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J B Bassingthwaighte

Publications and source records attributed to J B Bassingthwaighte.

At least 55 records · Page 3Linked to original sources
PubMed1992

Capillary endothelial transport of uric acid in guinea pig heart.

Much of the adenosine formed in the heart is degraded by endothelial enzymes to uric acid, which is exported across the coronary capillary endothelial cell membrane before renal excretion. Because previous experiments suggested that cell permeability for uric acid is either very high (similar to water) or very low, multiple indicator-dilution experiments were carried out to distinguish between the two possibilities. An intravascular reference tracer, 131I-labeled albumin, and an extracellular reference tracer, L-[3H]glucose, were injected together with [14C]uric acid as a bolus into the coronary inflow, while fractionating the venous outflow for 90 s. Recovery of injected uric acid averaged 99.0 +/- 2.9% (mean +/- SD, n = 12) that of L-glucose. Peak capillary extraction of L-glucose and uric acid averaged 0.38 +/- 0.032 and 0.42 +/- 0.035 (P less than 0.005) compared with albumin. Except at the peaks, the dilution curves for [14C]uric acid and L-[3H]glucose coincided closely, indicating that little uric acid was transported into cells. The dilution curves were analyzed using an axially distributed, multipathway, four region mathematical model, to estimate membrane permeability-surface area (PS) products. Since the endothelial cell PS for uric acid was low (0.12 +/- 0.09 ml.g-1.min-1), approximately 3% of the PS reported for adenosine, the possibility of flow-limited exchange for uric acid is ruled out. To estimate steady-state endothelial concentrations of uric acid in vivo, equations were developed describing electrochemical potential gradients for dissociated and undissociated forms of a weak acid. Despite endothelial production, intracellular concentrations that are lower than outside are expected because the negative membrane potential and lower cellular pH assist uric acid efflux.

Algorithms↗
PubMed1992

Contribution of labeled carbon dioxide to PET imaging of carbon-11-labeled compounds.

11CO2 is one of the major metabolites of many [11C]-labeled radiopharmaceuticals, including glucose, thymidine, acetate, amino acids, and fatty acids. Our data contradict the notion that the contribution of labeled CO2 to PET images can be disregarded because of its rapid elimination through the lungs. We have measured the retention and excretion of 11CO2 in dogs after the intravenous injection of labeled CO2/HCO3-, which had been equilibrated ex vivo with blood. Only 58% of the label was exhaled as CO2 over the first 60 min after injection, with the rest retained in the body. The injection of [11C]thymidine labeled in the ring-2 position or [11C]acetate labeled in the carboxylate position resulted in the production of large amounts of labeled CO2 with the exhalation of about 47% and 23%, respectively, of the injected label over 60 min. At 10 min after injection of either [11C]thymidine and [11C] acetate, approximately 60% to 70% of total blood activity was in labeled CO2 or bicarbonate. On the other hand, the use of [1-11C]glucose only resulted in exhalation of 5% of the injected dose and CO2/HCO3- made up less than 10% of blood activity at 10 min. Our results indicate that retention and distribution of labeled CO2 needs to be considered when interpreting PET data obtained from 11C-labeled compounds.

Acetates↗
PubMed1991

Mathematical modelling in nuclear medicine.

Modern imaging techniques can provide sequences of images giving signals proportional to the concentrations of tracers (by emission tomography), of X-ray-absorbing contrast materials (fast CT or perhaps NMR contrast), or of native chemical substances (NMR) in tissue regions at identifiable locations in 3D space. Methods for the analysis of the concentration-time curves with mathematical models describing the physiological processes and the appropriate anatomy are now available to give a quantitative portrayal of both structure and function: such is the approach to metabolic or functional imaging. One formulates a model first by defining what it should represent: this is the hypothesis. When translated into a self-consistent set of differential equations, the model becomes a mathematical model, a quantitative version of the hypothesis. This is what one would like to test against data. However, the next step is to reduce the mathematical model to a computable form; anatomically and physiologically realistic models account of the spatial gradients in concentrations within blood-tissue exchange units, while compartmental models simplify the equations by using the average concentrations. The former are known as distributed models and the latter as lumped compartmental or mixing chamber models. Since both are derived from the same ideas, the parameters are usually the same; their differences are in their ability to represent the hypothesis correctly, quantitatively, and sometimes in their computability. In this essay we review the philosophical and practical aspects of such modelling analysis for translating image sequences into physiological terms.

Computer Simulation↗
PubMed1991

Interstitial adenosine concentration during norepinephrine infusion in isolated guinea pig hearts.

