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Structural and electrical remodeling of cardiac tissue: Consequences for impulse generation and propagation at the cellular network level

English title Structural and electrical remodeling of cardiac tissue: Consequences for impulse generation and propagation at the cellular network level
Applicant Rohr Stephan
Number 105916
Funding scheme Project funding (Div. I-III)
Research institution Institut für Physiologie Medizinische Fakultät Universität Bern
Institution of higher education University of Berne - BE
Main discipline Cardiovascular Research
Start/End 01.10.2004 - 30.09.2007
Approved amount 335'000.00
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Keywords (4)

basic cardiac electrophysiology; arrhythmia; triggered activity; structure-function relationship

Lay Summary (English)

Lead
Lay summary
It is well established that structural and functional non-uniformitieswithin the working myocardium are importantly contributing to thegeneration of cardiac arrhythmias. Whereas there exists a vast body ofinformation regarding both the macroscopic characteristics of arrhythmiasand the ionic mechanisms underlying arrhythmogenic changes in function atthe single cell level, there is only limited information availableconcerning the question of how localized changes in tissue structureand/or cell function interact with the surrounding myocardium at the fewcell level as to give rise to manifest arrhythmias. In this context, thefirst subproject is centered around the question as to which extentelectrotonic interactions between cardiomyocytes and cardiac fibroblastsaffect impulse initiation/propagation and arrhythmogenesis in fibroticcardiac tissue. Specifically, we will investigate in a novel cell culturemodel of fibrotic ventricular tissue to which extent electrical couplingbetween the two cell types affects conduction and whether such couplingevokes abnormal automaticity and/or triggered activity. Moreover, givenour previous findings of large conduction delays across fibroblastsinserted into strand of cardiomyocytes, we will investigate whether thistissue configuration might give rise to reflected reentry. The results ofthese experiments are expected to provide insights into the consequencesof ‘promiscuous’ cell coupling in the heart and might therefore berelevant not only for cardiomyocyte-fibroblast interactions, but also forunderstanding the functional integration of therapeutic cell transplants(stem cells). The second subproject is aimed at characterizingbidirectional electrotonic interactions between cardiomyocytes exhibitingabnormal electrical activity and the surrounding myocardium with the goalto explore conditions and mechanisms favoring the generation and escape ofectopic activity at the few cell level. Specifically, we will investigateto which extent the contact geometry between sources of abnormal activityand the surrounding myocardium affect arrhythmogenesis and how thisprocess is modulated by graded changes in excitability as occurring duringacute myocardial infarction. These experiments are expected to providefurther insights into the mechanisms underlying arrhythmogenesis duringacute myocardial infarction. The third subproject finally deals with thequestion of how acute and chronic reductions of oxygen tension affect theelectrophysiological phenotype of cultured cardiomyocytes. Theseexperiments are not only expected to contribute to a more detailedcharacterization and possibly a refinement of this valuable experimentalmodel but, by disclosing the timecourse and the type of channels affectedby variations in oxygen tension, the results are expected to advance ourunderstanding of mechanisms underlying electrical remodeling as occurringin the context of chronic ischemic heart disease.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
64914 Structural and electrical remodeling of cardiac tissue: Consequences for impulse generation and propagation at the cellular network level 01.10.2001 Project funding (Div. I-III)
118247 Structural and electrical remodeling of cardiac tissue: Consequences for impulse generation and propagation at the cellular network level 01.10.2007 Project funding (Div. I-III)

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