Multiple tracer dilution estimates of D- and 2-deoxy-D-glucose uptake by the heart using a three region, 7-path, Blood-Tissue-Exchange (BTEX) model. Model fit to all experiments published in Kuikka et al. 1986 paper (See model #0163 for more detatils).
This model fits 23 data sets obtained from rabbit and dog hearts first published in: KUIKKA, JYRKI, MICHAEL LEVIN, AND JAMES B. BASSINGTHWAIGHTE, Multiple tracer dilution estimates of D- and 2-deoxy-D-glucose uptake by the heart. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H29-H42, 1986. Also see Model #163 for details. Multiple indicator dilution (MID) analysis for the estimation of capillary permeability in the heart. The MID principle is to analyze the cellular permeability surface area product for the target solute, D-glucose, against two reference solutes, one to characterize the intravascular transport function, href(t) through the intact organ ( (131)I-albumin in this case ), an extracellular one of the same molecular weight as the target solute in order to characterize the combination of permeation through the inter-endothelial cleft (using L-glucose), and the target solute, D-glucose that is taken up by cells and metabolized. 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 I(131)-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 PS, 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*min), in the dog hearts the PSc, for D-glucose was 0.72 +- 0.17 ml/(g*min) (mean t SD; n = ll), and PSpc, was 0.57 t 0.15 ml/(g*min). In the rabbit hearts with perfusate flow of 2.0 ml/(g*min)(n = 6), PSc, was 1.2 +- 0.1 and PSpc, was 0.4 +- 0.1 ml/(g*min). PSc, for 2-deoxy-Dglucose 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.
There are two related models: Kuikka 1986 three region, which is the same model as presented here but includes parameter fits to reproduce the figures in the Kuikka et al 1986 paper, and Kuikka 1986 two region BTEX, a simplified, two region model where the permeability and consumption term for the third region (myocardial cells) are replaced with just a consumption term in the second region (interstitial fluid). This model is only fit to Table 3 example data of Kuikka 1986 paper.
Kuikka MID Data
The MID glucose datasets published in the Kuikka et al. 1986 paper are available on the Physionet web site. At the Physionet web site search for 'Cardiac Physiome Kuikka glucose' in the PhysioNetWorks area (you will need a free, personal account to access it).
The equations for this model may be viewed by running the JSim model applet and clicking on the Source tab at the bottom left of JSim's Run Time graphical user interface. The equations are written in JSim's Mathematical Modeling Language (MML). See the Introduction to MML and the MML Reference Manual. Additional documentation for MML can be found by using the search option at the Physiome home page.
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Model development and archiving support at https://www.imagwiki.nibib.nih.gov/physiome provided by the following grants: NIH U01HL122199 Analyzing the Cardiac Power Grid, 09/15/2015 - 05/31/2020, NIH/NIBIB BE08407 Software Integration, JSim and SBW 6/1/09-5/31/13; NIH/NHLBI T15 HL88516-01 Modeling for Heart, Lung and Blood: From Cell to Organ, 4/1/07-3/31/11; NSF BES-0506477 Adaptive Multi-Scale Model Simulation, 8/15/05-7/31/08; NIH/NHLBI R01 HL073598 Core 3: 3D Imaging and Computer Modeling of the Respiratory Tract, 9/1/04-8/31/09; as well as prior support from NIH/NCRR P41 RR01243 Simulation Resource in Circulatory Mass Transport and Exchange, 12/1/1980-11/30/01 and NIH/NIBIB R01 EB001973 JSim: A Simulation Analysis Platform, 3/1/02-2/28/07.