We have chosen this rat model since myocardial infarction is the underlying etiology of heart failure in nearly 70% of patients42. Myocardial infarction was induced by a permanent ligation of the left anterior descending coronary artery in Wistar normotensive male rats at 12 weeks of age43. Rats were anesthetized intraperitoneally with ketamine (50 mg Kg−1) and xylazine (10 mg Kg−1), endotracheally intubated, and mechanically ventilated with room air (respiratory rate of 60–70 breaths per minute and tidal volume of 2.5 mL). Left thoracotomy between the fourth and fifth ribs was performed and the left anterior descending coronary artery was permanently ligated44. Four weeks later, echocardiography (Acuson Sequoia, 14 MHz) to evaluate fractional shortening was performed and rats showing heart failure symptoms were included in the study. Heart failure was defined when animal presented pathological cardiac remodeling accompanied by left ventricle dysfunction and cardiac dilation, according to the Guidelines of American Heart Association45. Left thoracotomy with equal procedure duration, but without left anterior descending coronary artery ligation, was undertaken in the sham group.
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