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Biomedical subjects

J B Bassingthwaighte

Publications and source records attributed to J B Bassingthwaighte.

At least 91 records · Page 5Linked to original sources
PubMed1985

Modeling of transendothelial transport.

Capillary-tissue exchange of inert hydrophilic solutes in the heart occurs through aqueous channels, the clefts between endothelial cells (ECs). For adenosine (and other vasoactive agents and substrates), there is also transport across the plasmalemma of the ECs. The multiple-indicator dilution technique comparing tracer adenosine flux with that of 9-beta-D-arabinofuranosylhypoxanthine (an analog that is not transported by the nucleoside carrier) can be used to estimate the conductance of the facilitated transport mechanism, which is equivalent to a permeability-surface area product. Analysis by using a model of exchanges among capillary, EC, interstitium, and myocardial cells suggests that the abluminal surface of the ECs is also highly permeable to adenosine. The inference is that ECs may be an important component of a system for adenosine exchange and regulation in the heart.

Adenosine↗
PubMed1984

Diffusional arteriovenous shunting in the heart.

Previous indicator dilution experiments in isolated blood-perfused dog hearts suggested that there was intramyocardial diffusional shunting of water relative to a flow-limited solute, antipyrine. Two sets of studies have been done to assess the importance of this shunting, since it implies the possibility of a diffusional bypass for oxygen and other substances, which may be important in ischemia. Nonconsumed tracers were used to show the phenomenon. In the first set, bolus injections of 133Xe dissolved in saline were made into the coronary inflow and the tracer content of the organ recorded by an external gamma detector. The initial Xe washout was disproportionately rapid at low flows, and the late phase was also relatively retarded. In the second set, boluses of cool saline containing indocyanine green were injected into the coronary arterial inflow while coronary sinus outflow dilution curves were recorded via a thermistor and a dye densitometer over a wide range of flows. The thermal curves showed emergence of heat preceding the dye; the degree of precession was much greater at low flows, and, unlike the dye curves, the thermal dilution curves showed dramatic differences in shape at different flows. A model for diffusional countercurrent exchange shows similar changes in residue curves and outflow dilution curves. The conclusion is that there is diffusional shunting of small lipid-soluble molecules whose diffusion coefficients in tissue are high. While the shunting of heat is great, the shunting of soluble gases will not be large and that of normal substrates will be negligible.

Animals↗
PubMed1984

Sensitivity functions in the estimation of parameters of cellular exchange.

The analysis of multiple-indicator dilution curves to estimate the rates of transport of ions and substrates across the sarcolemma of myocardial cells requires the formulation of models for the blood-interstitial fluid-cell exchanges. The fitting of models to the sets of experimental data is dependent on acquiring a large enough data set, in one physiological state, that there is at least as much information in the data as there are unknown model parameters to be determined. Inasmuch as data are necessarily noisy, redundancy of data and overdetermination of the unknowns are highly desirable. Sensitivity functions are useful in demonstrating which portions of the data relate to which unknown parameters. They are also useful in adjusting model parameters to fit the model to the data, and therefore in parameter evaluation.

Biological Transport↗
PubMed1983

Uphill sodium transport driven by an inward calcium gradient in heart muscle.

Heart cells were loaded with sodium by treatment with toxic doses of acetyl strophanthidin. After this treatment, an increase in extracellular calcium resulted in a transient net outward sodium flux against its electrochemical gradient and in net cellular uptake of calcium. It is concluded that the free energy for the net outward sodium movement was derived from the increased calcium gradient and that these ion movements took place through the sodium-calcium exchange. While in the normal physiological state the sodium-calcium exchange produces calcium extrusion from the cell, these experiments demonstrate its reversibility.

Animals↗
PubMed1983

Plasma-soluble marker for intraorgan regional flows.

Measurement of regional plasma flow is needed to quantitate the delivery of substrates and drugs to cells. For estimating regional plasma flows an ideal deposition marker should be 100% extracted during transorgan passage and retained until local tissue concentrations can be measured. To escape quickly, the tracer must penetrate capillary endothelial cells rapidly. To be retained, it must bind or be transformed or accumulated by cells. Desmethylimipramine (DMI, mol wt 266.3), a norepinephrine reuptake inhibitor, is suitable. On injection of [3H]DMI and 131I-albumin simultaneously into the coronary artery inflow of isolated Ringer-perfused rabbit hearts at 37 degrees C, extractions were greater than 99% at plasma flows (Fs) up to 2.3 ml X g-1 X min-1 and greater than 94% with Fs up to 5.1. Retention at Fs less than 2.3 averaged 99.0 +/- 0.55% (SD, n = 6) at 0.5 min, 98.4 +/- 0.5% at 1 min, and 96.6 +/- 1.1% or greater than 95% at 3 min. Retentions were similar in two dog hearts in situ. With Fs greater than 3 ml X g-1 X min-1, there was greater escape, 4.2 +/- 2.7% at 1 min and 6.8 +/- 4.2% at 3 min. The fractional escape rates of loss at 2 min or more were about 1%/min at all flows, suggesting that the spatial profiles of deposition did not change thereafter. Thus DMI is nearly ideal as a "molecular microsphere."

