In vivo Electrophysiological Study of Induced Ventricular Tachycardia in Intact Rat Model of Chronic Ischemic Heart Failure

Kyle Weigand, Russell S Witte, Talal Moukabary, Ike Chinyere, Jordan Lancaster, Mary Kaye Pierce, Steven Goldman, Elizabeth B Juneman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: The objective of this study was to define the clinical relevance of in vivo electrophysiologic (EP) studies in a rat model of chronic ischemic heart failure (CHF). Methods: Electrical activation sequences, voltage amplitudes, and monophasic action potentials (MAPs) were recorded from adult male Sprague-Dawley rats six weeks after left coronary artery ligation. Programmed electrical stimulation (PES) sequences were developed to induce sustained ventricular tachycardia (VT). The inducibility of sustained VT was defined by PES and the recorded tissue MAPs. Results: Rats in CHF were defined (p <; 0.05) by elevated left ventricular (LV) end-diastolic pressure (5 ± 1 versus 18 ± 2 mmHg), decreased LV + dP/dt (7496 ± 225 versus 5502 ± 293 mmHg/ s), LV - dP/dt (7723 ± 208 versus 3819 ± 571 mmHg), LV ejection fraction (79 ± 3 versus 30 ± 3%), peak developed pressure (176 ± 4 versus 145 ± 9 mmHg), and prolonged time constant of LV relaxation Tau (18 ± 1 versus 29 ± 2 ms). The EP data showed decreased (p <; 0.05) electrogram amplitude in border and infarct zones (Healthy zone (H): 8.7 ± 2.1 mV, Border zone (B): 5.3 ± 1.6 mV, and Infarct zone (I): 2.3 ± 1.2 mV), decreased MAP amplitude in the border zone (H: 14.0 ± 1.0 mV, B: 9.7 ± 0.5 mV), and increased repolarization heterogeneity in the border zone (H: 8.1 ± 1.5 ms, B: 20.2 ± 3.1 ms). With PES we induced sustained VT (>15 consecutive PVCs) in rats with CHF (10/14) versus Sham (0/8). Conclusions: These EP studies establish a clinically relevant protocol for studying genesis of VT in CHF. Significance: The in vivo rat model of CHF combined with EP analysis could be used to determine the arrhythmogenic potential of new treatments for CHF.

Original languageEnglish (US)
Article number7559740
Pages (from-to)1393-1399
Number of pages7
JournalIEEE Transactions on Biomedical Engineering
Volume64
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Rats
Polyvinyl chlorides
Chemical activation
Tissue
Electric potential

Keywords

  • Activation mapping
  • arrhythmias
  • chronic heart failure (CHF)
  • electrophysiology (EP)
  • ischemia
  • monophasic action potential (MAP)
  • myocardial infarction (MI)
  • rat model CHF
  • ventricular tachycardia (VT)

ASJC Scopus subject areas

  • Biomedical Engineering

Cite this

In vivo Electrophysiological Study of Induced Ventricular Tachycardia in Intact Rat Model of Chronic Ischemic Heart Failure. / Weigand, Kyle; Witte, Russell S; Moukabary, Talal; Chinyere, Ike; Lancaster, Jordan; Pierce, Mary Kaye; Goldman, Steven; Juneman, Elizabeth B.

In: IEEE Transactions on Biomedical Engineering, Vol. 64, No. 6, 7559740, 01.06.2017, p. 1393-1399.

