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Acute myocardial ischemia causes a transmural gradient in glucose extraction but not glucose uptake
W C Stanley1, J L Hall, C K Stone
1Section of Cardiology, University of Wisconsin, Madison 53706.
Insights
Acute myocardial ischemia increases glucose extraction but not uptake due to reduced blood flow. Glycolysis relies on glycogen breakdown, not increased glucose uptake, during ischemia.
Area of Science:
- Cardiovascular Physiology
- Metabolic Regulation
- Ischemic Heart Disease Research
Background:
- Myocardial glucose metabolism is crucial for energy production, especially during ischemia.
- Understanding substrate utilization during reduced coronary blood flow is vital for treating ischemic heart disease.
Purpose of the Study:
- To investigate the relationship between myocardial glucose metabolism and blood flow during acute ischemia.
- To determine if increased glucose extraction compensates for reduced coronary artery flow.
- To elucidate the primary source of energy for glycolysis under ischemic conditions.
Main Methods:
- Utilized an open-chest swine model with controlled coronary perfusion.
- Measured myocardial glucose uptake (Rg) using 2-deoxy-D-[14C]glucose infusion.
- Assessed myocardial blood flow with radiolabeled microspheres and analyzed myocardial biopsies.
Main Results:
- Subendocardial blood flow significantly decreased by 60% in the left anterior descending (LAD) coronary artery bed during ischemia.
- Arterial-venous glucose difference increased in the ischemic LAD bed, indicating higher glucose extraction.
- Despite increased extraction, the overall rate of glucose uptake did not significantly differ between ischemic and normally perfused beds.
- Subendocardial glycogen concentration was markedly reduced in the ischemic LAD bed.
Conclusions:
- Acute ischemia enhances myocardial glucose extraction but fails to increase overall glucose uptake due to severe blood flow reduction.
- Glycolysis during acute ischemia is primarily fueled by accelerated glycogenolysis, not increased glucose uptake.
- These findings highlight the limited capacity of glucose uptake to meet energy demands under significant ischemic conditions.
Abstract:
We assessed the relationship between myocardial glucose metabolism and blood flow during ischemia in eight open-chest swine. Coronary flow was controlled by an extracorporeal perfusion circuit. Left anterior descending coronary arterial (LAD) flow was reduced by 60%, while left circumflex flow was normally perfused. The rate of glucose uptake (Rg) was measured with a coronary infusion of 2-deoxy-D-[14C]glucose and myocardial blood flow with radiolabeled microspheres. Myocardial biopsies were taken after 50 min of ischemia. Regional arterial-venous glucose difference was calculated as Rg per myocardial blood flow. Subendocardial blood flow decreased from 1.27 +/- 0.19 to 0.25 +/- 0.11 ml.g-1.min-1 (P less than 0.0001). The subendocardial arterial-venous glucose difference was greater in the LAD bed (1.38 +/- 0.35 mumol/ml) than the left circumflex coronary arterial perfusion bed (0.10 +/- 03; P less than 0.01); however, there was no statistically significant difference in the rate of glucose uptake between the two beds. Subendocardial glycogen concentration in the LAD perfusion bed was reduced to 26% of circumflex bed values. In conclusion, acute ischemia stimulated a dramatic increase in glucose extraction; however, this did not compensate for the decrease in blood flow, and thus the rate of glucose uptake did not increase significantly. The high rate of glycolysis is primarily supported by accelerated net glycogen breakdown rather than increased glucose uptake.