Cardiac And Electrical Remodeling In Dilated Cardiomyopathy And Arrhythmias

Cardiac and Electrical Remodeling inDilated Cardiomyopathy and ArrhythmiasAbstractBackground Ventricular and electrical remodeling were the pathophysiologic basis for the onset and development of various cardiovascular diseases. In the former three parts of this study, we aimed to investigate the correlation between autoimmune antibodies and electrical disturbance in the procession of ventricular remodeling. In the last part, the mechanism of atrial remodeling, fibrosis and atrial fibrillation(AF)-induced cardiomyopathy were further studied as well as electrical remodeling in AF on the model of right atriapacing induced AF rabbits. Therefore, ventricular remodeling and electrical remodeling were combined efficiently.Methods(1): Using sythetic 24-mer peptide to establish ELISA technique to determine the titer of anti- ~ 1 and anti-M2R autoantibodies in patients with DCM or primary arrhythmia.(2): Semi-quantitative RT-PCR method was applied to estimate the gene expression (messenger RNA) level.(3): Serum or tissue ANP, NO and AngII concentration were determined by radio-immune method.(4): Double antibodies sandwich ELISA was applied to estimate cardiac injury marker cTnI level.(5): Establish three model: cultured neonatal cardiomyocyte, hypertension-diabetes and DCM rats, right-atria pacing induced AF rabbits.Results1.(1 )The P/N value and positive rate of anti- ~ 1 and anti-M2R autoantibodies in DCM patients increased markedly than healthy group, and there was an positive-relation between two antibodies; The autoantibodies showed remarkable augment in patients withI0primary ventricular arrhythmias (PVA) or DCM patients with PVAthan healthy persons or DCM patients without any arrhythmias; (2)QT dispersion was much longer in cardiogenic sudden death andventricular arrhythmias population. In DCM grouP, patients withani- D l-autoantibody had significan longer QT dispersion thanpatients without this antibody; (3) In 45 DCM cases with Wholeclinical data, the anti D l auoantibody positive rate showedsignificant higher in NYHA III~IV grouP than in NYHA I~IIgrouP. In positive anibody grouP, LVEDV LVESV EF and FSmarkedly decreased, togather with various degree of chamberdilation (LV LA); (4) The serum ANP and NO concentrationincreased significanly in DCM patients, especially withautoanibodies, and this tendency was associated with decreasedheart function (NYHA class III--IV); (5) The D l messenger RNAeXPression were downregulated in peripheral white blood ceIls inDCM patients and had slight decrease in patients with positiveani- fi l-antibody and worse heart function W III--IV) thanin patients with negative antibody and NYHA I~II. Nosignificance was observed in different heart function and thetreatment withD -blocker; (6) In DCM patients, the effect oftfeatment with Betaloc were correlated with the time (l,3,6,l2months) of theraPy. EF and FS had been remarkably improved asearly as one month after administration of Betaloc, LVEDV andLVESV began to reverse at three months later, LA and SV alsoshowed significance at six months, heart function (N'YHA class)had significant imProved till twelve months.2. l:40 titer of ani 0 l autoanibody positive serum from DCMpatients were put into cultured neonatal cardiomyocytes, after48--72 hours, the myocardial beating rate increased significantly,and no cTnI augment was observed, together with decreased NOand ANP level in culture fluid. Bisoprolol could markedlydecrease cTnI level and slightly increase NO and ANPconcentfation. No alteration of Aam and 0 l-unA exceptl l. 1mcreased ATl eXPression were observed in grouP interfere with 0l-anibody, and Bisoprolol could increase 0 1-AR eXPression andreversed the upregulation of ATl-mRNA. Solely aPplyingBisoProlol could decrease the mRNA level of ANP and ATl.3. In 2KlC hyPertension, diabetic and dilated cardiomyopathy rats,there were significant increase of blood pressure (BP), blood...