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Biomedical subjects

R M Effros

Publications and source records attributed to R M Effros.

At least 73 records · Page 4Linked to original sources
PubMed1983

Deficiency of carbonic anhydrase in the vasculature of rabbit kidneys.

The transit of 14CO2 and H14CO3- through the renal vasculature was studied in rabbit kidneys perfused without erythrocytes and in an in vivo preparation in which erythrocytes were present. In the absence of erythrocytes, the transit of 14CO2 from the renal artery to renal vein was much more rapid than that of H14CO3-. This suggests that (a) there is insufficient carbonic anhydrase (c.a.) in the vasculature between the renal artery and the exchange vessels of the kidney to ensure equilibration between CO2 and HCO3- and (b) CO2 can diffuse directly between arterial and venous vessels in the kidney. Following infusions of carbonic anhydrase, the renal venous outflow patterns of 14CO2 and H14CO3- became the same in the perfused kidneys. Although the initial recovery of 14CO2 remained greater than that of H14CO3- after infusions of acetazolamide (a c.a. inhibitor), arteriovenous diffusion of 14CO2 was diminished by this agent. This is attributed to inhibition of renal tubular c.a. The outflow patterns of H14CO3- and 14CO2 were nearly the same in the presence of erythrocytes, indicating that erythrocyte c.a. is sufficiently accessible to permit virtual equilibration of these radionuclides during the interval required for transit between the renal artery and exchange vessels. However, addition of carbonic anhydrase to the plasma seemed to accelerate transit of both 14CO2 and H14CO3- through the kidneys, and a small disequilibrium between CO2 and HCO3- may therefore normally be present in the renal interstitium and capillaries.

Animals↗
PubMed1983

Rapidly reversible alterations of pulmonary epithelial permeability induced by smoking.

A radioaerosol procedure using 99mcTc-DTPA (diethylene triamine penta acetate) was used to evaluate the permeability of the pulmonary epithelium in smokers and nonsmokers. The average clearance of this indicator from the lungs of smokers without significant airway obstruction exceeded that found in normal subjects by an average factor of more than five. This abnormality was observed throughout all lung regions. 99mTc-DTPA clearance decreased rapidly during the week after smoking was discontinued. It is concluded that smoking results in a rapidly reversible increase in pulmonary epithelial permeability.

Adult↗
PubMed1983

Recent developments in pulmonary edema.

Research on lung fluid balance and pulmonary edema has increased during the last decade. New approaches have led to insights into the role of each component of the alveolar-capillary barrier. The capillary endothelium is the first line of defense against lung fluid accumulation. The interstitium may play a more important role in lung fluid balance than previously appreciated. Active and passive transport properties of alveolar epithelium may be important in the pathogenesis and resolution of alveolar edema. New methods for the determination of epithelial permeability and lung water are being evaluated. The developments reviewed here may have an impact on the institution of new diagnostic and therapeutic approaches to pulmonary edema during the next decade.

Animals↗
PubMed1981

Role of albumin in prevention of edema in perfused rabbit lungs.

Edema formation was studied using in situ rabbit lungs perfused with normal 5.0 g/dl) and low (0.1 g/dl) albumin solutions. Measurements were made of the ratio of wet weight to dry weight of the lungs corrected for the residual vascular volume, [(W/D)ev] and the ratio of extravascular 22Na+ to extravascular water volume. Edema formation in the 5 g/dl lungs was insignificant during a 60-min perfusion interval. A moderate amount of edema was found in 0.1 g/dl lungs: (W/D)ev = 5.30 +/- 0.12 (SE) compared with 4.66 +/- 0.11 in the 5 g/dl lungs. Much greater rates of edema formation were found in the 0.1 g/dl lungs when left atrial pressures were increased from 0 to 10 Torr; (W/D)ev reached 7.89 +/- 0.50 in 60 min compared with 5.66 +/- 0.23 in the 5 g/dl lungs. No additional edema formation occurred when albumin concentrations were decreased from 0.1 g/dl to below 0.01 g/dl. Albumin concentration gradients across the capillary wall appear to increase with elevations in capillary pressure.

