Dominant arrhythmia vulnerability of the right ventricle in senescent mice.
BACKGROUND
Several cardiac disorders affect the right ventricle (RV) and left ventricle (LV) equally, but nevertheless, RV vulnerability to conduction slowing and arrhythmias exceeds that of the LV.


OBJECTIVE
This study sought to assess the mechanism of dominant RV arrhythmia vulnerability in senescent mice as a model of general reduced myocardial integrity.


METHODS
Epicardial ventricular activation mapping was performed on senescent (22 months) and adult (3 months) Langendorff perfused mouse hearts. Arrhythmia inducibility was tested by programmed stimulation. Conduction velocity longitudinal and transversal (CVT) to fiber orientation, conduction heterogeneity, and effective refractory period were determined. Subsequently, hearts were processed for immunohistochemistry, Western blotting, and Sirius red staining.


RESULTS
In senescent RV, but not LV, CVT was reduced and wavelength decreased, whereas anisotropic ratio and conduction heterogeneity increased. Arrhythmias, based on anisotropic reentry, were induced in 55% of senescent hearts only and predominantly in RV. In senescent mice, Connexin 43 (Cx43) and Cardiac Sodium Channel (Nav1.5) were decreased and interstitial fibrosis increased comparably in RV and LV. However, in senescent mice, heterogeneously distributed patches of replacement fibrosis were present throughout the entire RV myocardium, but only in midendocardium and subendocardium of LV. Cx43 expression in these areas was disrupted.


CONCLUSIONS
Widespread presence of replacement fibrosis in senescent RV compared with LV, combined with Cx43 and Nav1.5 disruption, potentiate shorter wavelength, conduction slowing, and conduction heterogeneity in RV, resulting in greater vulnerability of senescent RV to arrhythmias.
Stein
Mera
M
Division Heart and Lungs, Department of Medical Physiology, University Medical Center Utrecht, Utrecht, the Netherlands.
Noorman
Maartje
M
van Veen
Toon A B
TA
Herold
Eva
E
Engelen
Markus A
MA
Boulaksil
Mohamed
M
Antoons
Gudrun
G
Jansen
John A
JA
van Oosterhout
Matthijs F M
MF
Hauer
Richard N W
RN
de Bakker
Jacques M T
JM
van Rijen
Harold V M
HV
D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D015153:Blotting, Western; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D005355:Fibrosis; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D007150:Immunohistochemistry; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL