Remodeling of the Purkinje Network in Congestive Heart Failure in the RabbitCitation formats

  • External authors:
  • Xue J. Cai
  • Joseph Yanni
  • Caroline B. Jones
  • Robert S. Stephenson
  • Luke Stuart
  • Gillian Quigley
  • Oliver Monfredi
  • Shu Nakao
  • Il Young Oh
  • Tobias Starborg
  • Robert C. Hutcheon
  • Antonio F. Corno
  • Jonathan C. Jarvis
  • Mark R. Boyett
  • George Hart

Standard

Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit. / Logantha, Sunil Jit R.J.; Cai, Xue J.; Yanni, Joseph; Jones, Caroline B.; Stephenson, Robert S.; Stuart, Luke; Quigley, Gillian; Monfredi, Oliver; Nakao, Shu; Oh, Il Young; Starborg, Tobias; Kitmitto, Ashraf; Vohra, Akbar; Hutcheon, Robert C.; Corno, Antonio F.; Jarvis, Jonathan C.; Dobrzynski, Halina; Boyett, Mark R.; Hart, George.

In: Circulation. Heart Failure, Vol. 14, No. 7, 01.07.2021, p. 800-816.

Research output: Contribution to journalArticlepeer-review

Harvard

Logantha, SJRJ, Cai, XJ, Yanni, J, Jones, CB, Stephenson, RS, Stuart, L, Quigley, G, Monfredi, O, Nakao, S, Oh, IY, Starborg, T, Kitmitto, A, Vohra, A, Hutcheon, RC, Corno, AF, Jarvis, JC, Dobrzynski, H, Boyett, MR & Hart, G 2021, 'Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit', Circulation. Heart Failure, vol. 14, no. 7, pp. 800-816. https://doi.org/10.1161/CIRCHEARTFAILURE.120.007505

APA

Logantha, S. J. R. J., Cai, X. J., Yanni, J., Jones, C. B., Stephenson, R. S., Stuart, L., Quigley, G., Monfredi, O., Nakao, S., Oh, I. Y., Starborg, T., Kitmitto, A., Vohra, A., Hutcheon, R. C., Corno, A. F., Jarvis, J. C., Dobrzynski, H., Boyett, M. R., & Hart, G. (2021). Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit. Circulation. Heart Failure, 14(7), 800-816. https://doi.org/10.1161/CIRCHEARTFAILURE.120.007505

Vancouver

Logantha SJRJ, Cai XJ, Yanni J, Jones CB, Stephenson RS, Stuart L et al. Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit. Circulation. Heart Failure. 2021 Jul 1;14(7):800-816. https://doi.org/10.1161/CIRCHEARTFAILURE.120.007505

Author

Logantha, Sunil Jit R.J. ; Cai, Xue J. ; Yanni, Joseph ; Jones, Caroline B. ; Stephenson, Robert S. ; Stuart, Luke ; Quigley, Gillian ; Monfredi, Oliver ; Nakao, Shu ; Oh, Il Young ; Starborg, Tobias ; Kitmitto, Ashraf ; Vohra, Akbar ; Hutcheon, Robert C. ; Corno, Antonio F. ; Jarvis, Jonathan C. ; Dobrzynski, Halina ; Boyett, Mark R. ; Hart, George. / Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit. In: Circulation. Heart Failure. 2021 ; Vol. 14, No. 7. pp. 800-816.

