Impact of Cardiac Contractility Modulation on Myocardial Remodeling in Rabbit Model of Chronic Heart Failure / 中国循环杂志

ABSTRACT

Objective: To observe the impact of cardiac contractility modulation (CCM) on myocardial remodeling in rabbit model of chronic heart failure (CHF) with its possible mechanism. Methods: Rabbit HF model was established by ascending aortic root ligation; the animals were divided into 3 groups Sham group, the animals received thoracotomy without aortic ligation, HF group and HF+CCM group, the HF animals received CCM treatment for 4 weeks. n=10 in each group. Cardiac function was measured by echocardiography at 12 and 16 weeks in each group respectively; myocardial tissue fibrosis and pathological changes were examined by Masson staining; plasma BNP level was assessed by ELISA; protein expressions of collagen I, collagen II, MMP2,MMP9, TIMP1 and galectin-3 in myocardial tissue were determined by Western blot analysis. Results: ① By echocardiography with 12 weeks treatment, compared with Sham group, HF group and HF+CCM group had increased LVESD, LVEDD and decreased LVFS, LVEF, all P<0.05; with 16 weeks treatment, compared with HF group, HF+CCM group had improved LVESD, LVEDD, LVEF and LVFS, all P<0.05. ② Pathological changescompared with Sham group, HF group showed increased collagen content in myocardial tissue, P<0.05; CCM treatment could partially decrease collagen accumulation, P<0.05. ③ After 12 weeks treatment, compared with Sham group, HF group and HF+CCM group presented elevated plasma BNP level, P<0.05; after 16 weeks treatment, compared with HF group, HF+CCM group presented reduced plasma BNP, while it was still higher than that in Sham group, P<0.05. ④ By Western blot analysis: compared with Sham group, HF group demonstrated increased protein expressions of collagen I, collagen II, MMP2, MMP9, TIMP1 and galectin-3 in myocardial tissue; the above indexes were much lower in HF+CCM group while still higher than those in Sham group, all P<0.05. Conclusion: CCM could improve myocardial remodeling in rabbit model of CHF which might be related to down-regulated protein expressions of collagen I, collagen III, MMP2, MMP9, TIMP1 and galectin3 in myocardial tissue.