This study determined the effect of norepinephrine (NE) on cardiac interstitial fluid adenosine concentration [( ADO]isf). Isolated guinea pig hearts were perfused with a Krebs-Henseleit buffer solution. Radiolabeled albumin, sucrose, and adenosine were injected under control conditions and after 3 and 20 min of NE infusion to obtain multiple indicator dilution curves that were used to determine capillary transport parameters for adenosine. These parameters together with venous adenosine concentrations were used in a mathematical model to a calculate [ADO]isf. Capillary transport parameters were not changed significantly by NE infusion. Because of uncertainty regarding two model parameters, two sets of [ADO]isf values were calculated. One set used best-fit values obtained from indicator dilution curves, and a second set used parameters chosen to provide the highest [ADO]isf values consistent with indicator dilution curves. Venous adenosine concentrations were 1.9 +/- 0.4 nM under control conditions and 243 +/- 110 and 45 +/- 25 nM after 3 and 20 min of NE infusion, respectively. Calculated [ADO]isf was 2.6-9.4, 591-1,288, and 166-324 nM, respectively, under these same conditions. We conclude that NE infusion greatly increases [ADO]isf, and adenosine is responsible for most of the vasodilation at 3 min. The subsequent fall in venous concentration is due to a fall in [ADO]isf rather than to decreased capillary permeability. Vascular resistance remained low while [ADO]isf fell, which suggests that additional vasodilators are important during maintained NE infusion.

Adenosine↗
PubMed1991

Applications of fractal analysis to physiology.

This review describes approaches to the analysis of fractal properties of physiological observations. Fractals are useful to describe the natural irregularity of physiological systems because their irregularity is not truly random and can be demonstrated to have spatial or temporal correlation. The concepts of fractal analysis are introduced from intuitive, visual, and mathematical perspectives. The regional heterogeneities of pulmonary and myocardial flows are discussed as applications of spatial fractal analysis, and methods for estimating a fractal dimension from physiological data are presented. Although the methods used for fractal analyses of physiological data are still under development and will require additional validation, they appear to have great potential for the study of physiology at scales of resolution ranging from the microcirculation to the intact organism.

Animals↗
PubMed1990

Microcirculatory considerations in NMR flow imaging.

Regional flow estimation can be accomplished either by measuring the concentration of a deposited tracer whose extraction during transit through the organ is 100%, or by observing the time course of concentration of a tracer whose transport passage through the organ is flow-limited. The deposition method is simpler and applies not only to microspheres or other large particles that lodge in the microcirculation, but also to molecular markers which are trapped. It has the advantage of having substantial time in which to observe the local concentrations by external detection. In contrast, flow-limited markers must traverse the tissue without barrier limitation or other diffusional influence on the exchange. When the marker is limited strictly to the intravascular space, the transit time through the organ is short and observations must be made rapidly with a high resolution technique. An indicator which distributes throughout a large volume of distribution within the tissue has a slower washout, providing more time in which to make observations; tracer water is a suitable marker, except perhaps in the brain. For flow measurement by NMR, markers which fulfill these criteria without causing side effects are needed.

Animals↗
PubMed1990

Fractal descriptions for spatial statistics.

Measures of spatial statistics have been available for estimating means, calculating or assessing differences, estimating nearest neighbor distances, and such, but have not provided a general approach to describing variances. Because measures of heterogeneity depend upon choosing a particular element size in the domain, estimates of apparent heterogeneity are larger with high-resolution observations than with low-resolution data. Many descriptors might be used to describe the relationships between apparent heterogeneity and the size of the observed spatial elements, but we have found that fractal relationships provide concise and precise descriptions of many types of data over large ranges of element sizes. Perhaps more importantly, the fractal approaches give additional insight, such as measures of spatial correlation, and often suggest ways of approaching the underlying basis of the heterogeneity.

Animals↗
PubMed1990

Heterogeneities in regional volumes of distribution and flows in rabbit heart.

The heterogeneity of volumes of distribution in the heart influences the rates of uptake and washout of substrates and metabolites; thus it is important to evaluate their variability in the normal heart. Several tracers were injected intravenously into anesthetized adult closed-chest rabbits, and time was allowed for equilibration in the heart. Tracer microspheres were injected into the left ventricular cavity at the apex for the measurement of regional flows, the chest was opened, another set of microspheres was injected, and the heart was frozen rapidly in situ with liquid nitrogen-cooled Freon-22. Each heart was divided into 72 pieces of less than 0.1 g weight, and the tracer content of each was determined by multichannel gamma-counting and the water content by desiccation. The regional myocardial flows were (closed chest) 0.62 +/- 0.16 ml.g-1.min-1 and (open chest) 0.63 +/- 0.37 ml.g-1.min-1. The volumes of distribution (ml/g) for the 432 pieces for six rabbits, given as mean +/- SD (% coefficient of variation), were as follows: for plasma, VP = 0.11 +/- 0.03 (26%); erythrocytes, VRBC = 0.041 +/- 0.015 (37%); vascular space, VV = 0.15 +/- 0.04 (26%); extracellular space, VECF = 0.33 +/- 0.05 (15%); interstitial space, VISF = 0.21 +/- 0.03 (15%); and water space, VW -0.79 +/- 0.022 (2.8%). Regional hematocrits were 77% +/- 9% of the large-vessel hematocrits.

