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Class III antiarrhythmic effects of LY-190147 on defibrillation threshold.

Abstract：

:Defibrillation strength shocks delivered within an action potential (AP) delay repolarization. Shock-induced AP duration extension (APDE) may prolong refractoriness and terminate or prevent reinitiation of reentry, favoring defibrillation. This study examined LY-190147 (LY) effects on defibrillation threshold (DFT) in 11 dogs. Ventricular effective refractory period (VERP) and epicardial monophasic AP duration at 75% repolarization (APD75) were recorded at 300-, 400-, 500-, and 600-ms pacing cycle length (CL). APDE was measured as the time to 50% repolarization after a DFT strength shock delivered at 50, 25, and 0 ms before or 25 ms after VERP during pacing at 300 ms CL in 4 of the dogs. We made all recordings before drug administration and after infusions of 0.03, 0.3, and 3.0 mg/kg LY, using 1.5-h dosing intervals. LY lowered DFT in a saturating dose-response manner whether expressed as shock peak voltage (V) or energy. LY decreased DFT-V from 357 +/- 77 V before drug to 331 +/- 60 V (-6 +/- 12%), 290 +/- 43 V (-17 +/- 13%, p < 0.001), and 312 +/- 45 V (-11 +/- 12%, p < 0.05) at 0.03, 0.3, and 3.0 mg/kg, respectively. Similarly, LY treatment decreased defibrillation energy requirements from 6.9 +/- 2.7 J before drug by 7 +/- 25%, 26 +/- 24%, and 12 +/- 25% at the same doses. At 300-600 ms CL, LY prolonged APD75 by an average of 10 +/- 8% at 0.03 mg/kg, 17 +/- 6% at 0.3 mg/kg, and 24 +/- 9% at 3 mg/kg. At these CL, LY prolonged VERP by an average of 4 +/- 6% at 0.03 mg/kg, 15 +/- 10% at 0.3 mg/kg, and 11 +/- 9% at 3 mg/kg. APDE was increased from 62 +/- 9 ms before to 68 +/- 14, 80 +/- 16 (p < 0.001) and 72 +/- 13 ms (p < 0.05) at 0.03, 0.3, and 3.0 mg/kg LY, respectively. Therefore, LY prolonged VERP and APDE and affected DFT in the same saturating dose-response manner. LY may facilitate defibrillation by increasing the duration of postshock refractoriness.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Beatch GN,Dickenson DR,Wood RH,Tang AS

doi

10.1097/00005344-199602000-00007

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

218-25

issue

eissn

0160-2446

issn

1533-4023

journal_volume

pub_type

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Class III antiarrhythmic effects of LY-190147 on defibrillation threshold.