Cardiosphere derived cell secretome therapy after experimental myocardial infarction: effects of intracoronary administration on ventricular tachycardia inducibility and cardiac function

Abstract

Abstract Background Myocardial infarction (MI) carries high risk of sudden cardiac death due to the development of ventricular tachycardia (VT) which is caused by viable myocytes located within the infarct scar tissue [1]. Cardiosphere derived cell secretome (S-CDCs) has been demonstrated to possess antiarrhythmic properties when delivered transendocardially [2]. Further, S-CDCs has been proven to reduce scar size and increase viable myocardial mass in chronic MI [3]. Purpose The objective of this study was to evaluate the effects of an intracoronary (IC) administration of S-CDCs on VT inducibility and cardiac function in a porcine MI model. Methods After obtaining the approval of the Institutional Animal Care and Use Committee, 14 Large White swine were subjected to closed chest MI induction carrying out balloon occlusion of the left anterior descending coronary artery (below the second diagonal branch) for 150 minutes. One month after MI creation, pigs received an IC administration of saline (CON; 5mL; n=7) or S-CDCs (S-CDCs; 9.16 mg of protein in 5mL of saline; n=7). VT inducibility and magnetic resonance (MR) studies were performed pre- and four months post-injection determining ejection fraction (EF), infarct size (IS) and indexed end diastolic and systolic volumes (EDVi, ESVi). Results Before injection VT was inducible in all cases and no differences were observed between groups in any MR-derived parameter (figure). IC infusion was successful in all swine. At four months VT inducibility study revealed lower inducibility rates in S-CDCs compared to CON (57% versus 100%; p=0.05). At this timepoint EF was higher in S-CDCs (35±10% versus 29±10%) although differences between groups were not statistically significant. Conversely, IS was significantly lower in S-CDCs (12±3% versus 16±2% (p=0.03)). Moreover, a trend towards lower ventricular volumes (EDVi: 83±18mL/m² versus 88±29mL/m² and ESVi: 56±20mL/m² versus 64±27mL/m²) was detected in this group. Conclusions The IC administration of S-CDCs suggests a potential reduction on post-MI VT development as well as a beneficial effect on cardiac function. This therapy seems to reduce IS in this porcine MI model.MR derived parameters