Effects of chronic intermittent hypoxia on atrial electrical remodeling in rats

doi:10.12047/j.cjap.6279.2022.072

Abstract

Abstract: Objective: The aim of this study was to investigate the effects of chronic intermittent hypoxia (CIH) on atrial electrical remodeling in Sprague-Dawley (SD) rats, which provide the explication for the mechanisms of CIH promoting atrial fibrillation (AF). Methods: Eighty SD rats were randomly divided into 2 groups: control group and CIH group (n=40). CIH rats were subjected to CIH 8 h/d for 30 days. After the echocardiography and hemodynamics examination, cardiac electrophysiological experiments, histological experiments, and molecular biological experiments were executed. AF susceptibility was measured by isolated heart electrophysiological experiments. Masson's trichrome stain was used to assess the degree of atrial fibrosis. The protein expression levels of sodium voltage-gated channel alpha subunit 5 (SCN5A/Na_v1.5), calcium voltage-gated channel subunit alpha1 C (CACNA1C/Ca_v1.2) and potassium voltage-gated channel subfamily D member 3 (KCND3/K_v4.3) were measured by Western blot. In whole-cell patch clamp experiments, current clamp mode was used to record AP, and APD₉₀ and APD₅₀ were analyzed and compared between the two groups. In voltage clamp mode, I_Na, I_Ca-L, I_to and their kinetic parameters were recorded and compared between the two groups. Results: Compared to the control rats, atrial interstitial collagen deposition (P＜0.01) and AF inducibility (P＜0.05) were increased in CIH rats, whereas the expression levels of Na_v1.5, Ca_v1.2 and K_v4.3 were decreased (P＜0.05). APD₉₀ and APD₅₀ in CIH rats' atrial myocytes were longer than those of control rats, and CIH rats showed decreased current density of I_Na, I_Ca-L(P＜0.01) and I_to(P＜0.01). Conclusion: CIH-induced changes in the protein expression levels of ion channel subunits, current intensity, APD, and AF susceptibility, which may be the mechanisms of CIH promoting AF.

Key words: atrial fibrillation, chronic intermittent hypoxia, atrial remodeling, ion channels, rat

CLC Number:

R541.7

ZHANG Kai, MA Jing-xia, MA Zuo-wang, YANG Yu, LI Guang-ping. Effects of chronic intermittent hypoxia on atrial electrical remodeling in rats[J]. CJAP, 2022, 38(5): 385-391.

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