Cellular Basis Of Abnormal Calcium Cycling Of Failing Rabbits Myocytes And Effects Of Metoprolol And Losartan

ObjectiveIn this study, we established animal model of heart failure induced by volume plus pressure overload in rabbits in order to investigate cellular basis of abnormal calcium cycling of failing myocytes. Then we observed the effects of Metoprolol and Losartan on the failing hearts to understand its molecule mechanism deeply.Methods38 rabbits were divided into four groups: sham-operated rabbits (n=11), heart failure animals without (n=11) or with treatment with Metoprolol (n=8, 5mg Bid) or Losartan (n=8, 10mg qd). Firstly, in order to establish heart failure model, we obtained a volume overload by creation of an aortic insufficiency, which was followed 14 days later by pressure overload induced by constricting the abdominal aorta. Cardiac structure and function were detected via echocardiography for 6 weeks. Secondly, the changes of caffeine-induced calcium transients of myocytes that were loaded by Fluo-3/AM were examined by laser scanning confocal microscope to access the function of calcium regulatory proteins indirectly. Thirdly, the abundances of calcium regulatory proteins were determined by Western blot analysis. All measurements were compared for statistical significance among the four groups using ANOVA analysis, followed by LSD for multiple comparisons. A p value of <0.05 was considered significant. Data were expressed as means±SE.ResultsThe ratio of left ventricular mass to body weight, inter-ventricular septum thickness and left ventricular end diastolic dimension were increased markedly in heart failure...