Capillary Permeability-surface Area Product Research Articles

Adrenergic and histaminergic neural interactions in dog paws.

The mechanisms underlying the vascular responses of superficial fibular nerve stimulation (SFNS) have not been defined. Right hindpaws of anesthetized heparinized dogs were vascularly and neurally isolated, enclosed in a volume recorder, and perfused with controlled pressure. Vascular volume (VV) (131I-labeled albumin) and rate of tissue volume changes (VT) (plethysmography) were determined. SFNS increased blood flow resistance, reduced capillary filtration coefficient (CFC) and permeability-surface area product (PS) of 86Rb, increased VV, and reduced 131I-albumin recovery. VT increased at the rate of 3.35 +/- 0.45 ml/min. SFNS during terbutaline increased resistance, CFC, PS, and VV were unchanged, 131I-albumin recovery was complete, and VT increased at one-fourth the control rate. Phentolamine and yohimbine blocked all responses to SFNS. Prazosin with SFNS attenuated hemodynamic changes and VT increased to two-thirds of control, decreased VV, albumin, and Rb recovery but not PS and CFC. SFNS during pyrilamine maleate reduced VT increase to two-thirds of control rate and blocked decreases in PS and CFC. Metiamide did not change the SFNS responses, except to reduce vascular volume and VT. The combined histamine H1 and H2 blockers reduced VT increase to one-third of control and attenuated albumin loss, prevented histamine dilation, attenuated vasopressin and norepinephrine but not angiotensin constriction. SFNS stimulation increased precapillary resistance by alpha 1- and alpha 2-receptors and venous resistance by alpha 2-receptors and increased permeability by histamine release from endothelium.

Glucose transfer into rat brain during acute and chronic hyperglycemia.

Chronic hyperglycemia has been reported to decrease the maximum velocity of glucose transport across the blood-brain barrier by 30 to 40%. However, available measurements of brain glucose content during chronic hyperglycemia are consistent with an unaltered transport system. Because of this discrepancy the brain capillary permeability-surface area product (PA) was measured in awake-restrained rats during acute and chronic hyperglycemia. Acute hyperglycemia was produced by intraperitoneal injection of glucose, and chronic hyperglycemia was produced by treatment with streptozotocin. PA was measured using an intravenous tracer method. PA decreased during hyperglycemia, consistent with saturation kinetics for transfer. However, PA was similar in acutely and chronically hyperglycemic rats. These data suggest that down-regulation of facilitated glucose transport into the brain does not occur during chronic hyperglycemia.

Muscle capillary permeability for [14C]inulin and [51Cr]EDTA in human forearm.

Capillary permeability of [14C]inulin and [51Cr]EDTA was examined in human forearm in five healthy, subjects by indicator diffusion technique. Injections of, initially [125I]albumin and [14C]inulin, and after 30 min resting, of [125I]albumin and [51Cr]EDTA, were given in a brachial artery. During light exercise of the forearm, blood was sampled in 2-s periods from a deep cubital vein primarily draining muscles. The plasma flow rate, calculated as the dose of [125I]albumin in the injectate divided by the area under the curve for the venous concentration of 125I, was, on average, 8.5 ml min-1 100 g-1 forearm. Assuming [125I]albumin is a partially permeable tracer, a correction for extraction of albumin was performed. This gave extraction fractions of 0.107 +/- 0.015 (mean +/- SEM) for [14C]inulin and 0.377 +/- 0.033 for [51Cr]EDTA, respectively. The capillary permeability surface area product per 100 g tissue (CDC) was for [14C]inulin 0.90 +/- 0.19, and for [51Cr]EDTA 3.31 +/- 0.38 ml min-1 100 g-1 forearm. The average of the ratios of the CDC values of [51Cr]EDTA to those of [14C]inulin, 4.0 +/- 0.5, is significantly higher than the corresponding ratio between the measured free diffusion coefficients in water at 37 degrees C, 3.07 +/- 0.002 (N = 36 and 17, respectively). This indicates that there is some degree of restriction for [14C]inulin (MW 5200) relative to [51Cr]EDTA (MW 340.2) and it points to an 'equivalent pore radius estimate' of about 160 A in human muscle capillaries.

