Transmural metabolic heterogeneity at high cardiac work states

This study compared the transmural distribution of high-energy phosphate (HEP) depletion during oxidative stress induced by pacing- and dobutamine-induced tachycardia in myocardium perfused by a flow-limiting coronary stenosis. Myocardial blood flow (MBF) was measured with radioactive microspheres. Creatine phosphate (CrP), ATP, and P-i were measured with transmurally localized P-31 NMR spectroscopy. In normal dogs a hydraulic occluder was used to produce a left anterior descending coronary artery stenosis, which maintained constant flow measured with a Doppler probe. Tachycardia was induced by rapid pacing (200 beats/min, n = 11) or by dobutamine infusion (20 mu g . kg(-1) . min(-1) iv, n = 13) to produce a similar heart rate. In the presence of stenosis, pacing and dobutamine caused similar reductions of subendocardial (Endo)-to-subepicardial (Epi) MBF ratios (0.66 +/- 0.06 vs. 0.63 +/- 0.08, respectively). Stenosis plus pacing caused a decrease of the CrP-to-ATP ratio (CrP/ATP) in Endo from 2.00 +/- 0.07 to 1.65 +/- 0.08 (P < 0.05) with no significant change in Epi. Stenosis plus dobutamine caused HEP changes across the left ventricular wall, which were most marked in the outer myocardial layer (Epi CrP/ATP decreased from 2.33 +/- 0.11 to 1.67 +/- 0.12; Endo CrP/ATP decreased from 1.99 +/- 0.09 to 1.64 +/- 0.12). Thus HEP changes during oxidative stress that are produced by pacing parallel the pattern of hypoperfusion and are most severe in the subendocardium. In contrast, in response to inotropic stimulation, the transmural metabolic changes did not correspond to the pattern of the hypoperfusion.