Cardiotonic Effects of Oral Antimalarial Drugs on In-Situ Frog Heart
DOI:
https://doi.org/10.51412/psnnjp.2025.35Keywords:
Chloroquine, artemether-lumefantrine, artesunate, frog heart, cardiotoxicity, chronotropic effect, inotropic effectAbstract
Background: Antimalarial drugs remain essential for malaria control, but concerns persist about their potential cardiovascular effects. Chloroquine, artemether-lumefantrine, and artesunate are widely prescribed, yet their impact on myocardial activity is incompletely understood. This study evaluated the cardiotonic effects of these drugs using an in-situ frog heart model.
Methods: Three frogs were pithed, and isolated heart preparations were mounted on a force transducer. Baseline heart rate, contraction amplitude (mV), and force of contraction (gram force, gF) were recorded. Chloroquine was administered at 10 mg/kg (therapeutic) and 100 mg/kg (supratherapeutic), artemether-lumefantrine at 4 mg/kg and 40 mg/kg, and artesunate at 4 mg/kg and
40 mg/kg. Saline served as control. Percentage changes in cardiac parameters relative to baseline were analyzed.
Results: Chloroquine produced a dose-dependent bradycardia, reducing heart rate from 75 bpm at baseline to 66 bpm at therapeutic and 60 bpm at supratherapeutic doses. Contractile amplitude fell modestly at the therapeutic dose (−3.7%) but increased at supratherapeutic concentration (+0.5%). Force of contraction decreased slightly at therapeutic dose (2.6 gF) but rose at higher concentration (2.8 gF) at supratherapeutic dose. Artemether-lumefantrine exhibited minimal cardiac impact: heart rate remained unchanged at therapeutic dose (39 bpm) and decreased only slightly at supratherapeutic dose (36 bpm). Contractile force fell consistently by 2.3% across both doses. Artesunate demonstrated a contrasting profile, increasing heart rate markedly at therapeutic dose (from 36 to 51 bpm) but reducing contractile amplitude (−18%) and force of contraction (from 11.7 to 9.6 gF). At supratherapeutic levels, heart rate rose to 42 bpm, while contractile force remained depressed (9.8 gF).
Conclusion: Chloroquine exerted a dose-dependent negative chronotropic effect, with paradoxical increases in contractility at higher doses, consistent with its cardiotoxic profile. Artemetherlumefantrine showed negligible cardiodepressive effects, reinforcing its safety. Artesunate induced pronounced tachycardia but reduced myocardial contractility, warranting further mechanistic studies. The in-situ frog heart model effectively revealed these drug-specific cardiac effects, highlighting the need for pharmacovigilance in antimalarial therapy
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