Oxidative stress and free radicals shortens the cardiac action potential, which is proarrhythmic, i.e. increasing the likelihood of ventricular and supraventricular arrhythmias. We want to test if perfusing a healthy heart with hydrogen peroxide changes the electrophysiological properties of the heart and if it alters the proarrhythmic potential of both the atria and the ventricles. We will use mouse hearts under oxidative stress to elicit pacing-induced delayed afterdepolarizations and perpetuating arrhythmias. We will test if the afterdepolarizations are Na-dependent or Ca-dependent. We will test if there are differences in the effects of reactive oxygen species in the atria and the ventricles. If consistently large effects are identified, we will proceed to feed the mice nitrates prior to experiments to test if this can negate the deleterious effects of oxidative stress.
The hypothesis is that oxidative stress is proarrhythmic in the heart and that this can be altered by dietary nitrates.