Craig A. Lygate

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Hypoxia-inducible factor (HIF) regulates expression of genes involved in adaptation to hypoxia and ischemia. Three prolyl hydroxylases (PHD1-3) underlie oxygen-regulated destruction of HIFalpha chains. We have investigated the organ distribution of the PHDs in the rat, their regulation by hypoxia and changes in local expression after experimental myocardial(More)
PURPOSE To establish fast, high-resolution in vivo cine magnetic resonance imaging (cine-MRI) on a vertical 11.7-T MR system and to investigate the stability of normal and failing mouse hearts in the vertical position. MATERIALS AND METHODS To optimize the method on a high-field system, various MR-related parameters, such as relaxation times and the need(More)
BACKGROUND Heart failure is associated with deranged cardiac energy metabolism, including reductions of creatine and phosphocreatine. Interventions that increase myocardial high-energy phosphate stores have been proposed as a strategy for treatment of heart failure. Previously, it has not been possible to increase myocardial creatine and phosphocreatine(More)
A neuronal isoform of nitric oxide synthase (nNOS) has recently been located to the cardiac sarcoplasmic reticulum (SR). Subcellular localization of a constitutive NOS in the proximity of an activating source of Ca2+ suggests that cardiac nNOS-derived NO may regulate contraction by exerting a highly specific and localized action on ion channels/transporters(More)
RATIONALE Creatine is thought to be involved in the spatial and temporal buffering of ATP in energetic organs such as heart and skeletal muscle. Creatine depletion affects force generation during maximal stimulation, while reduced levels of myocardial creatine are a hallmark of the failing heart, leading to the widely held view that creatine is important at(More)
Conventional methods to quantify infarct size after myocardial infarction in mice are not ideal, requiring either tissue destruction for histology or relying on nondirect measurements such as wall motion. We therefore implemented a fast, high-resolution method to directly measure infarct size in vivo using three-dimensional (3D) late gadolinium enhancement(More)
High-resolution magnetic resonance cine imaging (cine-MRI) is a method that allows for a non-invasive assessment of left ventricular function and mass. To perform this quantitation, hearts are imaged from the base to the apex by a stack of two-dimensional images. Thus, analysis of myocardial mass and function by cine-MRI does not rely on geometric(More)
BACKGROUND The role of the creatine kinase (CK)/phosphocreatine (PCr) energy buffer and transport system in heart remains unclear. Guanidinoacetate-N-methyltransferase-knockout (GAMT-/-) mice represent a new model of profoundly altered cardiac energetics, showing undetectable levels of PCr and creatine and accumulation of the precursor(More)
AIMS To determine whether post-infarction LV dysfunction is due to low energy availability or inefficient energy utilization, we compared energy metabolism in normal and failing hearts. We also studied whether improved coupling of glycolysis and glucose oxidation by knockout of malonyl CoA decarboxylase (MCD-KO) would have beneficial effects on LV function(More)
BACKGROUND The neuronal isoform of nitric oxide synthase (nNOS) has been implicated in the regulation of basal and beta-adrenergic inotropy in normal and chronically infarcted hearts. Furthermore, myocardial nNOS expression and activity increase in failing hearts, raising the possibility that nNOS may influence left ventricular (LV) remodeling progression(More)