Author + information
- Tu Tao1,
- Qiu Jie1,
- Zhou Shenghua1,
- Li Xuping1,
- Liu Zhenjiang1,
- Wu Zhihong1,
- Yang Hui1 and
- Liu Qiming1
The aim of the present study was to evaluate the effect of metformin (MET) on the rate-limiting enzymes of myocardium glycolysis during acute atrial fibrillation (AF) in canine model.
Experimental group: 20 male hybrid canines of clean grade were divided into four groups: 5 in sinus rhythm group, 5 in MET treatment group (every dog was treated with MET 100mg/Kg/day for 2 weeks), 5 in atrial rapid pacing (ARP) group (acute atrial fibrillation model was established by atrial rapid pacing), 5 in MET+ARP group (all canines were rapid pacing for 6 hours to establish AF model after being treated with MET for 2 weeks.)
The p-wave parameters were recorded by the 12-channel electrocardiogram during the experiment, such as P-wave maximum duration, P-wave minimum duration and P wave dispersion. The electrocardiophysiological examination was used to record the atrial effective refractory period and atrial effective refractory period dispersion. Using the Elisa method and biochemical detection method to test the content of ATP, ADP, AMP, PCr, F-2,6-BP、F-1,6-BP, glucose, pyruvate acid and glycosterone in the left atrial appendage of the canines. Also, the contents of myocardial glycogen were detected by PAS staining. The rate-limiting enzymes of myocardium glycolysis like HK, PFK-1 and PK were test by western blot.
Many energy supply indicator like the content of ADP/ATP, AMP/ATP, glucose, pyruvate acid and glycosterone were decreased and level of the lactate was increased in canine atria with acute AF (P<0.05). Meanwhile, the expression of PFK-1 and PK were also downregulated in the acute AF group (P<0.05). Thus, the energy supply from glycolysis was impaired in the atria myocardium during acute AF. What is more, the P-wave maximum duration, P wave dispersion, atrial effective refractory period and atrial effective refractory period dispersion were abnormal during AF.
MET could promote the myocardium glycolysis and could not affect the normal electrical activity in the canines of MET group. In MET+ARP group, MET showed a positive effect on myocardium glycolysis and can promote the glucose utilization and increase the production of pyruvate and glycogen. Besides, MET can effectively mitigate the reduction of PFK1 and PK expression. MET showed improvement in cardiac electrical activity disorder during AF.
MET could improve the myocardium glycolysis and energy status of atrial during AF through regulating glycolysis rate-limiting enzymes which may contribute to the positive effect on cardiac electrical activity disorder during AF.