Key result
Hydroxychloroquine and azithromycin reduce contractile force by ~49% in porcine heart slices.
Why the study?
Do hydroxychloroquine and azithromycin alter contractile force and contraction kinetics in living porcine heart slices?
Do hydroxychloroquine and azithromycin alter contractile force and contraction kinetics in living porcine heart slices?
Absolute Event Rate: 51% vs 100%
p-value: p=<0.0001
Hydroxychloroquine and azithromycin induce significant contractile dysfunction in intact porcine cardiac tissue, likely via inhibition of L-type calcium channels, extending their known cardiotoxicity beyond QT prolongation.
May impair myocardial contractility at clinical concentrations; extends QT concerns but remains hypothesis-generating in humans.
platform that maintains native cardiac tissue architecture and physiological electrical and contractile properties. Here, we evaluated the cardiotoxic effect of HCQ and AZM applied alone or in combination on cardiac contractility by measuring contractile force and contraction kinetics in heart slices prepared from porcine hearts. Our results show that clinically relevant concentrations of HCQ monotherapy (1-10 µM) reduced contractile force and contraction kinetics in porcine slices in a dose-dependent manner. However, AZM monotherapy decreased contractile force and contraction kinetics only at higher concentrations (30 µM). Combination of HCQ and AZM induced a dose-dependent effect similar to HCQ alone. Furthermore, pre-treating porcine heart slices with the L-type calcium channel agonist Bay K8644 prevented the effect of both drugs, while administration of Bay K8644 after drugs interventions largely reversed the effects, suggesting a mechanism involving inhibition of L-type calcium channels. These findings indicate that HCQ and AZM alter cardiac function beyond QT prolongation with significant contractile dysfunction in intact cardiac tissue. Our porcine heart slices provide a powerful platform to investigate mechanisms of drug cardiotoxicity.
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Wu et al. (2023) studied Cardiotoxicity. Hydroxychloroquine and Azithromycin vs. Vehicle control was evaluated on Contractile force (% of baseline) (p=<0.0001). Clinically relevant concentrations of hydroxychloroquine (1-10 µM) and azithromycin (30 µM) significantly reduced contractile force and contraction kinetics in living porcine heart slices.
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