Early voltage/calcium uncoupling predestinates the duration of ventricular tachyarrhythmias during ischemia/reperfusion.
Himel HD., Bub G., Yue Y., El-Sherif N.
BACKGROUND: Abnormal intracellular calcium (Ca(i)) kinetics during ischemia/reperfusion (I/R) can alter membrane voltage (V(m)) and destabilize wavefront propagation. OBJECTIVE: We used optical mapping to investigate the hypothesis that early V(m)/Ca(i) uncoupling during a ventricular tachyarrhythmia (VT) can play a primary role in perpetuation of VT episodes. METHODS: Seventeen Langendorff-perfused guinea pig hearts were subjected to 15 min I/15 min R. Simultaneous optical recordings of V(m) and Ca(i) signals were obtained using a dual-photodiode array. Spatiotemporal entropy (E) was used to quantify differences in V(m)/Ca(i) kinetics during VT and compare wavefront topology during the first 500 ms of a VT episode. RESULTS: A total of 39 episodes of VT were analyzed; VT was classified as self-terminating (ST, n = 28) and non-self-terminating (NST, n = 11). The ST/VTs were further classified into short ST/VT (1 to 5 s in duration; n = 16) and long ST/VT (>5 s, n = 12). E values for NST/VTs were significantly higher than E values for both short and long ST/VTs separately as well as E values for ST/VTs as a group. Further, E values for long ST/VTs were significantly higher than E values for short ST/VTs. Wave breaks were consistently identified during periods of high E. CONCLUSION: High E during the first 500 ms of the onset of VT (the first 2 to 3 beats) is significantly correlated with long ST or NST episodes. This may be related to destabilization of wave propagation that helps to perpetuate VT. Early V(m)/Ca(i) uncoupling can predestinate the development of a malignant NST/VT.