Albumins↗
PubMed1981

Asymmetric distribution of carbonic anhydrase in the alveolar-capillary barrier.

Pulmonary carbonic anhydrase (CA) activity was studied by injecting 0.5 ml of a buffered solution of NaH14CO3 and 3H2O into the distal airways of perfused rabbit lungs. The early recovery of 14C in the pulmonary venous outflow averaged 0.28 +/- 0.02 (SE) that of 3H under control circumstances. Incorporation of a CA inhibitor (20 mg/l acetazolamide) in the perfusate reduced 14C recovery relative to 3H by two-thirds, whereas this inhibitor had no effect when placed in the airway injection fluid. Addition of 100 mg/l Ca to the perfusate did not increase 14C recovery, but addition of the enzyme to the bronchial fluid increased 14C recovery relative to 3H by a factor of more than 5. It is concluded that CA is associated with the endothelial side of the alveolar-capillary barrier but is absent on the airway surfaces.

Animals↗
PubMed1981

Role of perfusion and diffusion in 14CO2 exchange in the rabbit lung.

The rate of transfer of H14CO-3 and 14CO2 from the alveoli to the capillaries was studied in rabbit lungs perfused without erythrocytes. Aliquots of 0.5 ml of buffered solutions containing these 14C indicators and 3H2) were injected into the distal airways, and the recoveries of 14C and 3H were compared in the left atrial outflow. It was assumed that 3H2O had equilibrated between the alveoli and fluid leaving the pulmonary capillaries, and a decline in the initial 14C recovery relative to that of 3H was attributed to incomplete equilibration of 14C between these compartments. No disequilibrium of 14C could be detected at pH 7.4 when excess carbonic anhydrase was present. When the pH was increased to 8.4, 14C equilibration was only 69% complete at 36 ml/min and 41% complete at 160 ml/min. Confirmatory evidence was obtained that carbonic anhydrase is associated with the endothelial side of the alveolar-capillary barrier but is absent on the epithelial surface. The data suggest that the barrier is at least 600 times more permeable to 14CO2 than to H14CO-3, and diffusion of 14CO2 would not limit exchange at normal pH unless pulmonary flow reached extremely high values.

Acetazolamide↗
PubMed1980

Carbonic anhydrase activity of rabbit lungs.

Pulmonary carbonic anhydrase (CA) activity was studied in rabbit lungs perfused with solutions containing no CA. Measurements were made of the amount of 14CO2 appearing in the expired gas following injections of H14CO3(-), 14CO2, or a 20:1 mixture of each into the pulmonary artery. The fraction of the injected label in the expired gas was only 17% greater for 14CO2 than for the mixture, suggesting that equilibration between H14CO3(-) and 14CO2 was nearly complete during the capillary transit time. Inhibition of pulmonary CA decreased excretion of H14CO3(-) and the mixture by 40 and 49% and increased the excretion of 14CO2 by 96%. Addition of CA to the perfusate had no effect. Thus, CO2 exchange is not significantly limited by pulmonary CA if inhibitors are absent. Tissue binding of [3H]acetazolamide injected into the pulmonary artery was diminished by 50% when acetazolamide concentrations reached 0.13 x 10(-6) M. Each liter of extravascular lung water contained 1.25 x 10(-6) mol of receptors for acetazolamide that were accessible to plasma during a single circulation. Binding of [3H]acetazolamide was also observed in lungs of anesthetized rabbits, suggesting that pulmonary CA is accessible to plasma in vivo as well as in situ.

Acetazolamide↗
PubMed1980

Accelerated clearance of small solutes from the lungs in interstitial lung disease.

