Capillary Permeability Coefficient Research Articles

Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability.

The rat brain capillary permeability coefficient was determined for 27 compounds. The relationship of permeability to octanol/water partition coefficient and molecular weight was found to be predictable for drugs with molecular weights less than 400.

Capillary filtration and permeability coefficients calculated from measurements of interendothelial cell junctions in rabbit lung and skeletal muscle

The depth and width of interendothelial junctions were measured in pulmonary capillaries of the adult and fetal rabbit and in capillaries of the gastrocnemius muscle of the adult rabbit. These dimensions were used to determine the resistance to filtration and diffusion of junctions in each tissue. The resistances, together with the stereologically determined values for the total length of junction per unit weight of tissue, were used to calculate maximal capillary filtration coefficients (CFC) and diffusion coefficients (CDC) for sodium and inulin under conditions in which all vessels (except those in the fetal lung) were assumed to be perfused. The calculated filtration coefficients, expressed per 100 g tissue, were 2.7, 0.8, and 0.05 ml min −1 mm Hg −1 100 g −1 for capillaries in adult lung, fetal lung, and skeletal muscle, respectively. The corresponding values for capillary surface area in each tissue were 3490, 844, and 62 cm 2 g −1, respectively. When the data were expressed per square centimeter of capillary surface area the resultant filtration and permeability coefficients were similar for all three tissues. Permeability coefficients for sodium ranged from 33 × 10 −5 to 42 × 10 −5 cm sec −1 and for inulin from 1.2 × 10 −5 to 1.9 × 10 −5 cm sec −1. The filtration and diffusion coefficients per 100 g tissue were approximately 50 times greater in adult lung than muscle and 16 to 20 times greater in fetal lung than muscle. These differences were due to the greater length of junction (open along the capillary axis) per unit depth of junction in lung compared to muscle. The effective width of the junctions in all three tissues was similar.

Quantitative observations of the acute effects of X-irradiation on brain capillary permeability: Part I

Rats were irradiated with single and multiple dally dose fractions of 200–2500 rad; the capillary permeability coefficients (P) for 14C-urea, 3H-galactitol, 3H-VM-26, and bleomycin were determined after completion of each course. The drugs have a wide range of molecular weights and lipophilicities. Radiation doses of 200 rad × 5 days and 400 rad × 1 day increased the urea P 14–32%, while other dose fractions had no effect on P. The P for galactitol was increased more consistently (52–116%) by single and multiple 200 rad fractions and single fractions of 400 and 1000 rad. The P for galactitol paradoxically was reduced approximately 60% by 200 rad × 10 days and 2500 rad × 1 day fractions. Permeability to galactitol was determined at various times 3–24 hr after single radiation doses of 200, 400, and 1000 rad; at all times P was increased over nonirradiated animals. No radiation dose had an effect on the P for bleomycin. Except for a single fraction (400 rad × 1 day), the P for VM-26 was also unaffected by radiation, and in that instance the P was reduced from normal. We conclude that the radiation fractions used in these studies produced little acute effect on the permeability of normal brain capillaries to the antitumor antibiotic bleomycin, the large lipophilic podophyllotoxin derivative VM-26, and urea, a small nonionized hydrophilic molecule. The only consistent increase in P occurred with galactitol, a hydrophilic molecule (molecular weight of 182 Daltons) that is normally quite restricted in its transcapillary transit in the brain.

Quantitative observations of the subacute effects of X irradiation on brain capillary permeability: Part II

Male Fischer 344 rats received cerebral irradiation at 300 rad/day, four days/wk for three wk, to a total dose of 3600 rad. The capillary permeability coefficients for galactitol, urea, and sodium determined at 6, 10 and 12 wk postirradiation were not statistically different when they were compared to control rats. We found no evidence for the “early” delayed effects of X irradiation based on alteration of brain capillary permeability. We feel this syndrome is the result of alteration in the processes that control the maintenance of myelin. Further investigation of cellular and biochemical effects of irradiation would be more informative than additional capillary membrane studies.

