Does inverse ratio ventilation predispose to pulmonary edema?
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R M Effros
Publications and source records attributed to R M Effros.
Hydroxyl radical production and lung injury in the rat following silica or titanium dioxide instillation in vivo.
The hydroxyl radical (.OH) is a highly reactive oxygen free radical that has been implicated as a cause of lung injury following exposure to silica and silicates. Despite evidence that silica generates .OH in vitro, there has been no previous demonstration of in vivo production of .OH after exposure to nonfibrous mineral oxide dusts. We tested the hypothesis that instillation of silica into rat lungs is associated with greater .OH production and acute lung inflammation in vivo relative to the instillation of a less toxic nonsilicate particle, titanium dioxide. The production of .OH in the lungs following dust instillation was measured using sodium salicylate as an .OH trap. Seven days after dust exposure, the rats were given intraperitoneal salicylate, the lungs isolated, and salicylate hydroxylation products (2,3- and 2,5-dihydroxybenzoic acid), reflecting .OH, were measured. There was significantly more 2,3-dihydroxybenzoic acid in silica-exposed lungs compared with lungs instilled with titanium dioxide. In addition, the instillation of silica into rat lungs in vivo was associated with a greater acute inflammatory response. We conclude that following in vivo exposure, silica stimulates greater .OH production relative to the less toxic particle, titanium dioxide. These differences in .OH generation correspond to disparities in acute lung inflammation.
Animals↗
Respiratory consequences of postoperative hyponatremia in young women.
Explore the source record for details and available documents.
Adult↗
Responses to pressure and vasoactive agents by isolated pulmonary arteries from monocrotaline-treated rats.
Intralobar and side branch pulmonary arteries removed from rats 7, 14, and 21 days after injection with monocrotaline (MCT) were cannulated and pressurized, and their responses to potassium chloride, norepinephrine, acetylcholine, and angiotensin II were measured. Static pressure-diameter curves were also performed, and arterial distensibility was calculated. Arteries from all three MCT-treated groups showed reduced responses to potassium chloride and angiotensin II compared with control arteries (P < 0.05). The norepinephrine response was significantly reduced in arteries from the 14- and 21-day groups (P < 0.05). Dilations in response to acetylcholine were similar in arteries from the control and 7-day groups but were reduced compared with those in control vessels from the 14- and 21-day groups (P < 0.05). Compared with control values, the slopes of the pressure-diameter curves and the arterial distensibility decreased significantly with time after MCT treatment (P < 0.05). Values for arterial distensibilities obtained in the isolated pulmonary arteries support the theory that structural changes that occur as a result of MCT administration contribute to vessel stiffness. The acetylcholine-induced dilation of vessels from MCT-treated rats indicates that endothelium-derived factors are still produced, but diminished vasodilation coupled with decreased distensibilities after MCT suggest that abnormal vascular remodeling rather than a change in agonist sensitivity may be responsible for the reduced responsiveness seen in these arteries.
Acetylcholine↗
Reduction and uptake of methylene blue from rat air spaces.
The use of methylene blue (MB) to estimate dilution of epithelial lining fluid, which occurs during bronchoalveolar lavage (BAL), is complicated by loss of this redox dye from the air spaces. The rate of MB uptake from the air spaces of isolated rat lungs and the effects of oxidation and reduction on this process were investigated in this study. Movement of MB from the air spaces to perfusate was compared with the corresponding transport of 125I-labeled albumin, [14C]-dextran, 99mTc-labeled diethylenetriaminepentaacetate, [3H]-sucrose, and 3H2O. By the end of 2 min, MB concentrations in the BAL had fallen by 58 +/- 4% (SE; n = 11) and 3H2O by 78 +/- 2% (n = 13), whereas concentrations of the other indicators decreased by approximately 6%. All but 10% of the 3H2O lost from the air spaces was found in the perfusate, whereas 19% of the lost MB was not recovered in the perfusate, suggesting retention of MB in the pulmonary tissues. Absorption of MB from the air spaces was slowed by 20% when the lungs were left unperfused, and absorption was accelerated threefold by reduction of MB to leukomethylene blue with Na2S2O4. In contrast, MB losses from the air space were slowed by the oxidizing agent K3Fe(CN)6 and by addition of superoxide dismutase or ascorbic oxidase. It is therefore possible that ascorbic acid and O2- entering the air spaces reduce MB to the uncharged leuko form. Lowering the pH of the BAL fluid to 3.5 also slowed MB reabsorption. This suggests that acid aspiration may stimulate release of oxidants into the air spaces.
