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The regulation of mammalian myocardial carbohydrate metabolism is complex in that it is linked to arterial substrate and hormone levels, coronary flow, inotropic state and the nutritional status of the tissue. Optimal cardiac function under normal and pathological conditions is dependent upon glycolysis and pyruvate oxidation. The purpose of this review is to examine the regulation of myocardial carbohydrate metabolism under physiological conditions, and during myocardial ischaemia and reperfusion. The therapeutic potential of a variety of pharmacological interventions affecting myocardial carbohydrate metabolism will then be discussed.

The tricarboxylic acid cycle (TCA cycle) provides reducing equivalents for mitochondrial oxidative phosphorylation, resulting in the condensation of ADP and inorganic phosphate to regenerate ATP, and is fueled by acetyl-CoA formed primarily from oxidation of pyruvate and fatty acids (Fig. 1). Cardiomyocytes oxidise fatty acids derived from both the plasma and the breakdown of intracellular triacylglycerol stores, while pyruvate is derived from either lactate dehydrogenase or glycolysis. The rates of these metabolic pathways are tightly coupled to the rate of contractile work, and conversely, contractile work is coupled to the supply of oxygen and the rate of oxidative phosphorylation (Fig. 1). Early studies in animals [1] and human [2, 3] showed that after an overnight fast the heart extracts free fatty acids (FFA), lactate and glucose from the blood, and that if one assumes complete oxidation of extracted substrates, fatty acids are the major oxidative fuel for the heart (60–100% of the oxygen consumption), with a lesser contribution from lactate and glucose (0–20% from each) [2, 3]. Subsequent studies by others using a variety of experimental approaches have confirmed these early results (see [4–7] for reviews).



Fig. 1 
Schematic depiction of myocardial substrate metabolism. Abbreviations: G 6-P, glucose 6-phosphate; TCA, tricarboxylic acid; GT, GLUT 1 and GLUT 4 glucose …

Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions

The effects of diabetes on myocardial metabolism are complex in that they are tied to the systemic metabolic abnormalities of the disease (hyperglycemia and elevated levels of free fatty acid and ketone bodies), and changes in cardiomyocyte phenotype (e.g., down-regulation of glucose transporters and PDH activity). The cardiac adaptations appear to be driven by the severity of the systemic abnormalities of the disease. The diabetes-induced changes in the plasma milieu and cardiac phenotype both cause impaired glycolysis, pyruvate oxidation, and lactate uptake, and a greater dependency on fatty acids as a source of acetyl CoA. Studies in isolated hearts suggest that therapies aimed at decreasing fatty acid oxidation, or directly stimulating pyruvate oxidation would be of benefit to the diabetic heart during and following myocardial ischemia.

/pdf/regulation-of-energy-substrate-metabolism-in-the-diabetic-2aolj0fv0p.pdf

Regulation of energy substrate metabolism in the diabetic heart

To investigate whether the energy derived from glycolysis is functionally coupled to Ca2+ active transport in sarcoplasmic reticulum (SR), we determined whether glycolytic enzymes were associated with SR membranes and whether metabolism through these enzymes was capable of supporting 45Ca transport. Sealed right-side-out SR vesicles were isolated by step sucrose gradient from rabbit skeletal and cardiac muscle. Intravesicular 45Ca transport was measured after the addition of glycolytic substrates and cofactors specific for each of the glycolytic reactions being studied or after the addition of exogenous ATP and was expressed as transport sensitive to the specific Ca(2+)-ATPase inhibitor thapsigargin. We found that the entire chain of glycolytic enzymes from aldolase onward, including aldolase, GAPDH, phosphoglycerate kinase (PGK), phosphoglyceromutase, enolase, and pyruvate kinase (PK), was associated with SR vesicles from both cardiac and skeletal muscle. Iodoacetic acid, an inhibitor of GAPDH, eliminated 45Ca transport supported by fructose-1,6-diphosphate, the substrate for aldolase, but transport was completely restored by phosphoenolpyruvate (the substrate for PK), indicating that both of the ATP-producing glycolytic enzymes, GAPDH/PGK and PK, were associated with the SR and functionally capable of providing ATP for the Ca2+ pump. Addition of a soluble hexokinase ATP trap eliminated 45Ca transport fueled by exogenous ATP but had markedly less effect on 45Ca transport supported by endogenously produced ATP (via glycolysis). Similarly, at very low concentrations of ATP and ADP (10 to 50 nmol/L), ATP that was produced endogenously from ADP and phosphoenolpyruvate supported 15-fold more 45Ca transport than ATP that was supplied exogenously at the same concentration. These results are consistent with functional coupling of glycolytic ATP to Ca2+ transport and support the hypothesis that ATP generated by SR-associated glycolytic enzymes may play an important role in cellular Ca2+ homeostasis by driving the SR Ca2+ pump.

