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J B Bassingthwaighte

Publications and source records attributed to J B Bassingthwaighte.

At least 37 records · Page 2Linked to original sources
PubMed1998

Transport of long-chain fatty acids across the muscular endothelium.

Both skeletal and cardiac muscle cells rely heavily on the oxidation of long-chain fatty acids to utilize chemically stored energy for contractile work. Under normal conditions fatty acids are continuously supplied from the microvascular compartment to the contracting myocytes. Exogenous fatty acids are transported to muscle tissue via the blood either complexed to albumin or covalently bound in triacylglycerols forming the neutral lipid core of circulating lipoproteins such as chylomicrons or very low-density lipoproteins. The first barrier met by fatty acids on their way from the vascular compartment to the myocytes is the endothelium constituting the capillary wall. After dissociation of the albumin-fatty acid complex or release from the triacylglycerol core of lipoproteins, fatty acids most likely transverse the endothelium by crossing the luminal membrane, the cytosol, and subsequently the abluminal wall of the endothelial cell. Transfer through the interendothelial clefts or lateral diffusion within the phospholipid bilayer of the endothelial plasmalemma should be considered as inconsequential. The mechanism responsible for transmembrane movement of fatty acids is incompletely understood, although recent findings suggest the involvement of a number of membrane-associated proteins. Kinetic studies have revealed that interaction of the albumin-fatty acid complex with the endothelial membrane may accelerate the dissociation of the complex, which facilitates the uptake of fatty acids by the endothelium. Albumin-binding proteins (ABP) might be instrumental in this interaction. Moreover, plasmalemmal fatty acid-binding protein (FABPpm), fatty acid translocase (FAT) and fatty acid-transport protein (FATP) are putatively involved in transmembrane movement of the fatty acid molecules. Diffusion through the endothelial cytosol might be facilitated by a cytoplasmic fatty acid-binding protein, the type of which may be related to the epithelial fatty acid-binding protein (E-FAPBc).

Animals↗
PubMed1998

Blood flows and metabolic components of the cardiome.

This is a plan for the first stage of The Cardiome Project. The cardiome is the representation, in quantitative, testable form, of the functioning of the normal heart and its responses to intervention. The goal is to integrate the efforts of many years into a comprehensive understandable scheme. Past efforts have spanned the fields of transport within blood vessels, the distributions of regional coronary blood flows, permeation processes through capillary and cell walls, mediated cell membrane transport, extra- and intracellular diffusion, cardiac electrophysiology, the uptake and metabolism of the prime substrates (fatty acid and glucose), the metabolism of the purine nucleosides and nucleotides (mainly adenosine and ATP), the regulation of the ionic currents and of excitation-contraction coupling and finally the regulation of contraction. The central theme is to define the coronary flows and metabolic components of a computer model that will become a part of a three-dimensional heart with appropriate fibre shortening and volume ejection. The components are: (a) coronary flow distributions with appropriate heterogeneity, (b) metabolism of the substrates for energy production, (c) ATP, PCr and energy metabolism and (d) calcium metabolism as it relates to excitation-contraction coupling. The modeling should provide: (1) appropriate responses to regional ischemia induced by constriction of a coronary artery, including tissue contractility loss and aneurysmal dilation of the ischemic region; (2) physiological responses to rate changes such as treppe and changes in metabolic demand and (3) changes in local metabolic needs secondary to changes in the site of pacing stimulation and shortening inactivation or stretch activation of contraction.

Adenosine↗
PubMed1997

Design and strategy for the Cardionome Project.

The Physiome Project has the goal of providing the quantitative description of the integrated functions of the living organism. This is too large an undertaking to be begun all at once. What needs to be developed first are large comprehensive databases containing genomic, biochemical, anatomical and physiological information that can be searched and retrieved via the Internet. A more modest and achievable goal is the Cardiome Project, whose goal is to describe the functioning heart. Since it is impractical to develop this from the genetic and molecular level, we begin it as a multicenter collaborative effort at the level of the functioning organ. The work of Hunter, Noble, and others provides a central scheme, a description of the spread of excitation and contraction through an anatomically detailed cardiac model with fiber directions. This will be augmented by the additions of regional blood flows, substrate uptake and metabolism, and energy production and utilization in serving contraction and ionic balances. Later stages will involve cellular regulation and responses to interventions. The organization of such projects is by the assembling of components whose linkages one to another are first minimized and then augmented to improve the approximation to reality.

