Does local coronary flow control metabolic flux rates? A 13C-NMR study.

Abstract

Coronary flow; NMR; Metabolic flux Left ventricular perfusion is inhomogeneous even under resting conditions. While at a resolution of 6 x 6 x 6 mm 3 local coronary flow in 1/2 of the my- ocardium is within 20% of the normalized mean, 1/10 of the myocardium receives less than 50% and another 1/10 more than 150% of mean flow [1]. There is thus at least a 3-fold difference in local perfusion and conse- quently oxygen and substrate supply between low and high flow areas. A correlation of fatty acid and glucose uptake and local flow has been demonstrated [1 3]. It is however unclear, whether there is in fact spatial heterogeneity of tricarboxylic acid cycle turnover (VTcA) and thus MVO2 and whether local perfusion influences other metabolic flux rates, e.g. anaplerosis. In the open chest dog, radioactive microspheres were applied for the determination of local coronary flow and MVO 2 measured. [3-13C]pyruvate (2 raM) was in- fused into the left anterior descending artery (LAD) for a defined period of time. Immediately thereafter the left ventricular free wall was excised and rapidly frozen. Lyophyllized tissue was cut into 40 mg pieces following a standardized scheme (256 samples/heart), r-radioac- tivity was counted and local flow determined. In each dog, a similar number of low ( 150%) flow samples were extracted. [3JgC]lactate and alanine as well as [4-~3C] and [3-~3C]glutamate were measured by ~3C-NMR spectroscopy. Glutamate and TCA cycle intermediates were determined by classical biochemical techniques in each individual sample. * Corresponding author. After [3-~3C]pyruvate infusion for 12 rain, glutamate