Effect Of Metoprolol On Ventricular Arrhythmia In Rabbits With Myocardial Hypertrophy

Objective: To observe the effect of Metoprolol on ventricular arrhythmia in hypertrophic myocardium and transmembrane action potential of both wedge myocardium, and to explore the drug's anti-arrhthmic mechanism.Method: Rabbits are divided into sham operation group, hypertrophic-myocardium group and Metoprolol group. In sham operation group, laparotomy is performed but no abdominal aorta constriction. In both hypertrophic-myocardium group and Metoprolol group, hypertrophic-myocardium models are made through abdominal aorta constriction, which will be fed for 8 weeks. After 8 weeks, the protein would be extracted in myocardium of the left ventricular free wall from three groups, and then the change of CaMKII expression would be observed in myocardium by using the western-blot technique. Using floating glass micro-electrode method, transmembrane action potential of both wedge myocardium and myocardial cells in outer membrane and cross-wall ECG. Were recorded srmultaneously. The potential during QT intervals and transmembrane action in myocytes of inner and outer membranes and transmural dispersion of repolarization (TDR) would be observed. Induced rate of early afterdepolarization (EAD) and Torsade de Pointes (Tdp) would be recorded by using the programmed electrical stimulation.Results: hypertrophic-myocardium models are successfully made. CaMKII protein expression in the hypertrophic-myocardium group significantly increases compared to sham operation group (P <0.05). CaMKII protein expression in the Metoprolol group significantly decreases compared to hypertrophic-myocardium group (P <0.05). 1. APD90 and TDR during QT intervals and transmembrane action in myocytes of inner and outer membranes of hypertrophic-myocardium group are significantly longer than that of the sham group (p <0.05); Above indices in Metoprolol group are significantly shorter than that in hypertrophic-myocardium group (p<0.05);2. The incidence of EAD in sham group, hypertrophic-myocardium group and Metoprolol group are 0/10, 10/10 and 4/10 respectively, and the incidence of Tdp are 0/10, 7/10 and 1/10 in these three groups respectively. There is significant difference between the incidence of EAD and Tdp in hypertrophic-myocardium group and sham group (p <0.05). Incidence of EAD and Tdp in Metoprolol group is significantly reduced compared witht that in hypertrophic-myocardium group (p <0.05).Conclusion: 1.CaMKII expression significantly increases in the condition of myocardral hypertrophy.2.Metoprolol can inhibit the CaMKII expression in hypertrophic myocardium.3.TDR in hypertrophic myocardium increases the incidence of arrhythmia significantly.4.Metoprolol can reduce TDR, and inhibit the incidence of EAD and Tdp.