Experimental Study Of Apoptosis In The Rabbit Model Of Tachycardia Cardiomyopthy

Objective:(1) To study the role of apoptosis in the tachycardiomyopathy of ra bbit as well as the relationship of brain natriuretic peptide and tumour necrosis factor alpha with the apoptosis of myocardial cells, for the aim of exploring t he pathogenesis of tachycardia cardiomyopathy(TCM);(2) To investigate the e ffect of oral Carvedilol on the apoptosis of myocardial cells in the tachycardio myopathy of rabbit, providing some theoretical reference for clinical drug thera py in tachycardia cardiomyopathy patients.Methods:(1) Subjects: 32 New Zealand rabbits(purchased from Tianqin Biotec hnology Co.Ltd.in Changsha, License Number: SCXK(Hunan) 2014-0010). The y are all full-term male rabbits with an average weight of 2.25±0.5kg;(2) Gro uping and procedure: The rabbits were randomly divided into four groups: Gro up A(sham + normal saline, 6); group B(sham + drug, 6); group C(pace-ma king + normal saline, 10); group D(pace-making + drug, 10). 1 week after t he operations, half of rabbits in each group were killed, while the remaining r abbits were killed 4 weeks after the operations. All the New Zealand rabbits w ere implanted with homemade 6F arterial sheath via the right jugular vein, an d a 10-pole coronary sinus electrode was sent to the right ventricule of rabbits though the above-mentioned arterial sheath. Group A and B rabbits were not processed with pacemaker stimulus, while the group C and D rabbits were pro cessed with pacemaker stimulus in the right ventricle at 400 bpm. Each array lasted 5 to 8 premature ventricular contractions in order to form non-sustained ventricular tachycardia(30 array/min). The pacemaker stimulus was taken for3 hours per day on a daily basis. After operation, Group B and D rabbits wer e fed with carvedilol(10mg/kg/d), while group A and C rabbits were fed wit h the same dose of solvent(normal saline).(3) Observation indexes: The rabbit s’ blood was drawn before the operation and 1 week, 2 weeks, 3 weeks and 4 weeks after the operations respectively and the serum-concentration of BNP a nd TNF-α of the rabbits were detected and indexes of the two in each time p eriod were compared. The left ventricular ejection fraction(LVEF), left ventricu lar end-systolic diameter(LVESD) and left ventricular end-diastolic diameter(L VEDD) of the New Zealand rabbits were measured and recorded by ultrasonog raphy. The myocardial tissues were took out immediately after killing the New Zealand rabitts. The tissues were fixed by formalin, embedded in paraffin and c ut into slices, then the apotosis index of myocardial was deteced by terminal d UTP nick-end-labeling(TUNEL) method.Results:(1) Effects of pacemaker stimulus: 5 days after the operations the rabb its of pace-making groups(group C, D) developed paralysis, unresponsiveness,anorexia, hair gloss reduction, and sluggish and etc. 1 week after pacemaker st imulus, the BNP and TNF-α serum levels, cardiac myocyte apoptosis index, L VESD and LVEDD of group C and D rabbits were significantly increased com pared with group A and B rabbits(P < 0.05), while the LVEF was decreased remarkablely(P < 0.05). The cardiac myocyte apoptosis index was positively c orrelated with serum levels of BNP and TNF-α(P < 0.05). The effect of BNP on the variation of cardiac myocyte apoptosis index was greater than TNF-αafter 1 week operations, while the above same effect of TNF-α was greater th an BNP after 4 week operations.(2) Effects of carvedilol: The following 1 we ek to 4 weeks after operations, the BNP and TNF-α serum levels, LVESD, LV EDD, and cardiac myocyte apoptosis index of group D rabitts were significantl y decreased compared with group D rabitts(P < 0.05), while the LVEF was i ncreased remarkablely(P < 0.05). All the tested indexes between group A and group B rabitts had no significant differences(P > 0.05).Conclusion:(1) The increase of myocardial apoptosis appeared along with the prolongation of pace-making time and the heart failure increase of TCM.(2)The cardiac myocyte apoptosis index was positively correlated with serum lev els of BNP and TNF-α, so the cell apoptosis may be involved in the develop ment of TCM of rabbit and the progress of cardiac insufficiency, it may be on e of the pathogenesis of TCM.(3) Carvedilol could reduce the rabbits cardiac myocyte apoptosis rate of TCM to a certain extent, it may reversal the progres s of TCM.