Elevated Swelling-Activated Chloride Current Densities in Hypertrophied Ventricular Myocytes in a Rabbit Heart Failure Model

Abstract

Background: The status of the swelling-activated chloride channel (I_{Cl, swell}) during heart failure remains unclear. This study aimed to investigate whether the I_{Cl, swell} activity is altered during heart failure and to determine how the I_{Cl, swell} influences atrial arrhythmias of the failing heart.

Methods: We established a heart failure rabbit model and analyzed the hemodynamic indicators 8 weeks after myocardial infarction, which include left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVDEP). Five untreated rabbits and 5 receiving a sham operation served as the control group. Left auricular appendage tissues were obtained and CLCN3 mRNA/CLCN3 protein expression levels were examined by using reverse transcription–polymerase chain reaction and Western blot, respectively.

Results: Compared to the control group, the heart failure group showed a significantly decreased LVSP (14.2 ± 0.27 versus 16.9 ± 0.86 kPa, P <.05)and elevated LVDEP (2.49 ± 0.30 versus 0.15 ± 0.03 kPa, P <.05), indicating that myocardial infarction leads to progressive heart failure of rabbits in the heart failure group. CLCN3 mRNA and CLCN3 protein expression were both significantly elevated in the heart failure group compared to the control group (P <.05).

Conclusion: In sum, we propose that the dynamic nature of I_{Cl, swell} upregulation may contribute to the elevated expression of CLCN3 mRNA and CLCN3 protein, resulting in myocardial cell remodeling induced by heart failure. However, further study is needed to investigate the potential functions of I_{Cl, swell}, especially the relation between I_{Cl, swell} augmentation and arrhythmia after heart failure.