Effects Of Gap Junction On Ventricular Arrhythmias In Left Ventricular Hypertrophy

Partâ… Changes of Electrophysiological Characteristics in Hypertrophied MyocardiumBackground:Left ventricular hypertrophy is associated with a greater prevalence of ventricular arrhythmias. In contrast to normal myocardium, which shows gap junctions labeling largely confined to the intercalated disks, hypertrophied myocardium shows dispersion of gap junctions labeling over the entire cell surface, and are frequently displaced from their usual locations to form side-to-side contacts distant from the disk. En face views of intercalated disks of myocardial hypertrophy reveals a reduction of gap junctions in the disk center, which gives rise to an increased risk of incidence of ventricular arrhythmias. As a result, the incidence of ventricular arrhythmias in myocardial hypertrophy may be closely related to gap junctions and with the improvement of gap junctions, the incidence of ventricular arrhythmias is decreased.Objective:This experiment was designed to explore the relationship between gap junctions and ventricular arrhythmias in left ventricular hypertrophy.Methods:To explore the effects of gap junctions on ventricular arrhythmias in left ventricular hypertrophy, twenty rabbits were randomly divided into two groups: Sham group and Left ventricular hypertrophy group (LVH group). In the LVH group, the abdominal aorta was partially constricted. In the Sham group, the abdominal aorta was only exposed without constriction. The arterially perfused left ventricular wedge preparations were made after three months. The wedge preparations were perfused with Tyrode's solution in the Sham group and the LVH group. Volume electrocardiogram, stimulus response interval, transmural repolarization dispersion, the incidence of early afterdepolarization and the occurrence of ventricle arrhythmias at different cycle lengths were recorded. The weight of whole heart and left ventricle was obtained at the end of the experiment.Results:At different cycle lengths, transmural repolarization dispersion and QT interval in the LVH group were increased significantly compared with those in the Sham group (P<0.05). LVH rabbits exhibited significant frequency-dependent APD90 and transmural repolarization dispersion prolongation compared with those in the Sham group(P<0.05). Early afterdepolarization and ventricular arrhythmias were not induced in the Sham group, but at basic cycle lengths of 5000 ms , the incidence of early afterdepolarization and the occurrence of ventricular arrhythmias in the LVH group were 10/10, 4/10 respectively.Conclusion:Prolongation of stimulus response interval in hypertrophied myocardium can lead to increase in transmural repolarization dispersion and QT interval, induce early afterdepolarization and cause ventricular arrhythmias. Partâ…¡Effects of Antiarrhythmic Petide on Ventricular Arrhythmias in Rabbit hypertrophied myocardiumBackground:Gap junctions play a crucial role in the excitation spread in the heart and it is now showed that changes in the amount and distribution of gap junctions in the heart may be an important factor contributing to arrhythmogenesis under hypertrophied mycardium. However, there is no antiarrhythmic drug acting on gap junction and classical antiarrhythmic drugs acting on transmembrane ion channels have a proarrhythmic tendency. These results led to the hypothesis that an improvement of cellular coupling, i.e. an increase in gap junction conductance, might act antiarrhythmically. It is reported that AAP may act via an increase in gap junction conductance. Thus, AAP may reduce the occurrence of ventricle arrhythmias without a proarrhythmic tendency.Objective:This experiment was designed to explore the relationship between antiarrhythmic peptide acting on gap junctions and ventricular arrhythmias in left ventricular hypertrophy.Methods:Twenty rabbits were constructed by partial constriction of abdominal aorta and then randomly divided into two groups: LVH group and antiarrhythmic peptide group (AAP group). The arterially perfused left ventricular wedge preparations were made after three months. The wedge preparations were perfused with Tyrode's solution in the LVH group and with Tyrode's solution containing AAP10 in the AAP group. At different cycle lengths, transmural repolarization dispersion, stimulus response interval and transmembrane action potentials from epicardium and endocardium were simultaneously recorded together with a transmural ECG. The incidence of early afterdepolarization and the occurrence of ventricle arrhythmias were recorded. The weight of whole heart and left ventricle was obtained at the end of the experiment.Results:At different cycle lengths, transmural repolarization dispersion and stimulus response interval in the AAP group were decreased significantly compared with those in the LVH group (P<0.05). AAP10 reduces significantly frequency-dependent APD90 and QT interval prolongation (P<0.05). At basic cycle lengths of 5000 ms, the incidences of early afterdepolarizations in the LVH group and the AAP group were 10/10, 3/10 respectively. The incidences of ventricular arrhythmias in the LVH group and the AAP group were 4/10, 1/10, respectively. There was a significance difference in the incidence of early afterdepolarization and ventricular arrhythmias between the LVH group and the AAP group (P<0.05).Conclusion:AAP10 can short stimulus response interval and reduce transmural repolarization dispersion in ventricular hypertrophy and result in lower incidence of early afterdepolarization and ventricular arrhythmias by improving gap junctions.