Mouse Transverse Aortic Constriction Model

SIRT3 ECKO mice and their control mice (SIRT3 LoxP) were subjected to LV PO‐induced by transverse aortic constriction (TAC) for up to 7 weeks, following a previous procedure.20 Briefly, the mice were anesthetized with a single intraperitoneal injection of ketamine (50 mg/kg) and xylazine (10 mg/kg), and successful anesthesia was confirmed by lack of reflex to toe pinching. All hair in the neck and chest area was removed using a topical depilatory agent, and the area was cleaned with betadine and alcohol. The mice were then placed in a supine position on a heating pad, and the temperature was maintained at 37°C. A 2‐ to 3‐mm longitudinal cut was made in the proximal portion of the sternum at the level of the suprasternal notch. After the thyroid was retracted, the aortic arch was visualized under low power magnification. A 6‐0 silk suture was then placed under the aorta between the origin of the right innominate and the left common carotid arteries, followed by 2 loose knots around the transverse aorta. A small piece of a 25‐gauge blunt needle is placed parallel to the transverse aorta. A bent 25‐gauge blunt needle was then placed next to the aortic arch, and the suture was snugly tied around the needle and the aorta. Following ligation, the needle was quickly removed to yield a constriction of 0.51 mm in diameter. The rib cage and skin were closed, and mice were allowed to recover on a warming pad until they were fully awake. The sham procedure was identical except that the aorta was not ligated. Cardiac function and coronary blood flow reserve were evaluated by echocardiography at 1, 4, and 7 weeks after the surgery.