Research output: Contribution to journalArticle

@article{2738bd0bafed4951bfb5ecc8b3bc97fa,
title = "In vivo Electrophysiological Study of Induced Ventricular Tachycardia in Intact Rat Model of Chronic Ischemic Heart Failure",
abstract = "Objective: The objective of this study was to define the clinical relevance of in vivo electrophysiologic (EP) studies in a rat model of chronic ischemic heart failure (CHF). Methods: Electrical activation sequences, voltage amplitudes, and monophasic action potentials (MAPs) were recorded from adult male Sprague-Dawley rats six weeks after left coronary artery ligation. Programmed electrical stimulation (PES) sequences were developed to induce sustained ventricular tachycardia (VT). The inducibility of sustained VT was defined by PES and the recorded tissue MAPs. Results: Rats in CHF were defined (p <; 0.05) by elevated left ventricular (LV) end-diastolic pressure (5 ± 1 versus 18 ± 2 mmHg), decreased LV + dP/dt (7496 ± 225 versus 5502 ± 293 mmHg/ s), LV - dP/dt (7723 ± 208 versus 3819 ± 571 mmHg), LV ejection fraction (79 ± 3 versus 30 ± 3{\%}), peak developed pressure (176 ± 4 versus 145 ± 9 mmHg), and prolonged time constant of LV relaxation Tau (18 ± 1 versus 29 ± 2 ms). The EP data showed decreased (p <; 0.05) electrogram amplitude in border and infarct zones (Healthy zone (H): 8.7 ± 2.1 mV, Border zone (B): 5.3 ± 1.6 mV, and Infarct zone (I): 2.3 ± 1.2 mV), decreased MAP amplitude in the border zone (H: 14.0 ± 1.0 mV, B: 9.7 ± 0.5 mV), and increased repolarization heterogeneity in the border zone (H: 8.1 ± 1.5 ms, B: 20.2 ± 3.1 ms). With PES we induced sustained VT (>15 consecutive PVCs) in rats with CHF (10/14) versus Sham (0/8). Conclusions: These EP studies establish a clinically relevant protocol for studying genesis of VT in CHF. Significance: The in vivo rat model of CHF combined with EP analysis could be used to determine the arrhythmogenic potential of new treatments for CHF.",
keywords = "Activation mapping, arrhythmias, chronic heart failure (CHF), electrophysiology (EP), ischemia, monophasic action potential (MAP), myocardial infarction (MI), rat model CHF, ventricular tachycardia (VT)",
author = "Kyle Weigand and Witte, {Russell S} and Talal Moukabary and Ike Chinyere and Jordan Lancaster and Pierce, {Mary Kaye} and Steven Goldman and Juneman, {Elizabeth B}",
year = "2017",
month = "6",
day = "1",
doi = "10.1109/TBME.2016.2605578",
language = "English (US)",
volume = "64",
pages = "1393--1399",
journal = "IEEE Transactions on Biomedical Engineering",
issn = "0018-9294",
publisher = "IEEE Computer Society",
number = "6",

}

TY - JOUR

T1 - In vivo Electrophysiological Study of Induced Ventricular Tachycardia in Intact Rat Model of Chronic Ischemic Heart Failure