Animals↗
Continuous measurements of changes in pulmonary capillary surface area with 201Tl infusions.
The impact of physiological and pathological processes on metabolism and transport of a variety of substances traversing the pulmonary vasculature depends in part on the capillary surface area available for exchange, and a reliable method for detecting changes in this parameter is needed. In this study, a continuous-infusion approach was used to investigate the response of the pulmonary capillary surface area to increases in flow and left atrial pressure. Isolated rat lungs were perfused with an acellular perfusion solution containing 125I-labeled albumin (an intravascular indicator) and 201Tl, a K+ analogue which is concentrated within lung cells. The extraction of 201Tl from the perfusate was 61% greater at low flow (8.5 ml/min) than at high flow (26 ml/min), and rapid changes in extraction were observed when flow was altered. In contrast, the permeability-surface area product was 76% greater when lungs were perfused at high flow than at low flow, suggesting comparable increases in pulmonary capillary surface area in these zone 2 lungs (airway pressure = 5 cmH2O, left atrial pressure < 0 cmH2O). In a second group of experiments, increases in left atrial pressure to 14 cmH2O (zone 3 lungs) at a constant flow of 8.5 ml/min increased the permeability-surface area product by only 18% despite increases in average intravascular pressure that were at least as high as those associated with high perfusion rates. 201Tl infusions provide a useful method for detecting and quantifying changes in pulmonary capillary surface area.
Animals↗
Hydroxyl radicals are formed in the rat lung after asbestos instillation in vivo.
The hydroxyl radical (.OH) has been implicated as a cause of lung injury following asbestos exposure. However, despite in vitro evidence associating asbestos with .OH production, there has been no demonstration of such generation in vivo. We tested the hypothesis that .OH is formed in the lungs of rats exposed to asbestos in vivo by using salicylate as a free radical trap. Asbestos was instilled intratracheally, and control rats were sham-exposed. Six to seven days after exposure, the rats were given salicylate, the lungs were isolated, and salicylate hydroxylation products (2,3- and 2,5-dihydroxybenzoic acid), reflecting .OH production, were measured. There was significantly more 2,3-dihydroxybenzoic acid in asbestos-exposed lungs compared with control lungs (2.32 +/- 0.360 nmol/lung versus 0.292 +/- 0.125, respectively, P < 0.001) and 2,5-dihydroxybenzoic acid (9.69 +/- 1.65 nmol/lung versus 2.63 +/- 0.274, respectively, P < 0.001). To demonstrate that the dihydroxybenzoic acid was actually formed in the lungs, the lungs from asbestos-exposed and control rats were isolated and perfused with either salicylate or 2,3-dihydroxybenzoic acid. In the lungs perfused with salicylate, 2,3- and 2,5-dihydroxybenzoic acids were detectable only in asbestos-exposed lungs. In the isolated lungs perfused with 2,3-dihydroxybenzoic acid, there was no significant difference in 2,3-dihydroxybenzoic acid between asbestos-exposed and control lungs. We conclude that asbestos stimulates .OH production in lungs in vivo.
Animals↗
pH-induced calcium transients in type II alveolar epithelial cells.
