Characteristics of atrial substrates for atrial tachyarrhythmias induced in aged and hypercholesterolemic rabbits

Abstract

Background: Old age and dyslipidemia increase the occurrence of atrial tachyarrhythmias (ATR). This study investigated the effect of age and hypercholesterolemia on the atrial substrates for ATR.

Methods: Five 3-year-old rabbits fed standard chow were categorized into an old-age group, five 3-month-old rabbits fed high cholesterol chow were used as a hypercholesterolemia group, and five 3-month-old rabbits fed standard chow were controls. Effective refractory period, atrial vulnerability to ATR, expressions of connexin40 (Cx40) and connexin43 (Cx43), phosphorylated c-Jun N-terminal Kinase (P-JNK), and degree of fibrosis in the right (RA) and left (LA) atria were compared.

Results: Old-age and hypercholesterolemia rabbits were more vulnerable to ATR than the controls (18,628 ± 13,981 ms and 30,157 ± 39,548 ms vs 639 ± 325 ms, P < 0.05). Old-age rabbits had significantly decreased Cx40 expression in both atria (3.9-fold decrease in RA, P < 0.01 and 4.8-fold in LA, P < 0.01) and significantly decreased Cx43 in RA (14-fold, P < 0.01). Hypercholesterolemia rabbits had significantly decreased Cx40 expression in both atrial (18-fold decrease in RA, P < 0.01 and 17-fold in LA, P < 0.01) and significantly increased Cx43 expression in LA (five-fold increase, P < 0.01). Hypercholesterolemia, but not old-age rabbits, had greater expression of P-JNK in both atria (1.8-fold in RA and 2.3-fold in LA, P < 0.01). There were no significant group differences in ERP or degree of atrial fibrosis in both atria.

Conclusions: ATR is more easily induced in the atria of old-age and hypercholesterolemia rabbits than younger rabbits with normal cholesterol levels. The age and hypercholesterolemia induced changes in gap junctions expression may have partially contributed to the higher atrial vulnerability to ATR.