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J Vis Exp. 2018 May 22;(135). doi: 10.3791/57617.

Impact of Intracardiac Neurons on Cardiac Electrophysiology and Arrhythmogenesis in an Ex Vivo Langendorff System.

Author information

1
Department of Cardiology-Electrophysiology, cNEP (cardiac Neuro- and Electrophysiology research group), University Heart Center, University Hospital Hamburg-Eppendorf; DZHK (German Center for Cardiovascular Research).
2
DZHK (German Center for Cardiovascular Research); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf.
3
Department of Cardiology-Electrophysiology, cNEP (cardiac Neuro- and Electrophysiology research group), University Heart Center, University Hospital Hamburg-Eppendorf.
4
Department of Cardiology-Electrophysiology, cNEP (cardiac Neuro- and Electrophysiology research group), University Heart Center, University Hospital Hamburg-Eppendorf; DZHK (German Center for Cardiovascular Research); chr.meyer@uke.de.

Abstract

Since its invention in the late 19th century, the Langendorff ex vivo heart perfusion system continues to be a relevant tool for studying a broad spectrum of physiological, biochemical, morphological, and pharmacological parameters in centrally denervated hearts. Here, we describe a setup for the modulation of the intracardiac autonomic nervous system and the assessment of its influence on basic electrophysiology, arrhythmogenesis, and cyclic adenosine monophosphate (cAMP) dynamics. The intracardiac autonomic nervous system is modulated by the mechanical dissection of atrial fat pads-in which murine ganglia are located mainly-or by the usage of global as well as targeted pharmacological interventions. An octapolar electrophysiological catheter is introduced into the right atrium and the right ventricle, and epicardial-placed multi-electrode arrays (MEA) for high-resolution mapping are used to determine cardiac electrophysiology and arrhythmogenesis. Förster resonance energy transfer (FRET) imaging is performed for the real-time monitoring of cAMP levels in different cardiac regions. Neuromorphology is studied by means of antibody-based staining of whole hearts using neuronal markers to guide the identification and modulation of specific targets of the intracardiac autonomic nervous system in the performed studies. The ex vivo Langendorff setup allows for a high number of reproducible experiments in a short time. Nevertheless, the partly open nature of the setup (e.g., during MEA measurements) makes constant temperature control difficult and should be kept to a minimum. This described method makes it possible to analyze and modulate the intracardiac autonomic nervous system in decentralized hearts.

PMID:
29889210
PMCID:
PMC6101334
[Available on 2020-05-22]
DOI:
10.3791/57617
[Indexed for MEDLINE]

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