Myocardial serotonin exchange: negligible uptake by capillary endothelium.

The extraction of serotonin from the blood during transorgan passage through the heart was studied using Langendorff-perfused rabbit hearts. Outflow dilution curves of 131I- or 125I-labeled albumin, [14C]sucrose, and [3H]serotonin injected simultaneously into the inflow were fitted with an axially distributed blood-tissue exchange model to examine the extraction process. The model fits of the albumin and sucrose outflow dilution curves were used to define flow heterogeneity, intravascular dispersion, capillary permeability, and the volume of the interstitial space, which reduced the degrees of freedom in fitting the model to the serotonin curves. Serotonin extractions, measured against albumin, during single transcapillary passage, ranged from 24 to 64%. The ratio of the capillary permeability-surface area products for serotonin and sucrose, based on the maximum instantaneous extraction, was 1.37 +/- 0.2 (n = 18), very close to the predicted value of 1.39, the ratio of free diffusion coefficients calculated from the molecular weights. This result shows that the observed uptake of serotonin can be accounted for solely on the basis of diffusion between endothelial cells into the interstitial space. Thus it appears that the permeability of the luminal surface of the endothelial cell is negligible in comparison to diffusion through the clefts between endothelial cells. In 18 sets of dilution curves, with and without receptor and transport blockers or competitors (ketanserin, desipramine, imipramine, serotonin), the extractions and estimates of the capillary permeability-surface area product were not reduced, nor were the volumes of distribution. The apparent absence of transporters and receptors in rabbit myocardial capillary endothelium contrasts with their known abundance in the pulmonary vasculature.

Transcapillary exchange in the hindlimb and intestine of dogs with right heart failure.

The effects of chronic right ventricular volume overload, congestive heart failure (HF) on transcapillary exchange of lipid-insoluble solutes in the hindlimb and small intestine were studied in anesthetized dogs. Using the single injection indicator diffusion method, extractions (E), capillary clearances (C), and capillary permeability surface area products (PS) of urea, sucrose, and inulin were measured in the hindlimb and small intestine of 16 control and 14 HF dogs. Right HF was caused by surgically produced tricuspid insufficiency. The HF dogs exhibited increased central venous pressures, right ventricular end diastolic pressure, and heart rates as well as gross ascites and pleural effusion. The small intestine of the HF dogs demonstrated increased E, C and PS values for all three solutes, while no changes were seen in the hindlimb. These changes in the capillary bed of the small intestine could be due to an increase in capillary permeability, and/or capillary surface area.

Regulation of jejunal blood flow and oxygenation during glucose and oleic acid absorption.

To differentiate the mechanisms whereby actively absorbed glucose and passively absorbed oleic acid increase blood flow and oxygen uptake during their absorption, the effects of these two nutrients on jejunal blood flow, arteriovenous oxygen difference [(a-v)O2], O2 uptake, absorption, rubidium extraction, and capillary permeability-surface area product (PS) were compared in anesthetized dogs. Oleic acid (37 mM) produced significantly greater hyperemia (+28.2%) than glucose (270 mM) did (+12.5%). As estimated by (a-v)O2, tissue oxygen extraction was decreased by oleic acid (-12%) but increased by glucose (+6.5%); the increases in O2 uptake by these two nutrients did not differ significantly. Glucose absorption was accompanied by an increase in rubidium extraction and capillary PS (+11.3%), whereas oleic acid absorption was not. Unlike glucose, intra-arterial infusion of oleic acid decreased vascular resistance and increased blood flow equally to the mucosa and muscularis layers. A significant relation existed between oleic acid absorption and blood flow but not between glucose absorption and blood flow. The enhancement of glucose-induced hyperemia by bile was not related to glucose absorption. Unmasking of oleic acid-induced hyperemia by bile is unrelated to oleic acid absorption but is related to solubility of oleic acid in aqueous solution. The above findings suggest that glucose absorption affects both resistance and exchange vessels, whereas oleic acid absorption affects primarily resistance vessels.

