Similar to HF myocardial infarction MI is followed
Similar to HF, myocardial infarction (MI) is followed by significant down-regulation of multiple K currents in the peri-infarct zone. These changes may contribute to after-depolarization and ventricular arrhythmia in MI ventricles. However, none of the previous studies reported MI in an increased IKAS. By delicate control of infarction size, Lee et al. studied IKAS in a rabbit model of chronic MI (5 weeks) with normal left ventricular function . In that model, they found that apamin prolonged the APD in the peri-infarct zone by 9.8%, which is greater than that (2.8%) of normal ventricles. Post-pacing APD shortening is also prevented by apamin. A patch clump study showed that the sensitivity of IKAS to Cai was significantly increased in myocytes isolated from the peri-infarct zone. This study firstly proved that MI is associated with IKAS up-regulation, even without HF.
From the serial studies of IKAS in diseased hearts, it was clear that up-regulation of IKAS during slow jak inhibitors rate might increase the repolarization reserve and prevent after-depolarizations, whereas IKAS up-regulation at tachycardia (short CL) might shorten APD and steepen APDR, promoting ventricular arrhythmia. Therefore, similar to other K channel blockers, IKAS blockers can be both pro-arrhythmic and anti-arrhythmic, depending on the clinical situations associated with arrhythmogenesis. IKAS blockade may prevent transition from ventricular tachycardia (VT) to VF and prevent the spontaneous re-initiation of VF. On the other hand, if the arrhythmia is bradycardia dependent, such as that induced by EAD, IKAS blockers may promote triggered activity and ventricular arrhythmia. However, the optimal heart rate for preventing VT to VF transition while avoiding bradycardia-induced EAD in terms of IKAS blockade remains to be determined. Our knowledge of IKAS is derived from experimental animal models (i.e., HF, MI); whether the IKAS hypothesis could be applied to human anti-arrhythmic therapy warrants further investigation. Apamin is a neurotoxin that may induce significant neurological side effects when used in live animals and humans. We need to develop non-toxic IKAS blockers before we can test the effects of IKAS blockade on VF storm in human patients. Amiodarone is effective in the treatment of recurrent VT/VF and is commonly used as the first line therapy for ES. Recently, Turker et al. used a patch-clamp technique to study the effects of amiodarone on IKAS in human embryonic kidney 293 (HEK-293) cells transiently expressing human SK2 channel . They found that amiodarone inhibited IKAS in a dose-dependent manner. The degree of IKAS inhibition by amiodarone is dependent on the Cai concentration. This study indicated that SK2 current inhibition might in part underlie the effects of amiodarone in preventing ES in failing ventricles. A better understanding of the effects of anti-arrhythmic drugs on IKAS may be important in the prevention of sudden death in patients with HF in the future.
Conflict of interest
Introduction Autonomic influences in the heart are generated by both the extrinsic and intrinsic cardiac autonomic nervous system (ganglionated plexi; GP) [1,2]. Experimental and clinical studies suggest that GP activation plays a significant role in the initiation and maintenance of atrial fibrillation (AF) [3–5]. In an animal model, stimulation of the GP produces repetitive short bursts of rapid, irregular firing in the adjacent pulmonary vein (PV); these bursts initiate sustained AF. Recent clinical studies have demonstrated that the combination of GP ablation and PV isolation produces a better outcome than PV isolation alone [6,7]. These findings indicate a relationship between GP activation and PV activation during clinical AF. However, it is unclear whether GP stimulation alters AF cycle length (AFCL) in the PV before and/or after GP ablation. In the present study, we assessed whether high-frequency stimulation (HFS)-induced changes in AFCL in the PV occur before or after GP ablation.