[Effects of chronic trimetazidine treatment on atrial energy metabolism in a canine model of chronic atrial fibrillation].
OBJECTIVE
Aim of the present study was to investigate the effect of chronic trimetazidine treatment on atrial energy metabolism and endothelial function in a canine model of chronic atrial fibrillation (AF).


METHODS
Eighteen canines were randomly divided into sham-operated group (n = 6), atrial pacing group (n = 6), and trimetazidine group (n = 6). In atrial pacing group and trimetazidine group, dogs were atrial paced at 400 beats per minutes for 6 weeks. Trimetazidine at 5 mgxkg(-1)xd(-1) was given one day before rapid atrial pacing for 6 weeks. Creatine phosphate (CrP), adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in atrial tissue were analyzed by high-performance liquid chromatography. Total adenosine (TAN) was calculated. The expression of endothelial nitric oxide synthase (eNOS) in atrial tissue was determined by Western blot and immunohistochemical staining. In addition, plasma levels of von Willebrand factor (vWF) was quantified with enzyme-linked immunoadsorbent assay and NO(2)(-)/NO(3)(-) (NOx) was determined by nitrate reductase method.


RESULTS
Atrial CrP (P < 0.01) and CrP/ATP were significantly decreased in paced atrium compared to atrium from sham-operated group (P < 0.05) while ATP, ADP, AMP and TAN remained unchanged (all P > 0.05). Plasma vWF was significantly increased and plasma NOx significantly decreased in paced animals compared to sham-operated animals. Atrial expression of eNOS was also significantly reduced in paced animals (P < 0.01). Trimetazidine treatment did not alter the contents of CrP, ATP, ADP, AMP and TAN, but significantly increased atrial eNOS expression (P < 0.05), decreased plasma vWF (P < 0.01) and increased plasma NOx concentration.


CONCLUSIONS
Trimetazidine treatment affect chronic AF induced disturbance in energy metabolism but may improve endothelial function through a NOx depended manner.
Han
Wei
W
Department of Cardiology, The First Clinical College of Harbin Medical University, Harbin 150001, China.
Yang
Shu-sen
SS
Wei
Na
N
Huo
Hong
H
Li
Wei-min
WM
Zhou
Hong-yan
HY
Zhou
Guo
G
Cao
Yong
Y
Dong
Guo
G
Fu
Song-bin
SB
D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D004734:Energy Metabolism; D005260:Female; D008297:Male; D014292:Trimetazidine / Q000494:pharmacology* / Q000627:therapeutic use
D014292:Trimetazidine