Myocardial regions perfused through a coronary stenosis may cease contracting, but remain viable. Clinical observations suggest that increased glucose utilization may be an adaptive mechanism in such "hibernating" regions. In this study, we used a combination of 13C-NMR spectroscopy, GC-MS analysis, and tissue biochemical measurements to track glucose through intracellular metabolism in intact dogs infused with [1-13C]glucose during a 3-4-h period of acute ischemic hibernation. During low-flow ischemia [3-13C]alanine enrichment was higher, relative to plasma [1-13C]glucose enrichment, in ischemic than in nonischemic regions of the heart, suggesting a greater contribution of exogenous glucose to glycolytic flux in the ischemic region (approximately 72 vs. approximately 28%, P < 0.01). Both the fraction of glycogen synthase present in the physiologically active glucose-6-phosphate-independent form (46 +/- 10 vs. 9 +/- 6%, P < 0.01) and the rate of incorporation of circulating glucose into glycogen (94 +/- 25 vs. 20 +/- 15 nmol/gram/min, P < 0.01) were also greater in ischemic regions. Measurement of steady state [4-13C)glutamate/[3-13C]alanine enrichment ratios demonstrated that glucose-derived pyruvate supported 26-36% of total tricarboxylic acid cycle flux in all regions, however, indicating no preference for glucose over fat as an oxidative substrate in the ischemic myocardium. Thus during sustained regional low-flow ischemia in vivo, the ischemic myocardium increases its utilization of exogenous glucose as a substrate. Upregulation is restricted to cytosolic utilization pathways, however (glycolysis and glycogen synthesis), and fat continues to be the major source of mitochondrial oxidative substrate.
P H McNulty, A J Sinusas, C Q Shi, D Dione, L H Young, G C Cline, G I Shulman
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Exercise 18FDG Imaging for the Detection of CAD: What Are the Clinical Hurdles?
D Jain, ZX He, A Ghanbarinia |
Current Cardiology Reports | 2010 |
Direct Imaging of Myocardial Ischemia With 18FDG: A New Potentially Paradigm-Shifting Molecular Cardiovascular Imaging Technique
D Jain, ZX He, A Ghanbarinia, J Baron, A Gavriluke |
Current Cardiovascular Imaging Reports | 2010 |
Myocardial Fatty Acid Metabolism in Health and Disease
GD Lopaschuk, JR Ussher, CD Folmes, JS Jaswal, WC Stanley |
Physiological reviews | 2010 |
Transmural distribution of metabolic abnormalities and glycolytic activity during dobutamine-induced demand ischemia
MN Jameel, X Wang, MH Eijgelshoven, A Mansoor, J Zhang |
American journal of physiology. Heart and circulatory physiology | 2008 |
Myocardial 18 F-FDG Uptake After Exercise-Induced Myocardial Ischemia in Patients with Coronary Artery Disease
KF Dou, MF Yang, YJ Yang, D Jain, ZX He |
Journal of Nuclear Medicine | 2008 |
Direct imaging of myocardial ischemia: A potential new paradigm in nuclear cardiovascular imaging
D Jain, Z He |
Journal of Nuclear Cardiology | 2008 |
Alterations in energy metabolism in cardiomyopathies
M Taha, GD Lopaschuk |
Annals of Medicine | 2007 |
[18F]Fluorodeoxyglucose as a memory marker of transient myocardial ischaemia
BG Abbott, YH Liu, JA Arrighi |
Nuclear Medicine Communications | 2007 |
Acute lipoprotein lipase deletion in adult mice leads to dyslipidemia and cardiac dysfunction
HL Noh, K Okajima, JD Molkentin, S Homma, IJ Goldberg |
American journal of physiology. Endocrinology and metabolism | 2006 |
Metabolic Therapy for Ischemic Heart Disease: The Rationale for Inhibition of Fatty Acid Oxidation
WC Stanley, HN Sabbah |
Heart Failure Reviews | 2005 |
Discrepancy between GLUT4 translocation and glucose uptake after ischemia
V Zaha, R Nitschke, H Göbel, U Fischer-Rasokat, C Zechner, T Doenst |
Molecular and Cellular Biochemistry | 2005 |
Myocardial Metabolism and Improved OutcomesAfter High Risk Heart Surgery
M Keith, L Errett |
Seminars in cardiothoracic and vascular anesthesia | 2005 |
Computational studies of the effects of myocardial blood flow reductions on cardiac metabolism
