Preconditioning and postconditioning with netrin-1 in acute myocardial infarction model of rat improves systolic and diastolic left ventricular dysfunction

Abstract

Introduction To evaluate the improvement of systolic and diastolic left ventricular(LV) dysfunction by preconditioning and postconditioning with netrin-1 after acute myocardial infarction(MI) in rat model, we examined the changes of echocardiographic parameters and compared with them before and after MI. Methods Male, 8-to 9-week-old, Spraque-Dawley rats with a mean body weight of 277.40 ±9.48 g were anesthesized with intraperitoneal injection of pentobarbital at a dose of 65 mg / kg, followed by intubation and positive pressure ventilation for 15 minutes as a stabilizing period. The acute MI model had the ligation of left coronary artery under heart exposure through 4-5th intercostal space then closed. After 30 minutes under mechanical ventilation, the left anterior descending artery (LAD) of the rat was ligated for 30 minutes And reperfusion for 2 hours to produce an ischemic / perfusion animal model of myocardial ischemia. After 30 minutes of ischemia, netrin-1(5mcg/kg) was slowly injected into MI group but vehicle(normal saline) into another MI group via tail vein. Netrin-1 preconditioning was administered intravenously 3 minutes before the induction of ischemia and 3 minutes after the induction of ischemia. Netrin-1 postconditioning was administered intravenously 5 minutes before the end of ischemic induction for 3 minutes and pentobarbital 35 mg / kg after 2 hours of reperfusion. And the echocardiographic evaluation was performed. Using Vevo2100, Echocardiographic studies were performed before surgery and After 120 minutes of reperfusion. Results Fractional shortening values were significantly increased in the pre-isch, pre-netrin, post-isch and post-netrin groups compared to the vehicle group. The EF (ejection fraction), And in the post-netrin group, the left ventricular systolic function was improved. E'(initial diastolic velocity) values were significantly higher in the post-iso, post-isch, and post-netrin groups than in the vehicle group. E / E', Post-isch, post-isch, and post-netrin, respectively. Discussion Preconditioning and postconditioning with netrin-1 makes meaningful improvemet of systolic dysfunction with significant increase with FS and EF after acute MI. Also it helps E’ recovery for LV diastolic function and E/E’ ratio for left atrial pressure.