In Vitro Arrhythmia Generation by Mild Hypothermia - a Pitchfork Bifurcation Type Process

Abstract : The neurological damage after cardiac arrest (CA) constitutes a big challenge of hospital discharge. The therapeutic hypothermia (34°C-32°C) has shown its benefit to reduce cerebral oxygen demand and improve neurological outcomes after the cardiac arrest. However, it can have many adverse effects, among them the cardiac arrhythmia generation represents an important part (up to 34%, according different clinical studies). Monolayer cardiac culture is prepared with cardiomyocytes from new-born rat directly on the multi-electrodes array, which allows acquiring the extracellular potential of the culture. The temperature range is 37°C - 30°C - 37°C, representing the cooling and rewarming process in the therapeutic hypothermia. Both experiments showed that at 35°C, the acquired signals are characterized by period-doubling phenomenon, compared to signals at any other temperatures. Spiral waves, commonly considered as a sign of cardiac arrhythmia, are observed in the reconstructed activation map. With an approach from nonlinear dynamics, phase space reconstruction, it is shown that at 35°C, the trajectories of these signals formed a bifurcation, even trifurcation. Another transit point is found between 30°C - 33°C, which agreed with other clinical studies that induced hypothermia after cardiac arrest should not be below 32°C. The therapeutic hypothermia after cardiac arrest can be represented by a Pitchfork bifurcation, which could explain the different ratio of arrhythmia among the adverse effects after this therapy. This nonlinear dynamics suggests that a variable speed of cooling / rewarming, especially when passing 35°C, would help to decrease the ratio of post-hypothermia arrhythmia and then improve the hospital output.
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Binbin Xu, Sabir Jacquir, Gabriel Laurent, Stephane Binczak, Oriol Pont, et al.. In Vitro Arrhythmia Generation by Mild Hypothermia - a Pitchfork Bifurcation Type Process. Physiological Measurement, IOP Publishing, 2015, pp.15. ⟨hal-01076401⟩

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