Heterogeneity in the failing right heart

It is known that variations in the way in which the muscle cells of the left side of the heart work are important in its normal function. Changes in these variations are also important when the heart becomes diseased and may lead to a breakdown in the rhythmic beating of the heart. However much less is know about these variations on the right side of the heart, which pumps blood to the lungs. We will investigate the right side of the heart in normal and failing hearts using techniques that will allow us to link changes in structure to changes in the electrical activity of the heart. We will discover whether specific areas of the right heart are more affected by disease than others. If this is the case these regions may be useful targets for treatment of right heart failure.

Heterogeneity (variations) in the structure and function of left ventricular myocytes is known to be important in both the normal and pathological function of the heart. However, although right ventricular failure may affect up to 1 in 20, much less is known about the role of heterogeneity in the right ventricle. Using an animal model of right heart failure induced by pulmonary hypertension, we will investigate heterogeneity in normal and failing hearts using techniques to image both the structure (by DT-MRI) and electrical activity (by optical mapping and monophasic action potentials) of whole hearts. Single cardiac myocytes isolated from regions of interest will be used to investigate cellular mechanism of action, including ion channel function and gene expression. We will test the hypothesis that specific regions of the right ventricle are more affected by disease than others and that these areas may be the source of disruption to electrical stability in the diseased right heart.