Cousineau D, Rose CP, Lamoureux D, Goresky CAChanges in cardiac transcapillary exchange with metabolic coronary vasodilation in the intact dog. Circ Res 53:719-730

Circulation Research (Impact Factor: 11.02). 01/1984; 53(6):719-30. DOI: 10.1161/01.RES.53.6.719
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The effects of metabolic coronary vasodilation on transcapillary exchange in the heart were examined in anesthetized dogs by use of the multiple indicator dilution technique. Animals were studied under basal conditions and during coronary sinus pacing. To obviate adrenal medullary stimulation, catheters were placed in coronary artery and coronary sinus in a closed chest preparation. Plasma catecholamine concentrations were determined to provide an index of the level of sympathetic tone. Labeled albumin and sucrose were injected into the coronary artery, and outflow dilution curves were secured. Analysis of these, with a model incorporating throughput and returning components, and heterogeneity of capillary transit times, provided parameters reflecting flow, permeability-surface product for sucrose, and capillary heterogeneity. Coronary sinus pacing increased both heart rate and plasma norepinephrine values; in response, myocardial oxygen consumption increased, metabolic vasodilation occurred, and coronary flow increased. The capillary permeability-surface product for sucrose increased with the flow but tended to plateau at higher values, showing a saturation phenomenon. Capillary heterogeneity, present in control animals with low sympathetic tone, was grossly decreased during cardiac metabolic activation. The Crone-Renkin approximation formula for the permeability-surface product yielded values that were too low at low flows and values approaching those from the complete model at high flows. The findings indicate an integrated pattern of circulatory response to cardiac metabolic activation characterized by decreased resistance, increased flow, increased permeability-surface product, and reduced heterogeneity. The last two effects amplify the capacity of increased flow to deliver substrates to heart muscle cells.

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Available from: Colin P Rose, Mar 08, 2014
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    • "Note that if CTH cannot be reduced, OEFmax decreases as MBF increases, owing to the poor extraction of oxygen from capillaries with very short transit times. This model property is consistent with the original observations by Rose and colleagues, namely that CTH must be reduced at high MBF in order to explain the efficient extraction of solutes by the myocardium during vasodilation [19, 89]. "
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    ABSTRACT: Ischemic heart disease (IHD) is characterized by an imbalance between oxygen supply and demand, most frequently caused by coronary artery disease (CAD) that reduces myocardial perfusion. In some patients, IHD is ascribed to microvascular dysfunction (MVD): microcirculatory disturbances that reduce myocardial perfusion at the level of myocardial pre-arterioles and arterioles. In a minority of cases, chest pain and reductions in myocardial flow reserve may even occur in patients without any other demonstrable systemic or cardiac disease. In this topical review, we address whether these findings might be caused by impaired myocardial oxygen extraction, caused by capillary flow disturbances further downstream. Myocardial blood flow (MBF) increases approximately linearly with oxygen utilization, but efficient oxygen extraction at high MBF values is known to depend on the parallel reduction of capillary transit time heterogeneity (CTH). Consequently, changes in capillary wall morphology or blood viscosity may impair myocardial oxygen extraction by preventing capillary flow homogenization. Indeed, a recent re-analysis of oxygen transport in tissue shows that elevated CTH can reduce tissue oxygenation by causing a functional shunt of oxygenated blood through the tissue. We review the combined effects of MBF, CTH, and tissue oxygen tension on myocardial oxygen supply. We show that as CTH increases, normal vasodilator responses must be attenuated in order to reduce the degree of functional shunting and improve blood-tissue oxygen concentration gradients to allow sufficient myocardial oxygenation. Theoretically, CTH can reach levels such that increased metabolic demands cannot be met, resulting in tissue hypoxia and angina in the absence of flow-limiting CAD or MVD. We discuss these predictions in the context of MVD, myocardial infarction, and reperfusion injury.
    Archiv für Kreislaufforschung 05/2014; 109(3):409. DOI:10.1007/s00395-014-0409-x · 5.41 Impact Factor
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    • "A more practical approach may be to analyze the overall network properties of the capillary plexus in a given location. Mounting evidence suggests that the heterogeneity of flow in the capillary network is adjusted based on the metabolic needs of the tissue, with flow being redistributed to more homogeneous patterns under metabolic challenge [42,47,49–52]. Modeling predicts this redistribution to significantly improve metabolite exchange with tissue, especially oxygen extraction [53]. "
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    ABSTRACT: Imaging the retinal vasculature offers a surrogate view of systemic vascular health, allowing noninvasive and longitudinal assessment of vascular pathology. The earliest anomalies in vascular disease arise in the microvasculature, however current imaging methods lack the spatiotemporal resolution to track blood flow at the capillary level. We report here on novel imaging technology that allows direct, noninvasive optical imaging of erythrocyte flow in human retinal capillaries. This was made possible using adaptive optics for high spatial resolution (1.5 μm), sCMOS camera technology for high temporal resolution (460 fps), and tunable wavebands from a broadband laser for maximal erythrocyte contrast. Particle image velocimetry on our data sequences was used to quantify flow. We observed marked spatiotemporal variability in velocity, which ranged from 0.3 to 3.3 mm/s, and changed by up to a factor of 4 in a given capillary during the 130 ms imaging period. Both mean and standard deviation across the imaged capillary network varied markedly with time, yet their ratio remained a relatively constant parameter (0.50 ± 0.056). Our observations concur with previous work using less direct methods, validating this as an investigative tool for the study of microvascular disease in humans.
    Biomedical Optics Express 12/2012; 3(12):3264-77. DOI:10.1364/BOE.3.003264 · 3.65 Impact Factor
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    ABSTRACT: 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.
    The American journal of physiology 02/1986; 250(1 Pt 2):H29-42. · 3.28 Impact Factor
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