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RESEARCH PRODUCT

Arrhythmia due to mild therapeutic hypothermia - a study in vitro

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International audience; Introduction: In case of resuscitation after CA, the brain suffers the ischemia and the inflammation from reperfusion. To days, the only therapy available is the mild therapeutic hypothermia (MTH) : put the patient under 34°C-32°C during 12-24 hours. MTH has been shown to increase the hospital survival rate, but it has many adverse effects, among which the cardiac arrhythmia generation represents an important part (up to 34%). Cardiac culture in vitro provides a better spatial resolution than study in vivo, which could bring some insights of the mechanism of post-hypothermia arrhythmia generation. Method: Monolayer cardiac culture is prepared with cardiomyocytes from new-born rat (1-4 days) directly on multi-electrodes array at 37°C. The experiments consist of culture cooling (37°C-30°C) and re-warming (30°C-37°C). The acquired signals are then analyzed with method phase-space reconstruction. Results: Decreasing temperature disturbed and extended the extracellular potential periods. The signals in 35°C-33°C became regular. At 35°C, period-doubling phenomena (1D) and spiral waves (2D) are observed, which can be interpreted as a transit point from normal state to chaos state. In the reconstructed phase-space, doubling-trajectories and even tripling-trajectories are observed. It implied that the general dynamics of MTH could be interpreted as a pitchfork bifurcation. These results at cellular level agreed with other clinical studies on MTH. Conclusion: Results in this study suggested that a variable speed would help to reduce the rate of post-hypothermia arrhythmia.