Reverse Electrical Remodeling in Rats with Heart Failure and Preserved Ejection Fraction

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2018 Oct 5

PMID 30282820

Citations 18

Authors

Jae Hyung Cho

Peter J Kilfoil

Rui Zhang

Ryan E Solymani

Catherine Bresee

Elliot M Kang

Kristin Luther

Russell G Rogers

Geoffrey de Couto

Joshua I Goldhaber

Eduardo Marban

Eugenio Cingolani

Affiliations

Soon will be listed here.

Abstract

Sudden death is the most common mode of exodus in patients with heart failure and preserved ejection fraction (HFpEF). Cardiosphere-derived cells (CDCs) reduce inflammation and fibrosis in a rat model of HFpEF, improving diastolic function and prolonging survival. We tested the hypothesis that CDCs decrease ventricular arrhythmias (VAs) and thereby possibly contribute to prolonged survival. Dahl salt-sensitive rats were fed a high-salt diet to induce HFpEF. Allogeneic rat CDCs (or phosphate-buffered saline as placebo) were injected in rats with echo-verified HFpEF. CDC-injected HFpEF rats were less prone to VA induction by programmed electrical stimulation. Action potential duration (APD) was shortened, and APD homogeneity was increased by CDC injection. Transient outward potassium current density was upregulated in cardiomyocytes from CDC rats relative to placebo, as were the underlying transcript (Kcnd3) and protein (Kv4.3) levels. Fibrosis was attenuated in CDC-treated hearts, and survival was increased. Sudden death risk also trended down, albeit nonsignificantly. CDC therapy decreased VA in HFpEF rats by shortening APD, improving APD homogeneity, and decreasing fibrosis. Unlike other stem/progenitor cells, which often exacerbate arrhythmias, CDCs reverse electrical remodeling and suppress arrhythmogenesis in HFpEF.

Citing Articles

Three-vessel coronary infusion of cardiosphere-derived cells for the treatment of heart failure with preserved ejection fraction in a pre-clinical pig model.

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PMID: 37400630 DOI: 10.1007/s00395-023-00995-2.

Biological Modification of Arrhythmogenic Substrates by Cell-Free Therapeutics.

Lin Y, Miguel-Dos-Santos R, Cingolani E Heart Lung Circ. 2023; 32(7):844-851.

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Diet modification reverses diastolic dysfunction in rats with heart failure and preserved ejection fraction.

Kim M, Pellot I, Bresee C, Nawaz A, Fournier M, Cho J J Mol Cell Cardiol Plus. 2023; 3.

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Pathological mechanism of heart failure with preserved ejection fraction in rats based on iTRAQ technology.

Xu H, Gao K, Liu C, Li T, Ding Y, Ma J PeerJ. 2023; 11:e15280.

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Inflammatory Mechanisms in Heart Failure with Preserved Ejection Fraction.

Daou D, Gillette T, Hill J Physiology (Bethesda). 2023; 38(5).

PMID: 37013947 PMC: 10396273. DOI: 10.1152/physiol.00004.2023.

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