Key result
Aging increases AF inducibility and alters regional HCN2 and HCN4 expression in canines.
Why the study?
Age-related atrial fibrillation mechanisms involving cardiac electrophysiological changes and HCN channel expression patterns were not fully understood.
Age-related atrial fibrillation is associated with sinoatrial node dysfunction and a reversal in the regional distribution of HCN2 and HCN4 channels in the heart.
Hypothesis-generating for HCN channel targets in age-related AF; human validation required before any clinical consideration.
BACKGROUND: We compared cardiac electrophysiological indicators and regional expression levels of cardiac hyperpolarization-activated cyclic nucleotide-gated (HCN) channels between adult and aged dogs to identify possible mechanisms of age-related atrial fibrillation. MATERIAL/METHODS: Corrected sinus node recovery time (SNRTc) and effective refractory period (ERP) of the atrium and pulmonary veins were measured in 10 adult (3-6 years old) and 10 aged dogs (>9 years old). Expression levels of HCN2 and HCN4 channel mRNAs and proteins were measured in the sinoatrial node, atrium, and pulmonary veins by real-time PCR and Western blotting. RESULTS: Aged dogs exhibited a higher induction rate of atrial fibrillation (AF) in response to electrical stimulation, longer AF duration after induction, longer SNRTc, longer right atrial effective refractory period (AERP), shorter left AERP, and increased AERP dispersion compared to adults. Expression levels of HCN2 and HCN4 channel mRNAs and proteins were lower in the sinoatrial node but higher in the atrium and pulmonary veins of aged dogs. CONCLUSIONS: Changes in atrial electrophysiological indicators in aged dogs revealed sinoatrial node dysfunction. There was a reversal in the local tissue distribution of HCN2 and HCN4 channel mRNA and protein, a decrease in sinoatrial node expression, and increase in atrial and pulmonary vein expression with age. Changes in atrial electrophysiological characteristics and regional HCN channel expression patterns were associated with the onset and maintenance of age-related atrial fibrillation.
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Baopeng Tang (2014) studied Age-related atrial fibrillation (n=20). Aging (aged dogs) vs. Adult dogs (3-6 years old) was evaluated on Cardiac electrophysiological indicators and regional expression levels of HCN2 and HCN4 channels. Aged dogs exhibited a higher induction rate of atrial fibrillation, longer AF duration, and a reversal in the local tissue distribution of HCN2 and HCN4 channel expression compared to adult dogs.
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