3.5 Optical mapping assessments of arrhythmic tendency inex vivo heart preparations
Finally, voltage dye optical mapping studies during ventricular pacing were used to assess susceptibility to arrhythmia induction before and after drug challenge in isolated perfused hearts (Fig.7A.B). Whilst 10 µM HCQ did not exert detectable arrhythmic effects at the cycle lengths (CL) used, a combination of HCQ and AZM produced AP alternans at 180 ms CL and episodes of non-sustained torsadogenic-like VT at 170 ms CL in 5 out of 5 hearts. The corresponding potentiometric maps obtained during the colour coded timepoints 1-6 are represented in C. At a CL of 170 ms, the conduction maps with HCQ+AZM demonstrated significant disruptions of the normally coherent propagation of excitation waves with evidence of excitation re-entry and wave break. Thus, the electrophysiological changes outlined above associated particularly with HCQ and AZM in combination were associated with a ventricular arrhythmic tendency.