University of Twente Student Theses


Drug Induced Cardiotoxicity by COVID-19 Treatments on Engineered Heart Tissues

Dannenberg, Maureen (2022) Drug Induced Cardiotoxicity by COVID-19 Treatments on Engineered Heart Tissues.

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Abstract:The COVID-19 pandemic has demanded for novel drug development. Drug-induced cardiotoxicity is a major side effect of drug treatments due to insufficient and non-representative testing methods. Antiviral drugs may be effective in inhibiting the virus, but may also potentially be damaging to the heart. Hospitalized COVID-19 patients are therefore at risk of getting cardiac damage after infection and receiving these treatments. In this research, a 3D-platform for engineered heart tissues that can predict the cardiotoxic effects of these drugs in hPSC-derived cardiomyocytes was used. The cardiotoxic effect of antiviral drugs such as Remdesivir, Chloroquine, and Molnupiravir was tested on the contraction force of cardiomyocytes for 10 days. Remdesivir and Chloroquine induced temporary dose-dependent cardiotoxicity after a single 24 h treatment for concentrations of 5 μM and higher. A repetitive 24 h drug treatment of 5 days (5 and 10 μM) induced cardiotoxicity such as loss of contractility and sarcomere breakdown of cardiomyocytes. Molnupiravir did not induce cardiotoxicity after a single or repetitive drug treatment. Therefore, clinically relevant concentrations and treatments of Remdesivir and Chloroquine induced cardiotoxicity but not after Molnupiravir treatment. Furthermore, cytokines were used to stimulate engineered heart tissues and understand if they can induce cardiotoxicity in this platform. Cytokine stimulation in combination with TNFα induce cardiotoxic effects similar to drug induced cardiotoxicity.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Programme:Biomedical Engineering MSc (66226)
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