Functional and regional selectivity of the cardiac preganglionic sympathetic neurones

Upregulation of sympathetic activity is known to be a significant factor in the development of life threatening arrhythmias that can lead to sudden cardiac death. Sympathetic pathways therefore pose as a target for treatment, however a better understanding of the anatomy and physiology of cardiac sympathetic nerves is necessary. Right and left spinal sympathetic neurones differentially innervate specific regions of the heart but whether they exhibit functional selectivity and distinct effects on cardiac electrophysiology has yet to be demonstrated. A novel refinement of the original isolated innervated rabbit heart preparation, that allows controlled segmental stimulation, was used to study the effects of left and right-sided sympathetic chain stimulation on effective refractory period, action potential duration restitution and ventricular fibrillation threshold. A right-left difference in the functional effects was observed, with the left sympathetics displaying a preferential effect on ventricular electrophysiology with shorter effective refractory periods, steeper restitution slopes and smaller ventricular fibrillation thresholds than the right. The results also reveal previously unidentified characteristics of the lower thoracic spinal outflow on the left side having a dominant effect on cardiac electrophysiology and high potential to cause ventricular arrhythmias. Optical mapping was used to investigate the heterogeneous regional selectivity of the left and right sympathetics. The base of the ventricle elicited the shortest action potential durations and steepest restitution curves with sympathetic stimulation, which was reversed by removal of the left sympathetics. This knowledge improves our understanding of sympathetic nerve control and highlights the potential for more focused clinical treatments for a variety of chronic cardiac arrhythmias, by selectively removing caudal sympathetic outflows on the left side. Our findings also suggest that the left sympathetics primarily innervate at the base of the ventricle and for the first time reveal the mechanisms that give rise to the antiarrhythmic results of left cardiac sympathetic denervation.