Animals↗
PubMed1982

Influence of parathyroid state on calcium uptake in bone.

The exchange of calcium and strontium ions in bone was studied in control dogs, dogs made hypocalcemic by parathyroidectomy, and dogs rendered hypercalcemic by injection of parathyroid hormone. After injections of tracer into the tibial nutrient artery, extraction of tracer during transcapillary passage was measured and expressed as a fraction of 1. Extraction over the first 3 min in normal dogs was 0.46 +/- 0.09 (n = 6), in hypocalcemic dogs it was increased to 0.53 +/- 0.07 (n = 6), and in hypercalcemic dogs it was decreased to 0.39 +/- 0.07 (n = 5). Subsequent washout was less rapid than normal in hypoparathyroid dogs and more rapid than normal in hyperparathyroid dogs. We conclude from this that the immediate volume of distribution in bone (or the number of available binding sites) for strontium diminishes as the parathyroid hormone level increases.

Animals↗
PubMed1982

Synthesis and use of radio cobaltic EDTA as an extracellular marker in rabbit heart.

A new gamma-labeled marker for extracellular space is the cobaltic form of 58Co-ethylenediaminetetraacetic acid (58Co-EDTA). The cobaltic ion has a much higher affinity for EDTA than the cobaltous ion; it is prepared as a potassium salt, K+(58Co3+-EDTA4-), and is apparently biologically inert. Testing by equilibration in intact rabbits and comparing the myocardial content with that of [14C]sucrose give values of the volume of distribution in the myocardium of 0.294 +/- 0.052 ml/g for 58Co-EDTA and 0.303 +/- 0.051 ml/g for [14C]sucrose (SD, n = 130, for two hearts), with the ratios of 58Co-EDTA/sucrose averaging 0.973 +/- 0.043 (n = 130). The average value of the extracellular fluid measured in isolated rabbit interventricular septum using Co-EDTA was 0.51 +/- 0.05 ml/g (SD, n = 16) and 0.46 +/- 0.04 ml/g using [14C]sucrose as an extracellular fluid space (ECF) marker. Flushing with a high concentration of nontracer Co-EDTA does not reveal any release from binding sites. The gamma-energy (811 KeV), long half-life (71.4 days), stability, and lack of binding to tissue components make 58Co-EDTA a useful marker for ECF.

Animals↗
PubMed1982

Exchange of potassium and strontium in adult bone.

The kinetics of exchange of strontium (85Sr) and potassium (42K) were studied in the mid-tibial cortical bone of 37 adult dogs. After injection of these two tracer cations and tracer-labeled albumin into the tibial nutrient artery, two types of observations were made: 1) collection of sequential venous samples to provide the outflow indicator-dilution curves and to calculate the extraction and retention at early times; and 2) detection of energy-selected gamma emissions via a detector over the tibia to give the time course of content of 42K and 85Sr in the tibia. Extractions of K+ and Sr2+ were 50 and 60% during a single transcapillary passage. More Sr2+ than K+ was retained in the first minutes. Their rates of washout over a 3-h period were similar. The interpretation is that the rate of uptake at extravascular sites is faster for Sr2+ than for K+, as is the rate of release, and that the extravascular volume of distribution for Sr2+ (adsorption sites in the interstitium or on bone) is much larger than that for K+ (intracellular).

Animals↗
PubMed1980

Transcapillary exchange and retention of fluoride, strontium, EDTA, sucrose, and antipyrine in bone.

The extractions of 85Sr2+, 18F-, sucrose-14C, EDTA-51Cr, and antipyrine-14C in bone were determined by the multiple indicator-dilution method. Fluoride and strontium extractions were 18 to 70% during a single transcapillary passage, and those of EDTA and sucrose were from 11 to 59%, whereas extraction of antipyrine was 87%. Injections of 85Sr2+ and 18F- made when perfusion was done alternately with blood and plasma resulted in similar fractional extractions. When flow and extraction were measured simultaneously, extraction was related inversely to flow.

