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J B Bassingthwaighte

Publications and source records attributed to J B Bassingthwaighte.

At least 73 records · Page 4Linked to original sources
PubMed1989

Blood-tissue exchange via transport and transformation by capillary endothelial cells.

The escape of solutes from the blood during passage along capillaries in heart and skeletal muscle occurs via diffusion through clefts between endothelial cells and, for some solutes, via adsorption to or transport across the luminal plasmalemma of the endothelial cell. To quantitate the rates of permeation via these two routes of transport across capillary wall, we have developed a linear model for transendothelial transport and illustrated its suitability for the design and analysis of multiple simultaneous indicator dilution curves from an organ. Data should be obtained for at least three solutes: 1) an intravascular reference, albumin; 2) a solute transported by endothelial cells; and 3) another reference solute, of the same molecular size as solute 2, which neither binds nor traverses cell membranes. The capillary-tissue convection-permeation model is spatially distributed and accounts for axial variation in concentrations, transport through and around endothelial cells, accumulation and consumption within them, exchange with the interstitium and parenchymal cells, and heterogeneity of regional flows. The upslope of the dilution curves is highly sensitive to unidirectional rate of loss at the luminal endothelial surface. There is less sensitivity to transport across the antiluminal surface, except when endothelial retention is low. The model is useful for receptor kinetics using tracers during steady-state conditions and allows distinction between equilibrium binding and reaction rate limitations. Uptake rates at the luminal surface are readily estimated by fitting the model to the experimental dilution curves. For adenosine and fatty acids, endothelial transport accounts for 30-99% of the transcapillary extraction.

Animals↗
PubMed1988

An efficient method for smoothing indicator-dilution and other unimodal curves.

A mathematical function has been developed for approximating unimodal functions, particularly those which are non-Gaussian, skewed, and incomplete. It is useful as an alternative to cubic splines in smoothing noisy experimental data. Particular applications are to indicator-dilution curves and probability density functions of varied form. In its Fortran implementation, SMOEX, it is computationally inexpensive compared to standard cubic spline smoothing routines and requires less storage to preserve the smoothed function for retrieval or interpolation.

Animals↗
PubMed1988

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.

Animals↗
PubMed1987

Through the microcirculatory maze with machete, molecule, and minicomputer (1986 Alza lecture).

This is a personal historical essay on meanderings through the jungle of the microcirculatory swamp. Because one pretends that the wandering was purposefully exploratory, a few guideposts are placed at positions where one could discern blaze-marks from earlier wanderers, and the path cut a little wider along some of the routes that may be enjoyed by investigators wanting to put their blazes along more distant paths. Naturally, one starts by coming up the broad rivers, then branching into the little streams. Each of us chooses to seek a different "mother lode," up a different stream.

Animals↗
PubMed1987

Validity of microsphere depositions for regional myocardial flows.

Due to the particulate nature of microspheres, their deposition in small-tissue regions may not be strictly flow dependent. To evaluate the importance of rheological and geometric factors and random error, their deposition densities in small regions of rabbit hearts were examined in comparison with those of a new "molecular microsphere," 2-iododesmethylimipramine (IDMI), whose high lipid solubility allows it to be delivered into tissue in proportion to flow, and whose binding in tissue prevents rapid washout. 141Ce- and 103Ru-labeled 16.5-micron spheres in one syringe and [125I]- and [131I]DMI in another syringe were injected simultaneously into the left atrium of open-chest rabbits, while obtaining reference blood samples from the femoral artery. Hearts were removed 1 min after injection, cut into approximately 100 pieces averaging 54 mg, and the regional deposition densities calculated for each tracer from the isotopic counts. Correlations between the differently labeled microspheres were r greater than 0.95 and for the two IDMIs were greater than 0.98. Scatter plots of sphere densities vs. IDMI densities showed that differences between microspheres and IDMI had substantial scatter, 0.87 less than r less than 0.96 and were not random. Microsphere depositions tended to be lower than IDMI depositions at low flows and higher at high flows. The tendency for spheres to be deposited preferentially in high-flow regions may be explained by a bias at bifurcations toward entering the branch with higher flow and secondarily toward entering those branches that are straighter. We conclude that microspheres are generally adequate for estimating regional flows but suffer systematic error when the regions of interest are supplied via arteries of diameters only a few times those of the microspheres.