The failure of serum albumin to affect capillary permeability in the isolated rabbit heart

The method of local tissue clearance was used to measure capillary permeability-surface area products ( PS) for [ 3H]inulin and [ 14C]sucrose in the left ventricular wall of the isolated rabbit heart. As soon as a heart was excised, its coronary arteries were perfused with Ringer solution at 37° for at least 30 min before clearance trials were begun. In paired trials, Ringer perfusion fluid containing 1% bovine serum albumin (Sigma) was compared with protein-free Ringer solution in terms of sucrose PS ( PS s ), inulin PS ( PS i ), and the PS ratio ( P i P s ). With or without protein, the mean P i P s was significantly less than the ratio of the free diffusion coefficients. With the untreated albumin, flow resistance rose markedly, and the PSs of both solutes fell but not P i P s . To remove the unidentified vasoactive contaminant (which apparently resisted dialysis), the albumin was “defatted” by the procedure of R. F. Chen (1967, J. Biol. Chem. 242, 173–181). Defatted albumin (1% in the perfusion fluid) did not affect the volume of distribution (λ) of sucrose or inulin in the myocardium, the heart rate, coronary flow, flow resistance, PS s , PS i , or P i P s . Apparently bovine serum albumin does not influence capillary permeability in the rabbit heart. A protein effect on permeability, however, could have been missed if it has a long latent period (more than 15 min) or a long persistence (more than 30 min).

Distribution of myocardial blood flow and capillary diffusion capacity across the canine heart wall.

Myocardial capillary permeability was determined in 20 dogs by applying a new method which resembles the tissue-uptake technique. The method consisted of a bolus injection of 51Cr-EDTA into the left atrium, determination of the average arterial tracer concentration and subsequent assay of myocardial tissue activity 10, 20 and 30 s after injection. Under the fundamental assumption of no back-diffusion of tracer to capillary blood, uptake of 51Cr-EDTA into myocardium allowed calculation of the transfer constant, Kin, independent of blood flow. Regional plasma flow, fpl, was simultaneously determined from tissue content and average arterial concentration of radioactive microspheres and haematocrit. From estimates of Kin and fpl the fractional extraction, E, of 51Cr-EDTA was calculated as E = Kin/fpl. The capillary permeability-surface area product, PS, was calculated as PS = -fpl X k X 1n (1 - E). Constant fractional extraction of 51Cr-EDTA indicates that the method can be employed 10 to 20 s after injection without risk of back-diffusion. From tissue samples taken from subendocardial and subepicardial layers of the left and right ventricular walls and from left and right side parts of the septal region we measured similar PS values. Letting capillary surface area, S, equal 500 cm2 X -1 the permeability coefficient for 51Cr-EDTA was 1.39 X 10(-5) cm X s-1.

Capillary permeability in the isolated rabbit heart as measured by local tissue clearance

The relatively simple method of local tissue clearance was used to measure capillary permeability-surface area products (PS) in the isolated, Ringer-perfused rabbit heart. Ten microliters of a mixture of [ 3H]inulin and [ 14C]sucrose was injected at a depth of 2 mm into the left ventricular myocardium and clearance rate constants ( k in min −1) were determined by analyzing the draining perfusion fluid. PS (ml/min per 100 ml) for each solute was calculated by the following equation: PS = −F ln(1 − λk F ) , where F is perfusate flow (ml/min per 100 ml) and λ is the equilibrium tissue/Ringer partition coefficient. At a perfusion pressure of 40 mm Hg, F = 133 ± 9.7 (mean ± SEM), PS sucrose = 77 ± 8.0, and PS inulin = 13.9 ± 0.7. These PS products are within the range of values previously reported by others using several different techniques. The mean inulin/sucrose permeability ratio was 0.189 ± 0.018 which is significantly less than the separately measured free diffusion coefficient ratio (= 0.41 ± 0.005), thus indicating that sucrose and inulin crossed myocardial capillary walls by restricted diffusion. The reasons why some investigators did not find similar evidence of restricted diffusion are discussed.