Although both intracellular pH (pHi) and intracellular Ca2+ concentration ([Ca2+]i) are highly regulated and have important metabolic effects in alveolar epithelial cells, little is known about the interrelationship between these two ions in alveolar epithelial cells. The present study examined changes in [pH]i and [Ca2+]i in isolated alveolar epithelial cells using the fluorescent dyes SNARF-1 and fura-2. Basal pHi values in freshly isolated and cultured alveolar epithelial cells were 7.27 and 7.24, respectively. Resting [Ca2+]i values in freshly isolated cells (53 +/- 5 nM) were lower than those in cultured type II cells (107 +/- 21 nM). pHi increased rapidly after addition of 25 mM NH4Cl in both cultured and freshly isolated cells and then decreased back toward baseline over the following 10 min. The rise in pHi was associated with a transient increase in [Ca2+]i. Resuspension of cells in an NH4Cl-free solution resulted in rapid intracellular acidification, which recovered over the subsequent 10 min. Removal of sodium or addition of 1 mM amiloride to the external solution slowed the rate of recovery from intracellular acidification, consistent with the participation of Na(+)-H+ exchanger in this process. In freshly isolated cells, [Ca2+]i increased following acidification and then decreased as the cells recovered from an acid load. In cultured cells, [Ca2+]i also increased following acidification but then remained elevated over the subsequent 10 min. The recovery of [Ca2+]i toward baseline values in fresh cells following acidification was dependent on the presence of external sodium. These data demonstrate that both increases and decreases in pHi of alveolar epithelial cells are associated with increases in [Ca2+]i and suggest that some of the metabolic effects of altering pHi may be secondary to increases in [Ca2+]i. The dependency of [Ca2+]i recovery following acidification on external sodium raises the possibility that freshly isolated type II cells have Na(+)-Ca2+ exchangers that contribute to the regulation of [Ca2+]i.
Amiloride↗
Effect of asthma and ventilatory loading on arterial PCO2 of humans during submaximal exercise.
In humans, attenuating carotid chemoreceptor activity by hyperoxia does not alter arterial PCO2 (PaCO2) during submaximal exercise, yet a transient hypercapnia occurs in carotid chemoreceptor-resected (CBR) asthmatic subjects during submaximal exercise. We hypothesized that this difference was due to asthma and not CBR causing the abnormal response. Accordingly, we determined the temporal pattern of PaCO2 during mild and moderate exercise in chemoreceptor-intact asthmatic (n = 10) and nonasthmatic subjects (n = 10). We also hypothesized that hyperoxia alters PaCO2 during exercise if exercise already has disrupted PaCO2 homeostasis. Accordingly, we studied, during exercise, asthmatic subjects while hyperoxic; nonasthmatic subjects during loaded breathing of room air, which increased PaCO2; and nonasthmatic subjects during loaded breathing while hyperoxic. While breathing room air, neither asthmatic nor nonasthmatic subjects maintained arterial isocapnia during exercise. An increase in PaCO2 between rest and exercise and between mild exercise and 1st min of moderate exercise was greater in asthmatic than in nonasthmatic subjects (P < 0.05). In six asthmatic subjects that were hypercapnic breathing room air during exercise, hypercapnia was accentuated by hyperoxia. The ventilatory load in nonasthmatic subjects resulted in a work load-dependent hypercapnia (P < 0.01) accentuated (P < 0.01) by hyperoxia. We conclude that normally in humans the carotid chemoreceptors contribute minimally to the hyperpnea of submaximal exercise. However, when PaCO2 is increased from resting values during exercise, then the chemoreceptors serve to augment ventilation and thereby minimize the hypercapnia.
Adult↗
Reversible inhibition of urea exchange in rat hepatocytes.
