Age-related increases in cardiac excitability, refractoriness and impulse conduction favor arrhythmogenesis in male rats

The effects of excitability, refractoriness, and impulse conduction have been independently related to enhanced arrhythmias in the aged myocardium in experimental and clinical studies. However, their combined arrhythmic effects in the elderly are not yet completely understood. Hence, the aim of the present work is to relate relevant cardiac electrophysiological parameters to enhanced arrhythmia vulnerability in the in vivo senescent heart. We used multiple-lead epicardial potential mapping in control (9-month-old) and aged (24-month-old) rat hearts. Cardiac excitability and refractoriness were evaluated at numerous epicardial test sites by means of the strength-duration curve and effective refractory period, respectively. During sinus rhythm, durations of electrogram intervals and waves were prolonged in the senescent heart, compared with control, demonstrating a latency in tissue activation and recovery. During ventricular pacing, cardiac excitability, effective refractory period, and dispersion of refractoriness increased in the aged animal. This scenario was accompanied by impairment of impulse propagation. Moreover, both spontaneous and induced arrhythmias were increased in senescent cardiac tissue. Histopathological evaluation of aged heart specimens revealed connective tissue deposition and perinuclear myocytolysis in the atria, while scattered microfoci of interstitial fibrosis were mostly present in the ventricular subendocardium. This work suggests that enhanced arrhythmogenesis in the elderly is a multifactorial process due to the joint increase in excitability and dispersion of refractoriness in association with enhanced conduction inhomogeneity. The knowledge of these electrophysiological changes will possibly contribute to improved prevention of the age-associated increase in cardiac arrhythmias.

Automated summary

The effects of excitability, refractoriness, and impulse conduction on arrhythmias in the aged myocardium have been studied independently, but their combined effects are not well understood. This study aims to explore the relationship between cardiac electrophysiological parameters and arrhythmia vulnerability in the senescent heart. Multiple-lead epicardial potential mapping was used to analyze control and aged rat hearts. The senescent heart showed prolonged electrogram intervals and waves during sinus rhythm, indicating delayed tissue activation and recovery. In addition, ventricular pacing increased cardiac excitability, effective refractory period, and dispersion of refractoriness in the aged animal, accompanied by impaired impulse propagation. Furthermore, both spontaneous and induced arrhythmias were more common in senescent cardiac tissue. Histopathological evaluation revealed connective tissue deposition and myocytolysis in the atria, and interstitial fibrosis in the ventricular subendocardium in aged hearts. These findings suggest that enhanced arrhythmogenesis in the elderly is a multifactorial process involving increased excitability, dispersion of refractoriness, and conduction inhomogeneity.