Changes in lung function after routine exposure manipulations during thoracotomy

The effect of manual retraction and bronchial occlusion upon right lung function during a 2-hr thoracotomy was evaluated in sheep. Group 1 (seven sheep) underwent manual lung retraction. Group 2 (seven sheep) underwent right bronchial occlusion. Group 3 (seven sheep) served as controls. Radioisotopic indicators (51Cr-RBC, 125I-albumin, [14C]urea, 3H2O) were used to assess changes in capillary permeability-surface area product (PS-urea), extravascular lung water (VE), and intravascular blood volume (Vv). Lung water was further quantified by gravimetric technique. Pulmonary vascular resistance increased following thoracotomy in both groups (34% Group 1, 66% Group 2) and compliance decreased (16% Group 1, 33% Group 2). Mean right lung shunt increased in Group 1 from 17 to 37% (P less than 0.05) and for Group 2 from 18 to 36% (P less than 0.02). A reduction (greater than 25%) in both groups for PS-urea and VE occurred (P less than 0.05). The fall in PS-urea and VE and the increase in PVR indicate a reduction in the right lung perfusion for both groups. It is concluded that a similar marked reduction in ventilation, perfusion, and V/Q occurred after reexpansion whether the lung was retracted or the bronchus occluded.

Microvascular exchange of albumin

The transcapillary exchange of albumin was examined in seven rabbits using plasma disappearance curves and black box kinetic analysis. From the experimental data and the Renkin and Kedem-Katchalsky equations it was found that the average whole body diffusional capillary permeability coefficient for albumin was 24 × 10 −8 cm/sec as the total whole body capillary permeability-surface area product was 0.0739 ml/100 g · min (surface area estimate 50 cm 2/g). The convective components of the net albumin tracer flux was found to be 15%, and the pure permeation ratio of influx to outflux ( R = 0.61) of systemic albumin was reduced to 0.57. The solvent drag component of either unidirectional flux relative to the permeative component was 0.037. The Casley-Smith hypothesis of solvent drag convection up a gradient across the capillary membrane could not be verified as possible. It is emphasized that the so-called transcapillary escape rate is an arbitrary rate constant which cannot be attributed to reflect any physiological process, especially not the transcapillary exchange of albumin.

Role of longitudinal diffusion in the extravascular pulmonary space on parameter estimates derived from data of multiple indicator dilution

A mathematical model of transcapillary exchange has been developed that considers in detail the role of axial diffusion in the extravascular tissue region on estimates of such physiological parameters as lung water (VE) and pulmonary capillary permeability-surface area products (PS), obtained from multiple indicator dilution studies. The experimental cases considered correspond to two animal models of pulmonary oedema in which the integrity of the pulmonary capillary membrane is disrupted and the effects of extravascular axial diffusion may be important. A novel feature of the computational scheme is the use of an Array Processor in the solution of the governing equations, initial and boundary conditions. Computer time is reduced to 2-3 min for parameter identification, thereby allowing a wide range of values for extravascular axial diffusion coefficients (D'/L2) to be studied at little computational expense. The results indicate that diffusion in the extravascular region does not influence parameter estimates for PS to urea. A statistical correlation is suggested between values for VE, PS to water, and D'/L2.

Effect of regional hypoxia and blood flow on capillary permeability in canine myocardium.

