Aging-induced atrial fibrosis in I_f current change and its effect on atrial fibrillation in dogs

Atrial fibrillation (AF) is a very common type of cardiac arrhythmia that threatens public health. Aging is an independent AF risk factor. However, the mechanism of age-related AF remains unclear.

A total of 36 Beagle dogs were selected and divided into three groups (12 in each group): two groups were 9-year-old aged dogs, and one group was 4-year-old adult dogs. Electrophysiological testing was employed to determine if modeling is successful. Patch-clamp technique was employed to measure the I_f current. The expression of protein and mRNA related to I_f current were also tested. Collagen deposition was observed with the use of Masson staining.

Aging resulted in a higher collagen deposition percentage in the left atrium. The hyperpolarization-activated cyclic nucleotide-gated (HCN)2 and HCN4 expressions were increased in the atria and pulmonary veins but decreased in the sinus node of the aged group. Moreover, in the aged group, the left atrium mRNA expressions of Kcnd2 (Potassium voltage-gated channel subfamily D member 2), Kcnh2, Kcnq1, Kcnj2, Kcnj11, and CACNA1H were significantly downregulated. The aged AF group also demonstrated sustained AF and significant changes in electrophysiological characteristics. The I_f current demonstrated an increased amplitude and was easier to activate in the aged AF group than in younger group. Finally, AF occurrence exacerbated aging-induced cardiac fibrosis, thereby aggravating the above-listed symptoms.

With age, the increase in atrial fibrosis affected the expression of the ion channels, thereby modulating the I_f current. Moreover, AF also further exacerbated the degree of atrial fibrosis.