greater VE than the HH (9.3 +/- 0.8 L/min vs 8.1 +/- 0.8 L/min; p < 0.005), because of increased respiratory rate (21 +/- 2/min vs 19 +/- 2/min; p < 0.05). Tidal volume was unchanged for HME and HH (470 +/- 32 mL vs 458 +/- 39 mL). The higher PaCO2 with HME than with HH (44 +/- 2 mm Hg vs 42 +/- 2 mm Hg; p < 0.005) revealed an insufficient alveolar ventilation response to the increase in dead space. Arterial Po2 rose with the HME, but not significantly above the HH values (103 +/- 6 mm Hg vs 97 +/- 6 mm Hg; p = 0.055), possibly because of a positive end-expiratory pressure effect of the HME. The need to increase VE in SV when an HME is used should be taken into account during difficult weaning from mechanical ventilation.

Adult↗
PubMed1995

Effect of polycations on barrier and transport properties of alveolar epithelium in situ.

We examined the effect of polycations, classes of which are released by activated leukocytes, on the transport properties of the alveolar epithelium in isolated-perfused rat lungs. Protamine, polylysines, and ruthenium red produced rapid, dose-dependent increases in mannitol permeability (PAmann) when instilled into airspaces. The coupling between active transepithelial Na+ transport and alveolar fluid absorption was not altered, despite > 10-fold increases in PAmann. The increase in albumin permeability compared with that in mannitol suggested preservation of alveolar barrier-size selectivity. Tracheal instillation of protamine produced no cellular abnormality, whereas its addition to the perfusate resulted in damage to endothelial and type I cells. Protamine produced an even larger (P < 0.05) increase in PAmann in the presence of isoproterenol or dibutyryl adenosine 3',5'-cyclic monophosphate + 3-isobutyl-1-methyl-xanthine. The stimulation of Na+ and fluid transport by these agents was unaffected by protamine. Mastoparan, a peptide that activates G proteins, produced effects comparable to those of the polycations. The protamine- and mastoparan-induced increase in PAmann was abolished by barium, a K+ channel blocker, but not by zinc, a membrane-protective cation. Other K+ channel blockers, tetraethylammonium and quinine, had no effect. Thus short-term apical application of polycations and mastoparan alter alveolar epithelium paracellular permeability by a noncytotoxic mechanism that is inhibited by barium. The resulting increase in paracellular permeability does not alter fluid absorption driven by active Na+ transport. Polycations have very different effects, depending on whether they are present on one side or the other side of the alveolar capillary barrier.

Absorption↗
PubMed1995

Mechanical ventilation-induced pulmonary edema. Interaction with previous lung alterations.

The risk of lung injury due to alveolar overdistension during mechanical ventilation has been clearly delineated in healthy animals with intact lungs. In contrast, the effect of high-volume ventilation (HV) on previously injured lungs is less well documented: whether HV would simply add its own deleterious effects or act synergistically with previous injury has not been addressed. We compared the effect of 7 ml/kg body weight tidal volume mechanical ventilation for 2 min with that of 25 (HV25), 33(HV33), and 45(HV45) ml/kg body weight HV in anesthetized rats previously exposed or not exposed to alpha-naphthylthiourea (ANTU). ANTU alone produced moderate permeability edema with significant increases in extravascular lung water (Qwl), dry lung weight (DLW), and albumin distribution space in lungs (ASp). HV alone resulted in a permeability edema in which severity was dependent on the magnitude of the tidal volume. The effects of HV25 and HV33 and those of ANTU were only additive, as indicated by the absence of any significant two-factor (ANTU-HV) interaction by analysis of variance (ANOVA). In contrast, HV45 after ANTU produced significantly greater increases in Qwl, DLW, and ASp than expected from the sum of the effects of either insult alone. Two-way ANOVA disclosed two-factor interactions with p values < 0.001, < 0.02, and < 0.01 for Qwl, DLW, and ASp, respectively, indicating synergistic adverse effects on pulmonary edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1995

[Deleterious effects of mechanical ventilation on the lower lung].

Mechanical ventilation may have adverse effects on the lung. The appearance of extra-alveolar air, either as a pneumothorax or as subcutaneous emphysema along with other manifestations, is a complication of barotrauma which has been known for a long time. Recent experimental studies have clearly shown that mechanical ventilation can also lead to alterations in the blood gas barrier. Mechanical ventilation with high inflation pressure and elevated tidal volumes induces pulmonary oedema; the genesis of which results principally from anomalies of alveolar capillary permeability. These anomalies are made as a result of pulmonary distension and not as a result of elevated pressures in the airways, thus justifying the term "volume traumatism". The existence of previous acute pulmonary injury considerably worsens the deleterious pulmonary effect of mechanical ventilation. Although the direct clinical implications of these experimental studies are difficult to confirm, these latter have nevertheless lead to profound changes in ventilatory strategy during the course of acute pulmonary disease such as the adult respiratory distress syndrome.