Urea exchange is enhanced in renal collecting duct cells and erythrocytes by transporters which can be inhibited by phloretin and urea analogs such as thiourea. In this study, evidence for a comparable transporter was found in rat livers perfused with solutions which contained no red cells and in suspensions of hepatocytes. Bolus injections containing 125I-albumin (intravascular indicator), 99mTc-DTPA (extracellular indicator), 3HOH (water indicator), and [14C]urea were administered into the portal vein and fluid was collected from the hepatic vein. Under control conditions, [14C]urea and 3HOH emerged from the hepatic vein at nearly the same rate. However when the perfusate contained 2.5 mM phloretin (equivalent to 0.058 mM phloretin not bound to albumin), the amount of [14C]urea which had been recovered in the hepatic venous outflow by the time of peak 125I-albumin concentrations exceeded 3HOH recovery by a factor of 2.31 +/- 0.23 (n = 7). When the perfusate contained 200 mM thiourea, the comparable recovery of [14C]urea from the hepatic veins exceeded that of 3HOH by a factor of 3.48 +/- 0.44 (n = 7). These effects were at least partially reversible and suggested inhibition of urea transporters in hepatocytes. This conclusion was supported by studies of unloading of [14C]urea from hepatocytes which were exposed to unlabeled solutions: in the presence of phloretin, the amount of [14C]urea remaining within hepatocytes at 4 s was approximately twice that remaining in hepatocytes which had not been exposed to phloretin. Rapid transport of urea out of hepatocytes may increase urea synthesis and minimize cellular swelling due to urea accumulation.
Animals↗
Kinetics of urea exchange in air-filled and fluid-filled rat lungs.
Urea has been used as an indicator for estimating 1) the dilution of epithelial lining fluid (ELF) that occurs during bronchoalveolar lavage (BAL) and 2) the permeability-surface area product (PS) of the pulmonary endothelium to this solute. Because relatively little is known about how urea equilibrates with fluid in the lung tissues and airspaces, we have undertaken a study of the kinetics of movement from the vasculature into the tissues of isolated, perfused rat lungs. Although instillation of 5 ml of 154 mM saline into the airspaces of this preparation increased the calculated extravascular volume of 3HOH from 0.64 +/- 0.23 to 2.10 +/- 0.58 ml (SE, n = 6) during a single transit through the pulmonary circulation, it did not have a detectable effect on the distribution of [14C]urea in the lung tissues. However, leakage of [14C]urea into saline within the airspaces was detected during constant infusions: concentrations in the airspace fluid reached 1.1 +/- 0.2% of those in the perfusate by 90 s and 1.90 +/- 0.2% at 120 s, levels that would significantly reduce estimates of the dilution of ELF by BAL. In contrast, concentrations of 99mTc-diethylenetriaminepentaacetic acetic acid (DTPA) in the airspaces remained < 0.2% of those in the perfusate, suggesting that 99mTc-DTPA may be a superior indicator for estimating dilution of ELF by BAL.(ABSTRACT TRUNCATED AT 250 WORDS)
Air↗
Solute exchange between the plasma and epithelial lining fluid of rat lungs.
Although the transport of solutes from air spaces to plasma has been extensively studied, comparatively little information is available concerning solute equilibration between the plasma and the epithelial lining fluid (ELF) of air-filled lungs. In the present study, 11 lipophobic indicators varying in molecular mass between 22 and 80,000 Da were injected intravenously and/or intramuscularly into anesthetized rats in a manner designed to keep blood concentrations constant. The animals were killed by rapid lavage of their lungs at various intervals up to 120 min after the injections had been made. Indicator concentrations in the bronchoalveolar lavage (BAL) fluid and plasma were determined, and BAL-to-plasma concentration ratios were calculated for indicators that were injected (exogenous: [14C]urea, 22Na+, [3H]mannitol, 99mTc-diethylenetriaminepentaacetate (a chelate), 51Cr-(ethylene dinitrilo)tetraacetate (a chelate), 113mIn-transferrin, human albumin, and Evans blue-labeled rat albumin) and those that were already present from the plasma and ELF (unlabeled urea, rat albumin, and rat transferrin). Leakage of exogenous indicators in the blood into the BAL fluid was observed during the lavage procedure. Leakage of [14C]urea, 22Na+, and [3H]mannitol exceeded that of the heavier solute molecules. Diffusion of proteins and the labeled chelates into the ELF before lavage occurred at similar rates, suggesting vesicular transport. Use of rapidly diffusible solutes such as urea for determining dilution of ELF by BAL should be accompanied by intravascular injections of labeled solutes to correct for diffusion from the blood during lavage. Alternatively, labeled chelates or serum proteins can be used to estimate dilution of ELF by BAL. Interstitial sampling may be inevitable if the epithelium has been injured before lavage.
