3.4 Optical mapping studies in ex vivo heart
preparations
We next investigated the effects of HCQ alone and in combination with
AZM using optical fluorescence mapping in sinus-paced
Langendorff-perfused hearts using the recording and ECG monitoring
configurations illustrated in Figure 6A(i). Voltage mapping measurements
of action potential initiation and conduction (Fig. 6A(ii)) demonstrated
bradycardic effects (A(iii)), visible conduction heterogeneities and
slowed conduction (A(ii)) at 10 µM HCQ, effects were augmented by
combination with 10 µM AZM (Fig. 6A (iv)). Similarly, optical
potentiometric mapping revealed that 10 µM HCQ prolonged action
potential duration at 90% repolarisation (APD90) (B(i
and ii)) with 10 µM HCQ, effects further prolonged by its combination
with AZM (Fig.5B(iii)).
Ca2+ dye, Rhod-2 AM (CaD), mapping of ventricular
calcium transient (CaT) characteristics demonstrated increased
magnitudes of and dispersions in CaD durations at 90% recovery
(CaD90) (Figure 6C(i)). The latter were attributed to
changes late in the CaT records (C(ii)). The quantified
CaD90 magnitudes (B(iii)) and dispersions (B(iv)) both
increased with 10 but not 1.0 µM HCQ. The combination of 10 µM HCQ with
either 1 or 10 µM AZM exerted significantly greater effects than 10 µM
HCQ alone.