Animals↗
PubMed1987

Strides in the technology of systems physiology and the art of testing complex hypotheses.

Scientific understanding in physics or physiology is based on models or theories devised to describe what is known, within the limits imposed by observation error. Carefully integrated models can be used for prediction, and the inferences assessed via further experiments designed to test the adequacy of the theory summarizing the state of knowledge. This is the systems approach, the basis of theoretical physiology; the models, like those of theoretical physics, should be firmly based on fundamental reproducible observations of a physical or chemical nature, held together with the principles of mathematics, logic, and the conservation of mass and energy. Modern computing power is such that comprehensive models can now be constructed and tested. For this approach data sets should include as many simultaneously obtained items of information of differing sorts as possible to reduce the degrees of freedom in fitting models to data. By taking advantage of large memories and rapid computation, modular construction techniques permit the formulation of multimodels covering more than a single hierarchical level, and thereby allow the investigator to understand the effects of controllers at the molecular level on overall cell or organism behavior. How does this influence the research and teaching practices of physiology? Because the computer also allows a new type of collaboration involving the networking of ideas, data bases, analytical techniques, and experiment designing, investigators in geographically distributed individual laboratories can plan, work, and analyze in concert. The prediction from this socioscientific model is therefore that networked computer-based modeling will serve to coalesce the ideas and observations of enlarging groups of investigators.

Models, Biological↗
PubMed1986

Indicator dilution estimation of capillary endothelial transport.

Mechanisms of transport of substrates and small solutes across the endothelial lining of the capillaries include passive diffusion (through clefts between cells or across the plasmalemma) and transporter-mediated flux across the plasmalemma. Because the transport rates are typically high, the multiple indicator dilution technique is usually the method of choice, as it provides the high temporal resolution required. In the simplest version of this technique, a test solute is injected into the inflow simultaneously with reference solutes that are restricted to intravascular and extracellular space. Interpretation of the resulting data requires models; the most precise approach is to fit the model solutions to the data. When appropriate combinations of indicators and sufficiently complex models (those that account for flow heterogeneity, arteriovenous gradients, passive and saturable transport, reaction, and diffusion in multicomponent systems) are used the transporters can be characterized. Features such as the rapidity of intracellular reaction can also be revealed by this technique.

Adenosine↗
PubMed1986

Multiple tracer dilution estimates of D- and 2-deoxy-D-glucose uptake by the heart.

Permeability-surface area products of the capillary wall, PSc, and the myocyte sarcolemma, PSpc, for D-glucose and 2-deoxy-D-glucose were estimated via the multiple indicator-dilution technique in isolated blood-perfused dog and Tyrode-perfused rabbit hearts. Aortic bolus injections contained 131I-albumin (intravascular reference), two of three glucoses: L-glucose (an extracellular reference solute), D-glucose, and 2-deoxy-D-glucose. Outflow dilution curves were sampled for 1-2.5 min without recirculation. The long duration sampling allowed accurate evaluation of PSpc by fitting the dilution curves with a multiregional axially distributed capillary-interstitial fluid-cell model accounting for the heterogeneity of regional flows (measured using microspheres and total heart sectioning). With average blood flow of 1.3 ml . g-1 . min-1, in the dog hearts the PSc for D-glucose was 0.72 +/- 0.17 ml . g-1 . min-1 (mean +/- SD; n = 11), and PSpc was 0.57 +/- 0.15 ml . g-1 . min-1. In the rabbit hearts with perfusate flow of 2.0 ml . g-1 . min-1 (n = 6), PSc was 1.2 +/- 0.1 and PSpc was 0.4 +/- 0.1 ml . g-1 . min-1. PSc for 2-deoxy-D-glucose was about 4% higher than for D-glucose and L-glucose in both preparations. Relative to L-glucose, there was no measurable transendothelial transport of either dextroglucose, indicating that transcapillary transport was by passive diffusion, presumably via the clefts between cells. The technique allows repeated measurements of D-glucose uptake at intervals of a few minutes; it may therefore be used to assess changes in transport rates occurring over intervals of several minutes.

Animals↗
PubMed1986

Endothelial cell uptake of adenosine in canine skeletal muscle.