Animals↗
Protein concentrations have little effect on reabsorption of fluid from isolated rat lungs.
A study was conducted to determine whether differences in the concentrations of large molecules between the air space and perfusate solutions altered the rates at which fluid was reabsorbed from isolated fluid-filled perfused rat lungs. Four groups of experiments were conducted: 1) 5 g/dl albumin in the air spaces and perfusate, 2) 15 g/dl albumin in the air space and 5 g/dl albumin in the perfusate, 3) 5 g/dl albumin in the air space and 15 g/dl albumin in the perfusate, and 4) a mixture of 5 g/dl albumin and 7 g/dl Dextran 70 in the air spaces and 5 g/dl albumin in the perfusate. Fluid reabsorption was determined by following the concentration of albumin labeled with Evans blue (T-1824) in the air space and perfusate compartments. Because leakage of protein between the air space and perfusate compartments is very slow, increases in T-1824 concentrations in the air spaces indicated loss of fluid from this compartment, whereas decreases in these concentrations in the perfusate compartment provided evidence of fluid transport into the vasculature. Approximately 30% of the air space fluid was reabsorbed in a 2-h period, and virtually all of this fluid reached the perfusate compartment. Despite oncotic differences that ranged from -65 to 65 Torr, variations in air space or perfusate albumin concentrations did not have a significant effect on this process. A 30% decrease in fluid reabsorption was observed when dextran was in the air space solution, but this decrease did not appear to be due to the oncotic properties of this solution because albumin did not have a measurable effect on reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
Calculations of fluid reabsorption from lungs.
Explore the source record for details and available documents.
Absorption↗
A new stimulation of the interaction between neutrophils and pulmonary endothelial cells.
To study the interaction between isolated homologous neutrophils and pulmonary endothelial cells under simulated in vivo conditions, we developed a model of the circulation in which neutrophils flow past endothelial cells. Endothelial cells from porcine pulmonary artery were grown on microcarriers, loaded into an elutriator chamber, and suspended (speed--300 rpm. flow--18 ml/min). Porcine neutrophils were labeled with 111In, mixed with a tracer dose of 125I-albumin, and injected into the elutriator inlet. Fractions were collected from the elutriator outlet and indicator dilution curves were plotted. Adherence of neutrophils was calculated by 1 - (area under 111In curve/area under 125I curve). In separate injections, neutrophils were preactivated with phorbol 12-myristate 13-acetate (100 ng/ml) or zymosan-activated plasma (10%, v/v). In three of eight lines of endothelial cells the adherence of activated neutrophils to cell-coated microcarriers was greater than that of nonactivated neutrophils. There was no difference in adherence to uncoated microcarriers or to the empty elutriator chamber between activated and nonactivated neutrophils. We conclude that this model will be useful for studying interactions between isolated neutrophils and endothelial cells because it incorporates flow in a physiologic milieu.
Animals↗
Solute concentrations of the pulmonary epithelial lining fluid of anesthetized rats.
Uncertainty persists concerning the best method of estimating the volume and solute concentrations of the pulmonary epithelial lining fluid (ELF) recovered during bronchoalveolar lavage (BAL). In the present study, measurements were made of the BAL-to-plasma concentration ratios of a variety of solutes in an anesthetized rat model. One minute after an intravenous injection of labeled Na+ and urea, 5 ml of isotonic mannitol, saline, or glucose were injected into the trachea and an initial aliquot of the BAL was immediately removed. Initial BAL-to-plasma concentration ratios of urea, Na+, Cl-, Ca2+, and total protein were similar (ranging from 0.013 to 0.017) after BAL with mannitol, but albumin and transferrin ratios were approximately 60% lower and K+ ratios were five times greater. Lavage with saline yielded BAL-to-plasma urea concentration ratios similar to those obtained with mannitol lavage. The BAL-to-plasma specific activity of urea was about twice that of Na+, indicating that urea diffused into the ELF more rapidly than Na+ during the 70 s that elapsed between the time the radioactive urea and Na+ were injected into the circulation and the time when lavage was complete. Subsequent lavage samples also indicated that urea rapidly diffuses into the fluid-filled lungs. These experiments suggest that isotonic mannitol may be a useful solution for lavage, because it allows use of Na+ and perhaps Cl- as additional indicators of ELF dilution by BAL.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
New evidence for active sodium transport from fluid-filled rat lungs.
