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Biomedical subjects

R M Effros

Publications and source records attributed to R M Effros.

At least 55 records · Page 3Linked to original sources
PubMed1988

Exchange of labeled bicarbonate and carbon dioxide with erythrocytes suspended in an elutriator.

An elutriator was used to study exchange of labeled CO2 and bicarbonate with erythrocytes. Rabbit erythrocytes were suspended by centrifugation in a stream of fluid and exposed to transient injections of an extracellular indicator (125I-albumin or 22Na+), a water indicator (3H2O), and H14CO3- and/or 14CO2. Diffusion of indicators into erythrocytes was judged by comparison of initial concentrations of diffusible and extracellular indicators in the elutriator outflow. It was possible to conduct these experiments at normal hematocrits because any carbonic anhydrase released from erythrocytes by hemolysis was washed away in the elutriator flow, and ambient pH, PO2, and PCO2 were kept constant by the inflow of fresh fluid. Equilibration of HCO3- with erythrocytes was complete during the 7- to 10-s transit time through the chamber. After this exchange was irreversibly inhibited by the anion exchange inhibitor, DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid), addition of carbonic anhydrase (100 mg/dl) accelerated exchange, but acetazolamide (20 mg/dl) was without effect. These observations were consistent with the absence of carbonic anhydrase on the surface of the erythrocytes.

Animals↗
PubMed1988

Pulmonary epithelial sieving of small solutes in rat lungs.

Transport and consumption of glucose from the air spaces of isolated, fluid-filled lungs can result in significantly lower glucose concentrations in the air spaces than in the perfusate compartment (11). This concentration difference could promote the osmotic movement of water from the air spaces to the perfusate, but the rate of fluid extraction from the air spaces would then be limited by the rates of electrolyte transport through the epithelium. In the present study, measurements were made of solute and water losses from the air spaces of fluid-filled rat lungs and the transport of these solutes and water into the vasculature after addition of hypertonic glucose or sucrose to the perfusate. Increases in the concentrations of Na+, Cl-, K+, and labeled mannitol in the air space were initially comparable to those of albumin labeled with Evans blue. Similarly, decreases in electrolyte concentrations in the perfusate were comparable to those of labeled albumin, indicating that very little solute accompanied the movement of water out of the lungs. Nor was evidence found that exposure of the vasculature to hypertonic glucose resulted in an increase in the rate at which fluid was reabsorbed from the air spaces over a 1-h interval, aside from an initial, abrupt loss of solute-free water from the lungs. These observations suggest that perfusion of fluid-filled lungs with hypertonic solutions of small solutes results in the extraction of water from the air spaces and pulmonary parenchyma across membranes that resist the movement of electrolytes and other lipophobic solutes.

Animals↗
PubMed1988

CO2 and bicarbonate exchange in the rat liver.

Several forms of carbonic anhydrase (CA) have been detected in hepatocytes. The distribution of these enzymes appears to be heterogeneous in the hepatic lobule, and the specific isoenzyme that predominates is influenced by sex steroid levels in the animal. In the present study, experiments were conducted in isolated male rat livers perfused with erythrocyte-free solutions, which were devoid of CA to see if there were sufficient tissue CA activity accessible to the plasma to ensure equilibration between labeled HCO3- and CO2 during a single passage from the portal vein to the hepatic vein. After injection of H14CO3- into the portal vein, emergence of the 14C label from the hepatic vein was slightly more rapid than after injections of 14CO2. After infusion of 5-250 microM of acetazolamide, an inhibitor of CA, H14CO3- was virtually confined to the extracellular space during a single transit through the organ, whereas the outflow of 14CO2 was very prolonged, suggesting that some of the 14C had been "trapped" within the hepatic cells as H14CO3-. Inhibition of CA activity in the intact organ with low doses of acetazolamide suggests the presence of a readily inhibitable isoenzyme of CA on the surface of the hepatocytes, which is directly accessible to both HCO3- and acetazolamide. The outflow patterns of 14CO2 and H14CO3- became the same after infusion of erythrocyte CA into the portal vein. On the basis of the pH of the perfusate and the cellular distribution of 14CO2 and H14CO3- in the presence of CA, an intracellular pH value of 7.26 was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Estimation of endothelial receptor sites with the mean transit time approach.

