Spatial heterogeneity of blood flow in the dog heart. I. Glucose uptake, free adenosine and oxidative/glycolytic enzyme activity

Abstract

The spatial heterogeneity of myocardial perfusion and metabolism was studied in 11 anaesthetized dogs under resting conditions. In each heart local myocardial blood flow was assessed using the tracer microsphere technique in 256 samples (mean mass: 83.1 mg) taken from the left anterior ventricular wall. In the same samples, the following biochemical parameters were determined: accumulation of [3H]-deoxyglucose (a measure of glucose uptake), free cytosolic adenosine (S-adenosylhomocysteine accumulation technique, a measure of tissue oxygenation and a possible mediator of blood flow regulation), and the specific activities of oxidative (citrate synthase, cytochrome-c-oxidase) and glycolytic (hexokinase, phosphoglycerate kinase) enzymes. Capillary density and mitochondrial and myofibril volume densities were determined by morphometry. Myocardial perfusion in each sample (average 0.77 ml min-1 g-1) varied between 0.1 and 2.5 times the mean (coefficient of variation 0.30+/-0.02). [3H]-deoxyglucose was deposited locally in proportion to perfusion. Samples showing low flow (<0.2 ml min-1 g-1) did not exhibit increased levels of cytosolic adenosine. The specific activities of the oxidative and glycolytic enzymes, however, were uniformly distributed between low and high flow areas. Furthermore, capillary density and mitochondrial and myofibril densities were similar in high and low flow regions. The results show firstly that local glucose metabolism in the heart occurs in proportion to local blood flow, suggesting that high flow regions have a higher than average metabolic rate. Secondly, regions of low flow are not compromized by critical oxygenation and most likely have a lower than average oxygen demand and finally, the homogeneous distribution of oxidative and glycolytic enzymes, as well as the homogeneous myocardial ultrastructure, suggest that areas with high and low blood flow under resting conditions may increase their metabolic rate to similar levels when required.

High-resolution imaging reveals a limit in spatial resolution of blood flow measurements by microspheres

“…The capillary volume fraction in myocardial crosssections from 12 low-and high-flow samples was 9.44 Ϯ 1.31%, the low coefficient of variation (0.14), indicating a homogenous distribution of capillary density (ϳ3,000 mm Ϫ2 ), consistent with a previous report from our group (25). In contrast, the arteriolar density in the same samples as estimated by light microscopy (57 Ϯ 34 mm Ϫ2 ) displayed a much greater spatial heterogeneity (CV 0.59).…”

“…In the other dog, radioactive microspheres were applied for local flow determinations in the alert animal. Cardiac excision was followed by glutaraldehyde fixation for electron and light microscopy analysis, as described previously (25).…”

Relationship of apparent myocardial T2 and oxygenation: Towards quantification of myocardial oxygen extraction fraction

“…First, heterogeneity of T 2 maps plays a major role. The T 2 variations come from following sources: 1) imprecision of T 2 calculations due to limited SNRs and limited number of TE values used; 2) inaccuracy of T 2 calculations due to imperfect refocusing 180°pulses and unsaturated flow artifacts along the phase encoding direction; 3) variations of intramyocardial oxygenation (33). Second, calculation of OEF value at each pixel relies on the MBV value at that pixel.…”

Coronary Reserve of High- and Low-Flow Regions in the Dog Heart Left Ventricle

“…However, when analysis of the local deposition density of microspheres [2][3][4][5] and diffusible plasma flow markers [6][7][8] in volume elements of a few millimeters diameter showed that the local flow distribution within individual hearts is markedly heterogeneous, covering a range from 20% to 200% of the mean value. This flow heterogeneity is remarkably stable over periods of several hours, 4 even if the heart is intermittently stimulated.…”

“…11 Thus, areas with a local oxygen supply of Ͻ50% of the average cannot have a normal oxidative metabolism. In fact, measurements of the local uptake of deoxyglucose 5,12 and fatty acids 13 indicate that local metabolic rates and transport capacities in left ventricular myocardium mirror those of local blood flow, ie, high-flow areas have a higher metabolic rate of glucose and a higher uptake of fatty acids than low-flow regions. This indicates that control high-flow areas are regions of high metabolism and consequently have a higher demand for oxygen.…”