[Calpain I inhibition prevents pacing-induced structural remodeling for atrial fibrillation in canine].
OBJECTIVE
To study the relation of the structural remodeling processes and activation of calpain I.


METHODS
Fifteen dogs were randomly divided into three groups. The dogs in pacing group (n=5) and inhibitor group (n=5) were subjected to 3 weeks of rapid atrial pacing at 600 beats/min, control dogs (n=5) were in sham-operated group. The dogs in inhibitor group were administered intravenous N-Acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, and in pacing group and sham-operated group were administered intravenous DMSO. The activity of calpain I was measured by hydrolyzing Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. The ultrastructure of atrium was examined by light and electron microscopy. TnT expression was assessed by Western blot. Echocardiography examination was performed in all the three groups.


RESULTS
Calpain I activity was significantly increased in pacing group (2.3-fold, P<0.01), and decreased in inhibitor group (1.1-fold, P>0.05), compared to sham-operated group respectively. The percentages of myolysis were (76.7 +/- 5.9)% and (20.8 +/- 8.1)% in pacing group and inhibitor group respectively (P<0.01). TnT expression decreased in the rapid pacing-induced persistent atrial fibrillation, and these effects were inhibited by calpain I inhibitor ALLM. The area and volume of left atrium tended to increase after 3 weeks ALLM treatment in inhibitor group, but the change was not as prominent as in pacing group (P<0.05).


CONCLUSIONS
ALLM can decrease calpain I activity, and prevent canine atrial cardiomyocyte structural remodeling during atrial fibrillation. This study provided a capacity of atrial cardiomyocyte protection.
Li
Wei-min
WM
Department of Cardiology, The First Clinical Hospital of Harbin Medical University, Harbin 150001, China.
Xue
Hong-jie
HJ
Li
Yue
Y
Zhang
Li
L
Gong
Yong-tai
YT
Sheng
Li
L
Chu
Shan
S
D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology*; D016279:Atrial Function, Left; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D006325:Heart Atria / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism
D020107:Troponin T; D002154:Calpain