Quantitative high-pressure liquid chromatographic procedure for the determination of plasma and tissue levels of 2,4-diamino-5-(3,4-dichlorophenyl)-6-methylpyrimidine (metoprine) and its application to the measurement of brain capillary permeability coefficients

A high-pressure liquid chromatographic assay for metoprine levels in aqueous media, serum, and tissue extracts has been developed that can measure concentrations of the drug in the 25–100 ng range with accuracy, reproducibility, and case. The half-time for metoprine disappearance from rat plasma and capillary permeability coefficients for metropine in rat brain tissue determined with this method are in excellent agreement with values determined for related drugs using labeled compounds.

Estimate of capillary permeability coefficients of canine heart to sodium and glucose

Measurements of fractional extraction ( E) were used to study the transcapillary diffusion of sodium and glucose in isolated, nonworking, spontaneously beating dog hearts, perfused with blood of low hematocrit at controlled flows. Papaverine, dipyridamole, and norepinephrine were used, in separate experiments, to increase vascular conductance and capillary density. E-Sodium fell from 0.77 to 0.23 and E-glucose from 0.70 to 0.11 as plasma flow ( F) was varied from 23 to 422 ml/min · 100 g. Permeability-surface area products ( PS), calculated from PS = − F ln (1 − E), for both molecules increased progressively over the range of flows. Assuming S to be 500 cm 2/g, capillary permeability coefficients were estimated from the maximal mean PS observed. Calculated P values (× 10 −5 cm/sec) for sodium and glucose were 3.91 and 2.13, respectively. The ratio of P-Na to P-glucose was analyzed statistically at various flow ranges. Mean P- Na P- glucose ratios were proportional to the D- Na D- glucose ratio ( D, free-diffusion constant) at all flows greater than 40 ml/min · 100 g. Comparison of D- Na D- glucose to D′- Na D′- glucose ( D′, restricted diffusion constant) at various pore radii showed that proportionality between Ps and Ds ratios is not a sufficient argument for free diffusion of Na and glucose across capillary walls.

The application of brain capillary permeability coefficient measurements to pathological conditions and the selection of agents which cross the blood-brain barrier.

Capillary permeability was analyzed in both normal rat brain and intracerebral 9L gliosarcoma tumor and in rhesus monkey brain using a newly derived formula for the capillary permeability coefficient (P).The Pvalue for isotopic urea and sodium was less in monkey brain than in rat brain. The Pvalue for tumor was 1 log unit higher in tumor for all but the most rapidly transported drugs. Amphotericin B increased the normal brain Pvalue for galactitol but not for urea. Glucocorticoids did not alter brain Pvalues for sucrose or urea. Using P,drugs can be categorized in terms of blood-brain barrier (BBB) exclusion, slow BBB passage, moderate BBB passage, and rapid BBB passage. The technique described in this article is applicable to the study of regional differences in brain capillary permeability associated with disease states.

Estimation of the capillary permeability coefficients of inulin in various tissues of the rabbit

Halftimes for inulin distribution were obtained in heart, lung, skeletal muscle, diaphragm, small intestine, and ear of the nephrectomized rabbit. The technique employed infusion of 5% inulin in Ringers into a vein near the heart with serial sampling from the pulmonary artery, carotid artery, and tissues. From these samples the time-dependent volumes of distribution on the tissues were estimated. The halftimes for inulin distribution could then be used to estimate capillary permeability coefficients. Literature values for capillary area were used for most of the tissues. In the case of the heart and ear, we used our own data obtained by microscopic examination of tissue sections. Since perfusion could in some cases limit the transport rate, halftimes were estimated for all of the tissues based on the concept of flow-limited distribution kinetics. In some cases, diffusion in the extracellular space could limit the inulin uptake rate so that estimates for diffusion-limited halftimes were also made. These estimates could then be compared with the measured halftimes to see which process seemed to fit the data best. In most cases capillary permeability appeared to be the rate-limiting step, and the estimates of this parameter ranged from 0.12 × 10 −5 cm sec −1 for skeletal muscle capillaries to 0.59 × 10 −1 for the capillaries in the ear. The values obtained for heart and lung capillaries compared well with those obtained in this laboratory using isolated Ringer perfused organs.

Permeability limitation in estimation of local brain blood flow with [14C]antipyrine.

