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We used optical mapping to capture theelectrical activity of paced whole mice heartsand recorded ECG simultaneously
Effects of Heart Rate Variability on Alternans Formation in Mice HeartsKanchan Kulkarni, Christopher Johnson, Steven W. Lee, Xueyi Xie, Elena G. Tolkacheva
Department of Biomedical Engineering, University of MinnesotaIntroduction
Objectives
Methods
ResultsConclusions
References
HRV is a physiologically inherent variation intime interval between two heart beats
To experimentally verify the effects of HRV onalternans formation in healthy Langendorff-perfused whole mice hearts
1.La Rovere, M. T. et al., 2003, “Short-Term Heart Rate Variability StronglyPredicts Sudden Cardiac Death in Chronic Heart Failure Patients,”Circulation,107, p. 565-570
2.Dvir, H., and Zlochiver, S., 2013, “Stochastic Cardiac Pacing IncreasesVentricular Electrical Stability—A Computational Study,” Biophys. J., 105,pp.533–542
3.McIntyre, S. et al., 2014, “Heart Rate Variability and Alternans Formation inthe Heart: The Role of Feedback in Cardiac Dynamics,” J. Theor. Biol.
4.Arora, R. et al., 2003, “Optical Mapping of Cardiac Arrhythmias”, IndianPacing Electrophysiol. J.
Periodic pacing: APDn+DIn=BCLnPacing with HRV: BCLn=BCL±δ(HRV)where, δ(HRV) has a mean of zero and standarddeviation (SD) of BCL*HRV, andHRV= SDRR*100%
AVGRR
Mouse1 Mouse2 Mouse3
AVGRR (ms) 140.44 152.23 101.92
SDRR (ms) 13.46 18.92 12.53
HR (bpm) 427 394 589
HRV (%) 9.58 12.43 12.30
Fig.4 Schematic of optical mapping system with a sample voltage trace; n= stimulus number, DI=Diastolic Interval and BCL=Basic Cycle Length4
0
10
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50 70 90 110 130
AP
D 8
0
BCL
Fig.7 A),B) and C) Bifurcation diagrams with BCLstart indicating onset of alternans; D) Quantification of the mice that developed alternans
Experimental results indicate that introductionof HRV in periodic pacing promotes the onset ofalternans
This supports our numerical simulation results3
and suggests that introduction of HRV in periodicpacing is potentially pro-arrhythmic
Numerical simulation studies of the effects ofHRV on alternans formation have showncontradictory results2,3
(B)
Fig.5 A) ECG signal recorded during sinus rhythm showing HRV; B) Average and standard deviation of RR interval with heart rate and HRV calculated from
captured ECGs
(A)RR1 RR2 RR3 ……
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AP
D 8
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BCL
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6% HRV
12% HRV
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BCLstart BCLstart
BCLstart0
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0% HRV 6% HRV 12% HRV
Total mice Mice exhibiting alternans
Future Scope
AcknowledgementThis research work was supported by NSF CAREER PHY-125541
Fig.8 Proposed pacemaker design with potentially anti-arrhythmic pacing
Radio Frequency (RF) telemetric pacemakerMicro-
controllerPulse
GeneratorElectrodesRF Transceiver
Battery Reed switch
Sensing circuit
Filtering and Detection
BCL(ms)
Fig.6 2D APD maps showing spatial distribution of APD for two consecutive beats B1 and B2 along with alternans maps, for decreasing BCL; BCLstart indicating
onset of alternans is highlighted in yellow squares; ∆APD=APD(B1)-APD(B2); # and * indicate pixels with and without alternans
+15
-15
0
130 120 110 90 80 70 60
12%
6%
0% B2
B1
B2
B1
B2
B1
75.8
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59.255.046.638.3
63.3
HRV
∆APD(ms)
APD(ms)
BCLstart
BCLstart
BCLstart
#
Onset of alternans has been studied primarilyunder the assumption of periodic pacingwithout heart rate variability (HRV)
(A) (B)
Fig.2 A) ECG trace of adult male during sinus rhythm3; B) Histogram of RR intervals calculated from (A) showing HRV3
Fig.3 A) Action potential traces during period pacing and pacing with HRV2 B)Restitution curves for ionic model of canine cardiac action potential for 0 and2.5% HRV; onset and end of alternans is indicated by BCLstart and BCLendrespectively3
(A) (B)
BCLnBCLn-1n-1 n n+1
APDn-1 APDnDInDIn-1 APDn+1
Fig.1 A) Representative action potential traces with constant APD; B) APD alternans; # and * indicate pixels in Fig.6; up arrows denote stimuli
(A) (B)
n-1 n
APD APD
#
n-1 n n+1
APD long
APD short
n+2
Fatal arrhythmias and ventricular fibrillation(VF) are preceded by alternans, a beat-to-beatalternation in the action potential duration(APD)
