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
Source: PubMed


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.
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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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