Animals↗
PubMed1997

Biological growth on a surface.

A new biological growth model is introduced. After random selection of possible growth sites, cells are added in an allowable random direction. Unlike the Eden model, the current model is grid independent and can be adapted to any curved surface. Growths of colonies of as many as 10(5) cells are simulated on planar, cylindrical, and spherical surfaces. It is found that the interior density is constant, whereas the boundary is fractal.

Algorithms↗
PubMed1997

Potassium and thallium uptake in dog myocardium.

UNLABELLED: We sought to ascertain the rates and mechanisms of uptake of markers for regional myocardial blood flows. METHODS: The rates of exchange of potassium and thallium across capillary walls and cell membranes in isolated blood-perfused dog hearts were estimated from multiple indicator dilution curves recorded for 131I-albumin, 42K and 201Tl from the coronary sinus outflow following injection into arterial inflow. Analysis involved fitting the observed dilution curves with a model composed of a capillary-interstitial fluid-cell exchange region and nonexchanging larger vessels. RESULTS: Capillary permeability surface products (PSc) for potassium and thallium were similar, 0.82 +/- 0.33 (mean +/- s.d., n = 19) and 0.87 +/- 0.32 ml min-1 g-1 (n = 24) with a ratio for simultaneous pairs of 1.02 +/- 0.27 (n = 19). For the myocardial cells, PSpc averaged 3.7 +/- 3.1 ml min-1 g-1 (n = 19) for K+ and 9.5 +/- 3.9 (n = 24) for Tl+; the ratio of potassium to thallium averaged 0.40 +/- 0.19 (n = 18), thereby omitting a single high value for potassium. This high cellular influx for thallium is interpreted as due to its passage through ionic channels for both Na+ and K+. CONCLUSION: The high permeabilities and large volumes of distribution make thallium and potassium among the best ionic deposition markers for regional flow. Their utility for this purpose is compromised by significant capillary barrier limitation retarding uptake; so regional flow is underestimated modestly in high-flow regions particularly.

Animals↗
PubMed1996

Modeling [15O]oxygen tracer data for estimating oxygen consumption.

The most direct measure of oxidative tissue metabolism is the conversion rate of oxygen to water via mitochondrial respiration. To calculate oxygen consumption from the analysis of tissue residue curves or outflow dilution curves after injection of labeled oxygen one needs realistic mathematical models that account for convection, diffusion, and transformation in the tissue. A linear, three-region, axially distributed model accounts for intravascular convection, penetration of capillary and parenchymal cell barriers (with the use of appropriate binding spaces to account for oxygen binding to hemoglobin and myoglobin), the metabolism to [15O]water in parenchymal cells, and [15O]water transport into the venous effluent. Model solutions fit residue and outflow dilution data obtained in an isolated, red blood cell-perfused rabbit heart preparation and give estimates of the rate of oxygen consumption similar to those obtained experimentally from the flow times the arteriovenous differences in oxygen contents. The proposed application is for the assessment of regional oxidative metabolism in vivo from tissue 15O-residue curves obtained by positron emission tomography.

Animals↗
PubMed1996

Modeling regional myocardial flows from residue functions of an intravascular indicator.

The purpose of the present study was to determine the accuracy and the sources of error in estimating regional myocardial blood flow and vascular volume from experimental residue functions obtained by external imaging of an intravascular indicator. For the analysis, a spatially distributed mathematical model was used that describes transport through a multiple-pathway vascular system. Reliability of the parameter estimates was tested by using sensitivity function analysis and by analyzing "pseudodata": realistic model solutions to which random noise was added. Increased uncertainty in the estimates of flow in the pseudodata was observed when flow was near maximal physiological values, when dispersion of the vascular input was more than twice the dispersion of the microvascular system for an impulse input, and when the sampling frequency was < 2 samples/s. Estimates of regional blood volume were more reliable than estimates of flow. Failure to account for normal flow heterogeneity caused systematic underestimates of flow. To illustrate the method used for estimating regional flow, magnetic resonance imaging was used to obtain myocardial residue functions after left atrial injections of polylysine-Gd-diethylenetriaminepentaacetic acid, an intravascular contrast agent, in anesthetized chronically instrumental dogs. To test the increase in dispersion of the vascular input after central venous injections, magnetic resonance imaging data obtained in human subjects were compared with left ventricular blood pool curves obtained in dogs. It is concluded that if coronary flow is in the normal range, when the vascular input is a short bolus, and the heart is imaged at least once per cardiac cycle, then regional myocardial blood flow and vascular volume may be reliably estimated by analyzing residue functions of an intravascular indicator, providing a noninvasive approach with potential clinical application.