Solutions of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and 99mTcO-4 were aerosolized and inhaled by subjects seated against a scintillation camera. Initial clearance rates of these radionuclides were determined over 6 posterior lung regions. Clearance of 99mTcO-4 (molecular weight, 163 dalton exceeded that of 99mTc-DTPA (molecular weight, 492 daltons) by an average factor of 3.3. Upper-lobe clearance of both radionuclides was greater than lower-lobe clearance in the normal subjects, but this gradient was abolished when the subjects exhaled against 7 cm of positive end-expiratory pressure. Twenty-one patients with clinical and roentgenographic evidence of interstitial lung disease (ILD) and diminished CO diffusion rates were studied with 99mTc-DTPA. Clearance of 99mTc-DTPA was increased in each of 5 patients with idiopathic pulmonary fibrosis, 4 of 8 with sarcoid, 2 of 5 with pneumoconiosis, and 2 of 3 patients with other forms of ILD. In contrast, the clearance of 99mTcO-4 was decreased in 4 patients with pulmonary alveolar proteinosis. Furthermore, no increase in 99mTc-DTPA clearance was found in 5 patients with chronic obstructive pulmonary disease. These studies suggest that the initial clearance of these aerosolized hydrophilic radionuclides is accomplished in part by diffusion through the epithelium of alveoli and respiratory bronchioles. Whereas radionuclide clearance is impaired by the presence of precipitated protein in these structures in pulmonary alveolar proteinosis, clearance is accelerated in ILD. This may indicate increased epithelial permeability in ILD related to injury and increased retractile forces.

Adult↗
PubMed1979

Vascular and extravascular compartments of the isolated perfused rabbit lung.

The vascular, interstitial, and cellular compartments of 15 isolated, perfused and ventilated rabbit lungs determined by a steady-state indicator-dilution procedure. Five lungs were perfused with constant pulmonary artery flow and zero left atrial pressure for more than 1 h. Edema formation was continuous and pulmonary vascular volume (PVV) decreased initially at a time when pulmonary vascular resistance (PVR) was falling. Increases in PVR were not seen until edema formation had become severe. In 10 other lungs, increases in pulmonary artery or left atrial pressure resulted in elevation of PVV and accelerated edema formation. The initially abrupt increase in PVV was followed by a more gradual increase over a 10-min period. Return of fluid to the vasculature was never observed in these studies. Labeled albumin readily entered the extravascular space but a relatively constant fraction of the interstitium remained inaccessible to albumin. No changes were found in the cellular volume during edema formation.

Animals↗
PubMed1979

Carbonic anhydrase activity of the cat hind leg.

The accessibility of tissue carbonic anhydrase to plasma was studied in five surgically isolated cat hind legs. After the leg was skinned and the paw circulation occluded with a tourniquet, it was perfused with a solution that contained neither red cells nor carbonic anhydrase. Solutions containing either H14CO3- or 14CO2 were injected with 125I-albumin, 22Na+, and 3H2O into the femoral artery and the concentrations of each were measured in the femoral venous outflow. Under control circumstances the outflow patterns of H14CO3- and 14CO2 were very similar. However, after carbonic anhydrase inhibition with 20 mg/l acetazolamide in the perfusion solution, the initial exchange of H14CO3- ("extraction") was greatly decreased, whereas the extraction of 14CO2 was slightly increased. Because there was insignificant carbonic anhydrase activity in the venous outflow, these data suggest the presence of carbonic anhydrase at a readily accessible site, possibly bound to the endothelial surface. In this location it would promote CO2 exchange and minimize disequilibrium between plasma HCO3- and CO2.

Animals↗
PubMed1977

Effect of osmolality on red blood cell viscosity and transit through the lung.

The mean transit times of labeled red blood cells and albumin were compared in eight isolated rabbit lungs perfused with physiological albumin solutions. The osmolality of these solutions was adjusted by altering the concentration of sodium chloride. The ratios of the mean transit times of injected red blood cells to those of albumin increased as perfusion osmolality increased from hypotonic to isotonic and from isotonic to hypertonic levels. This change occurred despite a decline in pulmonary vascular resistance and red blood cell size as osmolality was increased. Red blood cell viscosity (determined with a cone-plate viscometer) increased with osmolality and it was concluded that this change of viscosity impaired the relative rate of red blood cell transit through the lungs. Passage of red blood cells through rigid homoporous membranes appeared to be related primarily to red cell size rather than vascosity. These observations suggest that both red blood cell viscosity and capillary distensibility play an important role in determining the velocity of red blood cells through the capillaries.

Animals↗