Effects of cytochalasin D on electrical restitution and the dynamics of ventricular fibrillation in isolated rabbit heart.
Cytochalasin D in Rabbit Ventricle.


BACKGROUND
Cytochalasin D (cyto-D) has been used as an excitation-contraction uncoupler during optical mapping studies. However, its effects on action potential duration restitution (APDR) and dynamics during ventricular fibrillation (VF) are unclear.


RESULTS
Langendorff-perfused rabbit hearts (N = 6) were immersed in a tissue chamber. Transmembrane potential was recorded using glass microelectrodes. APD measured to 90% repolarization (APD90) was used to construct the APDR curve. During regular pacing at 300-msec cycle length, increasing concentrations of cyto-D resulted in progressively prolonged APD90 (131 +/- 26 msec, 171 +/- 14 msec, and 177 +/- 14 msec) and steepened maximum slope of the APDR curve (1.1 +/- 0.2, 1.3 +/- 0.2, and 1.6 +/- 0.4 for control, 5 micromoles, and 10 micromoles, respectively; P < 0.01). Resting membrane potential, AP amplitude, and maximum dV/dt did not change. Cyto-D lengthened VF cycle length and APD90, and steepened the maximum slope of the APDR curve. However, cyto-D did not significantly change the diastolic interval. The dominant frequency of pseudoelectrocardiogram progressively decreased with increasing concentrations of cyto-D (15.2 +/- 0.6 Hz, 11.1 +/- 2.4 Hz, and 9.8 +/- 3.2 Hz for control, 5 micromoles, and 10 micromoles, respectively; P < 0.01). Sustained (>1 min) VF was repeatedly inducible at baseline and with 5 or 10 micromoles of cyto-D.


CONCLUSIONS
Continuous perfusion of cyto-D at 5 or 10 micromoles prolonged APD90, steepened APDR slope, and reduced dominant frequency in rabbit ventricles. Cyto-D at these concentrations allowed induction of sustained VF.
Hayashi
Hideki
H
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, and David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Miyauchi
Yasushi
Y
Chou
Chung-Chuan
CC
Karagueuzian
Hrayr S
HS
Chen
Peng-Sheng
PS
Lin
Shien-Fong
SF
D000200:Action Potentials / Q000187:drug effects*; D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D046508:Culture Techniques; D015638:Cytochalasin D / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects*; D011817:Rabbits; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000503:physiopathology*
D015638:Cytochalasin D