Pathogenesis of arrhythmias in a model of CKD

Chia Hsiang Hsueh, Neal X. Chen, Shien Fong Lin, Peng Sheng Chen, Vincent H. Gattone, Matthew R. Allen, Michael C. Fishbein, Sharon M. Moe

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Patients with CKD have an increased risk of cardiovascular mortality from arrhythmias and sudden cardiac death. We used a rat model of CKD (Cy/+) to study potential mechanisms of increased ventricular arrhythmias. Rats with CKD showed normal ejection fraction but hypertrophic myocardium. Premature ventricular complexes occurredmore frequently in CKDrats than normal rats (42%versus 11%, P =0.18). By optical mapping techniques, action potential duration (APD) at 80% of repolarization was longer in CKD rats (78±4ms) than normal rats (63±3ms, P<0.05) at a 200-ms pacing cycle length. Calcium transient (CaT) duration was comparable. Pacing cycle length thresholds to induce CaT alternans or APD alternans were longer in CKD rats than normal rats (100±7 versus 80±3 ms and 93±6 versus 76±4 ms for CaT and APD alternans, respectively, P<0.05), suggesting increased vulnerability to ventricular arrhythmia. Ventricular fibrillation was induced in 9 of 12 CKD rats and 2 of 9 normal rats (P<0.05); early afterdepolarization occurred in two CKD rats but not normal rats. The mRNA levels of TGF-Β, microRNA-21, and sodium calcium-exchanger type 1 were upregulated, whereas the levels of microRNA-29, L-type calcium channel, sarco/endoplasmic reticulum calcium-ATPase type 2a, Kv1.4, and Kv4.3 were downregulated in CKD rats. Cardiac fibrosis was mild and not different between groups. We conclude that cardiac ion channel and calcium handling are abnormal in CKD rats, leading to increased vulnerability to early afterdepolarization, triggered activity, and ventricular arrhythmias.

Original languageEnglish (US)
Pages (from-to)2812-2821
Number of pages10
JournalJournal of the American Society of Nephrology
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Nephrology

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