Animals↗
PubMed1980

Anatomy of the microvasculature of the tibial diaphysis of the adult dog.

UNLABELLED: The microvasculature in the cortex and marrow of the adult canine tibial diaphysis was filled with the silicone elastomer Microfil, the bone was decalcified, and the water was replaced with methylsalicylate to permit three-dimensional visualization of the microvascular arrangements. The tibial nutrient artery was seen to supply the marrow and the cortex via parallel, independent sets of arterioles and terminal capillary beds. No arteriolar or capillary anastomoses were observed linking these separate beds. The major portion of the venous drainage was found to be via small venules through the cortex into periosteal veins. Many small venules draining the medullary capillaries penetrated the cortex, and there were a few larger emissary veins, including the nutrient vein. Because the marrow and cortex have separate capillary beds in parallel, microsphere deposition should be appropriate for estimating the regional blood flows. CLINICAL RELEVANCE: The results of this study should be of concern to surgeons who perform whole diaphyseal bone replacements, as the effluent venous vessels are important in re-establishing the circulation by microsurgical methods.

Animals↗
PubMed1978

Diffusion of water in cat ventricular myocardium.

The rates of diffusion of tritiated water (THO) and [14C]sucrose across cat right ventricular myocardium were studied at 23 degrees C in an Ussing-type diffusion cell, recording the time-course of increase in concentration of tracer in one chamber over 4--6 h after adding tracers to the other. Sucrose data were fitted with a model for a homogeneous sheet of uneven thickness in which the tissue is considered to be an array of parallel independent pathways (parallel pathway model) of varying length. The volume of the sucrose diffusion space, presumably a wholly extracellular pathway, was 23% of the tissue or 27.4 +/-1.7% (mean +/- SEM; n=11) of the tissue water. The effective intramyocardial sucrose diffusion coefficient, D8, was 1.51 +/- 0.19 X 10(-6)cm2.s-1 (n=11). Combining these data with earlier data, D8 was 22.6 +/- 1.1% (n=95) of the free diffusion coefficient in aqueous solution D degrees 8. The parallel pathway model and a dead-end pore model, which might have accounted for intracellular sequestration of water, gave estimates of DW/D degrees W (observed/free) of 15%. Because hindrance to water diffusion must be less than for sucrose (where D8/D degrees 8=22.6%), this showed the inadequacy of these models to account simultaneously for the diffusional resistance and the tissue water content. The third or cell-matrix model, a heterogeneous system of permeable cells arrayed in the extracellular matrix, allowed logical and geometrically reasonable interpretations of the steady-state data and implied estimates of DW in the cellular and extracellular fluid of approximately 25% of the aqueous diffusion coefficient.

Animals↗
PubMed1977

Calcium diffusion in transient and steady states in muscle.

Rates of diffusion through the extracellular space of thin sheets of myocardium from the right ventricular outflow tract of kittens were estimated at 23 degrees C for 45Ca2+ and an inert reference tracer, [14C]sucrose. The myocardial sheets were mounted in an Ussing chamber and equilibrated with Tyrode solution with varied calcium concentrations, Cao. The tracers were added to one side and their concentrations on the other side measured at 5-15-min intervals for 6 h. The apparent tracer diffusion coefficient for sucrose was 1.11 +/- 0.06 X 10(-6) cm2s-1 (mean +/- SEM, n = 74), 22% of the free diffusion coefficient; the lag time before reaching a steady state provided estimates of the intratissue volume of distribution or diffusion space of 0.41 +/- 0.15 ml/ml tissue (n = 74), a value compatible with expectations for extracellular fluid space. Over the range of Cao from 0.02 to 9.0 mM, the intratissue apparent diffusion coefficient for Ca, DCa, averaged 1.65 +/- 0.10 X 10(-6) cm2s-1, n = 74, which is 21% of the free DoCa, and was not influenced by Cao. Because transsarcolemmal Ca permeation is slow, DCa is the diffusion coefficient in the extracellular region. The paired ratios DCa/Ds averaged 1.32 +/- 0.05 (n = 67) for all levels of Cao but at physiologic or higher Cao averaged 1.45 +/- 0.07 (n = 39), close to the ratio of free diffusion coefficients, 1.53. Equations distinguishing transient from steady state diffusion were fitted to the data, showing that the apparent distribution volume of "binding sites" external to the diffusion pathway diminished at higher Cao in a fashion suggesting that a least two different Ca2+ binding sites were present.

Animals↗