Myocardial O₂consumption in porcine left ventricle is heterogeneously distributed in parallel to heterogeneous O₂delivery

Abstract

and correlated well (r ϭ 0.85, P ϭ 0.02, n ϭ 7) with oxygen consumption calculated from blood flow, hemoglobin, and blood gas measurements (mean 22.8 Ϯ 4.7 mol⅐min Ϫ1 ⅐g dry wt Ϫ1). Local blood flow and oxygen consumption were significantly correlated (r ϭ 0.63 for pooled normalized data, P Ͻ 0.0001, n ϭ 60). We calculate that, in the heart at normal workload, the variance of left ventricular oxygen delivery at submilliliter resolution is explained for 43% by heterogeneity in oxygen demand. regional blood flow; metabolism; myocardium; magnetic resonance spectroscopy MYOCARDIAL BLOOD FLOW is highly heterogeneous, as demonstrated in many different species, with various methods (radioactive, colored and fluorescent microspheres, molecular tracers, MRI, and PET), and under different experimental circumstances, such as open-versus closed-chest and anesthetized versus awake animals (5,9,19,22,26,27). Myocardial perfusion shows similar heterogeneity in the human heart (47). This heterogeneity is largely of spatial nature, although there is also some temporal variation (27). Local blood flow can differ by a factor five among small areas of the left ventricle, even in the normal heart. Interestingly, regional blood flow is rather stable over a substantial time period, at least for several hours, but some data even indicate a relatively stable local blood flow over days (44). From an anatomic and mechanical point of view, this heterogeneity is difficult to understand because the heart appears rather homogeneous and biomechanical models predict homogeneous contraction. The question thus remains: which factors contribute to heterogeneous blood flow? Heterogeneity in oxygen consumption (V O 2 ) between different areas of the left ventricle may explain at least part of the heterogeneity of myocardial blood flow. Indeed, it has been shown in previous studies (9,19) that indirect indicators of local aerobic metabolism show heterogeneity. For instance, a correlation between local blood flow and fatty acid uptake has been shown (24). Others (38, 39) have reported a rather good correlation between local myocardial blood flow and local myocardial V O 2 (MV O 2 ) measured by [18 O]water in the isolated buffer-perfused rabbit heart. Low-flow areas had lower V O 2 and highflow areas had higher V O 2 . Further studies showed that areas of the left ventricle that receive a relatively low amount of blood flow are not in a hypoxic state, suggesting local adaptation of blood flow to oxygen demand (8,11,14). However, direct measurement of aerobic metabolic flux in small myocardial regions became possible only recently. Regional V O 2 and regional blood flow can be estimated with PET, although this technique still does not permit analysis at sufficiently high spatial resolution to study cardiac heterogeneity in small tissue areas (1,34,37).To investigate the distribution of MV O 2 at high spatial resolution, a new combination of isotope labeling protocol and mathematical analysis of 13 C incorporation into the tricarboxylic acid (TCA) cycle ...

Progressively heterogeneous mismatch of regional oxygen delivery to consumption during graded coronary stenosis in pig left ventricle

“…To obtain a metabolic steady state of substrate use, unlabeled sodium acetate (40 mmol/l infused at 2.25 ml/min) was infused directly into the LAD for 30 min. Acetate concentrations in systemic arterial blood, measured in five hearts of the control group, were 159 Ϯ 176 mol/l (means Ϯ SD) and did not change significantly over the 30-min period of intracoronary infusion of unlabeled acetate, as reported previously (2). Coronary venous acetate concentration was 44 Ϯ 44 mol/l at the start of the infusion and increased rapidly to 870 Ϯ 459 mol/l after 10 min of acetate infusion, remaining at Ͼ700 mol/l thereafter, indicating a stable metabolic situation.…”

“…2; n ϭ 4, see Ref. 1) from studies that have been published previously (2,21), where blood flow and metabolism were measured at t ϭ 30 or 90 min, respectively. Therefore, the pooled control group is denoted as "t ϭ 30/90" in the present study.…”

“…Blood flow was measured in that study with microspheres, and O 2 uptake was estimated from the tricarboxylic acid (TCA) cycle flux using quick-frozen tissue samples after [ 13 C]acetate infusion followed by nuclear magnetic resonance (NMR) analyses. However, the metabolism-perfusion matching, although statistically significant, was imperfect (1,2).…”

“…Regional matching of O 2 supply to demand was demonstrated by a fair correlation between regional coronary blood flow and oxygen uptake in the normal pig heart without obstructed coronary vessels (2). Blood flow was measured in that study with microspheres, and O 2 uptake was estimated from the tricarboxylic acid (TCA) cycle flux using quick-frozen tissue samples after [ 13 C]acetate infusion followed by nuclear magnetic resonance (NMR) analyses.…”

“…Myocardial blood flow, measured with microspheres, is highly heterogeneous under basal conditions without coronary obstruction, even within the same myocardial layer, and regional flow varies by a factor up to seven from one area to the other (1,2,4,5,12,15,21,25,31). Regional matching of O 2 supply to demand was demonstrated by a fair correlation between regional coronary blood flow and oxygen uptake in the normal pig heart without obstructed coronary vessels (2).…”