Animals↗
PubMed1995

Toward modeling the human physionome.

The physionome is the description of the physiological dynamics of the normal intact organism. The march of science brings us now into the era where integration of the various facets of the knowledge of biology and medicine has become a major issue. Modeling is a vehicle for the combining of information from molecular biology, biophysics, and medical biology, but must be combined with strategies for databasing the raw data with greater efficiency than is currently possible. The lessons from the genome project can be applied to the next level major projects, the morphonome and the physionome, the objective being to put integrated forms of the data into the hands of physicians and medical scientists.

Animals↗
PubMed1995

Fractal 15O-labeled water washout from the heart.

To characterize the washout of water from the heart, we used a flow-limited (not diffusion- or permeability-limited) marker for blood-tissue exchange, namely, tracer-labeled water. Experiments were performed by injecting 15O-labeled water into the inflow to isolated blood-perfused rabbit hearts and by recording the tracer content in the heart and in the outflow simultaneously for up to 5 minutes. The data exhibit a particular combination of power law forms: (1) The downslopes of the residue and outflow curves were both power law functions, with the residue diminishing as t-alpha and the outflow as t-alpha-1, where alpha is interpreted to be the dimensionless exponent of a fractal power law relation characterizing the self-similarity inherent in each curve. (2) The fractional escape rate, given by the outflow curve divided by the residue curve, diminished almost exactly as t-1. In 18 sets of curves, alpha averaged 2.21 +/- 0.27. These results lead to an improved method for extrapolating the downslopes of indicator dilution curves to estimate their areas and therefore the blood flows. The evidence also points strongly to the conclusions that myocardial water washout is a fractal process and that stirred tank models are inappropriate for the heart.

Animals↗
PubMed1995

Autoradiographic assessment of blood flow heterogeneity in the hamster heart.

OBJECTIVE: Provide regional flow measurement in the hearts of small mammals using a new, higher-resolution technique based on the deposition of a molecular marker. METHODS: We determined the instantaneous extraction and retention of the "molecular microsphere" radiolabeled desmethylimipramine in retrogradely perfused hamster hearts. In a separate series of experiments, autoradiography was used to measure regional myocardial deposition densities in hamster hearts of about 0.5 g with spatial area resolution of 16 x 16 microns. RESULTS: Radiolabeled desmethylimipramine is almost 100% extracted during a single transcapillary passage and is retained in the tissue for many minutes. Autoradiographic images demonstrated a spatial flow heterogeneity with standard deviations of 31 +/- 4% of the mean flow (N = 5) in 16 x 16 x 20-micronm3 voxels. This is equivalent to the projections made using fractal relationships from cruder observations obtained with microspheres in the hearts of baboons, sheep, and rabbits. CONCLUSIONS: Autoradiography using a molecular deposition marker provides quantitative information on myocardial flow heterogeneities with resolution at the size of cardiac myocytes. Because the regions resolved are smaller than the volume of regions supplied by single arterioles, the results must slightly exaggerate the true heterogeneity of regional flows.

Animals↗
PubMed1994

Regional myocardial flow and capillary permeability-surface area products are nearly proportional.

Analyses of data on the transcapillary exchange and cellular uptake in the normal heart have generally been based on the assumption that local membrane conductances and volumes of distribution are everywhere the same. The question is whether such an assumption is justified in view of the marked (sixfold) heterogeneity of local blood flows per gram tissue. The method was to estimate both flow and capillary membrane permeability-surface area products (PS) locally in the heart. For each of five dogs running on a sloped treadmill, the deposition of tracer microspheres and of [131I]iodophenylpentadecanoic acid (IPPA), after left atrial injection, was determined in 256 pieces of left ventricular myocardium by killing the animals at approximately 100 s after radiotracer injection. A hydraulic occluder stopped the flow to a portion of the myocardium supplied by the left circumflex coronary artery 30 s before tracer injection. Regional flows ranged from 0.1 to 7.0 ml.g-1.min-1. IPPA extractions ranged from 20 to 49%. Using the known flows, we assumed the applicability of an axially distributed blood-tissue exchange model to estimate the PS for the capillary (PSc) and the parenchymal cell. It was impossible to explain the data if the PSc values for membrane transport were uniform throughout the organ. Rather, the only reasonable descriptors of the data required that local PSc values increase with local flow, almost in proportion. Current methods of analysis using data based on deposition methods need to be revised to take into account the near proportionality of PS to flow for at least some substrates.