A new procedure for quantitating endothelial receptor sites is described. The mean transit time of the passage of an appropriate radio-labeled ligand from the artery to vein of an organ is compared to the mean transit times of a vascular indicator and a water label. The concentration of the unlabeled ligand is progressively increased to define that concentration at which half of the enzyme sites are occupied. Values are calculated for the number of receptor sites accessible during a single circulation in each ml of exchangeable tissue water. This approach is illustrated by estimating the sites of carbonic anhydrase present on the pulmonary endothelium, utilizing labeled acetazolamide as a ligand. Preliminary studies of the receptor sites on isolated endothelial cells suspended in an elutriator are also presented.

Acetazolamide↗
PubMed1987

Fluid reabsorption and glucose consumption in edematous rat lungs.

Solute and water uptake were studied in isolated perfused rat lungs with airspaces filled with the perfusion fluid. The albumin in this solution was labelled with Evans blue (T-1824), and uptake of fluid from the airspaces was documented by an increase in T-1824 concentration in airway fluid of 6.5 +/- 1.6% (n = 5, SEM) at 1 hour and 12.2 +/- 0.9% (n = 10) at 2 hours. The only detectable osmotic force that could have contributed to a loss of fluid from the alveolar fluid was a decrease in airspace glucose concentrations, which fell much more rapidly (from 150 mg/dl to 58.7 +/- 7.1 mg/dl, n = 10, after 2 hours) than plasma glucose (from 150 mg/dl to 128.9 +/- 3.7 mg/dl). Addition of 5 X 10(-5) M terbutaline to the perfusate and airspace solutions nearly doubled fluid reabsorption at 1 hour, an effect that was inhibited by propranolol and did not appear to be related to glucose consumption. Exposure to terbutaline for 2 hours increased epithelial permeability to 3H-mannitol and 22Na+. These observations suggest that active sodium transport and epithelial metabolism or transport of glucose in airway fluid may each play a role in the reabsorption of edema fluid.

Absorption↗
PubMed1987

Reabsorption of solutes and water from fluid-filled rabbit lungs.

Uncertainty persists concerning the mechanisms responsible for fluid clearance from the lungs after the air spaces become flooded in severe pulmonary edema. In this study, solute and water fluxes were investigated in an isolated, fluid-filled, perfused rabbit lung preparation. These lungs were perfused with physiologic 1.0 or 5.0 g/dl albumin solutions, and the air spaces were flushed and filled with the same solutions. Samples were obtained at intervals from the perfusate, and at the end of 1 or 2 h, fluid was pumped from the trachea into collection tubes. Concentrations of albumin (labeled with Evans blue) in the air space increased by 2.4 +/- 0.7% (SEM) at 1 h and by 7.0 +/- 0.8% at 2 h. Approximately half of the increase at 2 h could be attributed to dehydration (as judged by increases in perfusate and air-space Na+ concentration). Because previous studies have indicated that the movement of labeled protein between these compartments is very slow in this preparation, it can be concluded that fluid is being reabsorbed from the air spaces. However, reabsorption appears to be slower in rabbits than in rats and it is not stimulated by terbutaline, an effect observed in other species. Under control conditions, potassium concentrations in the air-space fluid fell from 4.01 +/- 0.05 (SEM) mEq/L to 3.37 +/- 0.14 mEq/L at 1 h. Concentrations of K+ in the perfusate rose during this interval from 3.95 +/- 0.05 mEq/L to 4.39 +/- 0.08 mEq/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1987

Accelerated solute clearance in Pneumocystis carinii pneumonia.

A radioaerosol clearance test was used to detect lung injury in 12 patients with acquired immune deficiency syndrome (AIDS) and Pneumocystis carinii pneumonia documented by bronchoscopy. The clearance of 99mTc-DTPA was elevated over most regions of interest in all of these patients. In each of 7 subjects who responded to trimethoprim-sulfamethoxazole therapy, clearance returned toward normal. Average clearances were either normal or very slightly above the 95% expected upper limit of normal in each of 6 patients with either AIDS or AIDS-related complex without clinical evidence of Pneumocystis infection. The radioaerosol diffusion test may prove useful for determining whether patients who are predisposed to this infection require bronchoscopy and may provide information concerning their response to therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Oxygen uptake kinetics and lactate concentration during exercise in humans.