Bibtex

@article{9f78352c2b6341a7b3edf6c8debcf394,
title = "Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit",
abstract = "BACKGROUND: Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs. METHODS: Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used. RESULTS: Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca 2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca 2+-channels, and K +-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P<0.0001), and arrhythmic events in HF. Similar electrical remodeling was seen at the left PF-ventricular junction. In the failing left ventricle, upstroke velocity and amplitude were increased, but action potential duration at 90% repolarization was unaffected. CONCLUSIONS: Severe volume- followed by pressure-overload causes rapidly progressing HF with extensive remodeling of PFs. The PF network is central to both arrhythmogenesis and contractile dysfunction and the pathological remodeling may increase the risk of fatal arrhythmias in HF patients. ",
keywords = "Electron microscopy, Heart failure, Ion channels, Purkinje fibers, Rabbits, Tomography",
author = "Logantha, {Sunil Jit R.J.} and Cai, {Xue J.} and Joseph Yanni and Jones, {Caroline B.} and Stephenson, {Robert S.} and Luke Stuart and Gillian Quigley and Oliver Monfredi and Shu Nakao and Oh, {Il Young} and Tobias Starborg and Ashraf Kitmitto and Akbar Vohra and Hutcheon, {Robert C.} and Corno, {Antonio F.} and Jarvis, {Jonathan C.} and Halina Dobrzynski and Boyett, {Mark R.} and George Hart",
note = "Publisher Copyright: {\textcopyright} 2021 The Authors. Circulation: Heart Failure is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc.",
year = "2021",
month = jul,
day = "1",
doi = "10.1161/CIRCHEARTFAILURE.120.007505",
language = "English",
volume = "14",
pages = "800--816",
journal = "Circulation: Heart Failure",
issn = "1941-3289",
publisher = "Lippincott Williams & Wilkins",
number = "7",

}

RIS

TY - JOUR

T1 - Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit

AU - Logantha, Sunil Jit R.J.

AU - Cai, Xue J.

AU - Yanni, Joseph

AU - Jones, Caroline B.

AU - Stephenson, Robert S.

AU - Stuart, Luke

AU - Quigley, Gillian

AU - Monfredi, Oliver

AU - Nakao, Shu

AU - Oh, Il Young

AU - Starborg, Tobias

AU - Kitmitto, Ashraf

AU - Vohra, Akbar

AU - Hutcheon, Robert C.

AU - Corno, Antonio F.

AU - Jarvis, Jonathan C.

AU - Dobrzynski, Halina

AU - Boyett, Mark R.

AU - Hart, George

N1 - Publisher Copyright: © 2021 The Authors. Circulation: Heart Failure is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc.

PY - 2021/7/1

Y1 - 2021/7/1

N2 - BACKGROUND: Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs. METHODS: Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used. RESULTS: Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca 2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca 2+-channels, and K +-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P<0.0001), and arrhythmic events in HF. Similar electrical remodeling was seen at the left PF-ventricular junction. In the failing left ventricle, upstroke velocity and amplitude were increased, but action potential duration at 90% repolarization was unaffected. CONCLUSIONS: Severe volume- followed by pressure-overload causes rapidly progressing HF with extensive remodeling of PFs. The PF network is central to both arrhythmogenesis and contractile dysfunction and the pathological remodeling may increase the risk of fatal arrhythmias in HF patients.

AB - BACKGROUND: Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs. METHODS: Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used. RESULTS: Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca 2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca 2+-channels, and K +-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P<0.0001), and arrhythmic events in HF. Similar electrical remodeling was seen at the left PF-ventricular junction. In the failing left ventricle, upstroke velocity and amplitude were increased, but action potential duration at 90% repolarization was unaffected. CONCLUSIONS: Severe volume- followed by pressure-overload causes rapidly progressing HF with extensive remodeling of PFs. The PF network is central to both arrhythmogenesis and contractile dysfunction and the pathological remodeling may increase the risk of fatal arrhythmias in HF patients.

KW - Electron microscopy

KW - Heart failure

KW - Ion channels

KW - Purkinje fibers

KW - Rabbits

KW - Tomography

U2 - 10.1161/CIRCHEARTFAILURE.120.007505

DO - 10.1161/CIRCHEARTFAILURE.120.007505

M3 - Article

C2 - 34190577

VL - 14

SP - 800

EP - 816

JO - Circulation: Heart Failure

JF - Circulation: Heart Failure

SN - 1941-3289

IS - 7

ER -