Aging and Sinoatrial Node Dysfunction

Abstract

In the century since the discovery by Keith and Flack of the sinoatrial node in the mole heart, a detailed mosaic of its cellular, anatomic, and electrophysiological properties has emerged. The human sinus node has been found to be anatomically constant and well localized, occupying an approximately 10-mm subepicardial region on the sulcus terminalis at the superior cavo–atrial junction.1 Histologically, its ultrastructure of central P cells (likely corresponding to the leading pacemaker site) and outer transitional zone merging with surrounding atrial myocardium have been well characterized.1 Great progress also has been made in defining the ionic mechanisms responsible for the sinoatrial action potential and its spontaneous pacemaker activity, including important contributory roles for I Ca,L, I k, and the funny current, I f.1 This morphologically discrete, unifocal sinus node is not the exclusive force behind clinical sinus rhythm, however. Detailed animal and human mapping has demonstrated that normal cardiac pacemaker activity is widely distributed in the right atrium. In the human atrium, the pacemaker complex extends for up to 75 mm along the long axis of the sulcus terminalis and precaval band.2 At times, even left atrial pacemakers may be active during normal sinus rhythm.2 Graduated differential sensitivity to adrenergic and vagal inputs exists along the integrated pacemaker complex such that superior sites tend to dominate during periods of sympathetic drive, whereas inferior sites are activated by increased parasympathetic tone. Increasing the complexity, each sinus beat may have multicentric origin, and the nature of conduction out of the node also seems to be variable in response to autonomic tone.2 The presence of a diffuse pacemaker complex …