The vascularly isolated muscles in the hindlimbs of five dogs were perfused with an oxygenated physiological salt solution. The extractions of adenosine and of a nontransported analogue of adenosine, 9-beta-D-arabinofuranosyl hypoxanthine (AraH), were determined by the single-pass indicator-dilution technique. A bolus containing [125I]albumin (reference tracer), [14C]adenosine, and [3H]AraH was injected into the artery while samples of venous effluent were collected over the next minute. This injection was repeated with dipyridamole (10(-5) M) in the perfusate. Early extractions of AraH (EAra) and adenosine (EAdo) under control conditions were 48 +/- 4 and 80 +/- 4%, respectively. In the presence of dipyridamole, EAra was unchanged (47 +/- 5) while EAdo decreased to 45 +/- 7%. Since early extraction reflects primarily the barrier posed by endothelial cells, these results demonstrate significant endothelial uptake of adenosine. Analysis of these data using a mathematical model of blood-tissue exchange indicates that, under the conditions of these experiments, at least 78% of the adenosine taken up by skeletal muscle entered endothelial cells.

Adenosine↗
PubMed1986

Terminology for mass transport and exchange.

Virtually all fields of physiological research now encompass various aspects of solute transport by convection, diffusion, and permeation across membranes. Accordingly, this set of terms, symbols, definitions, and units is proposed as a means of clear communication among workers in the physiological, engineering, and physical sciences. The goal is to provide a setting for quantitative descriptions of physiological transport phenomena.

Animals↗
PubMed1986

Myocardial extraction and retention of 2-iododesmethylimipramine: a novel flow marker.

An ideal deposition marker for measuring regional flow is completely extracted during transcapillary passage and permanently retained. beta-Labeled desmethylimipramine ([3H]DMI) is a nearly ideal flow marker. To obtain gamma- and positron-emitting markers, DMI was iodinated to form 2-iododesmethylimipramine (IDMI). IDMI was more lipophilic than DMI. In isolated saline-perfused rabbit hearts its transorgan extraction was greater than 99%; and retention was greater than 98% at 5 min at mean flows of up to 3.5 ml X g-1 X min-1. During washout, the fractional escape rate was less than 0.1% X min-1 and was independent of flow. In isolated blood-perfused rabbit hearts, extraction was still 98%, but retention was as low as 86% after 5 min at a flow of 1.6 ml X g-1 X min-1. The fractional escape rate was up to 2% X min-1 but independent of flow. Despite this relatively rapid loss, regional IDMI deposition remains proportional to regional flow for many minutes. Therefore IDMI is useful as an externally detectable "molecular microsphere" for myocardial flow imaging in vivo.

Animals↗
PubMed1985

A comparison of ascorbate and glucose transport in the heart.

Multiple indicator-dilution experiments were done to compare the transcapillary exchange of tracer amounts of L-[14C]ascorbate and D-[3H]glucose (against an intravascular reference 131I-albumin) in Ringer-perfused (5 mM glucose) isolated rabbit hearts. The indicator-dilution curves for the two were virtually superimposed over the first 40-80 s. Estimates of the capillary permeability-surface area products, PSc, were the same, 2.3 +/- 0.7 (SD) ml X g-1 X min-1 (n = 18), in accord with the coincidence of their instantaneous extractions. The similarity of glucose and ascorbate permeabilities is explained by the similarity in molecular weights and passive diffusivity, their lipophobic nature, and the paucity of carrier-mediated endothelial transport for either molecule. The data were analyzed via a model composed of aggregates of spatially distributed capillary-tissue units (capillary blood, interstitium, myocytes) accounting for the heterogeneity of regional flows. The interstitial volumes in this preparation are enlarged, 0.30 +/- 0.04 ml/g. There is substantial entry into myocardial cells, the cell permeability-surface area products being approximately 2-3 ml X g-1 X min-1 for ascorbate and glucose. The estimated volumes of interstitial and intracellular space, 0.30 and 0.47 ml X g-1 X min-1, reflect interstitial edema and are very close to measured values, giving reassurance concerning the methods of modeling analysis.

Animals↗
PubMed1985

Polarographic measurement of ascorbate washout in isolated perfused rabbit hearts.

