Effects of μM-HCQ were studied in isolated perfused guinea-pig hearts by multielectrode, optical RH237 voltage, and Rhod-2 mapping. These revealed reversibly reduced left atrial and ventricular action potential (AP) conduction velocities increasing their heterogeneities, increased AP durations (APDs), and increased durations and dispersions of intracellular [Ca2+] transients, respectively. Hearts also became bradycardic with increased electrocardiographic PR and QRS durations. The (HCQ+AZM) combination accentuated these effects. Contrastingly, (HCQ+AZM) and not HCQ alone disrupted AP propagation, inducing alternans and torsadogenic-like episodes on voltage mapping during forced pacing.
(A) Recording and programmed stimulation configuration. (B) Optical action potential traces obtained under programmed pacing at 190, 180 and 170 ms cycle lengths (CLs), before (control) and following addition of 10 μM HCQ and 10 μM HCQ with added 10 μM AZM. (C) Corresponding voltage maps obtained at the numbered color-coded time points (n hearts).
ACS Pharmacol Transl Sci. (IF 3.7)
Wang G, Lu CJ, Trafford AW, et. Electrophysiological and Proarrhythmic Effects of Hydroxychloroquine Challenge in Guinea-Pig Hearts. ACS Pharmacol Transl Sci. 2021 Aug 30;4(5):1639-1653. doi: 10.1021/acsptsci.1c00166. PMID: 34661080; PMCID: PMC8506600.
