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Cardiac Contractility Modulation(CCM) is an novel diviced-based therapy which delivery of non-excitatory electrical signals resulting in improved ventricular function. In our study, We investigated the effect of CCM on myocardial fibrosis in heart failure and investigate the underlying mechanism.
Thirty rabbits are divided into three groups: sham operated controls (C group, n=10), where the rabbits underwent thoracotomy only; HF with no CCM (HF group, n=10), where the rabbits underwent thoracotomy and ligate the ascending aortic from the distally of its root about 1.0cm, make sure the circumference of aortic at the constriction is 60% of its original circumference; HF with CCM (CCM group, n=10), where the rabbits underwent thoracotomy and legate the ascending aortic. The temporary pacing electrode used to delivery CCM was respectively sutured to left ventricular anterior wall in each group. After the formation of chronic heart failure only CCM group received CCM, CCM(R sensed delay 30ms, 7V, duration 2ms) lasting six hours everyday for 4weeks. Histology examination was carried out to evaluate the myocardial pathological changes. Protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9, TIMP1, TGF-β1 and Smad3 were measured by western blot analysis. Expression of TGF-β1 and Smad3 mRNA were measure by real time polymerase chain reaction.
Histology examination results showed that CCM therapy attenuated myocardial fibrosis and collagen deposition in chronic heart failure rabbits. The myocardial collagen volume fraction (CVF) of heart failure reduced 10.11% by CCM. Moreover protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9 were down regulated by CCM (p < 0.05, respectively). Furthermore, CCM therapy decreases both protein and mRNA levels of TGF-β1 and Smad3 in heart failure rabbits (p < 0.05, respectively).
CCM therapy exerted protective effects against myocardial fibrosis may by inhibiting TGF-β1/Smad3 signaling pathway in chronic heart failure rabbits.