Influence of capillary permeability on local cerebral blood flow (LCBF) estimated by the autoradiograhpic diffusible-indicator method was analyzed by computer simulation. Its influence increases with increasing flow. With normal perfusion rates in gray matter, capillary permeability coefficient x surface area (PS value) must exceed 0.12 cm3-s(-1)-g(-1) for estimated LCBF to attain 95% of true values in all structures. In white matter, with its lower perfusion rates, the PS value must exceed 0.035 cm3-s(-1)-g(-1) for equivalent accuracy. [14C]antipyrine, widely used in the LCBF technique, has a PS value below these values and leads to undersestimation of LCBF. Experimental studies in cats in which LCBF was measured with either [14C]antipyrine or the freely diffusible, radioactive gas, [131I]trifluoroiodomethane, demonstrated consistently lower estimates of LCBF with [14C]antipyrine than with the gas; the deviations in the various cerebral structures approximated those predicted by the theoretical analyses. These results suggest that the uptake of [14C]antipyrine by cerebral tissues is diffusion limited as well as flow limited, and it therefore is not an ideal tracer for the autoradiographic LCBF technique.

Determinants of peritubular capillary fluid uptake in hydropenia and saline and plasma expansion.

Hydrostatic (HPc) and oncotic (phic) pressures within the peritubular capillary, tubular pressure (Pt), nephron filtration rate, and plasma flow, and proximal fractional and absolute reabsorption (APR) were measured in anesthetized rats during hydropenia and plasma and saline expansion. Net interstitial pressure (phii-HPi) was estimated from subcapsular hydrostatic and oncotic pressures during saline expansion and these data were applied to a mathematical model of peritubular capillary fluid uptake to determine the profile of effective reabsorption pressure (ERP) with distance (x*) alongthe capillary and calculate the peritubular capillary permeability coefficient (LpAr). ERPX* = (PHIC MINUS HPC)X* MINUS (PHII MINUS HPi) and APR = ERPX*LpAr. During saline expansion phii minus HPi was -12.1 plus or minus 0.8 mmHg and ERP,3.8 mm. The LpAr was 0.07 nl/s per g KW per mmHg, and this value was applied to hypropenia and plasma expansion to determine ERP and phii minus HPi. The phiiminus HPi was +6.0 and +5.0 mmHg, respectively, and ERP was 4.1 and 3.5 mmHg. Efective reabsorptive pressure remained positive along x* in all states, and phii minus HPi correlated best changes in phic and poorly with changes in efferent plasma flow. The APR did not correlate with either calculated phii minus HPi or the transepithelial driving pressure, Pt + phii minus HPi.

Relationship of peripheral venous hematocrit to brain hematocrit.

