Short-term hypertension is associated with the development of atrial fibrillation substrate: a study in an ovine hypertensive model.
BACKGROUND
Hypertension is frequently complicated by the development of atrial fibrillation (AF). However, the mechanisms of this link remain poorly understood. In addition, whether short-term hypertension can result in a substrate for AF is not known.


OBJECTIVE
The purpose of this study was to characterize the atrial substrate predisposing to AF due to short-duration hypertension.


METHODS
Sixteen sheep were studied: 10 had induced hypertension for 7 +/- 4 weeks via the "one-kidney, one-clip" model, and six were controls. Cardiac magnetic resonance imaging was used to assess functional changes. Open-chest electrophysiological study was performed using a custom-made 128-electrode epicardial plaque applied to both right (RA) and left atria (LA), including the Bachmann's bundle, to determine effective refractory periods (ERPs) and conduction velocity at four pacing cycle lengths from six sites. Tissue specimens were harvested for structural analysis.


RESULTS
The hypertensive group demonstrated the following compared with controls: higher blood pressure (P <.0001), enlarged LA (P <.05), reduced LA ejection fraction (P <.05), uniformly higher mean ERP (P <.001), slower mean conduction velocity (P <.001), higher conduction heterogeneity index (P <.0001), greater AF inducibility (P = .03), and increased AF durations (P = .04). Picrosirius red staining of atrial tissues revealed increased interstitial fibrosis (P <.0001). There was also evidence of increased inflammatory cell infiltrates (P <.0001).


CONCLUSIONS
Short-duration hypertension is associated with significant atrial remodeling characterized by atrial enlargement/dysfunction, interstitial fibrosis, inflammation, slowed/heterogeneous conduction, increased ERP, and greater propensity for AF.
Lau
Dennis H
DH
Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia.
Mackenzie
Lorraine
L
Kelly
Darren J
DJ
Psaltis
Peter J
PJ
Worthington
Michael
M
Rajendram
Arumuga
A
Kelly
Douglas R
DR
Nelson
Adam J
AJ
Zhang
Yuan
Y
Kuklik
Pawel
P
Brooks
Anthony G
AG
Worthley
Stephen G
SG
Faull
Randall J
RJ
Rao
Mohan
M
Edwards
James
J
Saint
David A
DA
Sanders
Prashanthan
P
D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D008955:Models, Cardiovascular; D012756:Sheep; D013997:Time Factors