Animals↗
PubMed1990

Molecular and particulate depositions for regional myocardial flows in sheep.

The deposition of microspheres in small tissue regions is not strictly flow dependent. In comparison with the soluble flow marker 2-iododesmethylimipramine (IDMI), deposition of 16.5-microns microspheres was mildly but systematically biased into high flow regions of rabbit hearts (Bassingthwaighte JB, Malone MA, Moffett T-C, King RB, Little SE, Link JM, Krohn KA. Am J Physiol 1987;253 (Heart Circ Physiol 22):H184-H193). To examine the possibility of bias in larger hearts, a similar study was undertaken in sheep. 141Ce- and 103Ru-labeled 16.5-microns microspheres in one syringe and 125I- and 131I-DMI in another syringe were injected simultaneously into the left atrium of five open-chest sheep while obtaining reference blood samples from the femoral artery. In six other sheep, one microsphere type and one IDMI were used. Hearts were removed 1 minute after injection, cut into approximately 254 pieces averaging 217 mg, and regional deposition densities calculated for each tracer from the isotopic counts. Correlations in the five animals between the two differently labeled IDMIs and between the two microspheres were both greater than or equal to 0.98. In all 11 sheep, scatter plots of microsphere deposition densities versus IDMI densities showed that differences between microspheres and IDMI had substantially more scatter (0.84 less than r less than 0.98) but were not random. Microsphere depositions tended to be lower than IDMI depositions in low flow regions and higher in high flow regions, in accord with the expected bias that at a bifurcation a microsphere is most likely to enter the branch with higher flow. There was less bias ascribable to endomyocardial/epicardial maldistribution. Thus, while microsphere depositions appear to err systematically with respect to flow when the regions of interest are small enough that the diameters of their arterioles are only a few times those of the microspheres, microspheres are, in sheep as in rabbits, adequate for estimating regional flows.

Animals↗
PubMed1990

Iodophenylpentadecanoic acid-myocardial blood flow relationship during maximal exercise with coronary occlusion.

Imaging 123I-labeled iodophenylpentadecanoic acid (IPPA) uptake and clearance from the myocardium following exercise has been advocated as a means of detecting myocardial ischemia because fatty acid deposition is enhanced and clearance prolonged in regions of low flow. However, normal regional myocardial blood flows are markedly heterogeneous, and it is not known how this heterogeneity affects regional metabolism or substrate uptake and thus image interpretation. In five instrumented dogs running at near maximal workload on a treadmill, 131I-labeled IPPA and 15-micron 46Sc microspheres were injected into the left atrium after 30 sec of circumflex coronary artery occlusion. Microsphere and IPPA activity were determined in 250 mapped pieces of myocardium of approximately 400 mg. Myocardial blood flows (from microspheres) ranged from 0.05 to 7.6 ml/min/g. Deposition of IPPA was proportional to regional flows (r = 0.83) with an average retention of 25%. The mean endocardial-epicardial ratio for IPPA (0.90 +/- 0.43) was similar to that for microspheres (0.94 +/- 0.47; p = 0.08). Thus, initial IPPA deposition during treadmill exercise increases in proportion to regional myocardial blood flow over a range of flows from very low to five times normal.

Animals↗
PubMed1989

Temporal fluctuations in regional myocardial flows.

Considerable spatial heterogeneity has been observed in regional myocardial blood flow in isolated hearts and in both anesthetized and conscious animals. In order to study how local blood flow varies with time, the data obtained by King et al. (1985) from ten awake, healthy baboons were analyzed to estimate the role of temporal fluctuations. Four to six distributions of regional flows were estimated at intervals of 4 min to 27 h, using 15 mu diameter microspheres and dividing each heart into 204 locatable pieces (average piece mass = 0.17 g). The technique averages over the 40 s of the injection giving no measure of fluctuations over a few seconds. The temporal variation in regional blood flow, expressed as the relative dispersion (SD/mean) of the temporally separated measurements about the mean flow for each piece and corrected for methodological noise, was 12% for the whole heart (10828 observations). For the left ventricle, the temporal variation was 10% (8806 observations), for the right ventricle 14% (1455 observations), and for the atria 22% (567 observations). On a relative basis, temporal fluctuation was greatest in regions having low flows. Since the magnitude of the changes in flow distributions was the same after 4 min as it was in several hours, we conclude that much of the "twinkling" is a high frequency phenomenon occurring over seconds to a few minutes. Further, it is concluded that regional myocardial blood flow in conscious primates is relatively stable with time, temporal fluctuations causing only about one third of the variation between regions.

Animals↗
PubMed1989

Transcapillary adenosine transport and interstitial adenosine concentration in guinea pig hearts.

We used the multiple-indicator-dilution technique to observe the capillary transport of adenosine in isolated Krebs-Henseleit-perfused guinea pig hearts. Tracer concentrations of radiolabeled albumin, sucrose, and adenosine were injected into the coronary inflow; outflow samples were collected for 10-25 s and analyzed by high-performance liquid chromatography (HPLC) and by gamma- and beta-counting. The albumin data define the intravascular transport characteristics; the sucrose data define permeation through interendothelial clefts and dilution in interstitial fluid (ISF). Parameters calculated from adenosine data include permeability-surface area products for endothelial cell uptake at the luminal and abluminal membranes and intraendothelial metabolism. We found that in situ endothelial cells avidly take up and metabolize adenosine. Tracer adenosine in the capillary lumen is twice as likely to enter an endothelial cell as it is to permeate the clefts. There was no adenosine in the arterial perfusate. Under control conditions, the steady-state venous adenosine concentration was 3.6 +/- 0.8 nM, which from the flow and the parameters estimated from the tracer data gave a calculated ISF concentration of 6.8 +/- 1.5 nM. During dipyridamole infusion (10 microM) at constant pressure, the cell permeabilities went essentially to zero, whereas the venous adenosine concentration increased to 44.0 +/- 12.6 nM, giving an estimated ISF concentration of 191 +/- 53 nM. With constant flow perfusion, venous concentration during dipyridamole infusion was 30.9 +/- 6.3 nM, and estimated ISF concentration was 88 +/- 20 mM. We conclude that in this preparation, at rest, the ISF adenosine concentration is about twice the venous concentration and the ISF adenosine concentration increases with dipyridamole administration.

Adenosine↗
PubMed1989

Regional myocardial flow heterogeneity explained with fractal networks.

There is marked heterogeneity in regional myocardial blood flow. To explain how the distribution of flow broadens with an increase in the spatial resolution of the measurement, we developed fractal models for vascular networks. A dichotomous branching network of vessels represents the arterial tree and connects to a similar venous network. A small difference in vessel lengths and radii between the two daughter vessels, with the same degree of asymmetry at each branch generation, predicts the dependence of the relative dispersion (mean +/- SD) on spatial resolution of the perfusion measurement reasonably well. When the degree of asymmetry increases with successive branching, a better fit to data on sheep and baboons results. When the asymmetry is random, a satisfactory fit is found. These models show that a difference in flow of 20% between the daughter vessels at a branch point gives a relative dispersion of flow of approximately 30% when the heart is divided into 100-200 pieces. Although these simple models do not represent anatomic features accurately, they provide valuable insight on the heterogeneity of flow within the heart.

Animals↗
PubMed1989

Fractal nature of regional myocardial blood flow heterogeneity.

Spatial variation in regional flows within the heart, skeletal muscle, and in other organs, and temporal variations in local arteriolar velocities and flows is measurable even with low resolution techniques. A problem in the assessment of the importance of such variations has been that the observed variance increases with increasing spatial or temporal resolution in the measurements. This resolution-dependent variance is now shown to be described by the fractal dimension, D. For example, the relative dispersion (RD = SD/mean) of the spatial distribution of flows for a given spatial resolution, is given by: RD(m) = RD(mref).[m/mref]1-Ds where m is the mass of the pieces of tissue in grams, and the reference level of dispersion, RD(mref), is taken arbitrarily to be the RD found using pieces of mass mref, which is chosen to be 1 g. Thus, the variation in regional flow within an organ can be described with two parameters, RD(mref) and the slope of the logarithmic relationship defined by the spatial fractal dimension Ds. In the heart, this relation has been found to hold over a wide range of piece sizes, the fractal Ds being about 1.2 and the correlation coefficient 0.99. A Ds of 1.2 suggests moderately strong correlation between local flows; a Ds = 1.0 indicates uniform flow and a Ds = 1.5 indicates complete randomness.

Animals↗