Local myocardial glucose uptake is proportional to, but not dependent on blood flow

Abstract

In nonischaemic myocardium local deoxyglucose deposition is proportional to local blood flow (y = 0.77x + 0.25 for normalized deoxyglucose deposition and blood flow). The cause for this relationship was evaluated using a mathematical model of (deoxy)glucose metabolism to elucidate whether differences in local deoxyglucose deposition are dependent on local blood flow or whether they reflect differences of the local metabolic rate. The axially distributed model consists of two blood-tissue exchange regions arranged concentrically representing the capillary and the extracapillary regions, the latter being a composite of the endothelial, interstitial and parenchymal cell regions. Exchange between the two model regions is described by a permeability-surface area product, consumption in the extracapillary region is modelled by an intraregional clearance term. Twenty blood-tissue exchange units are arranged as parallel pathways to account for the effects of flow heterogeneity and in series with a single, nonexchanging, large vessel segment (0.1 ml/g). Regional volumes (capillary 0.07 ml/g, extracapillary 0.60 ml/g) and the permeability-surface area product (0.2 ml min-1 g-1) are taken from published sources, the local myocardial blood flow is that determined experimentally (between 0.1 and 2.5 ml min-1 g-1). The only free parameter in the model is the extracapillary clearance term (0.0275-0.102 ml min-1 g-1) which was used to fit the measured tissue radioactivity concentration taking the measured arterial concentration of 3H-deoxyglucose into account. The results obtained indicate that variations in local myocardial blood flow, and hence differences in deoxyglucose supply, can not explain quantitatively the differences in local deoxyglucose deposition. However, differences of the metabolic rate (0.326 versus 0.120 micro;mol min-1 g-1) assumed to occur in parallel to the flow differences (1.26 versus 0.42 ml min-1 g-1) can well explain the different mean deoxyglucose deposition in high and low flow areas. This result supports the view that blood flow heterogeneity in the heart is paralleled by a spatial heterogeneity of glucose metabolism.