| dc.description.abstracteng | Ventricular fibrillation, a frequent cause of death, is a heart condition
associated with complex patterns of electric activity on the heart surface.
In spite of a century of research many aspects of how ventricular
fibrillation is maintained or terminated remain unclear. One hypothesis is that
rotating spiral waves of excitation pin to heterogeneities in the heart tissue, are thereby
stabilized and maintain the fibrillation. Even though, extensive research was
done on the control of single pinned spiral waves, little was previously known
on how multiple spirals can be controlled and unpinned.
I filled this
gap with my theoretical and numerical work using a simple model system where I
presented a technique that allows simultaneous unpinning of multiple spiral
waves. The proposed method is thereby considerably more effective than an underdrive method that
is very effective in the case of single pinned spiral waves and that was
suggested for unpinning of multiple spiral waves previously. I demonstrated
that a problem that arises in systems with multiple heterogeneities is that
electric far field pulses that are supposed to unpin spiral waves can create
new pinned spiral waves. This problem is minimized with the proposed method
that first synchronizes pinned spirals in order to allow simultaneous unpinning
with another specifically timed pulse.
My colleagues and I designed a novel defibrillation method, Syncrolation, that is based on the
same approach: A sequence of electric far field pulses synchronizes the heart
tissue and an additional pulse unpins spiral waves and thereby terminates the
ventricular fibrillation. In whole heart perfusion experiments with rabbit and
pig hearts, I investigated the appropriate parameters of such a pulse sequence
and finally compared the new method with conventional single shock
defibrillation. Unfortunately, the new method could not be proven to be
advantageous compared to conventional defibrillation. In contrast, many
experimental results were unexpected such that the
postulated mechanism of pinned spiral waves that maintain ventricular
fibrillation is challenged.
Nevertheless, the investigation of Syncrolation and especially the basic
research on the control via periodic pulse sequences provide exciting new
insights. It was postulated in literature that periodic far field pulses
synchronize the cardiac tissue and thereby terminate fibrillation. However, no
experimental evidence was published on how this depends on parameters of the
pulse sequence or on the dynamics in the heart. I consider it one of my main
contributions that I provide comprehensive, quantitative, experimental evidence
on control of cardiac activity via periodic electric far field pulses. In particular, I
demonstrated that the synchronization strongly depends on the ratio of the
pacing frequency and the dominant frequency of the ventricular fibrillation.
Furthermore, I showed that the synchronized area fraction, a measure for the
frequency synchronization, on average reaches a maximum
after a comparably short time of 1 to 2 s.
This however again depends on the
ratio of pacing frequency and dominant frequency of the ventricular
fibrillation.
I believe that the findings presented in this thesis, especially the knowledge
when synchronization of pulse sequences is strongest, contribute to the
understanding of ventricular fibrillation and its control. This work supports
future investigation and development of means to control and terminate
fibrillating activity in the heart in general and of methods that employ
periodic pulses to synchronize cardiac tissue in particular. | de |