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The effect of aging on the specialized conducting system: a telemetry ECG study in rats over a 6 month period.

Rossi S, Fortunati I, Carnevali L, Baruffi S, Mastorci F, Trombini M, Sgoifo A, Corradi D, Callegari S, Miragoli M, Macchi E - PLoS ONE (2014)

Bottom Line: 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.We found that the duration of ECG waves and intervals gradually increased and heart rate variability gradually decreased with age.Our results demonstrate that aging gradually modifies the terminal part of the specialized cardiac conducting system, creating a substrate for increased arrhythmogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, University of Parma, Parma, Italy; CERT, Center of Excellence for Toxicological Research, INAIL, ex ISPESL, University of Parma, Parma, Italy.

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.

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Atrial myocardial interstitial fibrosis.A: control heart section with no pathological interstitial collagen depositions; B: aged heart section with a focus of perivascular interstitial fibrosis (arrow); C: aged heart section with a focus of myocytolisis (arrow). Hematoxylin and Eosin staining. Original magnification: A and B ×10, C ×20 with scale bar in A and B 500 µm and in C 200 µm.
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pone-0112697-g006: Atrial myocardial interstitial fibrosis.A: control heart section with no pathological interstitial collagen depositions; B: aged heart section with a focus of perivascular interstitial fibrosis (arrow); C: aged heart section with a focus of myocytolisis (arrow). Hematoxylin and Eosin staining. Original magnification: A and B ×10, C ×20 with scale bar in A and B 500 µm and in C 200 µm.

Mentions: Microscopic analysis of atrial myocardium in control hearts revealed the presence of bundles of cardiomyocytes with various orientations. The inter-cardiomyocyte spaces were occupied by scanty connective tissue and microcirculation blood vessels usually running parallel to the major axis of the muscle fibers (Fig. 6A). Conversely, atrial myocardium in aged hearts was characterized bysignificant collagen deposition (Fig. 6B, arrow) and zonal phenomena of cardiomyocyte myocytolysis, i.e. perinuclear loss of sarcomeric elements resulting in an empty area (Fig. 6C, arrow).


The effect of aging on the specialized conducting system: a telemetry ECG study in rats over a 6 month period.

Rossi S, Fortunati I, Carnevali L, Baruffi S, Mastorci F, Trombini M, Sgoifo A, Corradi D, Callegari S, Miragoli M, Macchi E - PLoS ONE (2014)

Atrial myocardial interstitial fibrosis.A: control heart section with no pathological interstitial collagen depositions; B: aged heart section with a focus of perivascular interstitial fibrosis (arrow); C: aged heart section with a focus of myocytolisis (arrow). Hematoxylin and Eosin staining. Original magnification: A and B ×10, C ×20 with scale bar in A and B 500 µm and in C 200 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232439&req=5

pone-0112697-g006: Atrial myocardial interstitial fibrosis.A: control heart section with no pathological interstitial collagen depositions; B: aged heart section with a focus of perivascular interstitial fibrosis (arrow); C: aged heart section with a focus of myocytolisis (arrow). Hematoxylin and Eosin staining. Original magnification: A and B ×10, C ×20 with scale bar in A and B 500 µm and in C 200 µm.
Mentions: Microscopic analysis of atrial myocardium in control hearts revealed the presence of bundles of cardiomyocytes with various orientations. The inter-cardiomyocyte spaces were occupied by scanty connective tissue and microcirculation blood vessels usually running parallel to the major axis of the muscle fibers (Fig. 6A). Conversely, atrial myocardium in aged hearts was characterized bysignificant collagen deposition (Fig. 6B, arrow) and zonal phenomena of cardiomyocyte myocytolysis, i.e. perinuclear loss of sarcomeric elements resulting in an empty area (Fig. 6C, arrow).

Bottom Line: 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.We found that the duration of ECG waves and intervals gradually increased and heart rate variability gradually decreased with age.Our results demonstrate that aging gradually modifies the terminal part of the specialized cardiac conducting system, creating a substrate for increased arrhythmogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, University of Parma, Parma, Italy; CERT, Center of Excellence for Toxicological Research, INAIL, ex ISPESL, University of Parma, Parma, Italy.

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.

Show MeSH
Related in: MedlinePlus