Aging-related increase to inducible atrial fibrillation in the rat model.
BACKGROUND
Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging-related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging-related AF.


RESULTS
Interatrial conduction time and atrial response to burst atrial pacing were evaluated in 11 young (2-3 months) and 12 old (22-24 months) male rats (Fisher 344) in the Langendorff-perfused setting. At baseline, sustained (>30 sec) atrial tachycardia (AT) and AF were induced in 10 of 12 and in 7 of 12 old rats, respectively. No such arrhythmias could be induced in the young rats. Old rats had significantly (P < 0.01) longer interatrial conduction time and P wave durations than the young rats. Burst pacing failed to induce AT and AF in all 11 young rats studied. The effects of heptanol 2 to 10 microM were studied in both groups. Heptanol 2 to 5 microM promoted inducible AT in all 5 young rats studied; however, when its concentration was raised to 10 microM, AT could no longer be induced in any of the 5 young rats. No AF could be induced in any of the 5 young rats at heptanol concentrations of 2 to 10 microM. In the old rats, AF could still be induced during perfusion of 2 microM heptanol. However, when its concentration was raised to 5 and 10 microM, AF could not be induced in any of the 6 old rats studied. Optical mapping using a potentiometric dye showed a periodic single wavefront of activation during AT in both groups and 2 to 4 independent wavefronts propagating in different directions during AF in the old rats. Histology revealed a significant increase in interstitial atrial fibrosis (P < 0.01), atrial cell size (P < 0.05), and heart weight in old versus young rats. Fibrosis in the old rats was highly heterogeneous.


CONCLUSIONS
The rat model is suitable for study of aging-related AF. Uniform partial atrial cellular uncoupling with heptanol perfusion in the young rats, although promoting inducible AT, does not mimic aging-related AF. The results suggest that heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might contribute to the aging-related increase in atrial conduction slowing, conduction block, and inducible AF in the old rat model.
Hayashi
Hideki
H
Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048, USA.
Wang
Charles
C
Miyauchi
Yasushi
Y
Omichi
Chikaya
C
Pak
Hui-Nam
HN
Zhou
Shengmei
S
Ohara
Toshihiko
T
Mandel
William J
WJ
Lin
Shien-Fong
SF
Fishbein
Michael C
MC
Chen
Peng-Sheng
PS
Karagueuzian
Hrayr S
HS
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D018780:Body Surface Potential Mapping; D002304:Cardiac Pacing, Artificial; D048429:Cell Size; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D019850:Heptanol / Q000008:administration & dosage; D008297:Male; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013612:Tachycardia, Ectopic Atrial / Q000503:physiopathology
D019850:Heptanol