Functional Coupling Between Glycolysis and Sarcoplasmic Reticulum Ca2+ Transport

Background Myocardial ischemia increases heart glucose utilization in vivo. However, whether low-flow ischemia leads to the translocation of glucose transporter (GLUT)-4 and/or GLUT-1 to the sarcolemma in vivo is unknown. Methods and Results In a canine model, we evaluated myocardial glucose metabolism in vivo and the distribution of GLUT-4 and GLUT-1 by use of immunoblotting of sarcolemma and intracellular membranes and immunofluorescence localization with confocal microscopy. In vivo glucose extraction increased fivefold (P<.001) and was associated with net lactate release in the ischemic region. Ischemia led to an increase in the sarcolemma content of both GLUT-4 (15±2% to 30±3%, P<.02) and GLUT-1 (41±4% to 58±3%, P<.03) compared with the nonischemic region and to a parallel decrease in their intracellular contents. Immunofluorescence demonstrated the presence of both GLUT-4 and GLUT-1 on cardiac myocytes. GLUT-1 had a more prominent cell surface pattern than GLUT-4, which was primarily intracellular i...

Low-Flow Ischemia Leads to Translocation of Canine Heart GLUT-4 and GLUT-1 Glucose Transporters to the Sarcolemma In Vivo

Medical imaging is fundamental to modern healthcare, and its widespread use has resulted in the creation of image databases, as well as picture archiving and communication systems. These repositories now contain images from a diverse range of modalities, multidimensional (three-dimensional or time-varying) images, as well as co-aligned multimodality images. These image collections offer the opportunity for evidence-based diagnosis, teaching, and research; for these applications, there is a requirement for appropriate methods to search the collections for images that have characteristics similar to the case(s) of interest. Content-based image retrieval (CBIR) is an image search technique that complements the conventional text-based retrieval of images by using visual features, such as color, texture, and shape, as search criteria. Medical CBIR is an established field of study that is beginning to realize promise when applied to multidimensional and multimodality medical data. In this paper, we present a review of state-of-the-art medical CBIR approaches in five main categories: two-dimensional image retrieval, retrieval of images with three or more dimensions, the use of nonimage data to enhance the retrieval, multimodality image retrieval, and retrieval from diverse datasets. We use these categories as a framework for discussing the state of the art, focusing on the characteristics and modalities of the information used during medical image retrieval.

/pdf/content-based-medical-image-retrieval-a-survey-of-3g4b7ysuqa.pdf

Content-based medical image retrieval: a survey of applications to multidimensional and multimodality data.

Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium.

Part 1. Clinical and Technical Principles: Introduction Principles of PET/CT Imaging A Future for PET/CT Imaging PET/CT Image Acquisition Protocols and Imaging Data Workflow Acquisition Schemes for Combined 18F-FDG-PET/CT. Imaging: A European Experience From FDG-PET to FDG-PET/CT Imaging Normal Pattern and Common Pitfalls of FDG-PET Image Interpretation.- Part 2. Atlas: PET/CT Image Artifacts Physiological Variants Anatomical Masses vs Viable Tumor Cancers of Head and Neck Solitary Pulmonary Nodules Lung Cancer Cancers of the Gastrointestinal Tract Lymphoma Cancers of the Skin Breast Cancer Gynecological Cancers Cancers of the Genito-Urinary System Benign Diseases.

Atlas of PET/CT Imaging in Oncology

First human study of BMS747158, a novel F-18 labeled tracer for myocardial perfusion imaging

Phase 1 rest-stress study of F-18 labeled BMS747158 myocardial perfusion PET tracer: Human safety, dosimetry, biodistribution, and myocardial imaging characteristics

N-13 Labeled Ammonia and Positron Emission Computerized Axial Tomography

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