Complex Structure and Dynamics of the Heart

214 Pages·2015·9.52 MB·English

by  Philip Bittihn (auth.)

Springer Theses
Recognizing Outstanding Ph.D. Research
Philip Bittihn

Complex Structure
and Dynamics
of the Heart
Springer Theses
Recognizing Outstanding Ph.D. Research
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Philip Bittihn
Complex Structure and
Dynamics of the Heart
Doctoral Thesis accepted by
the University of Göttingen, Germany
123
Author Supervisor
Dr. PhilipBittihn Prof. StefanLuther
Research GroupBiomedical Physics Research GroupBiomedical Physics
Max PlanckInstituteforDynamics Max PlanckInstituteforDynamics
andSelf-Organization andSelf-Organization
Göttingen Göttingen
Germany Germany
ISSN 2190-5053 ISSN 2190-5061 (electronic)
Springer Theses
ISBN 978-3-319-12231-1 ISBN 978-3-319-12232-8 (eBook)
DOI 10.1007/978-3-319-12232-8
LibraryofCongressControlNumber:2014954604
SpringerChamHeidelbergNewYorkDordrechtLondon
©SpringerInternationalPublishingSwitzerland2015
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If you try and take a cat apart to see how
it works, the first thing you have on your
hands is a nonworking cat. Life is a level
of complexity that almost lies outside our
vision; […]
Douglas Adams (1952–2001)
TheSalmonofDoubt:HitchhikingtheGalaxy
One Last Time
’
Supervisor s Foreword
Spatiallyextendednon-equilibriumsystemsdisplayspatial-temporaldynamicsthat
canrange fromorderedtoturbulent.Controlling suchsystemsisoneofthecentral
problems in nonlinear science and has far-reaching technological consequences.
Fewexamplesofsuccessfulcontrolwithapplicationsinphysicsandchemistryhave
been demonstrated. In biological excitable media, the systems’ complexity makes
successful control challenging. This difficulty applies in particular to electrical
turbulence incardiac tissue, known as fibrillation. Duringfibrillation, synchronous
contraction of the muscle is disrupted by fast, vortex-like, rotating waves of elec-
tricalactivity.Although,inthepastdecades,significantprogresshasbeenmadein
understanding the processes that govern cardiac pattern formation, controlling the
complexspatial-temporaldynamicsunderlyinglife-threateningcardiacarrhythmias
such as ventricular fibrillation is extremely difficult, because of the nonlinear
interaction of excitation waves in a heterogeneous anatomical substrate.
In the European Union, an estimated 700,000 cardiac deaths per year are
associated with ventricular fibrillation (VF). In the absence of a better strategy,
strong, globally resetting electrical shocks remain the only reliable treatment for
VF. However, high-energy shocks (typically 1 kV, 30 A, 12 ms) have significant
side effects including tissue damage and intolerable pain, indicating a substantial
medical need. Currently, the only clinically effective method to terminate fibrilla-
tionuseshigh-energyshocksthatbothdepolarizeandhyperpolarizeeveryexcitable
cardiaccellusingelectricfieldstrengthsofatleast5V/cmeverywhereintheheart.
Consequently,theenergyrequiredbyconventionaldefibrillationtechnologycannot
be significantly reduced based on this approach.
Inthethesisyouareabouttoread,PhilipBittihnaddressestheproblemfroman
entirely different perspective. You will learn that the complex anatomical structure
of the heart not only has a strong effect on the development of irregular activation
patterns, but can also be harnessed for alternative control methods. Philip Bittihn
shows that for a promising low-energy defibrillation technique currently investi-
gatedinourgroup,thecomplexstructureoftheheartisatthecoreoftheunderlying
vii
viii Supervisor’sForeword
mechanismandthereforekeytosuccessfulcontrolofspatial-temporaldynamicsin
the heart.
To understand the ambivalent role of heterogeneity for the onset, perpetuation,
andcontrolofcardiacfibrillation,heputforwardthefollowingresearchquestions:
Whatistheeffectofheterogeneityinelectricalconductanceonthespatial-temporal
dynamics of cardiac fibrillation? What is the effect of an external electric field on
heterogeneities in electrical conductance and how does this depend on the surface
curvature? How can weak pulsedelectric fields beused tocontrolspatial-temporal
dynamics in a heterogeneous cardiac substrate?
Integratingquantitativebiologicalexperimentswithmathematicalmodelingand
analysis methods from nonlinear dynamics, Philip Bittihn’s findings significantly
enhance our fundamental understanding of cardiac dynamics and may result in
advanced therapeutic approaches to cardiac arrhythmias.
PhilipBittihn’sresultshavestronglyimpactedabroadinterdisciplinaryscientific
community, through numerous presentations at international conferences, invited
