Effect Of Cardiac Contractility Modulation Combined With Bisoprolol On Rabbits With Chronic Heart Failure

Objective: Cardiac contractility modulation(CCM)is an innovative diviced-based therapy which delivers non-excitatory electrical signals and results in improved ventricular function.This study examined the effects of cardiac contractility modulation combined with bisoprolol on left ventricular(LV)function and beta receptor density in rabbits with chronic heart failure(CHF)to further investigate the mechanism of positive action of cardiac muscle contraction.Methods:We selected fourty 6 months of health New Zealand white rabbits as experimental subject,whose weight is 2.5kg to 3.5kg no matter male or female.The experimental animals were provided by the Test Animal Center of Hebei Medical University.1 The animal models of CHF were made by increasing afterloading pressure: after opening the chest of experimental animals,ligated the a scending aortic from the distally of its root about 1.0cm,make sure the circumference of aortic at the constriction is 60% of it’s original circu mference.Then electrical pacing electrodes were fixed to left ventricular anterior wall,left ventricular posterior lateral wall,right ventricular ap ex.The tail of electrodes were hide in neck.Criteria for successful of modeling is cardiac output reduce 30% or left ventricular end-diastolic p ressure is above 2.4Kpa(18mmHg).2 Forty rabbits were divided into four groups: HF(HF group,n=10),Monotherapy with CCM(CCM group,n=10),Bisoprolol alone(Drug group,n=10),CCM combined with bisoprolol(Combined group,n=10).Rabbit’s models of chronic heart failure were made by ligating ascendi ng aortic root of rabbits.The successful standard is left ventricular ejection fraction decrease by 30% or th left ventricular end-diastolic pressure is above 2.4Kpa.3 CCM stimulation:Seprate the tail of electrodes and connect it to MircoPace EPS320 stimulator.Under the sinus rhythm,the absolute refr actory period electrical stimulation were applied to different sites of the heart.It delayed 30 ms,and pulse width was 2ms,pulse voltage was 7V.CCM stimulation lasting six hours everyday for seven days.4 Pre and post treatment,we use UCG to measure the cardiac parameters,including Interventricular septal thickness(IVSd),Left ventricular posterior wall thickness(LVPW),Left ventricular fractional shortening,LVFS(LVFS%),Left ventricular end systolic dimension(LVESD),Left ventricular end diastolic dimension(LVEDD),Left ventricular ejection fraction(LVEF%),E/A ratio.5 Pre and post ARPES treatment,we collected peripheral of intravenous blood 5ml use the ABC-ELISA method to test plasma BNP’s level.6 β1 receptor protein expression : After CCM stimulation and the parameters were measured,the animals were sacrificed by air injection.The expression of β1-AR protein was detected by Western blot and immunohistochemistry.Results:1 The result of animal models of CHF: we made the animal model s of rabbits with CHF by the method of ligating ascending aorta’s root.There were 33 rabbits survived immediately after the operation,1 rabbi t in HF group and combined group die of pneumothorax during the sur gery,respectively.1 rabbit in HF+CCM group die of hemorrhage due t o ascending aorta injuries,respectively.1 rabbit in drug group and com bined group die of improper operation.1 rabbit in combined group died from postoperative infection.Group: heart failure control group(n=9),C CM group(n=9),Drug group(n=8),Combined group(n=8);2 The general status of animals before CCM stimulation: There were no statistical differences among the four groups in general status(P>0.05),suchas weight,respiratory rate and heart rate;3 The results of UCG: before treatment,there were no statistical di fferences among the four groups of animals(P>0.05).After treatment,p arameters including LVESD,LVEDD,LVEF,E/A ratio and LVFS in C CM group,Drug group and Combined group are better than heart failur e control group.Combined group is the best(P<0.05).There were no statistical differences between CCM group and Drug group(P>0.05).IV Sd and LVPWd among four groups has no statistical differences(P>0.05);4 Effcet of treatment on plasma BNP’s level: There were no statist ical differences among the four groups of animals before treatment(P>0.05).After treatment plasma BNP’s level in CCM group,Drug group an d Combined group are lower than heart failure control group.Combined group is the best(P<0.05).There were no statistical differences betwee n CCM group,and Drug group(P>0.05);5 β1-AR protein expression5.1 Immunohistochemistry: Compared with the control group,the ex pression of β1-AR protein in the drug group,CCM group and the comb ined group was significantly higher(P<0.05).In particular,the Combine d group was the most significant(P<0.05).There was no significant diff erence between the drug group and the CCM group Statistical difference s(P>0.05);5.2 Western Blot: Compared with the control group,the expression of β1-AR protein in the other three groups was significantly higher tha n that in the control group(P<0.05).In particular,the combination grou p was the most significant(P<0.05).There was no significant difference between the drug group and the CCM group Differences(P>0.05).Conclusion:1 Cardiac contractility modulation can improve heart function.2 Cardiac contractility modulation combined with β1 receptor blockers can upregulate the expression of β1 receptor in myocardial tissue.