Ligation of Left Anterior Descending Coronary Artery in Rats for Developing Occlusive Myocardial Infarction Model.

Abstract

Cardiovascular disease (CVD), including ischemic heart disease and stroke, is a major cause of mortality and morbidity throughout the world. Myocardial infarction is a clinical syndrome of ischemic heart disease that occurs due to prolonged ischemia. Ischemic myocardium undergoes functional, metabolic, and structural alterations, leading to irreversible damage to a portion of the myocardium due to necrosis. Experimental models of myocardial infarction are crucial for understanding the acute and chronic cellular, molecular, and morphological changes occurring during and post-MI and for developing and optimizing novel targets or strategies for treatment. The surgical model of MI in small animals employing permanent closure of the left anterior descending coronary artery (LAD) nearly resembles human MI. The goal of this study is to establish a surgically induced MI model involving the closure of the LAD coronary artery indelibly in rats. The experimental protocol includes an initial induction of anesthesia with ketamine 80 mg/kg and xylazine 12 mg/kg i.p., intubation of an endotracheal cannula using an otoscope without performing tracheotomy under ventilator-assisted ventilation with the use of extrinsic positive end-expiratory pressure (PEEP) to prevent the collapse of alveoli. A thoracotomy procedure was adopted that limits the lesions caused to skeletal muscles during surgery. This approach is minimally invasive, repeatable, and lowers mortality post-surgery. In this model, animals survived 4 days post-MI to understand the short-term pathobiological changes, mainly post-MI inflammation, angiogenesis as a natural process of infarct healing, and ultimately, fibrosis in infarcted myocardium.