Heterogeneities in myocardial flow and metabolism: exacerbation with abnormal excitation

Abstract

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...

Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy

“…Evidence at the local level is slim, because it is so difficult to measure local stress simultaneously with local oxygen uptake or ATP utilization. Local oxygen consumption estimated from 15 O 2 imaging by positron emission tomography was correlated with local flows from microsphere data (14).…”

Reverse Perfusion-Metabolism Mismatch Predicts Good Prognosis in Patients Undergoing Cardiac Resynchronization Therapy A Pilot Study

“…18 An experimental study showed that early septal contraction in LBBB reduced septal workload, 19 which would lead to diminished glucose metabolism. 20,21 The relationship between workload and glucose metabolism is thought to be as follows. Glucose uptake is mediated by the glucose transporter, GLUT-4, which is an insulin-sensitive transporter in the cell membrane.…”

Integrated Computational Modeling of Oxygen Transport and Cellular Energetics Explains Observations on In Vivo Cardiac Oxygen Consumption and Energy Metabolites

“…Yet it has been observed that local myocardial blood flow can vary regionally by up to 10-fold in vivo [32][33][34][35]. Since oxygen [35] and fatty acid [36] uptake are tightly proportional to regional flow in the myocardium, it is proposed that ATP hydrolysis varies regionally as well. Future studies that link coronary blood flow, oxygen and substrate transport, cellular and wholeheart mechanics, and energy metabolism are expected to shed light on the physiological basis for regional heterogeneities in substrate delivery in the heart.…”