AU - Weigand, Kyle

AU - Witte, Russell S

AU - Moukabary, Talal

AU - Chinyere, Ike

AU - Lancaster, Jordan

AU - Pierce, Mary Kaye

AU - Goldman, Steven

AU - Juneman, Elizabeth B

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Objective: The objective of this study was to define the clinical relevance of in vivo electrophysiologic (EP) studies in a rat model of chronic ischemic heart failure (CHF). Methods: Electrical activation sequences, voltage amplitudes, and monophasic action potentials (MAPs) were recorded from adult male Sprague-Dawley rats six weeks after left coronary artery ligation. Programmed electrical stimulation (PES) sequences were developed to induce sustained ventricular tachycardia (VT). The inducibility of sustained VT was defined by PES and the recorded tissue MAPs. Results: Rats in CHF were defined (p <; 0.05) by elevated left ventricular (LV) end-diastolic pressure (5 ± 1 versus 18 ± 2 mmHg), decreased LV + dP/dt (7496 ± 225 versus 5502 ± 293 mmHg/ s), LV - dP/dt (7723 ± 208 versus 3819 ± 571 mmHg), LV ejection fraction (79 ± 3 versus 30 ± 3%), peak developed pressure (176 ± 4 versus 145 ± 9 mmHg), and prolonged time constant of LV relaxation Tau (18 ± 1 versus 29 ± 2 ms). The EP data showed decreased (p <; 0.05) electrogram amplitude in border and infarct zones (Healthy zone (H): 8.7 ± 2.1 mV, Border zone (B): 5.3 ± 1.6 mV, and Infarct zone (I): 2.3 ± 1.2 mV), decreased MAP amplitude in the border zone (H: 14.0 ± 1.0 mV, B: 9.7 ± 0.5 mV), and increased repolarization heterogeneity in the border zone (H: 8.1 ± 1.5 ms, B: 20.2 ± 3.1 ms). With PES we induced sustained VT (>15 consecutive PVCs) in rats with CHF (10/14) versus Sham (0/8). Conclusions: These EP studies establish a clinically relevant protocol for studying genesis of VT in CHF. Significance: The in vivo rat model of CHF combined with EP analysis could be used to determine the arrhythmogenic potential of new treatments for CHF.

AB - Objective: The objective of this study was to define the clinical relevance of in vivo electrophysiologic (EP) studies in a rat model of chronic ischemic heart failure (CHF). Methods: Electrical activation sequences, voltage amplitudes, and monophasic action potentials (MAPs) were recorded from adult male Sprague-Dawley rats six weeks after left coronary artery ligation. Programmed electrical stimulation (PES) sequences were developed to induce sustained ventricular tachycardia (VT). The inducibility of sustained VT was defined by PES and the recorded tissue MAPs. Results: Rats in CHF were defined (p <; 0.05) by elevated left ventricular (LV) end-diastolic pressure (5 ± 1 versus 18 ± 2 mmHg), decreased LV + dP/dt (7496 ± 225 versus 5502 ± 293 mmHg/ s), LV - dP/dt (7723 ± 208 versus 3819 ± 571 mmHg), LV ejection fraction (79 ± 3 versus 30 ± 3%), peak developed pressure (176 ± 4 versus 145 ± 9 mmHg), and prolonged time constant of LV relaxation Tau (18 ± 1 versus 29 ± 2 ms). The EP data showed decreased (p <; 0.05) electrogram amplitude in border and infarct zones (Healthy zone (H): 8.7 ± 2.1 mV, Border zone (B): 5.3 ± 1.6 mV, and Infarct zone (I): 2.3 ± 1.2 mV), decreased MAP amplitude in the border zone (H: 14.0 ± 1.0 mV, B: 9.7 ± 0.5 mV), and increased repolarization heterogeneity in the border zone (H: 8.1 ± 1.5 ms, B: 20.2 ± 3.1 ms). With PES we induced sustained VT (>15 consecutive PVCs) in rats with CHF (10/14) versus Sham (0/8). Conclusions: These EP studies establish a clinically relevant protocol for studying genesis of VT in CHF. Significance: The in vivo rat model of CHF combined with EP analysis could be used to determine the arrhythmogenic potential of new treatments for CHF.

KW - Activation mapping

KW - arrhythmias

KW - chronic heart failure (CHF)

KW - electrophysiology (EP)

KW - ischemia

KW - monophasic action potential (MAP)

KW - myocardial infarction (MI)

KW - rat model CHF

KW - ventricular tachycardia (VT)

UR - http://www.scopus.com/inward/record.url?scp=85027336462&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027336462&partnerID=8YFLogxK

U2 - 10.1109/TBME.2016.2605578

DO - 10.1109/TBME.2016.2605578

M3 - Article

C2 - 27608446

AN - SCOPUS:85027336462

VL - 64

SP - 1393

EP - 1399

JO - IEEE Transactions on Biomedical Engineering

JF - IEEE Transactions on Biomedical Engineering

SN - 0018-9294

IS - 6

M1 - 7559740

ER -