In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 106, No. 15 ( 2002-10-08), p. 2012-2018
Abstract:
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) (n=34), 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 ≈21 days of AVB and from 8 sham-operated controls with sinus rhythm. Action potential duration was prolonged in AVB myocytes compared with control (+61% at 0.5 Hz, +21% at 3 Hz). Both rapidly and slowly activating components of the delayed rectifier K + 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 2+ -independent transient outward current ( I to1 ). L-type Ca 2+ 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 + 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.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.0000031160.86313.24
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2002
detail.hit.zdb_id:
1466401-X
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