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

Autor: Sunil Jit R. J. Logantha, Joseph Yanni, Ashraf Kitmitto, Oliver J. Monfredi, Luke Stuart, Akbar Vohra, Shu Nakao, R Hutcheon, Tobias Starborg, Caroline Jones, GM Quigley, George Hart, Robert S. Stephenson, Jonathan C. Jarvis, X. Cai, Antonio F. Corno, Il Young Oh, Halina Dobrzynski, Mark R. Boyett
Rok vydání: 2021
Předmět:
Zdroj: Circulation. Heart Failure
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, vol. 14, no. 7, pp. 800-816 . https://doi.org/10.1161/CIRCHEARTFAILURE.120.007505
ISSN: 1941-3297
1941-3289
Popis: Supplemental Digital Content is available in the text.
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, Ca2+-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, Ca2+-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
Databáze: OpenAIRE