Effect of antiarrhythmic peptide on ventricular arrhythmia induced by lysophosphatidic acid / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.</p><p><b>METHODS</b>Twenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.</p><p><b>RESULTS</b>Compared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43.</p><p><b>CONCLUSIONS</b>LPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.</p>

Effects of combined amiodarone and antiarrhythmic peptide use on the cardiac gap junctions and incidence of induced ventricular arrhythmias in healed myocardial infarction rabbit models / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study is to observe the effect of combined amiodarone and antiarrhythmic peptide (AAP10) use on the incidence of induced ventricular arrhythmias in healed myocardial infarction (MI) rabbits.</p><p><b>METHODS</b>Twenty Japanese rabbits underwent thoracotomy without coronary artery ligation (Sham, group A), the middle left circumflex branch were ligated to induce MI in 180 Japanese rabbits. Eight weeks after operation, 124 rabbits survived MI operation and were divided into four groups: control group (group B, n = 31), amiodarone group (group C, n = 31), AAP10 group (group D, n = 31) and amiodarone plus AAP10 group (group E, n = 31). The A and B and D groups were treated with saline 2 ml/d, the C and E groups were treated with 2 ml saline containing amiodarone 100 mg×kg(-1)×d(-1). All rabbits were examined by echocardiogram at 12 weeks after operation, then anesthetized by sodium barbital, the left wedge ventricular preparations were cannulated and artery perfused by Tyrode's solution in vitro in the absence (Group A, B and C) and presence of AAP10 (500 nmol/L, Group D and E). The volume electrocardiogram, QT Interval, QRS interval, effective refractory period (ERP), the T-peak to T-end interval (T(p-e)), and ventricular tachycardia episodes induced by programmed stimulation were recorded. The T(p-e)/QT ratio was calculated. After perfusion, gap junctions protein connexin 43 (Cx43) expression was detected by Western blot and immunofluorescence.</p><p><b>RESULTS</b>The incidence of induced ventricular tachycardia episodes of group A, B, C, D, E was 0, 62.5%, 26.9%, 40.0%, 22.2% respectively. The incidence of induced ventricular tachycardia episodes of group E was less than group B. The T(p-e)/QT ratio in group B, C, D were greater than in group A. The T(p-e)/QT ratio of group E was less than group B. The myocardial Cx43 in the group B was down-regulated and disorganized compared to group A, up-regulated in group C and E compared to group B, up-regulated in group E compared to group D. The Cx43 in the heart of group D and E were well organized than in group B and C.</p><p><b>CONCLUSIONS</b>The artery perfused rabbits wedge preparations with healed myocardial infarction with high incidence of induced ventricular tachycardia episodes are good platform for ventricular arrhythmias research. Combined amiodarone and AAP10 use could decrease the T(p-e)/QT ratio and the incidence of induced ventricular tachycardia episodes. Amiodarone and AAP10 have synergistic effects on upregulating Cx43 and preventing ventricular arrhythmias in this rabbit model of healed myocardial infarction.</p>