To study the myocardial washout of ascorbate, the applicability of polarographic detection of ascorbate ions by a platinum electrode (sensitive area 0.03 mm2) was investigated, in both a calibration setup (sampling flow along the electrode: 100 microliter X s-1) and isolated, retrogradely perfused rabbit hearts. In the calibration setup at pH 7.4, the sensitivity of the electrode was 70 microA/mol. This sensitivity increased moderately with increasing pH (13%/unit pH) and increasing sampling flow rate (14% at an increase from 100 to 150 microliter X s-1). In the isolated hearts, ascorbate infused into the aorta was detected in a right ventricular drain by the electrode as well as by the use of 14C-labeled ascorbate. Both recorded time courses were similar except for a scaling factor dependent on flow velocity. During continuous infusion the arteriovenous difference of ascorbate was 2 +/- 2% (SD), indicating a relatively low consumption of ascorbate by the isolated heart. We conclude that polarographic measurement of ascorbate in the coronary effluent of an isolated rabbit heart can be performed on-line and relatively easily.

Animals↗
PubMed1985

Stability of heterogeneity of myocardial blood flow in normal awake baboons.

Regional myocardial blood flow has been thought to be relatively uniform, in accord with the singular function of myocardial cells. However, considerable spatial heterogeneity has been observed in the hearts of anesthetized animals and in isolated hearts. Studies were undertaken in a total of 13 baboons. Eleven were awake, healthy animals sitting in chairs at rest or feeding, some performed mild leg exercise (wheel turning), and others were subjected to whole body heating; two were anesthetized, methodological controls. Microspheres (15 +/- 3 micron diameter, 0.5 X 10(6)/kg body weight) were injected via a catheter into the apex of the left ventricle while arterial blood was sampled at a constant rate for calculating cardiac output. Microspheres with different labels were injected at six intervals of 20 minutes to several hours. On sacrifice, the hearts were sectioned into 204 locatable pieces (left ventricle, 168; right ventricle, 27; and atria, 9). Average resting myocardial flow was 2.1 +/- 0.2 ml/g per min (mean +/- SD, n = 11). Left and right ventricles and atria comprised 70 +/- 2% (n = 13), 20 +/- 2%, and 10 +/- 2% respectively of the total heart mass while receiving 80 +/- 3%, 16 +/- 2%, and 4 +/- 2% of the total myocardial flow. Thus, mean left ventricular flow was 114 +/- 5% of the average for the whole heart, right ventricular flow was 81 +/- 13%, and atrial flow was 41 +/- 13%. Myocardial flow heterogeneity was marked; in left ventricle, regional flows ranged from one-third to two times the mean, the relative dispersion (= standard deviation/mean) of regional flows, corrected for methodological scatter and temporal variation, was 0.33 +/- 0.06 (n = 67) in the whole heart, 0.26 +/- 0.07 in left ventricle, 0.32 +/- 0.11 in right ventricle, and 0.22 +/- 0.19 in the atria. The pattern of regional flows in each heart tended to remain stable with time. In each piece averaged over time, the relative dispersion due to temporal heterogeneity was 0.11 +/- 0.03 (n = 2040) in the whole heart, 0.09 +/- 0.03 in the left ventricle, 0.15 +/- 0.05 in the right ventricle, and 0.23 +/- 0.06 in the atria. The conclusion is that the degree of spatial heterogeneity of local myocardial flows in conscious primates is similar to that of anesthetized animals and isolated hearts, and is much greater than that due to temporal fluctuations.

Animals↗
PubMed1985

Capillary transport of adenosine.

We tested the hypothesis that capillary exchange of adenosine is influenced by the ability of endothelial cells (ECs) to take up adenosine. Triple-indicator diffusion experiments were performed by injecting [14C]adenosine, [3H]9-beta-D-arabinofuranosylhypoxanthine ( [3H]araH), and radioiodinated serum albumin (RISA) into the arterial perfusate of isolated nonworking guinea pig hearts. Tracer appearance in venous effluent was observed over time. The early extraction of [14C]adenosine was much higher than that of [3H]araH. Extracted [3H]araH returned to the vascular space, but [14C]adenosine did not. Quantitative analysis of the curves by using a mathematical model indicates that approximately half of the extracted adenosine enters ECs and is metabolized. The remainder enters the interstitium and is taken up by myocytes, ECs, or other cells and is metabolized. We conclude that uptake of adenosine by ECs represents a significant influence on the capillary exchange of adenosine.

Adenosine↗