Mechanism of acceleration of functional reentry in the ventricle: Effects of ATP-sensitive potassium channel opener

Takumi Uchida, Masaaki Yashima, Masamichi Gotoh, Zhilin Qu, Alan Garfinkel, James N. Weiss, Michael C. Fishbein, William J. Mandel, Peng Sheng Chen, Hrayr S. Karagueuzian

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Background-The effect of effective refractory period (ERP) shortening on the vulnerability and characteristics of induced functional reentry in the ventricle remain poorly defined. We hypothesized that ERP shortening increases ventricular vulnerability to reentry and accelerates its rate, as is the case in the atrium. Methods and Result-The epicardial surfaces of 19 isolated and superfused canine right ventricular slices (4x4 cm and < 2 mm thick) were mapped with 480 bipolar electrodes 1.6 mm apart. Vulnerability was tested during pacing at a cycle length (CL) of 600 ms and with a single premature stimulus of 5-ms duration at increasing current strength of 1 to 100 mA. Cromakalim (10 μmol/L), an ATP-sensitive potassium channel opener, caused a significant (P < 0.001) shortening of the ERP but had no effect on conduction velocity. Cromakalim increased (P < 0.01) the vulnerability (product of current and the stimulus coupling interval) for reentry induction. Reentry had a significantly shorter CL and lasted for a longer duration (P < 0.001). The central core around which the wave front rotated became smaller, which caused shortening of the CL of reentry. A significant (P < 0.001) linear correlation was found between core size and reentry CL. These effects of cromakalim were reversible. Two-dimensional simulation studies using the modified Luo-Rudy I model of cardiac action potential, in which the refractory period was variably shortened by a progressive increase of the time-independent potassium conductance, reproduced the experimental findings. Conclusions-ERP shortening by an ATP-sensitive potassium channel opener increases ventricular vulnerability to reentry and accelerates its rate by decreasing the core size around which the wave front rotates.

Original languageEnglish (US)
Pages (from-to)704-712
Number of pages9
JournalCirculation
Volume99
Issue number5
DOIs
StatePublished - Feb 9 1999

Keywords

  • Cromakalim
  • Potassium
  • Reentry
  • Tachycardia
  • Waves

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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