Heterogeneities in myocardial flow and metabolism: exacerbation with abnormal excitation.

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.