Background-The ionic basis of acquired QT prolongation and torsade de pointes (TdP) unrelated to drugs is not fully understood. Methods and Results-We created a rabbit model with chronic complete atrioventricular block (AVB) (nϭ34), which showed prominent QT prolongation (by 120%), high incidence of spontaneous TdP (71%), and cardiac hypertrophy. Patch-clamp experiments were performed in left ventricular myocytes from 9 rabbits (8 with TdP, 1 without TdP) at Ϸ21 days of AVB and from 8

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... ted controls with sinus rhythm. Action potential duration was prolonged in AVB myocytes compared with control (ϩ61% at 0.5 Hz, ϩ21% at 3 Hz). Both rapidly and slowly activating components of the delayed rectifier K ϩ current (I Kr and I Ks ) in AVB myocytes were significantly smaller than in control by 50% and 55%, respectively. There was no significant difference in Ca 2ϩ -independent transient outward current (I to1 ). L-type Ca 2ϩ current (I Ca,L ) in control and AVB myocytes was similar in peak amplitude, but the half voltage for activation was shifted to the negative direction (5.9 mV) in AVB myocytes. Voltage dependence of I Ca,L inactivation was not different in control and AVB myocytes. The inward rectifier K ϩ current (I K1 ) significantly increased in AVB myocytes compared with control. Conclusions-In the rabbit, chronic AVB leads to prominent QT prolongation and high incidence of spontaneous TdP. Downregulation of both I Kr and I Ks in association with altered I Ca,L activation kinetics may underlie the arrhythmogenic ventricular remodeling.