ABSTRACT
Objective To determine the effect of calmodulin-dependent kinase Ⅱ (CaMK Ⅱ ) -ryanodinereceptor pathway signaling in rabbits with left ventricular bypertrophy (LVH) and triggered ventricular arrhythmia.Methods Forty New Zealand rabbits were randomized into four groups ( n =10 per group):the sham operation group,LVH group,KN-93 (CaMKⅡ inhibitor) group (LVH + KN-93),and the ryanodinegroup ( LVH + ryanodine).Rabbits in the LVH,KN-93,and ryanodinegroups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while the rabbits in the sham operation group did not have the coarctation.After eight weeks,action potentials (APs) were recorded simultaneously in the endocardium and epicardium,and transmural electrocardiogram (ECG) was also recorded in the wedge shaped models of rabbits' left ventricular myocardium.Drugs were administered to animals in the KN-93 and ryanodinegroups respectively,and the frequency of triggered APs and ventricular tachycardia were recorded after isoprenaline ( 1 μmol/L),and high-frequency electrical stimulation were given to rabbits.Results The incidences (animals/group) of triggered APs were:sham,0/10 ; LVH,10/10; KN-93,4/10; and ryanodine,1/10.The incidences of ventricular tachycardia induced were 0/10,9/10,3/10,and 1/10,respectively.The incidences of triggered ventricular arrhythmias in the KN-93 group and ryanodine groups tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The incidences of triggered ventricular arrhythmias in the KN-93 group and ryanodine groups were much lower than that in the LVH group (P ＜ 0.05).Conclusions KN-93 and ryanodinecan effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMK Ⅱ-ryanodine signaling pathway can be used as a novel target site of treating ventricular arrhythmia.
ABSTRACT
Objectives This study aimed at investigating the cellular mechanism of isoproterenol (ISO) on delayed afterdepolarizations (DADs) and triggered activity (TA) of the noninfarcted myocardium in the myocardial infarcted rabbit model.Methods Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 wk (healed myocardial infarction, HMI). Myocytes were isolated from regions of the noninfarcted left ventricular free wall. ISO was added to cellular surface by perfusion way. Action potentials and ion currents were recorded with whole-cell patch clamp. Results The results showed that treatment with ISO induced more DADs and TA events in HMI myocytes. Iti and ICa-L of myocytes treated with ISO were increased significantly compared with HMI cells, which contributed to DADs-related triggered arrhythmia. Conclusions The results suggested that more arrhythmia events of DADs and TA developed in myocytes with ISO treatment. The underlying mechanism was associated with the augment of Iu and calcium influxing.