| Background- Ventricular tachycardia (VT) and fibrillation (VF) due to ischemic heart disease are some of the leading cause of death. However, large scale clinical trial shows that some antiarrhythmic drugs have no impact on mortality after myocardial infarction and others may even increase mortality due to their proarrhythmic potential because cardiac ion channel is the targets of these traditional drugs expect for amiodarone andβ-blocker. Recent study indicates that gap junctions plays a crucial role for impulse propagation in cardiac tissue and alterations in electrical coupling between ventricular myocytes play an important role in conduction delays and arrhythmogenesis in acute and chronic heart disease. Presently, several lines of evidence suggest that antiarrhythmic peptide AAP10 and its analogue ZP123 enhance gap junctional intercellular conductance during acute hypoxia, acidosis and acute ischemia and prevent reentrant ventricular tachycardia during ischemia, which offers a novel target for clinical antiarrhythmic therapy. However, the effect of antiarrhyth- mic peptide on gap junctional coupling of chronic ischemic heart disease remains unknown.Mathods and results-To evaluate the effects of antiarrhythmic peptide (AAP10), a kind of gap junctional activator, on ventricular arrhythmias in rabbits with healed myocardial infarction (HMI). 30 rabbits were randomly divided into three groups (n = 10 each): Sham group, HMI group, and AAP10 group. In HMI group and AAP10 group, the circumflex coronaries were ligated. In sham group, left thoracotomy was performed without coronary ligation. The animals were feed three months before the study and an arterially perfused rabbit left ventricular wedge preparation was made. Sham and HMI group were perfused with Tyrode's solution and AAP10 group was perfused Tyrode's solution + AAP10 (80nmol/L). Transmembrane action potentials were recorded simultaneously from endocardium, epicardium, together with a transmural ECG, in arterially perfused left ventricular preparations by use of 2 separate intracellular floating microelectrodes. The stimulus-response- interval (SRI) of the epicardium and the incidence of ventricular tachycardia (VT) were observed as well. At last, the weight of left ventricle, the weight of whole heart and the thickness of ventricular wall of infarct border zone (IBZ) were measured.The incidences of the ventricular arrhythmias induced were 0 %( 0/10), 80% (8/10) and 20 %( 2/10) respectively in Sham group, HMI group and AAP10 group. HMI rabbits exhibited significant high incidence compared with sham rabbits (P<0.01), AAP10 can significantly inhibit ventricular arrhythmia in HMI rabbits (P<0.05). In AAP10 group, AAP10 can markedly shorten SRI [SRI-1: (28.71±0.55) ms vs (20.59±0.79) ms; SRI-2: (38.67±0.49) ms vs (30.42±0.74) ms, P<0.001], which suggested that AAP10 can enhance impulse propagation in HMI rabbits.However, the action potential morphology and duration were not significantly altered by AAP10 at this concentration used. The heart weight and the heart weight-to-body weight ratio were elevated in the HMI and AAP10 groups compared with the control group (P<0.01), the thickness of IBZ ventricular walls were increased in HMI and AAP10 groups compared with the sham groups too (P<0.01).Conclusions - Remodeling of gap junction has been in concomitant with ventricular remodeling in HMI rabbits, which results in gap junctional uncoupling and contributes to development of reentrant arrhythmias. The antiarrhymic peptide (AAP10) can increase gap junctional intercellular conductance without affecting the action potential morphology and duration and decrease the incidence of ventricular arrhythmias, which suggests that enhancement of gap junctional conductance could be served as a new strategy for antiarrhythmic therapy in ischemic heart disease.
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