The hypothesis that fluid reabsorption from the air spaces is mediated at least in part by active transport of Na+ was investigated in six sets of experiments conducted in isolated fluid-filled rat lungs. Fluid reabsorption was monitored by following the changes in the air space concentration of labeled albumin. We found that incorporation of bicarbonate rather than a nonvolatile buffer (N-2-hydroxy-ethylpiperazine-N'-2-ethanesulfonic acid) in the air space solution more than doubled the rate of fluid reabsorption. Addition of 10(-4) M amiloride to the air space solution reduced the rate of fluid reabsorption over a 2-h experiment from 1.2 +/- 0.1 to 0.7 +/- 0.1 ml and decreased reabsorption of both labeled and unlabeled Na+ from the air spaces. To show that Na+ could be reabsorbed from the air spaces even if the concentrations of Na+ in the perfusate increased above those in the air space, mannitol (150 mM) was added to the perfusate and air space solutions and the concentrations of Na+ and Cl- were reduced to 90 and 60 mM, respectively. Mannitol diffuses across the pulmonary epithelium very slowly, and it osmotically restrained the movement of water out of the air spaces. Na+ concentrations in the perfusate increased by 10 +/- 2 mM, but concentrations in the air space remained unchanged. Despite an increasingly unfavorable concentration gradient for Na+, 0.2 mmol Na+ and 0.6 ml water were reabsorbed from the air spaces in 2 h. Ouabain (10(-4) M) did not appear to slow fluid reabsorption in the presence of mannitol, but it reduced K+ secretion into the air spaces and increased K+ appearance in the perfusate in a manner consistent with inhibition of Na+-K+-adenosinetriphosphatase at the basolateral surface of the epithelial cells. Fluid reabsorption was not altered when the lungs were exposed to a hypotonic solution (185 mM), but secretion of K+ into the air spaces was accelerated and K+ was lost from the perfusate. These experiments are consistent with active Na+ transport from the air spaces.
Amiloride↗
Abrupt changes in mixed venous blood gas composition after the onset of exercise.
It has been assumed that increases in both O2 uptake and ventilation occurring within the first few seconds after the onset of exercise cannot be the result of changes in blood gas composition reaching the central circulation because of the circulatory delay from the exercising limbs (A. Krogh and J. Lindhard, J. Physiol. Lond. 42: 112-136, 1913). We sought to validate this assumption by measuring the time course of pulmonary arterial blood gases during the transition from rest to exercise. Six healthy men underwent pulmonary arterial catheterization and then performed transitions from rest to moderate cycle ergometer exercise. An anaerobic sampling manifold withdrew 19 samples of blood during the rest-to-exercise transition; sampling interval was usually 4 s. Blood gas analysis showed that, on average, from rest-to-steady-state exercise, O2 saturation (Svo2) fell from 71 to 41% and mixed venous PCO2 (PvCO2) rose from 42 to 59 Torr. Contrary to our expectations, Svo2 decreased and PvCO2 increased with no discernible latency after exercise onset (by 10% and 2 Torr, respectively, within 6 s). The half time for the Svo2 decrease was 32 s, whereas for the PvCO2 increase it was 80 s. The time course of superior vena cava blood gas composition was determined in several experiments; no rapid changes after exercise onset were found. We conclude that at exercise onset there is a rapid fall in Svo2 and rise in PvCO2 well in advance of arrival of blood produced by exercising legs.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