Effects of Dexmedetomidine on Ventricular Arrhythmia in Myocardial Hypertrophy Model Rabbits and CaMK Ⅱ Expression in Cardiac Tissue / 中国药房

ABSTRACT

OBJECTIVE：To study th e effects of dexmedetomidine on ventricular arrhythmia in myocardial hypertrophy model rabbits and the expression of calcium ion /calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）in myocardial tissue of rabbits. METHODS： The rabbits were randomly divided into sham operation group ， model group ， dexmedetomidine low-dose ， medium-dose and high-dose groups （10，25，50 μ g/kg），CaMK Ⅱ inhibitor KN- 93 group （10 mg/kg），high-dose of dexmedetomidine+KN-93 group（50 μg/kg+10 mg/kg），with 10 rabbits in each group. Except for the sham operation group ，other groups received abdominal aortic coarctation to induce myocardial hypertrophy model. After surgery ，administration groups were given relevant dose of dexmedetomidine or/and intraperitoneal injection of KN- 93；sham operation group and model group were given constant volume of normal saline intravenously ，once every other day ，for consecutive 8 weeks. After last medication ， programmed stimulation was used to induce ventricular arrhythmia. The induction rate of early posterior depolarization （EAD）and tip torsion type ventricular tachycardia （Tdp）were recorded. Left ventricular ejection fraction （LVEF）and left ventricular shortener fraction（FS）were measured. QT interval ，transventricular wall repolarization dispersion （TDR）and transmembrane 90％ action potential duration （APD90）of endocardial and epicardial cardiomyocytes in wedge-shaped myocardium were recorded. The ratio of heart weight to body weight （HW/BW）and the thickness of left ventricular wall （LVT）were measured and calculated. The cross-sectional area of cardiomyocytes ，mRNA expression of ANP and BNP as well as protein expression of CaMK Ⅱ and p-CaMK Ⅱ in myocardial tissue was measured. RESULTS ：Compared with sham operation group ，the induction rate of EAD and Tdp ，HW/BM， LVT，mRNA expression of ANP and BNP and protein relative expression of CaMK Ⅱ and p-CaMK Ⅱ in cardiac tissue were all increased significantly ，while LVEF and FS were decreased significantly ；QT interval ，APD90 of endocardial and epicardial cardiomyocytes were all prolonged significantly ；TDR was increased significantly ，while cross-sectional area of cardiomyocytes was increased significantly in model group （P＜0.05）. Compared with model group ，induction rate of EAD and Tdp ，HW/BW （except for dexmedetomidine low-dose group ），LVT（except for dexmedetomidine low-dose group ），mRNA relative expression of ANP（except for dexmedetomidine low-dose group ）and BNP （except for dexmedetomidine low-dose group ）as well as protein relative expression of CaMK Ⅱ and p-CaMK Ⅱ were all decreased significantly in administration groups ；the levels of LVEF （except for dexmedetomidine low-dose group ） and FS （except for dexmedetomidine low-dose group ） were all increased significantly； QT interval ，APD90 of endocardial and epicardial cardiomyocytes were shortened significantly ； TDR and cross-sectional area of cardiomyocytes （except for dexmedetomidine low-dose group ）were decreased significantly （P＜0.05）；the improvement effects of dexmedetomidine high-dose group were significantly better than those of dexmedetomidine low-dose and medium-dose groups （P＜0.05）. Compared with dexmedetomidine high-dose group and KN- 93 group，the improvement of above indexes were all more significant in high-dose of dexmedetomidine+KN- 93 group（P＜0.05）. CONCLUSIONS ：Dexmedetomidine can reduce the induction rate of ventricular arrhythmia and improve myocardial hypertrophy in myocardial hypertrophy model rabbits，the mechanism of which may be associated with down-regulation of CaMK Ⅱ expression.