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.