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G Saumon

Publications and source records attributed to G Saumon.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1989

Cellular effects of beta-adrenergic and of cAMP stimulation on potassium transport in rat alveolar epithelium.

Alveolar fluid absorption is greatly enhanced by cAMP and by beta-adrenergic agonists via an increase in Na+ transport. Little is known about K+ homeostasis under these circumstances. We studied K+ transport across alveolar epithelium in isolated perfused rat lungs stimulated either by dibutyryl-cAMP or isoproterenol. K+ fluxes and the apparent permeability of 86Rb across the epithelium (alveoli to plasma) were interpreted according to a model involving two types of cells, B and L, distinguished by the location of Na+-K+-ATPases (basal and luminal). Water is considered to be absorbed by B cells in a solute-coupled process energized by a basolateral Na+-K+-ATPase that is stimulated by isoproterenol and cAMP. K+ transport out of the alveoli is due to the activity of a Na+-K+-ATPase located in the apical membrane of L cells. In the present study net transport rate of K+ was -0.5 +/- 0.15 nmol/s, n = 20 (out of alveoli) in control conditions. When the epithelium was stimulated by dibutyryl-cAMP (10(-4) mol/l) net absorption of K+ reversed to net 'secretion' into alveoli (3.2 +/- 0.31 nmol/s), fluid absorption was not stimulated. K+ 'secretion' was abolished by apical Ba2+, indicating it was due to opening of apical K+ channels. Basolateral ouabain reversed net K+ 'secretion' to net absorption indicating that K+ entry into alveoli was dependent on activity of B cell basolateral Na+-K+-ATPase (masking simultaneous K+ removal by apical L cell Na+-K+-pump). When larger concentrations of dibutyryl-cAMP (10(-3) mol/l) or when isoproterenol were used to stimulate the epithelium there was a tripling of fluid absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1989

Exercise tolerance in chronic obstructive pulmonary disease: importance of active and passive components of the ventilatory system.

We investigated which components of ventilatory function are related to exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. Physical characteristics, usual lung function, timing and neuromuscular components of ventilation were measured in 113 outpatients in whom FEV1/VC was less than 75% of the predicted value and exercise was limited by breathlessness. These variables were used to predict the maximum work load during progressive bicycle exercise. The prediction was obtained using a stepwise procedure in men and women separately. Among the variables selected, age, body weight, FEV1/VC, PImax, and P0.1/VT/TI accounted for 79% of the variability in maximum performance in men. The predictive model was statistically verified and was stable. The mean prediction error was 12 Watts. Among these variables, P0.1/VT/TI, PImax, and FEV1/VC were the main determinants of maximum work load (MWL). These results show that exercise limitation in COPD is related to impairment of both the active (inspiratory muscles) and passive (respiratory impedance) components of the ventilatory system. The same conclusions concerning passive components are proposed for women, despite a smaller population which prevented verification of the prediction.

Adult↗
PubMed1988

Apical sodium-sugar transport in pulmonary epithelium in situ.

The presence of an apical sodium-coupled transport system for D-glucose in lung alveolar epithelial cells has been demonstrated in lungs instilled with Ringer's fluid and perfused with either blood or Ringer's fluid (Basset et al. (1987) J. Physiol. 384, 325-345). The direction of transport is from alveoli towards interstitium. The characteristics of the system were evaluated in similar preparations by use of sugar analogues such as alpha-methyl-glucopyranoside, 2-deoxyglucose, 3-O-methylglucose and L-glucose. The main finding was the presence of a transport system for alpha-methylglucopyranoside and 2-deoxyglucose in the apical cell membrane. This system was unaffected by phloretin. Both alpha-methylglucopyranoside and 2-deoxyglucose transports were inhibited by phloridzin and by the presence of glucose (10(-2) mol.l-1). Competition was demonstrated between D-glucose and alpha-methylglucopyranoside or 2-deoxyglucose, but not for 3-O-methylglucose or L-glucose. 3-O-Methylglucose was cleared as slowly as L-glucose. The results comply partly with those known from intestinal epithelium and kidney proximal tubular epithelium, but the handling of 3-O-methylglucose was different. The relative transport rates of Na+ and glucose are compatible with a Na+: glucose coupling ratio larger than one.

Animals↗
PubMed1988

Doppler echocardiographic measurement of mitral flow volume: validation of a new method in adult patients.

Instantaneous intracardiac flow volumes can be calculated as the product of instantaneous flow velocity and instantaneous orifice area. This was accounted for in a new method of measuring stroke volume and cardiac output in the mitral orifice by pulsed Doppler echocardiography. This method was compared with simultaneous thermodilution in 30 adult patients in sinus rhythm without substantial atrioventricular or pulmonary valve abnormalities. The mitral orifice was assimilated to a conduit with 1) an ellipse-shaped inlet and outlet, 2) the same (and constant) long axis for the inlet and outlet ellipses (that is, the mediolateral anulus diameter measured on apical four chamber views), and 3) a varying outlet short axis (that is, the mitral anteroposterior leaflet separation derived from left parasternal M-mode recordings). This method design avoided the need for a short-axis view of the whole circumference of the mitral outlet orifice, which is difficult to obtain in many adult patients. The mitral flow velocity was recorded from the apex under two-dimensional guidance, within the mitral canal, close to the outlet section. Integration of instantaneous mitral leaflet separation multiplied by instantaneous flow velocity was performed using Simpson's rule. In addition to the proposed "instantaneous orifice area" method (method A), a "mean orifice area" method (method B) was also compared with thermodilution. In this simplified method, mitral flow was the product of mean orifice area and the diastolic mitral velocity integral, both derived from the same recordings as for method A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