Fundamental Research About Stimulation In Modals Of Pired Premature Ventriculars And Establishment Of A Rabbit Model On Tachy Cardia Myopathy

Objective:?To establish the tachycardiomyopathy animal model of premature ventricular contractions in pairs;?Preliminary discuss the expression of Kv4.3 and its mRNA in tachycardiomyopathy?Methods:?The objects and groups of this study:35 New Zealand rabbits(purchased from the Changsha City Tianqin Biotechnology Co.,Ltd.),License Number:SCX(Hunan)2009-0012);wre all foot-month-old male,with an average weight of 2.5 ± 0.2 kg;divided into A(pacing two weeks,n=10),B(pacing four weeks,n=15),C(Control groups,n=10)groups.A groups were divided equally into A1(were sacrificed affter pacing two weeks)and A2(observed for 4 weeks afte pacing two weeks)subgroup;B groups were divided equally into B1(were sacrificed affter pacing four weeks)and B2(observed for 4 weeks after pacing four weeks)subgroup and B3 subgroup(observed for 4 weeks after pacing eight weeks);C groups were divided equally into C1?C2?C3?C4?C5 subgroup?Control and experimental groupS were sacrificed at the same experimental,so that compared of all indicators.?Pacing electrode implantation and stimulation methods:Via right anterior vena cava implanted 5F arterial sheath,along which 10-pole coronary sinus electrode was sented to right ventricular of New Zealand rabbits.Connected procedures stimulator,adjust the sensitivity to the minimum.voltage 3.0±0.5volt?The frequency of pacing was 400times/min,paced right ventricular.Under ECG monitor,appeared large abnormal QRS wave after pacing signal,the direction of T wave was opposite to the main wave,which implied effective pacing of the right ventricular.Seted the stimulation mode as paired ventricular premature.Stoped atffer persistent stimulation for two hours,but started agein an hour later.Such as this,continuous stimulation was persisted for six hours a day.All New Zealand rabbits were intramuscular injectioned of penicillin 80 million units,twice a day for three consecutive days half an hour before surgery and after four hours.In the control groups,just implanted electrodes,but not stimuled.?Observed indicators:Before surgery and after stimulation,cardiac color Doppler was perfored weekly,mapping New Zealand rabbits left ventricular end-diastolic and end-systolic diameter?the mitral regurgitation area(MVRA),Detected the level of fasting serum BNP,MMP-9,TIMP-1.All of myocardial tissues were applied by H.E and Masson staining.Electron microscopy light microscope,observed myocardial cell pathological changes and interstitial fibrosis;observe the myocardial ultrastructure changes under Electron microscopy.Adopted Real-time RT-PCR and Western blot technology to messured the level of Kv4.3 and(mRNA)expression of New Zealand rabbits left ventricular.Results:All New Zealand rabbits in ppeared shortness of breath,fatigue,decreased exercise tolerance,loss of appetite and other early symptoms of heart failure after pacing for ten days.Changes in suptem markers:Compared with the pacing and control groups in the same period,the LVEDD and LVESD was enlarger,LVEF was droped,the level of TIMP-1 was decreased,the level of BNP.MMP-9 was increased,significantly,p<0.05.It appeared mitral regurgitation in the pacing group.These changes were obviously in the B1 subgroup,every p<0.05.The LVEDD and LVESD was smaller,LUEF was increased,the level of TIMP-1 was rised,the level of BNP?MMP-9 was decrersed in control of B2 and B1 subgroup,p<0.05,significantly.Such changes were notable in the B3 subgroup,p<0.05.There were no visible difference,compared among A2>B3 and C subgroup,every P>0.05.Myocardial pathological changes:It appeared cardiomyocyte hypertrophy?vacuolar degeneration.proliferation>aoptosis,interstitial fibrosis and a little inflammatory cell infiltration,muscle fiber disordered arrangement,observed by light microscope in the experimental groups.It showed that mitochondrial swelling,vacuolar degeneration,dissolution,destruction,Z line fuzzy,structure ambiguous,observaed by electron microscopy.Such changes were more notable compared with B1 and Alsubgroup.These pathological changes were different degrees recovery affter stop pacing.A group taked less time to recovery pathological reconstruction.But not completely backed to normal.Changese of Kvive group4.3 and mRNA:The levels of myocardial tissue Kv4.3 expression was dropped compared with A1and C subgroup,A2 and A1 subgroup,B2 and C subgroup,but all so B1 and A1 subgroup,respectivly;But significantly higher compared with B2 and B1,all p<0.05.There were no diffrence compared among A2?B3?C subgroups,all p>0.05.Bivariate linear correlation analysis:It showed that mRNA was linear positive correlation with LVEDD and LVEF(r=0.571,p=0.007;r=0.673,p=0.005).Conclusion:?No X-ray,a thoracic vein with electrode mapping procedure to stimulate and successfully establish paired ventricular premature of tachycardiomyopathy animal model,and is simple and easy to operate;? Paired ventricular premature can cause tachycardiomyo pathy;?Timely termination of premature ventricular contractions can make heart failure and enlargement of the heart reversed completely.But pathological reconstruction can be restored partially,whether can be fully,need further study;The downregulation of Kv4.3 and its mRNA is one of premature ventricular contractions induced cardiomyopathy important mechanisms.?The expression of Kv4.3 and its mRNA is closely related tocardiac function and structure(Linear positive correlation).