From the Departments of Pharmacology (Y.A., W.T.B., R.G., J.D., J.J.) and
Pediatrics (Cardiology) (R.M.), State University of New York Health Science
Center at Syracuse, NY. Dr Gray is presently at Department of Bioengineering,
University of Alabama at Birmingham.
Correspondence to Ravi Mandapati, MD, Department of Pharmacology, SUNY Health Science Center at Syracuse, 766 Irving Ave, Syracuse, NY 13210. E-mail mandapar{at}vax.cs.hscsyr.edu
Background—Ventricular
fibrillation (VF) leads to global ischemia of the heart. After
1 to 2 minutes of onset, the VF rate decreases and appears more
organized. The objectives of this study were to determine the effects
of no-flow global ischemia on nonlinear wave dynamics and
establish the mechanism of ischemia-induced slowing of the
VF rate.
Methods and Results—Activation patterns of VF in the
Langendorff-perfused rabbit heart were studied with the use of 2
protocols: (1) 15 minutes of no-flow global ischemia followed
by reperfusion (n=7) and (2) decreased excitability induced by
perfusion with 5 µmol/L of tetrodotoxin (TTX) followed by
washout (n=3). Video imaging (
Conclusions—This study suggests that rotating spiral waves are
most likely the underlying mechanism of VF and contribute to its
frequency content. Ischemia-induced decrease in the VF rate
results from an increase in the rotation period of spiral waves that
occurs secondary to an increase in their core area. Remarkably, similar
findings in the TTX protocol suggest that reduced excitability during
ischemia is an important underlying mechanism for the changes
seen.
© 1998 American Heart Association, Inc.
Basic Science Reports
Quantification of Effects of Global Ischemia on Dynamics of Ventricular Fibrillation in Isolated Rabbit Heart
7500 pixels per frame; 240 frames per
second) with a voltage-sensitive dye, ECG, and signal processing (fast
Fourier transform) were used for analysis. The dominant
frequency of VF decreased from 13.5±1.3 during control to 9.3±1.4 Hz
at 5 minutes of global ischemia (P<0.02). The
dominant frequency decreased from 13.9±1.1 during control to 7.0±0.3
Hz at 2 minutes of TTX infusion (P<0.001). The rotation
period of rotors on the epicardial surface (n=27) strongly correlated
with the inverse dominant frequency of the corresponding episode of VF
(R2=0.93). The core area, measured for 27
transiently appearing rotors, was 5.3±0.7 mm2 during
control. A remarkable increase in core area was observed both during
global ischemia (13.6±1.7 mm2;
P<0.001) and TTX perfusion (16.8±3.6 mm2;
P<0.001). Density of wave fronts decreased during both
global ischemia (P<0.002) and TTX perfusion
(P<0.002) compared with control.
Key Words: fibrillation • ischemia • Fourier analysis • ventricles • excitation
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