Downregulation of immunodetectable atrial connexin40 in a canine model of chronic left ventricular myocardial infarction: implications to atrial fibrillation.
BACKGROUND
The substrate(s) for atrial fibrillation associated with chronic left ventricular myocardial infarction remain poorly defined. Since atrial connexin40 has a rapid turnover rate and may cause atrial fibrillation, we hypothesized that chronic left ventricular myocardial infarction downregulates atrial Connexin40 and increases atrial fibrillation vulnerability.


RESULTS
The left anterior descending coronary artery was occluded distal to the first diagonal branch in five dogs and studied 7 weeks later. Five dogs with no left anterior descending coronary artery occlusion served as control. Vulnerability to atrial fibrillation was tested by burst atrial stimulation (50 milliseconds for 3 seconds). Atrial fibrillation was induced in all myocardial infarction dogs, lasting from 20 seconds to several minutes. In contrast, only rapid repetitive activity and short-lasting atrial fibrillation (< 5 seconds) could be induced in control dogs. The mean refractory periods of epicardial RA and LA appendages were not significantly different in the two groups. Mean left ventricular myocardial infarction size was 17 +/- 4% of the left ventricle. Histologic analyses showed no signs of atrial ischemic injury or interstitial fibrosis in either group. Atrial myocyte diameter measured at the level of the nuclei of longitudinally sectioned myocytes was not significantly different in the two groups (10.1 +/- 1.2 microm vs. 10.2 +/- 1.2 microm; P = 0.3). Atrial Connexin40 (both left and right atria) in the left ventricular myocardial infarction group was highly heterogeneous and had significantly smaller total area stained than in the control (0.48 +/- 0.09% vs. 0.82 +/- 0.13%; P < 0.01).


CONCLUSIONS
Chronic left ventricular myocardial infarction downregulates immunodetectable atrial Connexin40, a property that might contribute to the increased atrial fibrillation vulnerability in this model.
Ohara
Keiko
K
Division of Cardiology, Cedars-Sinai Research Institute, Los Angeles, CA 90048, USA.
Miyauchi
Yasushi
Y
Ohara
Toshihiko
T
Fishbein
Michael C
MC
Zhou
Shengmei
S
Lee
Moon-Hyoung
MH
Mandel
William J
WJ
Chen
Peng-Sheng
PS
Karagueuzian
Hrayr S
HS
D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology; D002908:Chronic Disease; D017630:Connexins / Q000032:analysis* / Q000172:deficiency / Q000276:immunology*; D004195:Disease Models, Animal; D004285:Dogs; D015536:Down-Regulation; D006325:Heart Atria / Q000378:metabolism* / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D000097003:Gap Junction alpha-5 Protein
D017630:Connexins; D000097003:Gap Junction alpha-5 Protein