QUANTIFICATION OF EFFECTS OF GLOBAL-ISCHEMIA ON DYNAMICS OF VENTRICULAR-FIBRILLATION IN ISOLATED RABBIT HEART

Background-Ventricular fibrillation (VE) leads to global ischemia of t he heart. After 1 to 2 minutes of onset, the VF rate decreases and app ears more organized. The objectives of this study were to determine th e effects of no-flow global ischemia on nonlinear wave dynamics and es tablish the mechanism of ischemia-induced slowing of the VF rate. Meth ods 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) decre ased excitability induced by perfusion with 5 mu mol/L of tetrodotoxin (TTX) followed by washout (n=3). Video imaging (approximate to 7500 p ixels per frame; 240 frames per second) with a voltage-sensitive dye, EGG, and signal processing (fast Fourier transform) were used for anal ysis. The dominant frequency of VF decreased from 13.5+/-1.3 during co ntrol to 9.3+/-1.4 Hz at 5 minutes of global ischemia (P<0.02). The do minant 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 rot ors on the epicardial surface (n = 27) strongly correlated with the in verse 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 ob served 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 decreas ed during both global ischemia (P<0.002) and TTX perfusion (P<0.002) c ompared with control. Conclusions-This study suggests that rotating sp iral waves are most likely the underlying mechanism of VF and contribu te to its frequency content. Ischemia-induced decrease in the VF rate results from an increase in the rotation period of spiral waves that o ccurs 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.