title: Shock-induced refractory period extension and pharmacologic modulation of defibrillation threshold.
abstract: Shock-induced refractory period extension (RPE) has been suggested as a mechanism of electrical defibrillation. We measured RPE caused by localized field stimulation measured before and during infusion of disopyramide (n = 5), flecainide (n = 5), or E-4031 (n = 5) in anesthetized dogs and determined the effect of the drugs on the internal defibrillation threshold (DFT). In the baseline state (n = 15), 16 V/cm S2 field stimulation prolonged the effective RP by 36 +/- 15 ms (22 +/- 12% of RP without S2), whereas 4 and 8 V/cm S2 stimuli did not cause marked RPE. The RPE normalized by the RP without S2 was not significantly influenced by any drug (16 V/cm: disopyramide 30 +/- 11 vs. 27 +/- 11, flecainide 25 +/- 5 vs. 19 +/- 12, and E-4031 18 +/- 13 vs. 22 +/- 14%). Disopyramide did not alter the defibrillation threshold (4.2 +/- 0.6-4.4 +/- 0.6 J). In 2 dogs given flecainide, ventricular fibrillation became refractory to defibrillation. In contrast, E-4031 lowered the threshold from 4.5 +/- 2.4 to 2.2 +/- 1.2 J (p < 0.01). The results suggest that flecainide and E-4031 do not modulate defibrillation efficiency through their effects on RPE.
authors.affiliation: Second Department of Internal Medicine, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Murakawa
authors.forename: K
authors.initials: K
authors.lastname: Sezaki
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Usui
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: K
authors.initials: K
authors.lastname: Ajiki
authors.forename: N
authors.initials: N
authors.lastname: Oikawa
authors.forename: K
authors.initials: K
authors.lastname: Iwasawa
authors.forename: M
authors.initials: M
authors.lastname: Omata
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004206:Disopyramide / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004554:Electric Countershock; D004558:Electric Stimulation; D005424:Flecainide / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007262:Infusions, Intravenous; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D015203:Reproducibility of Results
chemical_list: D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; C063968:E 4031; D004206:Disopyramide; D005424:Flecainide