Pharmacological blockade of I Ks destabilizes spiral-wave reentry under β-adrenergic stimulation in favor of its early termination

We tested a hypothesis that an enhancement of i ks may play a pivotal role in ventricular proarrhythmia under high sympathetic activity. a 2-dimensional ventricular muscle layer was prepared in rabbit hearts,and action potential signals were analyzed by optical mapping. during constant stimulation,isoproterenol (isp,0.1 μm) significantly shortened action potential duration (apd); chromanol 293b (30 μm),a selective i ks-blocker,reversed the apd shortening. vts induced in the presence of isp lasted longer than in the control,and this was reversed by 293b. e-4031 (0.1 μm),a selective i kr-blocker,did not cause such reversal. spiral-wave (sw) reentry with isp was characterized by more stable rotation around a shorter functional block line (fbl) than in the control. after application of 293b,sw reentry was destabilized,and rotation around a longer fbl with prominent drift reappeared. the apd abbreviation by isp close to the rotation center was more pronounced than in the periphery,leading to an opposite apd gradient (center < periphery) compared with controls. this effect was also reversed by 293b. in conclusion,β-adrenergic stimulation stabilizes sw reentry most likely though an enhancement of i ks. blockade of i ks may be a promising therapeutic modality in prevention of ventricular tachyarrhythmias under high sympathetic activity. © the japanese pharmacological society.