Adult↗
PubMed1993

Electrolyte and fluid transport across the mature alveolar epithelium.

The lungs must be kept "dry" for efficient gas exchange. The mechanisms that contribute to clear alveoli from fetal lung fluid at birth are still present during adult life and allow recovery from alveolar flooding. It has recently been shown with the use of different approaches in vitro, as well as in vivo, that alveolar epithelium performs solute-coupled fluid transport. Fluid absorption from alveoli occurs chiefly as a result of active transepithelial Na+ transport. The mechanisms of Na+ transport have been partly elucidated; Na+ enters alveolar cells through apical Na+ channels and Na(+)-coupled solute transporters and is pumped out at the basolateral membrane by a Na(+)-K(+)-adenosinetriphosphatase (ATPase). Transepithelial Na+ transport and fluid absorption are stimulated by beta-adrenergic agonists, with adenosine 3',5'-cyclic monophosphate being the likely intracellular second messenger. K+ is probably secreted into alveoli because its concentration in the epithelial lining fluid is larger than expected for passive distribution. K+ channels have been described that, in conjunction with Na(+)-K(+)-ATP-ase, might provide pathways for active transport. Active proton secretion or bicarbonate absorption have been reported, which may explain the low pH of the alveolar epithelial lining fluid. It is probable that active solute transports are the main determinants of epithelial lining fluid depth and composition. A challenge for the future is to understand how this homeostasis is achieved.

Animals↗
PubMed1993

Role of tidal volume, FRC, and end-inspiratory volume in the development of pulmonary edema following mechanical ventilation.

Mechanical ventilation with high peak inspiratory pressure and large tidal volume (VT) produces permeability pulmonary edema. Whether it is mean or peak inspiratory pressure (i.e., mean or end-inspiratory volume) that is the major determinant of ventilation-induced lung injury is unsettled. Rats were ventilated with increasing tidal volumes starting from different degrees of FRC that were set by increasing end-expiratory pressure during positive-pressure ventilation. Pulmonary edema was assessed by the measurement of extravascular lung water content. The importance of permeability alterations was evaluated by measurement of dry lung weight and determination of albumin distribution space. Pulmonary edema with permeability alterations occurred regardless of the value of positive end-expiratory pressure (PEEP), provided the increase in VT was large enough. Similarly, edema occurred even during normal VT ventilation provided the increase in PEEP was large enough. Furthermore, moderate increases in VT or PEEP that were innocuous when applied alone, produced edema when combined. The effect of PEEP was not the consequence of raised airway pressure but of the increase in FRC since similar observations were made in animals ventilated with negative inspiratory pressure. However, although permeability alterations were similar, edema was less marked in animals ventilated with PEEP than in those ventilated with zero end-expiratory pressure (ZEEP) with the same end-inspiratory pressure. This "beneficial" effect of PEEP was probably the consequence of hemodynamic alterations. Indeed, infusion of dopamine to correct the drop in systemic arterial pressure that occurred during PEEP ventilation resulted in a significant increase in pulmonary edema. In conclusion, rather than VT or FRC value, the end-inspiratory volume is probably the main determinant of ventilation-induced edema. Hemodynamic status plays an important role in modulating the amount of edema during lung overinflation but does not fundamentally modify the characteristics of this edema which is consistently associated with major permeability alterations. These results may be relevant for ventilatory strategies during acute respiratory failure.

Albumins↗
PubMed1993

Effect of metabolic inhibitors on Na+ transport in isolated perfused rat lungs.

Alveolar fluid absorption is a process driven by transepithelial alveolar Na+ transport. Since lungs produce significant amounts of lactate under anaerobic but also under aerobic conditions, glycolysis may conceivably contribute to producing the energy needed for transepithelial Na+ transport and fluid absorption. The effects of inhibition of oxidative phosphorylation or glycolysis on alveolar Na+ transport, fluid absorption, and preservation of alveolar epithelial barrier properties were examined using isolated, fluid-filled rat lungs. Basal lung lactate production was 65 +/- 1.0 mumol/h/g dry wt in the presence of 10 mmol/liter glucose. When oxidative phosphorylation was inhibited with rotenone, cyanide, or the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), lung lactate production increased 5- to 7-fold within 30 min (P < 0.001). No significant decrease in alveolar Na+ transport was observed over 1 h, whereas a 3-fold increase in passive epithelial permeability was observed. With rotenone and CCCP, but not cyanide, fluid absorption from airspaces was decreased but never abolished. Inhibition of aerobic glycolysis with iodoacetate did not significantly affect alveolar Na+ transport or fluid absorption. In the presence of isoproterenol or dibutyryl cyclic adenosine monophosphate (cAMP) + isobutylmethylxanthine, which have previously been shown to stimulate alveolar Na+ transport, lung lactate production increased 2-fold (P < 0.001). Inhibition of glycolysis depressed stimulated alveolar Na+ and fluid transports (P < 0.001). Inhibition of ion transport by ouabain or amiloride decreased lung lactate production (P < 0.001) under stimulated but not under unstimulated conditions. These observations suggest that glycolysis does not significantly contribute to energy provision for alveolar epithelial Na+ transport in lungs under basal, aerobic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1992

