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Congestive heart failure (CHF) is a common cause of atrial fibrillation (AF) and trimetazidine (TMZ) can decrease oxidative stress, improve myocardial metabolic abnormalities and increase eNOS, which are involved in CHF. We studied the effects of TMZ on atrial arrhythmogenesis in canines with ventricular tachypacing (VTP)–induced CHF.
Fifteen mongrel dogs were randomized into sham-operated (n = 5), control (n = 5) and TMZ (n = 5) groups. Transthoracic and transesophageal echocardiographic examinations were performed to measure atrial structural and functional changes. The inducibility and duration of AF were measured in all groups. Atrial ultrastructure was analyzed by transmission electron microscope. Creatine phosphate (CrP), ATP, ADP, guanosine triphosphate (GTP) and guanosine diphosphate (GDP) were measured using HPL. Expression of 3-nitrotyrosine (3-NT), Rac1, iNOS and eNOS was quantified using Western blot and immunofluorescence. Atrial NADPH oxidase activity was measured using chemiluminescence.
After 6-week pacing, although TMZ did not change LA ejection fraction (LAEF) and or size but treatment improved atrial ultrastructural remodeling, decreased AF inducibility and shortened AF duration. In the TMZ group, myocardial ATP, CrP, ADP and GTP were significantly higher than in controls (p<0.05). Furthermore, TMZ significantly increased atrial eNOS protein expression (p<0.05) indicating better endothelial function and treatment decreased Rac1, iNOS and 3-NT expression and NADPH oxidase activity.
Trimetazidine treatment decreased AF inducibility and persistence in chronic heart failure dogs induced by ventricular pacing by restoring the balance of energy demand and supply, enhancing expression of eNOS, and decreasing oxidative stress.