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

Kuikka, Jyrki T.; Levin, Michael; Bassingthwaighte, James B.

doi:10.1152/ajpheart.1986.250.1.h29

Cited by 72 publications

(79 citation statements)

References 32 publications

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“…Glucose extraction is only 2% or 3% (57) and fatty acid extraction is about 30%. Franzen et al (38) measured the regional concentrations of creatine kinase, lactate dehydrogenase, ATP, and glycogen, that is, two enzymes, one for cellular energetics, and one for glucose and lactate metabolism, and two energy sources, one being ATP, the main substrate for energy supply, and the other, glycogen, the storage vehicle for glucose.…”

Section: Energy Substrate Abundancementioning

confidence: 96%

The mechanical and metabolic basis of myocardial blood flow heterogeneity

Bassingthwaighte

Beard

2001

Basic Research in Cardiology

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Precise measurements of regional myocardial blood flow heterogeneity had to be developed before one could seek causation for the heterogeneity. Deposition techniques (particles or molecular microspheres) are the most precise, but imaging techniques have begun to provide high enough resolution to allow in vivo studies. Assigning causation has been difficult. There is no apparent association with the regional concentrations of energy-related enzymes or substrates, but these are measures of status, not of metabolism. There is statistical correlation between flow and regional substrate uptake and utilization. Attribution of regional flow variation to vascular anatomy or to vasomotor control appears not to be causative on a long-term basis. The closest relationships appear to be with mechanical function, but one cannot say for sure whether this is related to ATP hydrolysis at the crossbridge or associated metabolic reactions such as calcium uptake by the sarcoplasmic reticulum.

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Section: Energy Substrate Abundancementioning

confidence: 96%

The mechanical and metabolic basis of myocardial blood flow heterogeneity

Bassingthwaighte

Beard

2001

Basic Research in Cardiology

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“…The methods for using models to determine the parameters of transport and metabolism are discussed by Bassingthwaighte and Goresky, 19 Kuikka et al, 20 and Bassingthwaighte et al 21 Optimized parameter adjustment can be accomplished manually under XSIM, a graphic user-friendly interface developed by King and Butterworth,22 The standard thinking has been that the heart metabolizes uniformly, that is, all regions use the same amounts of oxygen and substrate. The same idea was applied to force generation: it is expected to be uniform, and mechanical models have been developed that support this concept.…”

Section: Oxygen Consumptionmentioning

confidence: 99%

“…The model accounts for intravascular convection, penetration of capillary and parenchymal cell barriers, the metabolism to 15 Owater in parenchymal cells, and 15 O-water transport into the venous effluent. Nonlinear binding of oxygen to hemoglobin in erythrocytes and to myoglobin in myocytes is explicitly incorporated in the model.The methods for using models to determine the parameters of transport and metabolism are discussed by Bassingthwaighte and Goresky, 19 Kuikka et al, 20 and Bassingthwaighte et al 21 Optimized parameter adjustment can be accomplished manually under XSIM, a graphic user-friendly interface developed by King and Butterworth,22 The standard thinking has been that the heart metabolizes uniformly, that is, all regions use the same amounts of oxygen and substrate. The same idea was applied to force generation: it is expected to be uniform, and mechanical models have been developed that support this concept.…”

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confidence: 99%

Heterogeneities in myocardial flow and metabolism: exacerbation with abnormal excitation

Bassingthwaighte

1999

The American Journal of Cardiology

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Because regional myocardial blood flows are remarkably heterogeneous-with a 6-to 10-fold range of flows in normal hearts-and because the spatial profiles of the flows are stable over long periods and over a range of conditions, the relation between flows and other physiologic functions has been explored. Local fatty acid uptake and oxygen consumption are almost linearly related to the flows. Coronary network structure and hydrodynamic resistances give suitable flow heterogeneity but are thought to be a response to local needs rather than being causative. Presumably the cause is the need for adenosine triphosphate (ATP) synthesis locally, and therefore flows, substrate delivery, and oxygen utilization are driven primarily by local rates of ATP hydrolysis, mainly by contractile proteins. This hypothesis is by no means fully tested. Data on pacing dog hearts from different sites, on patients with left bundle branch block, and on unloading transplanted rat hearts, all point in the same direction: unloading ventricular muscle leads to diminished flow and exaggeratedly diminished glucose uptake. The mechanism is likely to be that discovered by Taegtmeyer and colleagues, namely, the expression of fetal genes in regions where the muscle is unloaded and particular metabolic enzymes and transporters are downregulated.Regional blood flows in the left ventricle alone are remarkably heterogeneous. 1,2 The range of regional flows, per gram of tissue, is 6-to 10-fold at a spatial resolution of 0.5% of the left ventricular mass, even in awake baboons. 3 The standard deviation of the distribution is about 25% and is even broader if smaller tissue pieces are used for the measurement. 4 Fluctuations in flows over time are small, 5 so small that a high-flow region never diminishes its flow to the average, nor does a low-flow region ever raise its flow to the average for the heart.The heterogeneity is not random: near-neighbor regions tend to be alike, and there is selfsimilarity in the decay of the spatial correlation with increasing distance, a fractal phenomenon. The fractal relation is that, for a chosen ratio of distances between regions, there was a constant proportional diminution in correlation. We found that such flow distributions would theoretically occur with fractal self-similar branching of the coronary arteries. 6,7 Anatomic data, also fractal in nature, from van Bavel and Spaan 8 and Kassab et al, 9 serve as a more realistic basis for network reconstructions 10 than we achieved earlier with artificial branching algorithms. 7 These, Beard's new network reconstructions, exhibit appropriate pressure distributions, regional flow heterogeneities and fractal spatial correlations in flows, and the same power law form (∼1/t 3 ) for the washout time course as is observed. 11 But no matter how realistic the coronary network models may be, they are not the explanation for the regional flow heterogeneity; the vessels are mere conduits, constructed and remodeled under the influence of more fundamental processes. It is our...

