title: Aging-related increase to inducible atrial fibrillation in the rat model.
abstract: 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.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048, USA.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Charles
authors.initials: C
authors.lastname: Wang
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyauchi
authors.forename: Chikaya
authors.initials: C
authors.lastname: Omichi
authors.forename: Hui-Nam
authors.initials: HN
authors.lastname: Pak
authors.forename: Shengmei
authors.initials: S
authors.lastname: Zhou
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ohara
authors.forename: William J
authors.initials: WJ
authors.lastname: Mandel
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Hrayr S
authors.initials: HS
authors.lastname: Karagueuzian
mesh_terms: 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
chemical_list: D019850:Heptanol