Lack of scarring is not always a sign of cardiac health: Functional and molecular characterization of the rat heart’s following chronic reperfusion

• Published in: PloS one Vol. 13; no. 12; p. e0209190
• Main Authors: Omoto, Ana Carolina Mieko, Gava, Fábio Nelson, Silva, Carlos Alberto Aguiar, Silva, Hadder Batista, Parente, Juliana Montenegro, Costa, Rafael Menezes, Castro, Michele Mazzaron, Tostes, Rita de Cássia, Salgado, Helio Cesar, Fazan, Rubens
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.12.2018; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; Care and treatment; Cicatrix - metabolism; Cicatrix - pathology; Cicatrix - physiopathology; Collagen - metabolism; Coronary artery; Coronary artery disease; Coronary vessels; Disease Models, Animal; Fibrosis; Health aspects; Heart; Heart - physiopathology; Heart attack; Heart attacks; Heart diseases; Heart failure; Hydrogen; Hydrogen peroxide; Injuries; Ischemia; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Medical schools; Medicine and Health Sciences; Metalloproteinase; Myocardial infarction; Myocardial ischemia; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocardium; Myocardium - metabolism; Myocardium - pathology; Ostomy; Oxidative stress; Oxygen; Patient outcomes; Pharmacology; Physiology; Pulmonary arteries; Rats; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - metabolism; Recording; Reperfusion; Reperfusion (Physiology); Rodents; Scars; Superoxide; Superoxides - metabolism; Surgery; Surgical instruments; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Tumors; Veins & arteries; Ventricle; Ventricular Pressure; Germany; Brazil; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0209190

Even though the coronary reperfusion process is the most important tool to preserve cardiac function, after myocardial infarction, reperfusion of acutely ischemic myocardium can induce injury. We aimed to evaluate the functional and molecular aspects 4 weeks after myocardial ischemia-reperfusion (IR) in rats. Male Wistar rats (N = 47) were subjected to myocardial IR by short-term (30 min) ligation and subsequent reperfusion of the left descending coronary artery. Control rats (N = 7) underwent the same surgical maneuver without coronary ligation. After 4 weeks, rats had their cardiac function examined by ventricular pressure recording under basal condition or pharmacological stress. Myocardial fibrosis and molecular mediators of IR injury (reactive oxygen species, tumor necrosis factor-alpha and matrix-metalloproteinase-2) were assessed as well. Most of the rats subjected to IR did not show macroscopic signs of infarct, while only 17% of these animals showed large myocardial infarction scars. Of note, all animals submitted to IR presented the functional and molecular parameters altered when compared with the control subjects. Cardiac function was attenuated in all animals submitted to IR, regardless the presence or size of macroscopic cardiac scars. Interstitial fibrosis, matrix-metalloproteinase-2 activity and the expression of tumor necrosis factor-alpha were higher in the myocardium of all IR rats as compared to the control subjects (p<0.05). Myocardium superoxide anion and hydrogen peroxide were increased in rats without or with mild cardiac scars. These results show that IR leads to myocardial injury in rats. Besides, even the animals with an apparent healthy myocardium (without infarct scar) presented cardiac dysfunction and molecular changes that may contribute to the development of heart failure over time.