| With high incidence and poor prognosis, chronic heart failure (CHF) is the development of variety heart diseases in final. Cardiac contractility modulation(CCM), the electrical stimulation, which is applied during the cardiac absolute refractory period, can enhance myocardial contractility and then improve the cardiac function. But the detailed mechanism of CCM during improving the cardiac function has not been entirely revealed. In addition, the basic mechanism of heart failure is the ventricular myocardium remodeling of machine and electrophysiology. The incidence of malignant arrhythmia is higher than health population. Currently, we still do not know if CCM would make some effect to the susceptibility of ventricular arrhythmias, especially the ventricular fibrillation, which still needs further study.Objective:In the study, we want to know the effect of electric currents applied during absolute refractory period (ARP) on the cardiac function of New Zealand white rabbits model with chronic heart failure due to overloaded afterload. And then, ventricular fibrillation is induced by electric stimulation. We want to study the effect of CCM to ventricular fibrillation threshold of CHF animal model and analyze the messenger ribonucleic acid(mRNA) expression of sarcoplasmic reticulum calcium-ATPase(SERCA2a) and phospholamban(PLB). By the way, we want to investigate some possible mechanisms of improving cardiac function and susceptibility of ventricular arrhythmias possible mechanisms,especially ventricular fibrillation.Methods:1 Eighteen white New Zealand rabbits were randomly assigned equally to 3 groups:control group, CHF group, and CCM after CHF group. In the CHF group and CCM after CHF group, we caused increased afterload by making a partial constriction of ascending aorta after thoracotomy. We got the formation of CHF model after 6 weeks. In the control group,we made a thoracotomy without a partial constriction of ascending aorta. We got the heart function of all rabbits by echocardiography before thoracotomy and after 6 weeks.2 In the CCM after CHF group, we sent an electrode into the right ventricular endocardial apex via jugular vein under fluoroscopy. CCM was supplied by the electrode for 12 hours. After getting the heart function again by echocardiography, we got ventricular fibrillation threshold by iducing ventricular fibrillation. In the control group and CHF group,everything was same as above without supplying electric stimulation. Before inducing ventricular fibrillation, we needed to draw venous blood to test correlated ions and brain natriuretic peptide from every animal.3 Sacrificed the animal and got myocardium near the electrode. The same as the control group and CHF group and all the specimen were stored in liquid nitrogen. The expression of the sarcoplasmic reticulum genes SERCA2a and PLB in specimens were dected by the real-time fluorescence-based reverse transcription polymerase chain reaction. We wanted to study if there were some differences among the three groups.Results:1 The animal model of CHFEchocardiography:before surgery, the ejection fraction of the control group is 70.54±3.55 and 70.29±1.38 is the after. The difference is not statistically significant. In the HF group, the ejection fraction is71.28±2.55 begore surgery, and 38.52±2.58 is the after. The difference is statistically significant. In the CCM after CHF group, the ejection fraction is 67.83±2.67 before surgery, and 34.62±2.23 is the after. The difference is statistically significant. All of above demonstrates that there is nothing affect the ejection fraction of the control group during the sugery. In the other two group, we get the animal model of CHF successfully. After the sugery, the difference between CHF group and CCM after CHF group is not statistically significant, which indicates that BNP and the decrease of ejection fraction in the two group is nearly the same. The two groups is in the same stage of heart failure. After CCM, the ejection fraction of CCM after CHF group is 59.98±1.70. Compared with before CCM treatment, the increase of ejection fraction is statistically significant.2 The determination of ventricular fibrillationBefore inducing ventricular fibrillation, the difference of brain natriuretic peptide and ions about ventricular fibrillation amoung the three groups is not statistically significant. The average of ventricular fibrillation threshold is 9.07±0.35V in the control group,5.23±0.29V in the CHF group and 6.93±0.53V in CCM after CHF group. Compared with CHF group, the ventricular fibrillation threshold is increased in CCM after CHF group which is still lower than control group. The difference is statistically significant.3 The mRNA expression of SERCA2a and PLBThe mRNA expression of SERCA2a is 1.37±0.39 in CHF group and 2.31±0.49 in CCM after CHF group. The mRNA expression of PLB is 84.65±7.54 in CHF group and 32.56±5.39 in CCM after CHF group. Compared with CHF group, there is distinguished increased of the mRNA expression of SERCA2a in CCM after CHF group. The difference is statistically significant. But the mRNA expression of PLB is lower in CCM after CHF group than in CHF group. In CCM after CHF group, the ratio of the mRNA expression between PLB and SERCA2a (PLB/SERCA2a) is lower than which group (14.54±3.86vs66.12±20.50). The difference is statistically significant.Conclusions:We propose that CCM signal treatment can improve cardiac function in animal models of CHF, and increase the ventricular fibrillation threshold of animals with heart failure. The CCM signal treatment can normalizes the mRNA expression of SERCA2a and PLB, especially the mRNA ratio of SERCA2a/PLB. These changes may contribute to the clinical effects of CCM which can improve cardiac function and increase ventricular fibrillation threshold in CHF animal. But it needs more verification. The study supplies a theoretical possibility about the using of CCM to treat CHF in clinical. This novel approach may represent a useful adjunctive therapy for the treatment of patients with CHF.
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