Computing the Age-Related Dysfunction of Cardiac Pacemaker

摘要

In both human and animal mammals, the pacemaker of the heart, the sinoatrial node (SA node), deteriorates with age. The main features of the aged SA nodes are a slow pacemaking rate and possible SA node-atrium conduction exit block or arrest of SA node pacemaking (i.e., termination of the SA node pacemaker activity). The mechanisms underlying the age-related dysfunction of the heart are unclear. In this study, we developed a detailed computer model of normal and aged SA nodes. Using the model we evaluated the functional roles of age-dependent reduction in SA node i{sub}(Na) current and active cell population in initiation and conduction of pacemaker activity in the aged heart. Simulations have shown that decrease in the SA node i{sub}(Na) or active cell population results in an increase of pacemaking cycle length (equivalent to a decrease of pacemaking rate) and slowing down of SA node-atrium conduction. It also produces the SA node-atrium conduction block in which action potentials originating from the SA node can fail to conduct into the atrium, or termination of the SA node pacemaker activity. When considered together, combined actions have a greater impact on weakening the pacing and driving ability and producing impairment of impulse initiation and conduction that leads to the SA node-atrium conduction exit block. These simulations provide mechanistic insights for understanding the dysfunction of the SA node in aged hearts.