A5067455165- Cardiovascular Function and Risk Factors
- Cardiac Imaging and Diagnostics
- Cardiomyopathy and Myosin Studies
- Diet and metabolism studies
- Cardiac Valve Diseases and Treatments
- Heart Failure Treatment and Management
- Cardiac Ischemia and Reperfusion
- Advanced MRI Techniques and Applications
- Digestive system and related health
- Cardiovascular Effects of Exercise
- Cardiac electrophysiology and arrhythmias
- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Diet, Metabolism, and Disease
- Cardiac Arrest and Resuscitation
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Nitric Oxide and Endothelin Effects
- Renal cell carcinoma treatment
- Cardiovascular and exercise physiology
- Heart Rate Variability and Autonomic Control
- Amino Acid Enzymes and Metabolism
- Congenital heart defects research
- Anesthesia and Neurotoxicity Research
- Metabolomics and Mass Spectrometry Studies
University of Oxford
2013-2024
John Radcliffe Hospital
2010-2024
Aristotle University of Thessaloniki
2019
Resonance Research (United States)
2019
St George's, University of London
2019
Centre for Human Genetics
2010-2018
British Heart Foundation
2018
University of East Anglia
2015
University of Aberdeen
2010-2015
Imperial College London
2002-2014
Background— Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires novel approach to therapy. Perhexiline an antianginal drug augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects perhexiline treatment in CHF patients. Methods Results— In double-blind fashion, we randomly assigned patients with optimally medicated either (n=28) or placebo (n=28). The primary end...
Background— Hypertrophic cardiomyopathy patients exhibit myocardial energetic impairment, but a causative role for this energy deficiency in the pathophysiology of hypertrophic remains unproven. We hypothesized that metabolic modulator perhexiline would ameliorate and thereby improve diastolic function exercise capacity. Methods Results— Forty-six consecutive with symptomatic limitation (peak V̇ o 2 <75% predicted) caused by nonobstructive (mean age, 55±0.26 years) were randomized to 100...
The citric acid cycle (CAC) metabolite fumarate has been proposed to be cardioprotective; however, its mechanisms of action remain determined. To augment cardiac levels and assess fumarate's cardioprotective properties, we generated hydratase (Fh1) knockout (KO) mice. These fumarate-replete hearts were robustly protected from ischemia-reperfusion injury (I/R). compensate for the loss Fh1 activity, KO maintain ATP in part by channeling amino acids into CAC. In addition, stabilizing...
Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing neuroimaging can inform strategies therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years age in Scotland...
It has been proposed that under hypoxic conditions, nitrite may release nitric oxide, which causes potent vasodilation. We hypothesized would have a greater dilator effect in capacitance than resistance vessels because of lower oxygen tension and resistance-vessel dilation should become more pronounced during hypoxemia. The intra-arterial infusion on forearm blood flow venous volumes was assessed normoxia hypoxia.Forty healthy volunteers were studied. After baseline 0.9% saline, sodium...
Ischaemic preconditioning results in a reduction ischaemic-reperfusion injury to the heart. This beneficial effect is seen both with direct local of myocardium and remote easily accessible distant non-vital limb tissue. postconditioning comparable sequence brief periods ischaemia, when applied immediately after ischaemic insult, confers benefits similar preconditioning.To test hypothesis that ischaemia induces hence reduces experimental myocardial infarct size validated swine model acute...
Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only small proportion the clinical cases emphasising need alternative discovery approaches uncovering novel pathogenic hitherto unidentified pathways. Accordingly, as part large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified mouse mutant, Python, which develops DCM. We demonstrate that Python phenotype is attributable dominant fully penetrant mutation...
Background— Heart failure with preserved ejection fraction (HFpEF) is associated significant morbidity and mortality but currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested hypothesis that improves exercise capacity Methods Results— conducted randomized, crossover study comparing selective I f blocker ivabradine at 7.5 mg twice daily versus placebo for 2...
Abstract Autoimmunity can occur when a checkpoint of self-tolerance fails. The study familial autoimmune diseases reveal pathophysiological mechanisms involved in more common diseases. Here, by whole-exome/genome sequencing we identify heterozygous, autosomal-dominant, germline loss-of-function mutations the SOCS1 gene ten patients from five unrelated families with early onset manifestations. intracellular protein is known to downregulate cytokine signaling inhibiting JAK-STAT pathway....
Myocardial T1 relaxation times have been reported to be markedly abnormal in diverse myocardial pathologies, ascribed interstitial changes, evaluated by mapping and calculation of extracellular volume (ECV). is sensitive water content both intra- origin, but the effect intravascular compartment changes on has largely neglected. We aimed assess role native (pre-contrast) values studying adenosine-induced vasodilatation patients with severe aortic stenosis (AS) before after valve replacement (AVR).
Mutations in the gene encoding Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer affected individuals. FH-associated neoplasia is characterized by defective mitochondrial function upregulation of transcriptional pathways mediated hypoxia-inducible factor (HIF), although whether what means these processes are linked has been disputed. We analysed HIF pathway Fh1−/− mouse embryonic fibroblasts (MEFs), FH-defective neoplastic tissues MEFs...
The identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between dysregulation and cancer. Mutations the Krebs cycle enzyme, fumarate hydratase (FH), predispose affected individuals to leiomyomas, renal cysts, cancers, though respective pathogenic roles mitochondrial cytosolic FH isoforms remain undefined. On basis comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells tissues exhibit defects urea cycle/arginine...