University of Twente Student Theses
Arrhythmia-on-a-chip : Modeling cardiac arrhythmia on chip: Investigating anti-arrhythmic drug responses and assessing the impact of structural deformities on signal propagation
Radhakrishnan Senthilkumaran, Swathika (2024) Arrhythmia-on-a-chip : Modeling cardiac arrhythmia on chip: Investigating anti-arrhythmic drug responses and assessing the impact of structural deformities on signal propagation.
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| Abstract: | Ischemic heart disease (IHD) and stroke stand as the leading causes of death and disability on a global scale. Cardiovascular diseases (CVDs) contribute significantly to disability, with many cases attributed to the consumption of alcohol, tobacco, nicotine, and caffeine. Cardiac arrhythmia, affecting over 12 million people worldwide, poses a substantial burden on healthcare systems. Despite this, the development of anti-arrhythmic drugs has seen limited progress. The prevalence of arrhythmia is estimated to affect 1% to 1.5% of the population, with challenges in estimating occurrence rates due to some individuals experiencing no symptoms. A comprehensive total of 464 pharmaceutical products were withdrawn from the market due to safety concerns. The primary reason includes cardiovascular toxicity. It is imperative to conduct a comprehensive examination of the fundamental mechanisms causing cardiovascular toxicity to avert the prolonged usage of potentially hazardous drugs, especially given that specific cardiovascular medications persisted on the market for extended durations. This emphasizes the need for the advancement of a more reliable human-based in vitro model that can be employed to investigate the mechanisms of arrhythmia. Recent advancements in in vitro stem cell tech and in silico modeling offer more models for heart failure and arrhythmia evaluation, addressing these challenges. This study addresses this need by designing an arrhythmia shape, creating a vulnerable substrate for cardiac arrhythmia by mimicking the source-to-sink mismatch in cardiac tissue. Arrhythmia-like events were induced by subjecting cardiac tissues to Epinephrine and electrical pacing, and subsequent experimentation revealed that Amiodarone successfully counteracted the effects of Epinephrine on our cardiac tissue in the PDMS shape. Limited experiments on cardiac tissues cultured in the arrhythmia shapes showed minimal counteracting effects of Amiodarone. Despite these constraints, this study marks the next step in designing a heart-on-chip model for the study of cardiac arrhythmias. Looking ahead, there is potential to further develop this heart-on-chip model into a comprehensive, multidisciplinary platform for the risk assessment of cardiac arrhythmias. |
| Item Type: | Essay (Master) |
| Faculty: | TNW: Science and Technology |
| Subject: | 42 biology, 50 technical science in general |
| Programme: | Biomedical Engineering MSc (66226) |
| Link to this item: | https://purl.utwente.nl/essays/98105 |
| Export this item as: | BibTeX EndNote HTML Citation Reference Manager |
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