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“…The polylysine-Gd-DTPA content-versus-time curves for blood pool and tissue regions were analyzed (Fig 2b) with a multiple-pathway, axially distributed mathematical model of blood tissue exchange (Fig 4) developed from a model described earlier (18), to estimate regional MBF and MBV. The model included multiple, parallel flow pathways, identical except for their flow, to describe the effects of regional flow heterogeneity (19).…”

Section: Mr Blood Flow Estimatesmentioning

confidence: 99%

Regional myocardial blood volume and flow: First‐pass MR imaging with polylysine‐Gd‐DTPA

Wilke

Kroll

Merkle

et al. 1995

Magnetic Resonance Imaging

132

104

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The authors investigated the utility of an intravascular magnetic resonance (MR) contrast agent, poly-L-lysine-gadolinium diethylenetriaminepentaacetic acid (DTPA), for differentiating acutely ischemic from normally perfused myocardium with first-pass MR imaging. Hypoperfused regions, identified with microspheres, on the first-pass images displayed significantly decreased signal intensities compared with normally perfused myocardium (P < .0007). Estimates of regional myocardial blood content, obtained by measuring the ratio of areas under the signal intensityversus-time curves in tissue regions and the left ventricular chamber, averaged 0.12 mL/g ± 0.04 (n = 35), compared with a value of 0.11 mL/g ± 0.05 measured with radiolabeled albumin in the same tissue regions. To obtain MR estimates of regional myocardial blood flow, in situ calibration curves were used to transform first-pass intensity-time curves into content-time curves for analysis with a multiple-pathway, axially distributed model. Flow estimates, obtained by automated parameter optimization, averaged 1.2 mL/min/g ± 0.5 [n = 29), compared with 1.3 mL/min/g ± 0.3 obtained with tracer microspheres in the same tissue specimens at the same time. The results represent a combination of T1-weighted first-pass imaging, intravascular relaxation agents, and a spatially distributed perfusion model to obtain absolute regional myocardial blood flow and volume. Index termsContrast agent, blood pool; Contrast enhancement; Coronary vessels, diseases, 54.76; Heart, flow dynamics; Heart, MR, 51.12143; Model, mathematical; Myocardium, blood supply, 511.12143; Myocardium, MR, 511.12143 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptA growing body of evidence supports the feasibility of evaluating myocardial perfusion with magnetic resonance (MR) imaging with contrast agents. A variety of intravascular and extracellular MR contrast agents have been studied for delineation of infarcted myocardium (1-3) and for identification of acutely ischemic and reperfused cardiac muscle (4,5). The first-pass MR imaging technique with the extracellular contrast agent gadolinium diethylenetriaminepentaacetic acid (DTPA) has been used to assess myocardial perfusion in patients at rest (6,7) and during pharmacologic stress (8,9). Although experimental (10) and patient studies have demonstrated the suitability of extracellular contrast agents for detecting hypoperfused myocardium, such agents are inherently disadvantageous for flow quantification because they are not confined to a single volume compartment within the tissue. Consequently, first-pass kinetics of an extracellular agent are determined not only by blood flow but by the intravascular and interstitial distribution volumes and by permeability across the capillary wall. This exchange between the vascular and interstitial compartments greatly complicates quantification of tissue blood flow unless it is either very fast or slow compared with flow rates (11).The objective of the present study was to...

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

Cited by 72 publications

References 32 publications

The mechanical and metabolic basis of myocardial blood flow heterogeneity

The mechanical and metabolic basis of myocardial blood flow heterogeneity

Heterogeneities in myocardial flow and metabolism: exacerbation with abnormal excitation

Regional myocardial blood volume and flow: First‐pass MR imaging with polylysine‐Gd‐DTPA

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