The effect of hypoxia and blood flow on the capillary permeability-surface area product (PS) of 51Cr-EDTA was investigated in canine myocardium of open chest anesthetized dogs at constant aortic pressure, heart rate, and cardiac output. PS was determined by bolus injection of 51Cr-EDTA into the left anterior descending coronary artery (LAD) and external registration of the response curve. Vascular conductance (G) and PS were measured: (1) during pump perfusion of LAD with arterial blood (control state), and (2) during vasodilation obtained by LAD perfusion with deoxygenated blood at same blood flow as in control state, and (3) during increased blood flow with deoxygenated blood. Mean value of G in control state was 1.31 ml.min-1 (100 g)-1.(mmHg)-1. The ratio G-hypoxia/G-control used to assess the extent of vasodilation was 2.42 (range 1.67-3.56) during hypoxia and unchanged flow and 2.82 (range 1.81-4.47) during hypoxia and increased flow. Mean value of PS in control state was 36 ml-(100g)-1.min-1. With maximum vasodilation and constant blood flow PS increased to 47.3 ml.(100 g)-1.min-1 (37%) and during increased blood flow to 69.0 ml.(100 g)-1.min-1 (96%). The increase in PS most likely reflects an increase in capillary surface area available for exchange of 51Cr-EDTA indicating a 1.4- to 2-fold recruitment of capillaries.

Alterations of myocardial capillary permeability by albumin in the isolated, perfused rabbit heart.

1. Capillary permeability-surface area products for 22Na, 51Cr-EDTA (mol. wt. 357), [57Co]cyanocobalamin (mol. wt. 1353) and 125I-labelled insulin (mol. wt. approximately or equal to 6000) were measured using the single-passage, multiple-tracer dilution technique in isolated rabbit hearts perfused at constant flows between 0.2 and 4.7 ml. min-1 . g-1. 2. In hearts perfused with a Krebs-Ringer solution containing bovine albumin (10 g . l . -1), the permeability-surface area products for 51Cr-EDTA and [57Co]cyanocobalamin increased as the perfusion rate increased, but reached constant values at flows above 2 ml . min-1 . g-1. For 125I-labelled insulin a diffusion-limited value of 0.06 +/- 0.02 ml . min-1 . g-1 (mean +/- S.E., n = 10) was measured at significantly lower perfusion rates. As the value for 22Na increased continuously with increments in flow, only a flow-limited value could be estimated. 3. When hearts were initially perfused with albumin (10 g . l . -1) and then with an albumin-free Krebs-Ringer solution, a significant increase in the permeability-surface area for 22Na, 51Cr-EDTA and [57Co]cyanocobalamin was observed. 4. In hearts perfused with albumin capillary permeability coefficients calculated for 22Na, 51Cr-EDTA. [57Co]cyanocobalamin and 125I-labelled insulin were respectively: 10.5, 3.5, 2.1 and 0.21 x 10(-5) cm.sec-1. 5. These findings confirm that bovine albumin reduces the permeability of myocardial capillaries to hydrophilic solutes of varying molecular sizes and this effect may be the result of an interaction of albumin with the pathways for transcapillary exchange.

Cerebral extraction of N-13 ammonia: its dependence on cerebral blood flow and capillary permeability -- surface area product.

