Quantification of Effects of Global Ischemia on Dynamics of Ventricular Fibrillation in Isolated Rabbit Heart

Abstract

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 (≈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 ( R 2 =0.93). The core area, measured for 27 transiently appearing rotors, was 5.3±0.7 mm 2 during control. A remarkable increase in core area was observed both during global ischemia (13.6±1.7 mm 2 ; P <0.001) and TTX perfusion (16.8±3.6 mm 2 ; P <0.001). Density of wave fronts decreased during both global ischemia ( P <0.002) and TTX perfusion ( P <0.002) compared with control. 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.