| Chronic heart failure (CHF) is one syndrome of variety heart diseases infinal, which has a high rate of incidence and mortality. CHF is associated withmultiple pathophysiological alterations. The mechanism of CHF includesmyocyte dysfunction, apoptosis, cardiac remodeling, nerve-humoral factorsand activation of cytokine systems. In recent years, drug treatment of chronicheart failure has a larger development, but there are still many patients areineffective through drug therapy. So when doctors use the drug treatment, atthe same time people are actively seeking non-drug therapeutic method. Nowa new non-drug therapeutic method called cardiac contractility modulation(CCM) has caused doctors high attention, it can boost the myocardialcontractility and improve the heart function though electric stimulationsapplied during absolute refractory period (ARPES). At present, the domesticand foreign research in the isolated heart of animals and small-scale clinicaltrials shows that ARPES can enhance the myocardial contractility and improvethe cardiac function in patients with chronic heart failure. But the detailedmechanism of CCM has not been entirely revealed, and the differentamplitude stimulation amplitude needs to be studied in the further.Objective：In our study, we made the animal models of rabbits withchronic heart failure by the method of ligating ascending aorta's root. Anendocardial electrode was sent into the apex of the right ventricle under theX-ray. The different amplitudes during ARPES were given to the heart in vivocontinuously12hours. After the CCM treatment, the cardiac function wasexamined by ultrasonic cardiogram, the plasma level of brain natriureticpeptide (BNP) was tested by ABC-ELISA method and the differences of themRNA expression of Junctophilin-2by the real-time fluorescence-based reverse transcription polymerase chain reaction (RT-PCR). In our study, wewould reveal the effects of CCM for cardiac function and the possiblemechanisms, and then provide a theoretical basis for clinical treatment.Method: We selected twenty-four6months of health New Zealand whiterabbits as experimental subject, whose weight is2.5kg to3.5kg no matter maleor female. The experimental animals were provided by the Test Animal Centerof Hebei Medical University.1The animal models of CHF were made by overloading pressure: afteropening the chest of experimental animals, we increase after-load by making alocal constriction of ascending aorta. The animal models of CHF were madeafter4weeks. All the animal models of CHF were examined by non-invasivecardiac ultrasonic cardiogram (UCG). All the metered dates were taken theaverage of3consecutive measurements.The successful standard is leftventricular ejection fraction (LVEF)≤40%.2The experimental animals were dividing into groups: we use UCG toexamine the cardiac function, and then18rabbits were selected thorough thestandard of successful model. The model were randomly assigned equally to3groups: control group (n=6), ARPES-L group (n=6), ARPES-H group (n=6).3ARPES:(1) Control group: we sent an endocardial electrode into the apex of theright ventricle under the X-ray, but not any ARPES.(2) ARPES-L group: we sent an endocardial electrode into the apex of theright ventricle under the X-ray, and then given ARPES. Under the sinusrhythm, the stimulant apparatus felt the R wave by the endocardial electrode,and then triggered S1stimulations. It delayed30ms, and pulse width was2ms.The stimulant voltage was2times of diastolic threshold. The stimulationscontinued12hours.(3) ARPES-H group: we sent an endocardial electrode into the apex ofthe right ventricle under the X-ray, and then given ARPES. Under the sinusrhythm, the stimulant apparatus felt the R wave by the endocardial electrode,and then triggered S1stimulations. It delayed30ms, and pulse width was2ms. The stimulant voltage was10V. The stimulations continued12hours.4At the end of4th and CCM treatment, we use UCG to examine thecardiac function, it includes ventricular septum thickness at end diastole(IVSd), left ventricular posterior wall thickness at end diastole (LVPWd), leftventricular end-systolic dimension (LVESD), left ventricular end-diastolicdimension (LVEDD), left ventricular ejection fraction (LVEF), left ventricularfractional shortening (LVFS). We collected peripheral of intravenous blood5ml, and then tested the general conditions of the experimental animals,whichincluded electrolytes and the blood fat. We also used the ABC-ELISA methodto test plasma level of BNP.5After the CCM treatment, we opened the chest,and clamp the hart aorta,superior and inferior vena cava, pulmonary artery, pulmonary veins, then cutoff the heart blood vessels and surrounding tissues, and take out the hartquickly. we executed the animals, and then collected the myocardial tissuesnear the electrode in liquid nitrogen. We used the RT-PCR to test if there weresome differences of the mRNA expression of Junctophilin-2among the threegroups.Results:1The result of the experimental animals: we made the animal models ofrabbits with CHF by the method of ligating ascending aorta's root. There were22rabbits survived immediately after the operation, and20were survivedafter4weeks. According to the results of UCG, we made only18rabbits of thesuccessful model (LVEF≤40%). We sent an endocardial electrode into theapex of the right ventricle under the X-ray, and then given ARPES. In theprocess,2rabbits were death. The death reasons were anaesthetic accident inthe ARPES-L group and cardiac rupture in the ARPES-H group.2The general status of animals before randomly assigned equally to thegroups: There were no statistical differences among the three groups ofanimals in general status (P>0.05), such as age, weight, sex, electrolytes andblood fat.3The results of UCG: before CCM treatment, there were no statistical differences among the three groups of animals (P>0.05). After CCM treatment,the dates were a little decline in the control group, but the differences were nostatistically significant (P>0.05). Compared with the control group andARPES-L group, ARPES-H group, there were no statistical differences(P>0.05), including IVSd and LVPWd, but there were some statisticaldifferences (P<0.05), including LVESD, LVEDD, LVEF, and LVFS.Compared with ARPES-L group and ARPES-H group, all the results of UCGwere not statistically significant (P>0.05).4The result of BNP: before CCM treatment, there were no statisticaldifferences (P>0.05). After CCM treatment, there was a little ascend in thecontrol group, but the difference was no statistically significant (P>0.05).BNP of ARPES-L group and ARPES-H group were lower than control group,the differences were statistically significant (P<0.05). But compared withARPES-L group and ARPES-H group, all the results of BNP were nostatistically significant (P>0.05).5The mRNA expression of JPH-2: After CCM treatment, the mRNAexpression of JPH-2was higher in the ARPES-L group and the ARPES-Hgroup than the control group, the difference was statistically significant(P<0.05). But compared with ARPES-L group and ARPES-H group, therewas no statistically significant (P>0.05).Conclusions: The short-time CCM treatment could improve the heartfunction of rabbits with chronic heart failure. But the electric stimulations withdifferent amplitude in ARPES were no statistically significant. ARPES couldincrease the mRNA expression of JPH-2, which continued12hours. And it isone of the possible mechanisms that increases myocardial contractility thoughthe mRNA expression of JPH-2increased. |
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