13N-labeled ammonia was used to investigate 1) the cerebral extraction and clearance of ammonia, 2) the mechanism by which capillaries accommodate changes in cerebral blood flow (CBF) and 3) its use for the measurement of CBF. The unidirectional extraction of 13NH3 in rhesus monkeys was measured during PaCO2 induced changes in CBF and dog studies were performed using in vitro tissue counting techniques to examine 13NH3 extraction in gray and white matter, mixed tissue and cerebellum during variations in CBF produced by combinations of embolization, local brain compression, and changes in PaCO2. The single pass extraction fraction of 13NH3 varied from about 70 to 20% over a CBF range of 12 to 140 cc/min/100 g. Capillary permeability-surface area product (PS) estimates with a Renkin/Crone model show PS increasing with CBF. The magnitude and rate of increase in PS with CBF was highest in gray matter greater than mixed tissue greater than white matter. Tissue extraction of 13NH3 vs CBF relationship was best described by a unidirectional transport model in which CBF increases by both recruitment of capillaries and by increases of blood velocity in open capillaries. This saturable-recruitment model provides a possible explanation for the mechanism of flow changes at the capillary level. The net 13NH3 extraction subsequent to an i.v. injection increases non-linearly with CBF. Doubling or halving basal CBF produced from 35 to 50% changes in the 13N tissue concentrations with further increases in CBF associated with progressively smaller changes in 13N concentrations.

Transcapillary exchange and distribution of carbon‐11 labelled ethanol in the isolated perfused rat liver

The distribution kinetics of ethanol in the isolated perfused rat liver at various flow rates and ethanol concentrations were studied by the indicator diffusion technique using 11C-labelled ethanol. A double tracer solution with 99mTc-labelled red blood cells as the vascular reference and 11C-ethanol as the test substance was injected into the catheter connected to the portal vein. Time-activity curves were monitored by a NaI(Tl) scintillation detector above the outflow catheter. The following values were obtained: 0.95 +/- 0.01 for the maximal extraction (Emax), 3.0 +/- 0.1 x flow (r = 0.98) for the capillary permeability surface area product (PScap), 18.7 +/- 2.5% for the vascular volume (V1) and 56.2 +/- 9.0% for the ethanol distribution volume (V2). The volumes were calculated from the products of mean transit time (MTT) and flow (f), and PScap was calculated from the equation PScap = -f x ln(1-Emax). The results show that the ethanol distribution in the liver is flow limited since Emax was constant at various flow rates (0.67-2.55 ml/g x min-1). The distribution volumes obtained agree well with the values for liver vascular volume and water distribution volume reported in the literature.

Transcapillary exchange in the cat salivary gland during secretion, bradykinin infusion and after chronic duct ligation.

1. Capillary permeability-surface area products for 86Rb, [51Cr]EDTA (mol. wt. 357), [57Co]cyanocobalamin (mol. wt. 1353) and [125I]insulin (approximate mol. wt. 6000) have been measured using the single-circulation, multiple-tracer dilution technique in the in situ perfused submandibular salivary gland during parasympathetic nerve stimulation, close-arterial bradykinin infusion and following chronic duct ligation. 2. In glands with a natural blood supply, permeability-surface area for 86Rb and [51Cr]EDTA increased during parasympathetic stimulation, but this was shown to be related to the concomitant increase in blood flow rather than to a change in capillary permeability or in surface area. 3. In glands perfused at constant flow, parasympathetic stimulation led to a decrease in permeability-surface area for EDTA (-19.1 +/- 5.2%, mean +/- S.E., n = 5, P less than 0.05) cyanocobalamin (-12.3 +/- 6.0, n = 12, P less than 0.05), and insulin (-15.3 +/- 4.8, n = 11, P less than 0.02). It is suggested that this may be the result of a redistribution of flow from the acinar microcirculation to a less permeable ductal vasculature. 4. Bradykinin infusion had no significant effect on permeability-surface area for EDTA and cyanocobalamin in perfused glands. 5. In perfused glands, ligation of the submandibular duct for 3--12 days reduced permeability-surface area (ml.min-1.g-1) for [51Cr]EDTA from 5.26 +/- 0.60 (mean +/- S.E., n = 9) to 4.20 +/- 0.12 (n = 4, P less than 0.30), [57Co]cyanocobalamin from 3.22 +/- 0.12 (n = 48) to 2.02 +/- 0.08 (n = 15, P less than 0.001) and [125I]insulin from 1.52 +/- 0.07 (n = 39) to 0.72 +/- 0.23 (n = 11, P less than 0.001).