JE Salem, WC Stanley, ME Cabrera |
BioMedical Engineering OnLine | 2004 |
Myocardial Energy Metabolism During Ischemia and the Mechanisms of Metabolic Therapies
WC Stanley |
Journal of cardiovascular pharmacology and therapeutics | 2004 |
Myocardial Ischemia Differentially Regulates LKB1 and an Alternate 5′-AMP-activated Protein Kinase Kinase
JY Altarejos, M Taniguchi, AS Clanachan, GD Lopaschuk |
The Journal of biological chemistry | 2004 |
Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidine
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Fundamental and Clinical Pharmacology | 2003 |
Diabetes Mellitus and Heart Failure
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Congestive Heart Failure | 2003 |
Effect of hyperglycemia and fatty acid oxidation inhibition during aerobic conditions and demand-induced ischemia
PN Chavez, WC Stanley, TA McElfresh, H Huang, JP Sterk, MP Chandler |
American journal of physiology. Heart and circulatory physiology | 2003 |
Partial fatty acid oxidation inhibitors for stable angina
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Expert Opinion on Investigational Drugs | 2002 |
Glucose and insulin management in the post-MI setting
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Current Diabetes Reports | 2002 |
Energy metabolism in the normal and failing heart: potential for therapeutic interventions
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Heart Failure Reviews | 2002 |
Energy stores and metabolites in chronic reversibly and irreversibly dysfunctional myocardium in humans
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Journal of the American College of Cardiology | 2001 |
Cardiovascular implications of insulin resistance and non–insulin-dependent diabetes mellitus
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Journal of Cardiothoracic and Vascular Anesthesia | 2001 |
Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO
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Acute hibernation decreases myocardial pyruvate carboxylation and citrate release
AR Panchal, B Comte, H Huang, B Dudar, B Roth, M Chandler, CD Rosiers, H Brunengraber, WC Stanley |
American journal of physiology. Heart and circulatory physiology | 2001 |
Exercise-induced myocardial ischemia: can this be imaged with F-18-fluorodeoxyglucose?
D Jain, PH McNulty |
Journal of Nuclear Cardiology | 2000 |
In vivo models of myocardial metabolism during ischemia
WC Stanley |
Journal of Pharmacological and Toxicological Methods | 2000 |
Methodology for measuring in vitro/ex vivo cardiac energy metabolism
RL Barr, GD Lopaschuk |
Journal of Pharmacological and Toxicological Methods | 2000 |
Regulation of myocardial [ 13 C]glucose metabolism in conscious rats
PH McNulty, GW Cline, JM Whiting, GI Shulman |
American journal of physiology. Heart and circulatory physiology | 2000 |
In vivo magnetic resonance methods in pharmaceutical research: current status and perspectives
M Rudin, N Beckmann, R Porszasz, T Reese, D Bochelen, A Sauter |
NMR in Biomedicine | 1999 |
Reversible congestive heart failure caused by myocardial hibernation
JM Wilson |
Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital | 1999 |
Energy substrate metabolism, myocardial ischemia, and targets for pharmacotherapy
H Taegtmeyer, LM King, BE Jones |
The American Journal of Cardiology | 1998 |
Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart. A three tracer study of glycolysis, glycogen metabolism, and glucose oxidation
RR 3rd, GW Cline, PH Guthrie, GW Goodwin, GI Shulman, H Taegtmeyer |
Journal of Clinical Investigation | 1997 |
Effects of insulin on glucose uptake by rat hearts during and after coronary flow reduction
TM Chen, GW Goodwin, PH Guthrie, H Taegtmeyer |
American journal of physiology. Heart and circulatory physiology | 1997 |
Glucose Metabolism in the Ischemic Heart
GD Lopaschuk, WC Stanley |
Circulation | 1997 |
Advantages and limitations of experimental techniques used to measure cardiac energy metabolism
G Lopaschuk |
Journal of Nuclear Cardiology | 1997 |