ArticleRelationship of peripheral venous hematocrit to brain hematocrit.V A Levin, and J I AusmanV A Levin, and J I AusmanPublished Online:01 Apr 1969https://doi.org/10.1152/jappl.1969.26.4.433MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByWhole-brain perfusion mapping in mice by dynamic BOLD MRI with transient hypoxia28 July 2022 | Journal of Cerebral Blood Flow & Metabolism, Vol. 27Arterial versus Total Blood Volume Changes during Neural Activity-Induced Cerebral Blood Flow Change: Implication for BOLD fMRI20 December 2006 | Journal of Cerebral Blood Flow & Metabolism, Vol. 27, No. 6Magnetic resonance cerebral metabolic rate of oxygen utilization in hyperacute stroke patients29 January 2003 | Annals of Neurology, Vol. 53, No. 2Cerebral blood flow and vasodilatory capacity in anemia secondary to chronic renal failureKidney International, Vol. 61, No. 2Quantitative measurements of cerebral metabolic rate of oxygen utilization using MRI: a volunteer study1 January 2001 | NMR in Biomedicine, Vol. 14, No. 7-8Quantitative Measurements of Cerebral Blood Oxygen Saturation Using Magnetic Resonance Imaging31 August 2016 | Journal of Cerebral Blood Flow & Metabolism, Vol. 20, No. 8Effect of hemodilution on RBC velocity, supply rate, and hematocrit in the cerebral capillary networkAntal G. Hudetz, James D. Wood, Bharat B. Biswal, Ines Krolo, and John P. Kampine1 August 1999 | Journal of Applied Physiology, Vol. 87, No. 2Effects of acute normovolemic hemodilution onT2* - weighted images of rat brainMagnetic Resonance in Medicine, Vol. 40, No. 6Feasibility of simultaneous and sequentially administered dual tracer protocols for measurement of regional cerebral haematocrit using positron emission tomography5 December 2000 | Physics in Medicine and Biology, Vol. 35, No. 2Cerebral Vascular Volume after Repeated Ischemic Insults in the Gerbil: Comparison with Changes in CBF and Brain Edema29 June 2016 | Journal of Cerebral Blood Flow & Metabolism, Vol. 9, No. 2Quantitation of Blood-Brain Barrier PermeabilityHematocrit in Cerebral Capillaries and Veins under Control and Ischemic Conditions28 June 2016 | Journal of Cerebral Blood Flow & Metabolism, Vol. 7, No. 6The effects of galactosamine-induced hepatic failure upon blood-brain barrier permeabilityHepatology, Vol. 7, No. 3An In Vivo Kinetic Model with L-[ 35 S]Methionine for the Determination of Local Cerebral Rates for Methionine Incorporation into Protein in the RatJournal of Neurochemistry, Vol. 48, No. 2Transport of sodium from blood to brain in ischemic brain edema.Stroke, Vol. 18, No. 1Regional Cerebral Blood Volume and Hematocrit Measured in Normal Human Volunteers by Single-Photon Emission Computed Tomography29 June 2016 | Journal of Cerebral Blood Flow & Metabolism, Vol. 5, No. 2In vivo Measurement of Regional Cerebral Haematocrit Using Positron Emission Tomography29 June 2016 | Journal of Cerebral Blood Flow & Metabolism, Vol. 4, No. 3Regional Brain Blood Flow, Blood Volume, and Haematocrit Values in the Adult Rat29 June 2016 | Journal of Cerebral Blood Flow & Metabolism, Vol. 3, No. 2Transport of α-Aminoisobutyric Acid across Brain Capillary and Cellular Membranes29 June 2016 | Journal of Cerebral Blood Flow & Metabolism, Vol. 3, No. 1The application of brain capillary permeability coefficient measurements to pathological conditions and the selection of agents which cross the blood-brain barrier17 July 2015 | Journal of Pharmacokinetics and Biopharmaceutics, Vol. 4, No. 6Cerebral microvascular volume flow: Its measurement and responses to hemorrhagic hypotension in the ratMicrovascular Research, Vol. 8, No. 2Disorders of the Cerebral CirculationCan Plasma Skimming or Inconstancy of Regional Hematocrit Introduce Serious Errors in Regional Cerebral Blood Flow Measurements or Their Interpretation?Stroke, Vol. 3, No. 3Erythrocyte velocity and fluorescein transit time in the cerebral microcirculation of macroglobulinemic mice: Differential effect of a hyperviscosity syndrome on the passage of erythrocytes and plasmaMicrovascular Research, Vol. 3, No. 3Blood Volume, Hematocrit and Pressure Relationships in the Isolated Perfused Dog BrainStroke, Vol. 1, No. 4 More from this issue > Volume 26Issue 4April 1969Pages 433-7 https://doi.org/10.1152/jappl.1969.26.4.433PubMed5775328History Published online 1 April 1969 Published in print 1 April 1969 Metrics

PERMEABILITY OF MAMMALIAN HEART CAPILLARIES TO SUCROSE AND INULIN.

Rabbit hearts were perfused with modified Ringer's solution containing 10 g sucrose or inulin per liter. After various perfusion times, ventricular samples were analyzed for their content of the respective saccharide. The tissue content of sucrose rose to half its apparent maximum value in approximately 6 sec; the corresponding time for inulin was approximately 90 sec. We concluded that at the high perfusion rates employed (40 ml/min per heart) inulin permeation is limited by passage across the capillary membrane and is practically unaffected by perfusion rate and interstitial diffusion, while sucrose permeation is limited partly by passage across the capillary membrane and partly by perfusion rate. We calculated capillary permeability coefficients of 0.4 x 10–5 cm/sec for inulin and 11 x 10–5 cm/sec for sucrose.