Spontaneous resolution of pulmonary edema caused by short periods of cyclic overinflation.

Mechanical ventilation with high or even moderate peak inspiratory pressure produces pulmonary permeability edema. Besides the level of overinflation, duration may affect both severity and type of edema. We studied the effect of 2 min of 35-mmHg peak pressure mechanical ventilation (HV) on microvascular permeability and deep lung fluid balance in rats. It resulted in increased extravascular lung water (+50%), bloodless dry lung weight (+25%), and albumin uptake in lungs (+450%). The increase in dry lung weight and albumin uptake compared with that of lung water suggested major permeability alterations. Ultrastructural examination showed the presence of numerous endothelial blebs. Epithelial lining fluid (ELF) volume, its potassium and protein concentrations, and cellular composition were assessed by bronchoalveolar lavage. There was an increase in ELF volume (+180%), a decrease in ELF potassium concentration (-50%), and an increase in ELF protein content (+76%). A few blood cells were recovered, suggesting the presence of a few large epithelial breaks. Some animals were allowed to recover for periods less than or equal to 180 min after HV. Extravascular lung water, dry lung weight, and albumin distribution space returned to control levels within 45 min. ELF volume diminished but remained larger than in controls, and ELF protein concentration increased probably because of alveolar fluid resorption. No further hemorrhage was observed. These results indicate that periods of HV as short as 2 min transiently alter microvascular permeability in rats.

Animals↗
PubMed1991

Sodium-dependent phosphate and alanine transports but sodium-independent hexose transport in type II alveolar epithelial cells in primary culture.

Inorganic phosphate, amino acids and sugars are of obvious importance in lung metabolism. We investigated sodium-coupled transports with these organic and inorganic substrates in type II alveolar epithelial cells from adult rat after one day in culture. Alveolar type II cells actively transported inorganic phosphate and alanine, a neutral amino acid, by sodium-dependent processes. Cellular uptakes of phosphate and alanine were decreased by about 80% by external sodium substitution, inhibited by ouabain (30 and 41%, respectively) and displayed saturable kinetics. Two sodium-phosphate cotransport systems were characterized: a high-affinity one (apparent Km = 18 microM) with a Vmax of 13.5 nmol/mg protein per 10 min and a low-affinity one (apparent Km = 126 microM) with a Vmax of 22.5 nmol/mg protein per 10 min. Alanine transport had an apparent Km of 87.9 microM and a Vmax of 43.5 nmol/mg protein per 10 min. By contrast, cultured alveolar type II cells did not express sodium-dependent hexose transport. Increasing time in culture decreased Vmax values of the two phosphate transport systems on day 4 while sodium-dependent alanine uptake was unchanged. This study demonstrated the existence of sodium-dependent phosphate and amino acid transports in alveolar type II cells similar to those documented in other epithelial cell types. These sodium-coupled transports provide a potent mechanism for phosphate and amino acid absorption and are likely to play a role in substrate availability for cellular metabolism and in regulating the composition of the alveolar subphase. The decrease in phosphate uptake with time in culture is parallel to decrease in surfactant synthesis reported in cultured alveolar type II cells, suggesting that phosphate availability for surfactant synthesis may be accomplished by a sodium-dependent phosphate uptake.

Alanine↗
PubMed1991

Luminal glucose enhances transepithelial Na+ and fluid transports in rat lungs.

