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Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale(More)
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] develop cardiac hypertrophy and dysfunction. To investigate these contrasting effects, we applied a non-biased hypothesis-generating approach to(More)
BACKGROUND To investigate the utility of three-dimensional guide-point modeling (GPM) to reduce the time required for CMR evaluation of global cardiac function in mice, by reducing the number of image slices required for accurate quantification of left-ventricular (LV) mass and volumes. METHODS Five female C57Bl/6 mice 8 weeks post myocardial infarction(More)
BACKGROUND High-resolution magnetic resonance imaging (cine-MRI) is well suited for determining global cardiac function longitudinally in genetically or surgically manipulated mice, but in practice it is seldom used to its full potential. In this study, male and female guanidinoacetate N-methyltransferase (GAMT) knockout, and wild type littermate mice were(More)
AIMS Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We(More)
BACKGROUND Insufficient techniques exist for rapid and reliable phenotype characterization of genetically manipulated mouse models of cardiac dysfunction. We developed a new, robust, 3-dimensional echocardiography (3D-echo) technique and hypothesized that this 3D-echo technique is as accurate as magnetic resonance imaging (MRI) and histology for assessment(More)
OBJECTIVE Many patients with heart failure have whole-body insulin resistance and reduced cardiac fluorodeoxyglucose uptake, but whether these metabolic changes have detrimental effects on the heart is unknown. Here, we tested whether there is a link between insulin resistance and ischemic damage in the chronically infarcted Wistar rat heart, postulating(More)
MRI can accurately and reproducibly assess cardiac function in rodents but requires relatively long imaging times. Therefore, parallel imaging techniques using a 4-element RF-coil array and MR sequences for cardiac MRI in rats were implemented at ultra-high magnetic fields (9.4 Tesla [T]). The hypothesis that these developments would result in a major(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)
MRI has become an important tool to noninvasively assess global and regional cardiac function, infarct size, or myocardial blood flow in surgically or genetically modified mouse models of human heart disease. Constraints on scan time due to sensitivity to general anesthesia in hemodynamically compromised mice frequently limit the number of parameters(More)