talks, and publications in highly ranked journals. For his thesis, he has been
awarded the Dr.-Berliner–Dr.-Ungewitter prize by the Faculty of Physics of the
University of Göttingen. He has also received the Otto-Hahn medal by the Max
PlanckSocietyandtheDeutscherStudienpreisinhonorofhisoutstandingscientific
achievements.
Philip is driven by an exceptional and inspiring enthusiasm for science. I per-
sonally appreciate his remarkable ability to share this enthusiasm by communi-
cating complex scientific content across disciplines. It is this rare ability that lays
the foundation for successful interdisciplinary, translational research connecting
basic sciences with biomedical applications that may improve human health.
I would like to thank Philip for many exciting and inspiring discussions—as a
scientist and friend. I am convinced that the reader will appreciate Philip’s enthu-
siasm and enjoy the journey through the complex structure and dynamics of the
heart.
Göttingen, October 2014 Prof. Stefan Luther
Acknowledgments
At this point, I would like to thank the various people and organizations that have
supported me during the work for this thesis.
I would like to start by thanking my supervisor, Prof. Dr. Stefan Luther, for
giving me the opportunity to get involved into so many different and interesting
projects with scientific problems from theoretical, experimental, basic, and applied
research, not all of which are covered by this thesis. Thank you for creating a
research group with a unique and stimulating atmosphere, for giving me the free-
dom to take independent decisions on the scientific route to follow and for letting
mepresentmyworkonanumberofscientificconferences,whichbroughtmeinto
contact with the international cardiac and nonlinear dynamics community.
Moreover,Iwouldliketoexpressmygratitudetotheothertwomembersofmy
ThesisCommittee,Prof.Dr.UlrichParlitzandProf.Dr.EberhardBodenschatz,for
their scientific and personal guidance not only during Thesis Committee meetings.
I would also like to thank Prof. Dr. Jörg Enderlein for his interest in my work and
for agreeing to review this thesis.
ManythanksgotoProf.FlavioH.Fentonforlettingmevisithisformerplaceof
work, Cornell University, and for many useful discussions on the theory and
numerics of cardiac models, which significantly improved my understanding.
None of the work for this thesis would have been possible without the lab, IT,
and administrative infrastructure and the continuous support of the staff members
maintaining it, first of all Dr. Denny Fliegner, Gerhard Nolte, Marion Kunze, and
Angela Meister. Thank you!
Science is team work. For all kinds of theoretical, numerical, and technical
problems, the members of the Biomedical Physics Group have been an invaluable
source of inspiration and help. Special thanks go to my fellow “senior Ph.D.
student” (and now Ph.D.) Amgad Squires, who introduced me to the technique of
opticalmappingandthecorrespondingdataanalysisconcepts.Discussingscientific
problems and developing new strategies was always productive and stimulating,
even during phases of disappointment. Many thanks also to Daniel Hornung for
joiningthedevelopmentofMediaSimandtherebycontributingtothesuccessithas
become in the numerical work carried out in the Biomedical Physics Group.
ix
x Acknowledgments
Furthermore, I would like to thank my collaborator Marcel Hörning for getting
sointerestedinthetheoreticallypredictedboundarycurvatureeffectsthatheagreed
to immediately test its relevance in cell culture experiments.
IamgratefulforthefinancialsupportbytheInternationalMaxPlanckResearch
SchoolforthePhysicsofBiologicalandComplexsystems,notonlythroughaPh.D.
stipend, but also by covering the costs for two conference participations and a
one-month stay at Cornell University. I also acknowledge support by the Max
Planck Society (through a Ph.D. stipend), the DZHK (Deutsches Zentrum für
Herz-Kreislauf-Forschung—German Centre for Cardiovascular Research) and by
theBMBF(GermanMinistryofEducationandResearch).Theresearchpresentedin
this thesis has also received funding from the European Community’s Seventh
Framework Program FP7/2007–2013 under Grant Agreement No. HEALTH-F2-
2009-241526, EUTrigTreat.
Lastbutnotleast,Iamgratefultoallmyfriendsforthediversionoutsidework,
particularly in the form of making music, which was necessary to tackle scientific
problems with a fresh view and regained energy. Many thanks to my family for
their unconditional support in all possible situations, especially to my wife
Katharinaforherpatienceintimesofincreased workload andtomysonJuliusfor
bringing a whole new perspective to my life.