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Effects of ultrasound on cardiomyocyte contractions

Groener, Dafne (2020) Effects of ultrasound on cardiomyocyte contractions.

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Abstract:Typically cardiomyocyte contraction results from a cascade of events, whereby a calcium flux is induced by an action potential. This calcium flux is at the origin of actin and myosin filaments motion. This cascade can be externally triggered at various key nodes, namely by activation of calcium channels, by direct activation of myosin filaments, or by cAMP enhancement. Activation of calcium channels leads to an increased calcium flux, cAMP enhancement causes calcium channel activation and direct activation of myosin filaments leads to actin-myosin motion. Pacing is generally achieved either electrically or optically. The aim of this project is to investigate the use of ’Acoustical pacing of advanced human cardiac microtissues as platform to model heart rhythm disorders’. Ultrasonic pacing is useful in in vitro disease modeling, drug screening and study of drug pharmacology. More specifically, the primary purpose of this thesis is to determine the effects of ultrasound pulse duration and center frequency on cardiomyocyte contraction dynamics so as to unravel the mechanisms behind ultrasound-induced contractions. Experiments were conducted on ventricular cardiomyocyte microtissues placed on Mylar coverslips immersed in a temperature-controlled bath. A video was captured with 50 fps throough a microscope, and ultrasound was applied via a transducer located at the bottom of the bath. A modified PIV approach performed in MATLAB was used to quantify movement. Contractions were subsequently analyzed in terms of frequency, maximum displacement, peak area, maximum speed during contraction, maximum speed during relaxation, total contraction duration, and delay after ultrasound pulse. The responses were highly variable within the parameter space, varying from no effect at all to tachycardia. Pulse durations below 0.5 ms did not result in any visible alterations of the contractions, whereas pulses of 0.5 ms and 0.7 ms often resulted in a higher contraction frequency, higher contraction and relaxation speeds and shorter contraction times. After ultrasound driving, contarction parameters returned to their nominal values, suggesting a reversible effect of ultrasound. The specific alterations to contraction dynamics suggest that ultrasound does not drive cell contraction via direct activation of actin-myosin filaments and calcium channels, but most likely enhanced cAMP in the cell contraction cascade. However, during these experiments, the investigated range of ultrasound parameter set was not extensive enough to ascertain the main mechanism behind ultrasound pacing. Recommendations for further research can be done for methods, data analysis and experimental protocol. Optional research directions can be split in three categories: either focus on the ultrasound mechanisms that are involved, or extension of the ultrasound parameter space, or try to strengthen the conclusion regarding the biological mechanism by temporally disabling this mechanism and analyzing the results
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:33 physics, 42 biology
Programme:Biomedical Engineering MSc (66226)
Link to this item:http://purl.utwente.nl/essays/83611
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