| Objective: Atrial fibrillation, AF for short, is one of the most common clinical arrhythmia. AF often makes patients feel discomfort,such as palpitations, chest tightness, shortness of breath.Some patients may even be complicated by stroke, heart failure and other complications.In our country,the increasingly severe problem of aging and rising incidence of cardiovascular disease, make the burden on society and family caused by AF becoming more and more serious. The mechanisms of AF are extremely complex, which make the treatment of AF unsatisfactory. Previous studies have found the change of myocardial energy metabolism caused by AF.So more and more attention are paid on the treatment of atrial fibrillation by regulating energy metabolism. Currently, as the drug of energy metabolism, trimetazidine has been used in the treatment of ischemic heart disease. However, clinical studies and experimental studies have suggested that trimetazidine is also effective on the treatment of AF. The purpose of this study is to construct an animal model of AF by rapid pacing in rabbit right atrium,and to observe the influence of trimetazidine in energy metabolism on myocardial cells, in order to provide more evidence for the use of trimetazidine in the field of AF.Methods: 30 adult NZW rabbits,weighing 2.0-2.3kg,male or female,were selected in this study, which are provided by hebei medical university animal experiment center.These rabbits were divided into three groups: sham group(blank group,n=10), saline group(control group,n=10) and trimetazidine group(experimental group,n=10).All rabbits were adaptively feeded for three days. Then,trimetazidine group were fed trimetazidine(8mg/(kg.d)), while Sham group and physiological saline group were fed the same volume of 0.9% physiological saline for three weeks. Three weeks later, inject 10% chloral hydrate(50mg/kg) into the body of rabbits through their ear veins. After the success anesthetization of the rabbits, they were fixed in supine position. Connected limbs of these rabbits to electrocardiogram(ECG), to record their ECG.Then,made a incision in the middle of each rabbit’s neck,and intubated the rabbits. Successfully separated their right jugular veins. Put a 4F bipolar electrode from the right internal jugular vein into the right atrium. Adjusted the electrode position, until the BL-420 biological and functional experimental system showed the amplitude of A wave was more significant than V wave, which meant the electrode was in the right atrium. Fixed electrode, and protected the incision with gauze moistened with saline. Then,did not give the pace to the sham group’s rabbits. However,the rabbits of saline group and trimetazidine group were performed as follows: Provided rapid pacing to the right atrials of these rabbits for eight hours with 600 beats/min frequency. After completion of pacing, all rabbits were killed by air embolism.Removed the hearts in the aseptic environment. Immediately preserved the fresh myocardial tissue blocks about 0.5g(wet weight) of each rabbit in liquid nitrogen. These tissue blocks were made into experimental specimens. Measured the content of adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) of these specimens by high performance liquid chromatography(HPLC).The statistical software SPSS13.0 was used in this study for the tatistical analysis of all experimental data. All the measurement data indicators were executed normality test and homogeneity of variance test. Statistical indicators were expressed as mean ± standard deviation. The randomized block design ANOVA was used for the comparison of between groups. The comparison of each two groups used Student-Newman-Keuls(S-N-K). α=0.05 was taken as significance level in this study.Results:1 The Qualitative Separation of ATP, ADP and AMPBy Comparing the chromatogram chart of sham group, saline group and trimetazidine group with the standard chromatogram chart, we could get the conclusion that ATP, ADP and AMP peak pattern had reached their effective separation in 10 minutes. ATP elution time was 6.067 min, while ADP’s 5.058 min,and AMP’s 3.901 min. The elution time of ATP,ADP,AMP in sham group, saline group and trimetazidine group were almost consistent with the standard elution time(Fig.1,Fig.2,Fig.3,Fig.4).2 Quantitative analysis of ATP, ADP, AMP in rabbits myocardial cellsIn order to complete the measurement, we made the myocardial tissue of saline group and trimetazidine group as specimens, according to the above method. The results(table 1) showed that the content of ATP in sham group was 32.56±7.37μg/g, while the saline group’s was 19.69±4.73μg/g, and the trimetazidine group’s was 28.08±6.76μg/g. The content of ADP in sham group was 194.60±29.70μg/g, while the saline group’s was 224.05±31.92μg/g, and the trimetazidine group’s was 256.27±23.10μg/g. The content of AMP in sham group was 348.32±75.72μg/g, while the saline group’s was 462.53±88.60μg/g, and the trimetazidine group’s was 364.02±55.14μg/g. Compared with the sham group, the saline group’s ATP decreased by 39.53%, ADP increased by 15.13%, and AMP increased by 32.79%. The difference was statistically significant(P<0.05). Compared with the sham group,the change of ATP and AMP content of trimetazidine group were not statistically significant(P>0.05). But the increasing of ADP content by 31.69% was statistically significant(P<0.05). Compared with the saline group, trimetazidine group’s ATP increased by 42.61%, ADP increased by 14.38%, while AMP decreased by 21.30%.The difference was statistically significant(P<0.05).3 Changes of energy charge in myocardial cells of rabbitsTable 2 showed that the energy charge of sham group was 0.23 ± 0.02,while the saline group’s was 0.19±0.02,and the trimetazidine group’s was 0.24 ± 0.03. Compared with the sham group,the level of energy charge of the saline group was decreased.The difference was statistically significant(P <0.05). The change between trimetazidine group and sham group was not statistically significant(P>0.05).The energy charge level of trimetazidine group increased by 26.32%,compared with the saline group. The difference was statistically significant(P <0.05).Conclusions:1 AF resulted in the decrease of ATP content of myocardial cells. But increased the ADP and AMP content.In short,the myocardial energy metabolism was changed because of AF.2 Trimetazidine improved ATP and ADP contents of myocardial cells of rabbits,and reduced AMP content. It can enhance the energy charge level. So as to achieve the purpose of optimizing myocardial energy metabolism. |
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