Levosimendan Attenuates Myocardial Injury Induced by Coronary Microembolization in Swine by Inhibiting Myocardial Inflammation and Apoptosis

Abstract

Aims: In addition to its cardiotonic effect, Levosimendan (Levo) has been thought to have multiple cardiovascular benefits, including anti-inflammatory and anti-apoptotic effects. The present study was undertaken to determine whether the Levo pretreatment could attenuate myocardial apoptosis and inflammation and improve cardiac function in a swine model of coronary microembolization (CME). Materials and Methods: A total of 15 swine were randomly and equally divided into a sham-operated (control) group, CME group, and CME plus Levo group. Swine CME was induced by intracoronary injection of inertia plastic microspheres (42 μm diameter) into the left anterior descending (LAD) coronary artery, with or without pretreatment of Levo. Echocardiological measurements, a pathological examination, Terminal-deoxynucleoitidyl Transferase-Mediated dUTP Nick End-Labeling (TUNEL) staining, H and E staining, and Western blotting were performed to assess the functional, morphological, and molecular effects in CME. Results: The expression levels of caspase-3 and tumor necrosis factor-α (TNF-α) were increased in cardiomyocytes following CME. Downregulation of caspase-3 and TNF-α with Levo pretreatment was associated with improved cardiac troponin I (cTnI) and high sensitivity C-reactive protein. In addition, through Pearson correlation analysis, the left ventricular ejection fraction was negatively correlated with caspase-3, TNF-α, and cTnI. Conclusion: This study demonstrated that Levo pretreatment could significantly inhibit CME-induced myocardial apoptosis and inflammation and improve cardiac function. The data generated from this study provide a rationale for the development of myocardial apoptosis and inflammation-based therapeutic strategies for CME-induced myocardial injury.