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MULTI-MODAL FLUORESCENCE IMAGING OF
CONTRACTING INTACT HEARTS2nd BE-OPTICAL School: 2-5 May 2017, Torun
Vineesh Kappadan
Research Group Biomedical Physics
Max Planck Institute for Dynamics and Self-Organization
Project Supervisors
Prof. Ulrich Parlitz & Dr. Jan Christoph
Research Group Biomedical Physics
Max Planck Institute for Dynamics and Self-Organization
Introduction
Heart and Diseases
Sudden Cardiac Arrest (SCA) is a leading cause of death in Europe affecting0.35-0.7 million people every year.
About 25-30 % SCA victims have ventricular fibrillation (VF), a heartrhythm disorder [1].
1. European Resuscitation Council Guidelines for Resuscitation 2010, Rudolph W. Koster, Michael A Baubin
Heart Rhythm Disorders (Cardiac Arrhythmias)
Occurs due to malfunctioning of electrical activity of heart
Sinus Rhythm TachycardiaVentricular
Fibrillation[Numerical simulation by P. Bittihn,
Biomedical Physics Group, 2012]
ECG of heart
Cardiac Arrhythmias
Presence of spiral waves
Electrical Conduction System of Heart
Electrical impulses are responsible for mechanical contraction
Electrical Signal: SA Node AV node Bundle branches Purkinje Fibres
Atrial contraction Ventricular contraction
1. https://ceufast.com/course/ecg-interpretation
2. https://en.wikipedia.org/wiki/Electrical_conduction_system_of_the_heart
[1] [2]
Excitation-Contraction Coupling in Cardiomyocytes
Excitation
Contraction
Coupling
Coupling
t
Cardiomyocyte
contraction
[1] [2]
Goal : To study simultaneous electro-mechanical activity
of heart
1. PhD thesis, Jan Christoph, Biomedical Physics
2. Virtualheart.org F. Fenton
Experimental Methods and Results
Multiparametric Optical Mapping by Fluorescent Imaging
Left
Ventricle
10mm
Langendorff-
perfused
Rabbit Heart
2 x 250fps
Excitation
550nm
Excitation
650nm
Voltage-
sensitive
Calcium-
sensitive
10mm
2 channels:
interleaved
illumination +
exposure
scheme
dual-bandpass
filter
2ms
t
camera
Lee et al, 2011 [1]
fast-switching diode
drivers
Di-4-ANBDQPQRhod-2AM
250fps
500fps
1. P. Lee, P. Kohl; Heart Rhythm, 2011
2 I. Uzelac, J. Christoph, S. Luther, F. Fenton 2014
250fps
10mm
Dye 1Dye 2
[2]
Experimental Setup-Dual Imaging
Fast switching LED driver box
Intact heart in a
perfusion system
Sinus Rhythm with motion
Voltage Calcium
Motion Artifact
[B.Stender et al.]
Sinus Rhythm without motion[After adding Blebbistatin]
Voltage Calcium
Calcium signal and Activation Map
5 mm
Sinus rhythm
Calcium wave propagationActivation time
ms
5 mm5 mm
Voltage Calcium
Ventricular Tachycardia
Ventricular Fibrillation
voltage calcium
Cell culture studies-Rat heart
0.5 mm
Calcium waves
cell culture
stand
light sourcecamera
APPLICATIONS AND WORK PLAN
Electrical Restitution Curve
time (ms)
Voltage(mV)
APD: Action Potential DurationDI: Diastolic IntervalCL: Cycle Length
With electro mechanical un-
couplers
Figure: Electrical restitution curve during
ventricular fibrillation
Slope of the restitution curve is important in deciding the arrhythmic nature of heart
1. Sebastian Berg, Biomedical Physics
2. Marcus L. Koller, Mark L. Riccio, and Robert F. Gilmour, Am. J. Physiol. 275
[1]
[2]
Mechano Electric Feedback
Stability affected by
mechanics:
1. A. Panfilov et. al., Drift and break-up od spiral waves in reaction-diffusion-mechanics system, PNAS 2007
[1]
Shows how electrical activity of heart is affected by mechanics: Stretch activated
Channel.
Shortening of APD, reduction in AP amplitude and spiral wave break up closely
follows stretch in several studies.
THANK YOU FOR YOUR ATTENTION!