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Article
Open AccessDisrupting Na+ ion homeostasis and Na+/K+ ATPase activity in breast cancer cells directly modulates glycolysis in vitro and in vivo
Glycolytic flux is regulated by the energy demands of the cell. Upregulated glycolysis in cancer cells may therefore result from increased demand for adenosine triphosphate (ATP), however it is unknown what th...
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Article
Open AccessElevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart
Elevated intracellular sodium Nai adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused ...
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Article
Open AccessNaked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles
The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms...
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Protocol
Characterization and Validation of Radiotracer Kinetics Using the Langendorff Isolated Perfused Heart
The Langendorff isolated perfused heart is a physiologically relevant and controllable ex vivo model well suited to characterizing and validating novel radiotracers for a wide range of molecular imaging applic...
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Article
Open AccessDetecting Validated Intracellular ROS Generation with 18F-dihydroethidine-Based PET
To determine the sensitivity of the 18F-radiolabelled dihydroethidine analogue ([18F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.
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Article
Mitochondrial pyruvate carrier abundance mediates pathological cardiac hypertrophy
Cardiomyocytes rely on metabolic substrates, not only to fuel cardiac output, but also for growth and remodelling during stress. Here we show that mitochondrial pyruvate carrier (MPC) abundance mediates pathol...
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Article
Open AccessIntracellular sodium elevation reprograms cardiac metabolism
Intracellular Na elevation in the heart is a hallmark of pathologies where both acute and chronic metabolic remodelling occurs. Here, we assess whether acute (75 μM ouabain 100 nM blebbistatin) or chronic myoc...
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Article
Open AccessTissue acidosis does not mediate the hypoxia selectivity of [64Cu][Cu(ATSM)] in the isolated perfused rat heart
Copper-64-Diacetyl-bis(N4-methylthiosemicarbazone) [64Cu][Cu(ATSM)] is a hypoxia-targeting PET tracer with applications in oncology and cardiology. Upon entering a hypoxic cell, [64Cu][Cu(II)(ATSM)] is reduced to...
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Article
Open AccessDetection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT
By the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. 99mTc-sestamibi is used clinically to image cardiac perfusion by single phot...
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Article
Open AccessProteomic and metabolomic changes driven by elevating myocardial creatine suggest novel metabolic feedback mechanisms
Mice over-expressing the creatine transporter have elevated myocardial creatine levels [Cr] and are protected against ischaemia/reperfusion injury via improved energy reserve. However, mice with very high [Cr]...
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Article
Open AccessModification of intracellular glutathione status does not change the cardiac trap** of 64Cu(ATSM)
The trap** mechanisms of the PET hypoxia imaging agent copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu(ATSM)) remain unresolved, although its reduction prior to dissociation may be mediated by intrace...
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Article
Detection of the Prodrug-Activating Enzyme Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance
The purpose of this study is to evaluate if the differential exchange rates with bulk water between amine and amide protons can be exploited using chemical exchange saturation transfer magnetic resonance (CEST...
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Article
Open AccessAssessing radiotracer kinetics in the Langendorff perfused heart
The Langendorff perfused heart is a physiologically relevant and controllable model with potential for assessing the pharmacokinetics of new radiotracers under a range of pathophysiological conditions.. We ass...
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Article
Develo** Hyperpolarized 13C Spectroscopy and Imaging for Metabolic Studies in the Isolated Perfused Rat Heart
Hyperpolarized 13C magnetic resonance is a powerful tool for the study of cardiac metabolism. In this work, we have implemented protocols for the real-time hyperpolarized 13C investigation of Langendorff-perfused...
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Article
Normalized one-dimensional NOE measurements in isotopically labeled macromolecules using two-way cross-polarization
A novel one-dimensional NOE experiment is presented where a selected proton is excited by two-way heteronuclear cross- polarization between protons and nitrogen-15 or carbon-13. The utility of the method is de...
