The Effect of Aging on the Specialized Conducting System: A Telemetry ECG Study in Rats over a 6 Month Period

Abstract

Advanced age alone appears to be a risk factor for increased susceptibility to cardiac arrhythmias. We previously observed in the aged rat heart that sinus rhythm ventricular activation is delayed and characterized by abnormal epicardial patterns although conduction velocity is normal. While these findings relate to an advanced stage of aging, it is not yet known when and how ventricular electrical impairment originates and which is the underlying substrate. To address these points, we performed continuous telemetry ECG recordings in freely moving rats over a six-month period to monitor ECG waveform changes, heart rate variability and the incidence of cardiac arrhythmias. At the end of the study, we performed in-vivo multiple lead epicardial recordings and histopathology of cardiac tissue. We found that the duration of ECG waves and intervals gradually increased and heart rate variability gradually decreased with age. Moreover, the incidence of cardiac arrhythmias gradually increased, with atrial arrhythmias exceeding ventricular arrhythmias. Epicardial multiple lead recordings confirmed abnormalities in ventricular activation patterns, likely attributable to distal conducting system dysfunctions. Microscopic analysis of aged heart specimens revealed multifocal connective tissue deposition and perinuclear myocytolysis in the atria. Our results demonstrate that aging gradually modifies the terminal part of the specialized cardiac conducting system, creating a substrate for increased arrhythmogenesis. These findings may open new therapeutic options in the management of cardiac arrhythmias in the elderly population.

The impact of aging on cardiac extracellular matrix

“…Rats and mice also demonstrate reduced heart rate variability with age (Lin et al 2008; Rossi et al 2014). Increases in LV mass, due to increased wall thickness and volumes, and prolonged systolic contraction and diastolic relaxation occur first, before there is an appreciable decline in myocardial performance (Lindsey et al 2005).…”

Simultaneous Recordings of Central and Peripheral Bioelectrical Signals in a Freely Moving Rodent

“…In addition, the hippocampal LFP trace contained ripple events that could be detected from its band-pass (150-250 Hz) filtered trace. In peripheral area, ECG signals were recorded by implanting wire electrodes underneath the skin of the upper chest [8][9][10] (Figs. 1D, 2C).…”

Age-Related Electrophysiological Changes of the Atrial Myocardium in Patients with Paroxysmal Atrial Fibrillation

“…Nevertheless, controversies about AF genesis and its relation in the elderly have reemerged [49][50][51][52]. Advancing age is associated with atrial remodeling characterized by anatomical and structural substrate changes, reductions in atrial voltage with discrete areas of fractionated and prolonged atrial endocardial electrograms, widespread conduction slowing as well as anatomically determined functional conduction delay and block [53][54][55][56][57]. These changes may be responsible for the increased propensity to develop AF with increasing age in AF patients.…”