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Measurement of local myocardial O(2) consumption (VO(2)) has been problematic but is needed to investigate the heterogeneity of aerobic metabolism. The goal of the present investigation was to develop a method to measure local VO(2) using small frozen myocardial samples, suitable for determining VO(2) profiles. In 26 isolated rabbit hearts, 1.5 mmol/l [2-(13)C]acetate was infused for 4 min, followed by 1.5 min of [1,2-(13)C]acetate. The left ventricular (LV) free wall was then quickly frozen. High-resolution (13)C-NMR spectra were measured from extracts taken from 2- to 3-mm thick transmural layer samples. The multiplet intensities of glutamate were analyzed with a computer model allowing simultaneous estimation of the absolute flux through the tricarboxylic acid cycle and the fractional contribution of acetate to acetyl CoA formation from which local VO(2) was calculated. The (13)C-derived VO(2) in the LV free wall was linearly related to "gold standard" VO(2) from coronary venous O(2) electrode measurements in the same region (r = 0.932, n = 22, P < 0.0001, slope 1.05) for control and lowered metabolic rates. The ratio of subendocardial to subepicardial VO(2) was 1.52 +/- 0.19 (SE, significantly >1, P < 0.025). Local myocardial VO(2) can now be quantitated with this new (13)C method to determine profiles of aerobic energy metabolism.

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Myocardial perfusion is heterogeneous, even in the normal heart. It is unknown whether the resting normal blood flow level predicts the severity of mismatch between local blood flow and metabolism during acute ischaemia. In the present study local blood flow (measured with radioactively labelled microspheres) and metabolic indicators of ischaemia [tissue contents of lactate and inosine (INO), a breakdown product of adenosine triphosphate (ATP)] were determined in 84-102 simultaneously frozen samples (approximately 0.9 g) of normal (n = 7) and partially ischaemic (n = 4) porcine left ventricles. Ischaemia was induced for 20 min by partially occluding the left anterior descending artery to reduce perfusion pressure from 107 +/- 17 mm Hg to 39 +/- 10 mm Hg (mean +/- SD). Flow reduction in the ischaemic region was strongly variable, both within the subepicardium (range 6-66%, average 34%) and the subendocardium (range 33-84%, average 57%), indicating redistribution of blood flow inside transmural layers in addition to the well-known preferential decrease in subendocardial perfusion. The relative flow reduction during stenosis was not dependent on normal local perfusion level (Spearman rank correlation coefficient -0.002, P = 0.99). Samples with low or high myocardial blood flows before stenosis showed similar increases in lactate content and INO/ATP content ratio, as long as the percentage blood flow reduction was the same. It is concluded that regions with low and high resting flows in the normally perfused heart are equally susceptible to metabolism-perfusion mismatch resulting from coronary stenosis.

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