Animals↗
PubMed1993

Chaos in cardiac signals.

Chaotic dynamical systems analysis has become over the last two decades a standard tool for systems analysis in the hydrodynamics of turbulence, in mechanical systems, and in electrical signals. The label "chaotic" has summarized the lack of predictability of the weather and other complex systems. We can use "chaos" theory to enhance our understanding of cardiovascular pressures, flows, heart rates, and tracer exchanges. Explaining why we cannot predict exactly is an improvement over not understanding at all, and aids in taking the next steps toward deeper insight at the biochemical and electrophysiologic levels.

Animals↗
PubMed1993

A vascular transport operator.

A pulse or a sharp front in concentration of a tracer or a substrate in the blood within a vessel becomes dispersed while being transported along a vessel. Cross-stream mixing and pulsations in flow with the heartbeat cause the dispersion to be less than would occur with a parabolic velocity profile (Newtonian flow). These characteristics allow intravascular mass transport to be described well by a simple two-parameter differential operator, which is a one-dimensional representation of the rather complex real situation. The operator consists of two components in series, a pure delay and a fourth-order linear differential operator. The latter is merely two underdamped second-order operators in series, with fixed relationships between the natural frequencies and damping coefficients. The operator is useful because it provides a transport function with skewness and kurtosis suitable to intravascular transport where the mean velocity profile is blunter than in Newtonian parabolic flow. The parameters of the operator are its mean transit time, t, and its relative dispersion, RD, which is the standard deviation of the response impulse divided by t. The operator transport function describes blood transport through the human leg arterial system, where the RD values are approximately 15-20%.

Arteries↗
PubMed1992

Computationally efficient algorithms for convection-permeation-diffusion models for blood-tissue exchange.

Analysis of data on tissue depositions obtained by positron tomographic or NMR imaging, or of multiple tracer outflow dilution curves, requires fitting data with models composed of aggregates of capillary-tissue units. These units account for heterogeneities of flows and multisolute exchanges between longitudinally distributed regions across capillary and cell barriers within an organ. Because the analytic solutions to the partial differential equations require convolution integration, solutions are obtained relatively efficiently by a fast numerical method. Our approach centers on the use of a sliding fluid element algorithm for capillary convection, with the time step set equal to the length step divided by the fluid velocity. Radial fluxes by permeation between plasma, interstitial fluid, and cells and axial diffusion exchanges within each time step are calculated analytically. The method enforces mass conservation unless there is regional consumption. Solution for a 2-barrier, 3-region model, accurate to within 0.5%, are 100 to 1000 times faster than the corresponding, purely analytic solution, and over 10,000 times for a 4-region model. Applications include multiple indicator dilution studies of kinetics of transcapillary exchange and positron emission tomographic studies of the mechanisms of substrate transport into cells of organs in vivo.

Algorithms↗
PubMed1992

Triple-label beta liquid scintillation counting.

The detection of radioactive compounds by liquid scintillation has revolutionized modern biology, yet few investigators make full use of the power of this technique. Even though multiple isotope counting is considerably more difficult than single isotope counting, many experimental designs would benefit from using more than one isotope. The development of accurate isotope counting techniques enabling the simultaneous use of three beta-emitting tracers has facilitated studies in our laboratory using the multiple tracer indicator dilution technique for assessing rates of transmembrane transport and cellular metabolism. The details of sample preparation, and of stabilizing the liquid scintillation spectra of the tracers, are critical to obtaining good accuracy. Reproducibility is enhanced by obtaining detailed efficiency/quench curves for each particular set of tracers and solvent media. The numerical methods for multiple-isotope quantitation depend on avoiding error propagation (inherent to successive subtraction techniques) by using matrix inversion. Experimental data obtained from triple-label beta counting illustrate reproducibility and good accuracy even when the relative amounts of different tracers in samples of protein/electrolyte solutions, plasma, and blood are changed.

Animals↗