The Effects Of Antiarrhythmic Peptide On Ventricular Arrhythmias In Rabbits With Ischemia-reperfusion Injury

Background: Recently, ischemia-reperfusion injury is important with the generalization and development of PTCA (percutaneous transluminal coronary angioplasty),CABG( coronary artery bypass grafting) and coronary artery thrombolysis . Ischemia-reperfusion injury is reflected by ischemia-reperfusion arrhythmia. Acute alterations in electrical coupling during myocardial ischemia and reperfusion are associated with conduction slowing and heterogeneities of repolarization that are important factors for reentrant arrhythmias. Ischemia reperfusion induced gap junction uncoupling is determined by several factors including acidosis, calcium overload and accumulation of lipid metabolites. Therapeutics aimed at preventing uncoupling or re-establishing gap junction intercellular communication may be effective antiarrhythmic agents. However, the effect of antiarrhyth- mic peptide on gap junctional coupling of ischemia-reperfusion arrhythmia remains known little.Aim: To evaluate the effects of antiarrhythmic peptide (AAP10), a kind of gap junctional activator, on ventricular arrhythmias in rabbits with ischemia-reperfusion injury.Methods: 40 rabbits were randomly divided into four groups (n = 10 each): IR group, AAP10( 100nmol/L,500nmol/L,1000nmol/L) group. An arterially perfused rabbit left ventricular wedge preparation was made. IR group were perfused with Tyrode's solution, AAP10 group was perfused Tyrode's solution + AAP10(100nmol/L,500nmol/L,1000nmol/L).The wedge was subjected to a 40 min coronaryartery occlusion and 1 h reperfusion. Transmembrane action potentials were recordedsimultaneously from endocardium, epicardium by use of 2 separate intracellularfloating microelectrodes in arterially perfused left ventricular preparations. Thestimulus-response- interval (SRI) and the incidence of ventricular arrhythmias (VT)were observed as well. At last, the weight of left ventricular wedge preparation, leftventricle and whole heart were measured.Results: The high incidence of VT was observed in rabbits with ischemia-reperfusioninjury. AAP10 can markedly shorten SRI (P<0. 01, n =10) and decrease the incidenceof VT. The action potential morphology and duration were not significantly altered.Conclusions:â‘ Ischemia-reperfusion injury can increase the incidence of ventriculararrhythmias. The mechanism is that ischemia reperfusion induces gap junctionuncoupling which is associated with conduction slowing and heterogeneities ofrepolarization.â‘¡AAP10 can decrease SRI and the duration of recovery , increase gap junctionalinter-cellular conductance, decrease the incidence of ventricular arrhythmias .Themechanism may be associated with the improvement of gap junction electricalcoupling.â‘¢AAP10 does not influence the action potential morphology and duration, so it hasno proarrhythmia.. Gap junctional activator will be a new target of arrhythmictherapy.