Optical imaging of cardiac atrial activation and repolarisation in genetically altered models

A method for developing an optical mapping system to quantify electrical activation and repolarisation in murine left atria was created. The spread of activation is important in understanding the mechanisms for the rhythm of the heart in healthy and diseased states as cardiovascular disease is the leading cause of death worldwide. The activation spread was recorded using a novel 2nd generation high resolution (128x2048 pixels) CMOS camera with the voltage sensitive dye di-4-ANEPPS. Algorithms for automatic quantification of action potential duration and conduction velocities were implemented in MATLAB. Optical mapping results were validated against monophasic action potentials and microelectrode measurements showing comparable duration measurements. A genetic mouse model of atrial fibrillation was used (Pitx2c\(^+\)\(^/\)\(^-\)) and was found to have a shorter action potential duration in the left atrium compared to wild-type mice. The results showed a preferential antiarrhythmic effect of the sodium channel blocker, flecainide, to the left atrium of Pitx2c\(^+\)\(^/\)\(^-\) mice. A second mouse model was used to mimic arrhythmogenic right ventricular cardiomyopathy (plako\(^+\)\(^/\)\(^-\)). No significant changes were witnessed in young sedentary cohorts at baseline and flecainide slowed conduction in both WT and plako\(^+\)\(^/\)\(^-\). In endurance trained mice, a prolongation of the effective refractory period was seen after flecainide treatment. Plako\(^+\)\(^/\)\(^-\) sedentary mice treated with dihydrotestosterone showed a prolongation in action potential duration