For constant-load exercise of moderate intensity, oxygen uptake (VO2) increases monoexponentially, reaching a constant value within 3 min, i.e., steady state. However, at work rates associated with increased blood lactate, i.e., above the lactate threshold (LT), VO2 continues to increase slowly beyond 3 min; this delays or precludes steady state. We therefore correlated the characteristics of this slow phase of the VO2 kinetics with the increase in blood lactate during 6 randomized, constant-load cycle exercise tests in 6 normal men. One test was below and the others were at various levels above our gas exchange estimate of LT. The slow kinetic phase of VO2, characterized as the increase between the third and the sixth minute of exercise [delta VO2 (6-3)] or the third minute and termination of exercise [delta VO2 (term-3)], was linearly correlated with the blood lactate increase. The VO2 at termination of a given work rate above LT was greater than predicted from the sub-LT VO2 versus work-rate relationship. Work rates less than approximately 50% of the difference between VO2max and LT resulted in lactate and VO2 curves that reached recognizable asymptotes. At the higher work rates, both the lactate and VO2 curves continued to rise to the point of fatigue. We conclude that positive values for delta VO2 (6-3) and delta VO2(term-3) during constant-load exercise only occur at work rates above the LT, and the magnitudes of which are highly correlated with the increase in blood lactate.

Adult↗
PubMed1986

99mTc-DTPA aerosol deposition and clearance in COPD, interstitial disease, and smokers.

The application of 99mTc-DTPA radioaerosols to a variety of clinical disorders is described. With the development of simple equipment that can deliver very small droplets, this approach has become increasingly popular for measurements of the distribution of ventilation in patients with obstructive lung disease and suspected pulmonary embolism. In addition, by determining the rate at which the radionuclide is cleared from the lung, information has been obtained concerning the permeability of the pulmonary epithelium to extracellular indicators. Accelerated clearance rates have been found in patients with a variety of chronic interstitial lung diseases indicating that epithelial permeability is increased. Accelerated clearance rates have also been found with acute inflammation of the lung such as the adult respiratory distress syndrome and pneumocystis pneumonia. Furthermore, rapidly reversible increases in 99mTc-DTPA clearance occur in smokers and may be related to the inflammatory changes that contribute to the development of emphysema.

Aerosols↗
PubMed1986

Movement of ions and small solutes across endothelium and epithelium of perfused rabbit lungs.

In situ and isolated fluid-filled rabbit lungs were used to study the transport of indicators between the air space and vascular compartments. These indicators were placed in either the perfusate or air spaces and samples were collected from the perfusate at intervals during a 1-h perfusion period. At the end of the hour, fluid was pumped out of the air space compartment into serial tubes and indicator concentrations were determined in both the air space and perfusion fluids. One hour after introducing the indicators into the air space, the relative decreases in solute concentration were (arranged from the greatest to the least decline): [14C]urea greater than 36Cl- = 125I- greater than 22Na+ greater than [3H]mannitol. The relative rates at which the indicators appeared in the perfusate were similar. When the indicators were placed in the perfusate, a similar relationship was observed in the increase in air space concentrations, but the loss of 22Na+ from the perfusate was similar to those of 36Cl- and 125I-. Losses of all indicators from the perfusate were two or more times those from the air spaces, and although the loss of [3H]mannitol from the perfusate was similar to that of 22Na+ for about 30 min, subsequent loss was much slower. Very little 125I-albumin traversed the tissue barrier, and the small changes in the concentrations of 125I-albumin in the air spaces suggested that little fluid movement had occurred. These studies suggest that the epithelium is less permeable to solutes than the endothelium and permits passage of anions at a faster rate than 22Na+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Diffusion of labeled water and lipophilic solutes in the lung.

A perfused, in situ rabbit lung preparation was used to study the diffusion of tritiated water and labeled lipophilic solutes from the airways into the pulmonary vasculature. Following instillation into the airways, initial concentrations of labeled ethanol and butanol in the left atrial outflow usually exceeded those of 3H2O when the lungs were perfused at 37 degrees. In contrast, initial concentrations of [14C]acetone equaled 3H2O concentrations, and those of [14C]antipyrine were below 3H2O concentrations. Increasing the rate of perfusion increased concentrations of the labeled butanol and acetone but decreased that of antipyrine relative to 3H2O. This suggests that the tissues separating the gaseous and vascular compartments of the lung are more permeable to 3H2O than to antipyrine but less permeable to 3H2O than to the alcohols and acetone. Cooling slowed permeation of ethanol and antipyrine relative to 3H2O but seemed to slow diffusion of butanol less than that of 3H2O. These differences cannot be related to movement in the aqueous phase and suggest that cooling slows solute diffusion through lipid membranes. This phenomenon appears to be related to the activation energy of each molecule between the aqueous and lipid phases rather than a phase change in the membrane. 3H2O seems to diffuse through aqueous regions of the air-perfusate barrier.

Acetone↗
PubMed1985

Lung water measurements with the mean transit time approach.

