I(Ks) block by HMR 1556 lowers ventricular defibrillation threshold and reverses the repolarization shortening by isoproterenol without rate-dependence in rabbits.
INTRODUCTION: 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 beta-adrenergic stimulation. METHODS AND RESULTS: In...
| Publicado en: | Journal of Cardiovascular Electrophysiology Vol. 18; no. 7; pp. 750 - 757 |
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| Autores principales: | , , , |
| Formato: | Journal Article |
| Publicado: |
Wiley-Blackwell
Jul2007
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105835064&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105835064 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10453873 GSB jtl: Journal of Cardiovascular Electrophysiology issn: 10453873 maglogo: Y pubinfo: dt: Jul2007 vid: 18 iid: 7 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 105835064 2009652578 NLM17578345 105835064 ppf: 750 ppct: 7 formats: fmt: @attributes: type: P tig: atl: I(Ks) block by HMR 1556 lowers ventricular defibrillation threshold and reverses the repolarization shortening by isoproterenol without rate-dependence in rabbits. aug: au: So PP Backx PH Hu XD Dorian P affil: Division of Cardiology, St. Michael's Hospital, Toronto, Ontario, Canada. sug: subj: Action Potentials Drug Effects Benzopyrans Pharmacodynamics Cardioversion Methods Isoproterenol Pharmacodynamics Membrane Proteins Antagonists and Inhibitors Sulfonamides Pharmacodynamics Action Potentials Physiology Animals Benzopyrans Therapeutic Use Male Membrane Proteins Physiology Rabbits Sulfonamides Therapeutic Use Ventricular Fibrillation Drug Therapy Ventricular Fibrillation Physiopathology Male ab: INTRODUCTION: 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 beta-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 (MAPD90), 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 MAPD90 and VERP were studied at cycle lengths (CLs) 200-500 msec. In vivo, HMR 1556 prolonged MAPD90 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 MAPD90 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 beta-adrenergic stimulation contributes to ventricular repolarization without rate dependence. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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