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Updated: Jul 5, 2026
In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography
Published on: February 16, 2016
Transmural distribution of metabolic abnormalities and glycolytic activity during dobutamine-induced demand ischemia
Mohammad N Jameel1, Xiaohong Wang, Marcel H J Eijgelshoven
1Cardiovascular Division, Departments of Medicine, University of Minnesota Medical School. Minneapolis, Minnesota, USA.
Insights
This study investigated how the heart
Area of Science:
- Cardiovascular Physiology
- Metabolic Research
- Myocardial Ischemia
Background:
- Left ventricular wall exhibits transmural heterogeneity in oxygen consumption and energetics.
- Subendocardial layers have higher metabolic demands compared to subepicardial layers.
- The transmural distribution of metabolic changes during demand ischemia is not well understood.
Purpose of the Study:
- To determine the transmural distribution of energy demand and metabolic markers of ischemia during dobutamine-induced demand ischemia.
- To investigate myocardial metabolic responses under basal, dobutamine-stimulated, and ischemic conditions.
Main Methods:
- Measurement of hemodynamics, high-energy phosphates (HEP), 2-deoxyglucose-6-phosphate (2-DGP) levels, and myocardial blood flow (MBF).
- Experiments conducted under basal conditions, during dobutamine (DOB) infusion, and during coronary stenosis with DOB and 2-deoxyglucose (2-DG) infusion.
- Analysis of transmural metabolic changes and water content in ischemic zones.
Main Results:
- Dobutamine increased cardiac work (RPP) and MBF without altering the subendocardial-to-subepicardial flow ratio (ENDO/EPI) or HEP levels.
- Coronary stenosis combined with dobutamine and 2-DG decreased RPP, ischemic zone MBF, and the ENDO/EPI ratio.
- Significant decreases in creatine phosphate-to-ATP ratio and accumulation of 2-DGP were observed, particularly in subepicardial layers, indicating a shift towards carbohydrate metabolism.
- Increased tissue water content in the ischemic zone.
Conclusions:
- During dobutamine-induced high cardiac work in a stenotic bed, subepicardial layers exhibit greater metabolic changes.
- A shift towards higher carbohydrate metabolism in the subepicardium suggests a homeostatic response to increased energy demand.
- These findings highlight transmural differences in metabolic adaptation to ischemia and high cardiac workload.
Abstract:
The heterogeneity across the left ventricular wall is characterized by higher rates of oxygen consumption, systolic thickening fraction, myocardial perfusion, and lower energetic state in the subendocardial layers (ENDO). During dobutamine stimulation-induced demand ischemia, the transmural distribution of energy demand and metabolic markers of ischemia are not known. In this study, hemodynamics, transmural high-energy phosphate (HEP), 2-deoxyglucose-6-phosphate (2-DGP) levels, and myocardial blood flow (MBF) were determined under basal conditions, during dobutamine infusion (DOB: 20 microg x kg(-1) x min(-1) iv), and during coronary stenosis + DOB + 2-deoxyglucose (2-DG) infusion. DOB increased rate pressure products (RPP) and MBF significantly without affecting the subendocardial-to-subepicardial blood flow ratio (ENDO/EPI) or HEP levels. During coronary stenosis + DOB + 2-DG infusion, RPP, ischemic zone (IZ) MBF, and ENDO/EPI decreased significantly. The IZ ratio of creatine phosphate-to-ATP decreased significantly [2.30 +/- 0.14, 2.06 +/- 0.13, and 2.04 +/- 0.11 to 1.77 +/- 0.12, 1.70 +/- 0.11, and 1.72 +/- 0.12 for EPI, midmyocardial (MID), and ENDO, respectively], and 2-DGP accumulated in all layers, as evidenced by the 2-DGP/PCr (0.55 +/- 0.12, 0.52 +/- 0.10, and 0.37 +/- 0.08 for EPI, MID, and ENDO, respectively; P < 0.05, EPI > ENDO). In the IZ the wet weight-to-dry weight ratio was significantly increased compared with the normal zone (5.9 +/- 0.5 vs. 4.4 +/- 0.4; P < 0.05). Thus, in the stenotic perfused bed, during dobutamine-induced high cardiac work state, despite higher blood flow, the subepicardial layers showed the greater metabolic changes characterized by a shift toward higher carbohydrate metabolism, suggesting that a homeostatic response to high-cardiac work state is characterized by more glucose utilization in energy metabolism.