The potential usefulness and limitations of the double-indicator mean transit time approach for measuring lung water are evaluated from both theoretical and empirical points of view. It is concluded that poor tissue perfusion is the most serious factor that can compromise the reliability of this approach. Replacement of the conventional water isotopes with a thermal signal enhances indicator delivery to ischemic areas but the diffusion of heat is not sufficiently rapid to permit measurements of water in macroscopic collections of fluid which remain unperfused. The frequency of pulmonary vascular obstruction in patients with pulmonary edema related to lung injury suggests that interpretation of transit time data will be complicated by uncertainties concerning perfusion. Thermal-dye measurements of lung water may prove more helpful in situations where pulmonary blood flow remains relatively uniform.

Animals↗
PubMed1985

Small solute clearance from the lungs of patients with cardiogenic and noncardiogenic pulmonary edema.

The regional clearance of 99mTc-diethylenetriamine penta-acetate (99mTc-DTPA) from the lungs was measured in 14 patients with noncardiogenic pulmonary edema, six patients with acute pulmonary edema secondary to heart failure, and 29 normal subjects. The radionuclide was delivered in an aerosol which was inhaled for 120 seconds, and the subsequent decline of radioactivity from the lungs was monitored for seven minutes over each of six peripheral regions of interest with a computerized scintillation camera. The average 99mTc-DTPA clearance of these regions was accelerated above the 98 percent confidence limits in all but three of the patients with noncardiogenic edema. The mean clearance value in this group of patients was significantly greater than those in normal subjects or patients with cardiogenic pulmonary edema. Clearances returned toward normal in each of seven subjects who improved clinically. Only one of the patients with cardiogenic pulmonary edema had an elevated average clearance rate, and the mean clearance for this population was not statistically greater than normal. This procedure appears to detect increased epithelial permeability caused by lung injury and may help distinguish between cardiogenic and noncardiogenic pulmonary edema.

Adult↗
PubMed1984

Countercurrent diffusion in the renal cortex of the rabbit.

Evidence was obtained for countercurrent diffusion of 14C-n-butanol in the rabbit renal cortex. After injection into the renal artery of perfused, isolated rabbit kidneys, concentrations of both 14C-butanol and tritiated water in the initial samples collected from the renal venous outflow exceeded those of 125I-albumin when the rate of perfusion was low. When flow was increased, the 125I-albumin curve was shifted to earlier times relative to the other labels. These observations confirm the existence of arteriovenous diffusion of 14C-butanol and tritiated water in the kidney. In a second set of experiments, 14C-butanol and tritiated water were infused for 10 or 60 seconds into the renal arteries of anesthetized rabbits, and the kidneys were then removed and frozen in liquid nitrogen. Cores were cut from the kidney surface and sectioned in a cryostat, and the ratio of 14C-butanol to tritiated water was calculated at increasing depths in the cortex. This ratio rose from 0.54 +/- 0.03 (SEM) at the surface to 0.98 +/- 0.07 at 3 mm beneath the surface in kidneys perfused for 10 seconds. This gradient was less steep after 60 seconds of perfusion. The early appearance of 14C-butanol relative to tritiated water in the renal venous outflow and delayed equilibration of 14C-butanol in the outer renal cortical tissue are consistent with counter-current diffusion. It is suggested that this exchange may occur between adjoining interlobular arteries and veins in the cortex and may contribute to high carbon dioxide tensions found near the renal surface.

1-Butanol↗
PubMed1983

Flow of edema fluid into pulmonary airways.

An in situ rabbit preparation was used to characterize the manner in which edema fluid enters the airways when left atrial pressures are elevated. The airways were initially filled with fluid to minimize retrograde flow of edema fluid into the alveoli. The airway solution contained 125I-albumin and in some studies [14C]sucrose, and the lungs were perfused with a comparable solution which contained albumin labeled with Evans blue dye and 99mTc-diethylenetriaminepentaacetate (DTPA) or 99mTc-sulfur-colloid particles (0.4-1.7 micron diam). After 30 min of perfusion, fluid was pumped from the airways into serial tubes. When left atrial pressures were low, there was very little transfer of labels detectable between the airway and perfusate solutions. However when left atrial pressures were increased to either 15 or 22 cmH2O, fluid entered the airways containing approximately the same concentrations of Evans blue dye and 99mTc-DTPA as those present in the perfusate. In contrast, the concentration of colloid particles averaged less than 5% perfusate concentrations, indicating that the fluid had not escaped through a tear in the barriers separating the vascular and airway compartments. Concentrations of the perfusate fluid and indicators were highest in the initial samples pumped from the airways. These observations suggest that some of the fluid entering the airways may be derived from peribronchial cuffs or that there are marked regional differences in edema formation from alveoli.

Animals↗