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I Ks Block by HMR 1556 Lowers Ventricular Defibrillation Threshold and Reverses the Repolarization Shortening by Isoproterenol Without Rate‐Dependence in Rabbits
Author(s) -
SO PETSY PUISZE,
BACKX PETER H.,
HU XUDONG,
DORIAN PAUL
Publication year - 2007
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2007.00812.x
Subject(s) - medicine , defibrillation threshold , cardiology , defibrillation , repolarization , ventricular fibrillation , anesthesia , electrophysiology
The slow delayed rectifier K + current (I Ks ) contributes little to ventricular repolarization at rest. It is unclear whether I Ks plays a role during ventricular fibrillation (VF) or ventricular repolarization at rapid rates during β‐adrenergic stimulation. Methods and Results: In an in vivo rabbit model, we evaluated the effects of HMR 1556 (1 mg Kg −1 + 1 mg kg −1 hr −1 i.v.), a selective I Ks blocker, on monophasic action potential duration at 90% repolarization (MAPD 90 ), ventricular effective refractory period (VERP), and defibrillation threshold (DFT). In perfused rabbit hearts, the effects of HMR 1556 (10 and 100 nM) in the presence of isoproterenol (5 nM) on MAPD 90 and VERP were studied at cycle lengths (CLs) 200–500 msec. In vivo , HMR 1556 prolonged MAPD 90 by 6 ± 1 msec at CL 200 msec (P < 0.01, n = 6), lowered DFT from 558 ± 46 V to 417 ± 31 V (P < 0.01), and decreased the coefficient of variation in the VF inter‐beat deflection intervals from 8.9 ± 0.6% to 6.5 ± 0.4% (P < 0.05) compared with control. In perfused rabbit hearts, isoproterenol shortened MAPD 90 by 5 ± 1 msec at CL 200 msec and 11 ± 4 msec at CL 500 msec (P < 0.05, n = 7). This shortening was reversed by HMR 1556 (P < 0.05), and both effects were rate‐independent. Conclusion: I Ks block increases VF temporal organization and lowers DFT, and I Ks that is activated following β‐adrenergic stimulation contributes to ventricular repolarization without rate dependence.