The effects of luminal glucose on transepithelial Na+ and fluid transports were investigated in rat lungs. Two preparations were used: isolated, perfused lungs and lungs in situ perfused with blood (cross-circulations), a situation more comparable to that existing in vivo. Unidirectional (efflux from air spaces, J(out)) and net (Jnet) Na+ fluxes and fluid absorption from air spaces were estimated in lungs filled with bicarbonate-buffered solutions containing 10 mmol/l of either mannitol, glucose or alpha-methyl-D-glucopyranoside, or 0.1 mmol/l phlorizin in the presence of glucose. In the presence of mannitol J(out) was estimated to be 7.8 +/- 1.02 pmol cm-2 s-1 in isolated lungs and 9.2 +/- 0.97 pmol cm-2 s-1 in lungs in situ, and Jnet 1.0 +/- 0.33 and 2.5 +/- 0.35 pmol cm-2 s-1, respectively. When glucose replaced mannitol J(out) (+ 30% + 40%), Jnet (+200% + 300%) and fluid absorption (+ 100% + 400%) were enhanced in both preparations. Substituting methyl glucoside for mannitol increased Na+ and fluid absorption rates to the same extent as glucose. Phlorizin, in the presence of glucose, reduced Na+ and fluid transports to values similar to those observed in the presence of mannitol. These changes did not result from modifications of the paracellular permeabilities (assessed with [3H]mannitol).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Evidence for a sodium-dependent sugar transport in rat tracheal epithelium.

The presence of Na(+)-coupled sugar transport in rat trachea was investigated using the nonmetabolizable glucose analogs methyl alpha-glucopyranoside and 3-O-methylglucose. The rates of disappearance from tracheal instillates and the tissue uptake of these analogs were compared with those of L-glucose. Experiments were performed in vivo, using a cross-circulation preparation, and in vitro, on tracheal strips. The analog methyl alpha-glucopyranoside was removed in vivo from the tracheal lumen faster than L-glucose. The cellular uptake in vivo or in vitro was determined by lysing the cells lining the tracheal lumen with detergents. This uptake was inhibited by luminal glucose, phloridzin and Na+ substitution with choline. The transport rate of 3-O-methylglucose was very low and thus discouraged inhibition experiments. These results indicate the presence of a Na+/sugar cotransport system in rat trachea. The effects of luminal interactions suggest that the cotransport is located in the apical membrane of the tracheal epithelium. It resembles that previously described in the rat alveolar epithelium, but apparently differs from that found in the fetal sheep lung in which a significant 3-O-methylglucose cotransport with Na+ has been described.

3-O-Methylglucose↗
PubMed1990

A simple method for correcting single breath total lung capacity for underestimation.

The single breath method underestimates total lung capacity by comparison with the multiple breath method (TLCmb) because of inhomogeneity of ventilation distribution. This study proposes a simple correction for the single breath TLC (TLCsb), using inert gas phase III slope to account for the effects of uneven ventilation distribution. A model of a non-uniform lung ventilation was designed, composed of a serial dead space and two alveolar compartments arranged in parallel, whose relative ventilations were determined from the phase III plateau. Before correction TLCsb was 104-44% of TLCmb in 64 subjects (17 with diffuse interstitial disease, 42 with chronic obstructive pulmonary disease, and five healthy subjects). The limit of acceptability for the correction (TLCcorr) was determined from the 95% confidence interval of TLCsb/TLCmb in the healthy subjects. The correction resulted in a significant increase in TLCsb (p less than 0.004). TLCcorr remained under the limit of acceptability for only 12 patients with emphysema, and all 12 showed a large improvement in the TLC estimate. The presence of poorly ventilated zones during a single breath in these patients may explain this partial correction.

Adult↗
PubMed1990

Endothelial and epithelial permeabilities to antipyrine in rat and dog lungs.

Temperature effects on the permeabilities of the structured endothelium and epithelium to antipyrine (AP) have been determined with the indicator dilution technique in isolated rat and dog lungs perfused between 38 and 8 degrees C. Permeability coefficients of the endothelium to AP [Pendo(AP)] from the Crone equation are smaller than values for isolated endothelial cells but close to the permeability coefficient of the interstitial epithelial plasmalemma [Pepi(AP)] obtained from physical and mathematical models. In these, tracer water is flow limited at the endothelium and the epithelium at all temperatures; AP is flow limited at the endothelium at T greater than 20 degrees C but barrier limited at the endothelium for T less than 20 degrees C and at the epithelium at all temperatures. At T less than 20 degrees C, log Pendo(AP) decreases regularly with 1/T, with a slope close to that found in cultured bovine pulmonary artery endothelial cells. At 15 degrees C, Pendo(AP) for the endothelial plasmalemma in situ is 30 X 10(-5) cm/s and is 56 X 10(-5) cm/s for the isolated cells in support of transcellular rather than paracellular passage. At T greater than 20 degrees C, log Pepi(AP) in situ decreases slightly with 1/T, with a discontinuity at T = 20 degrees C, and for T less than 20 degrees C, decreases with 1/T with a slope close to that of Pendo(AP). At 15 degrees C, Pepi(AP) is 2.8 X 10(-5) cm/s. The discontinuity may represent a change in the physical state of lipids in the interstitial plasmalemma of the epithelial cells.

Animals↗