Simultaneous measurements of capillary diffusion and filtration exchange during shifts in filtration-absorption and at graded alterations in the capillary permeability surface area products (PS).

The diffusion exchange of Cr-EDTA, using the single injection indicator diffusion method, was followed simultaneously with estimations of the capillary filtration capacity (CFC) in an "isogravimetric" rat hindquarter preparation during artificial perfusion and maximal dilatation. Measurements were performed at constant flow and during 1) shifts in filtration-absorbtion, 2) alterations of perfused capillary wall area (graded rarification of capillary network by microsphere injection) and 3) during alterations of permeability (i.a. infusion of histamine). At maximal vasodilatation CFC was 0.037 +/- 0.001 ml/min X mmHg X 100 g and PS for Cr-EDTA 5.67 +/- 0.13 ml/min X 100 g. During filtration or absorbtion, Cr-EDTA transfer from vessels to interstitium changed only slightly but the situation may well be different for solute transfer from interstitium to vessels. Alterations in capillary wall area resulted in proportional changes in PS for Cr-EDTA while the CFC changes were always relatively smaller. Histamine increased CFC some threefold with a marked increase in protein transfer, while PS for Cr-EDTA increased only marginally. This histamine effect could be ascribed mainly to an increase in the number of large pores which, because of their relative paucity, are of little importance for small molecular diffusion exchange but highly important for convective and macromolecular exchange.

Single-passage extraction and permeability estimation of sodium in normal dogs lungs.

Bolus injections of 24NaCl, 131I-albumin, and indocyanine green dye were made into the right atria of anesthetized, ventilated dogs. Blood was sampled from the femoral artery, and from the dilution curves, instantaneous extractions, E2(t), and area averaged extractions, E3(t), were calculated for sodium at various plasma flows (Fp). Flow reduction was produced by transient inferior vena cava obstruction. E2(t) and E3(t) within any dilution curve generally started off with a high value, then decreased with time. The E3 that occurred at the peak of the albumin-dilution curve were about 0.11 for plasma flow of 0.75 liter/min and tended to decrease as flow increased. Parallel study of the sodium extravascular space at equilibrium gave values of 0.3-0.4 g of plasma sodium per g of tissue, suggesting that this volume is not infinitely small. Since the E was low it is unlikely that the high initial E(t) and the decreasing E(t) were due to early back flux. Calculation of capillary permeability surface area product [PS = Fp loge (1 - E)] showed an increasing PS with plasma flows. The injection of 9-mum microspheres at low and high total blood flow gave evidence supporting a decrease of capillary surface area (S) with decreasing total blood flow. Regional pulmonary blood flow also showed marked heterogeneity. Because of the low average extraction of sodium in the lung, insensitivity of the method in normal lungs cannot be excluded.

The identification of pulmonary capillary permeability from multiple-indicator data: Effects of increased capillary pressure and alloxan treatment in the dog

The purpose of this study was to determine the effects of increased intravascular pressure and alloxan treatment of anesthetized dogs on the pulmonary capillary permeability-surface area product (PS) for the tracers [ 14C]urea and 3HOH. 125I-labeled albumin, 51Cr-tagged erythrocytes, [ 14C]urea, and [ 3H]water were injected simultaneously. Values of PS were computed by the integral extraction method, the maximum extraction method, and by two organ-capillary mathematical models. The results indicate that while the extravascular volume is increased by both alloxan and increased pressure, only alloxan increases PS for [ 14C]urea significantly. More detailed calculations of PS based on the mathematical models provide more sensitive and reproducible values of PS. The value of PS for [ 3H]water, generally considered to be flow-limited and therefore insensitive to alterations in PS, was also found to increase slightly with alloxan, but not high pressure. We conclude that multiple-indicator experiments when analyzed by accurate mathematical techniques permit distinction between pulmonary edema caused by high pressure and that caused by increased permeability.