The effect of aging on the specialized conducting system: a telemetry ECG study in rats over a 6 month period.
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.
Department of Life Sciences, University of Parma, Parma, Italy; CERT, Center of Excellence for Toxicological Research, INAIL, ex ISPESL, University of Parma, Parma, Italy.
Stefano
S
Rossi
Department of Life Sciences, University of Parma, Parma, Italy.
Ilaria
I
Fortunati
Department of Neuroscience, University of Parma, Parma, Italy.
Luca
L
Carnevali
Department of Life Sciences, University of Parma, Parma, Italy.
Silvana
S
Baruffi
Department of Life Sciences, University of Parma, Parma, Italy.
Francesca
F
Mastorci
Department of Life Sciences, University of Parma, Parma, Italy.
Mimosa
M
Trombini
Department of Neuroscience, University of Parma, Parma, Italy.
Andrea
A
Sgoifo
Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Unit of Pathology, University of Parma, Parma, Italy.
Domenico
D
Corradi
Division of Cardiology, Fidenza Hospital, Fidenza, Italy.
Sergio
S
Callegari
CERT, Center of Excellence for Toxicological Research, INAIL, ex ISPESL, University of Parma, Parma, Italy; Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Michele
M
Miragoli
Department of Life Sciences, University of Parma, Parma, Italy; CERT, Center of Excellence for Toxicological Research, INAIL, ex ISPESL, University of Parma, Parma, Italy.
Emilio
E
Macchi
D000375:Aging / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004562:Electrocardiography / Q000379:methods*; D056149:Epicardial Mapping; D006321:Heart / Q000033:anatomy & histology; D006329:Heart Conduction System / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D008137:Longitudinal Studies; D051381:Rats; D013686:Telemetry / Q000379:methods