Animals and experimental protocol

The experiments were conducted on 12‐month‐old (middle‐aged) male (n = 10) and female (n = 10) Sprague–Dawley rats (Charles River Laboratories, Inc., Wilmington, MA). At the beginning of the experiments, all rats were weighed and evaluated by echocardiography to assess the LV dimensions, chamber volumes, myocardial mass, wall thickness, and systolic function at baseline. Then, a large transmural myocardial infarction (MI) was induced under ketamine (100 mg/kg intraperitoneal [i.p.]) and xylazine (10 mg/kg i.p.) anesthesia by the permanent ligation of the left anterior descending branch of the coronary artery, as previously detailed (Dedkov et al. 2005). Following surgery, the rats were housed under climate‐controlled conditions at a 12‐h light/dark cycle, and provided with standard rat chow and water ad libitum. The mortality rate among post‐MI rats was ~30% in males and ~10% in females, with all death occurring within first 48 h after surgery.

Two weeks after induction of an MI, an echocardiographic examination was repeated in all survived rats to measure the infarcted area. The animals were included in the following study only if the size of transmural MI was greater than ~35% of the LV circumference (Pfeffer et al. 1979). In all selected post‐MI male (M‐MI) and female (F‐MI) rats, the body weight and the same LV echocardiographic parameters were re‐examined with a 2‐week interval between second and eighth post‐MI week.

At the end of experiment, each rat was acutely instrumented with retrograde catheters in the left ventricle and the right atrium to examine systemic and cardiac hemodynamics, LV systolic and diastolic properties, and to perform an atrial fibrillation (AF) inducibility test, respectively (Zhang et al. 2013, 2014). Finally, animals were killed by arresting the heart in diastole with potassium chloride; the body was weighed, and the hearts and tibias were collected for further evaluation.