The objective of our current work is to understand the
mechanisms that change a normal heart into one that is
diseased. Our past studies have shown that most forms of heart disease
are associated with alterations in substrate metabolism.
Fatty acids and carbohydrates are the predominant fuels used
by the heart to power contraction, and we have shown that in
many diseases their is an imbalance between fatty acid and
glucose metabolism, leaving the heart energetically impaired
and metabolically inflexible. MR methods are unique in allowing the study of cardiac
problems by following biochemical changes over time, either
short- or long-term, in response to stress, perturbation or
therapy.
It is over thirty years since Professor Sir George Radda developed magnetic
resonance (MR) spectroscopy in the Department of Biochemisty at the University of Oxford for the in vivo study of bioenergetics. Since then MR imaging and spectroscopy have
become powerful, non-invasive tools for investigating the functional and
biochemical basis of human heart disease.
Our clinical studies are closely linked to basic biochemical and physiological research, in that we
use models of human cardiac diseases that are associated with high mortality,
such as diabetes, hypertension, obesity or heart failure. In these studies we
use MRS and MRI, combined with other molecular, physiological and biochemical
techniques, to determine alterations in energy function and metabolism.
In our clinical studies, we detect energetic and functional
changes in heart and skeletal muscle in patients to see whether
therapy reverses the abnormalities. We work on two Oxford sites;
basic scientific studies are in the Department of Physiology and
clinical studies are in the OCMR Facility at the John Radcliffe
Hospital. By understanding the disease process and the
mechanisms that lead to cardiac contractile dysfunction, we hope
to provide a rational basis for prevention or therapeutic
intervention.
