(31)P NMR 2D Mapping of Creatine Kinase Forward Flux Rate in Hearts with Postinfarction Left Ventricular Remodeling in Response to Cell Therapy

Utilizing a fast (31)P magnetic resonance spectroscopy (MRS) 2-dimensional chemical shift imaging (2D-CSI) method, this study examined the heterogeneity of creatine kinase (CK) forward flux rate of hearts with postinfarction left ventricular (LV) remodeling. Immunosuppressed Yorkshire pigs were assigned to 4 groups: 1) A sham-operated normal group (SHAM, n = 6); 2) A 60 minutes distal left anterior descending coronary artery ligation and reperfusion (MI, n = 6); 3) Open patch group; ligation injury plus open fibrin patch over the site of injury (Patch, n = 6); and 4) Cell group, hiPSCs-cardiomyocytes, -endothelial cells, and -smooth muscle cells (2 million, each) were injected into the injured myocardium pass through a fibrin patch (Cell+Patch, n = 5). At 4 weeks, the creatine phosphate (PCr)/ATP ratio, CK forward flux rate (Flux (PCr→ATP)), and k constant of CK forward flux rate (k(PCr→ATP)) were severely decreased at border zone myocardium (BZ) adjacent to MI. Cell treatment results in significantly increase of PCr/ATP ratio and improve the value of k(PCr→ATP) and Flux (PCr→ATP) in BZ myocardium. Moreover, the BZ myocardial CK total activity and protein expression of CK mitochondria isozyme and CK myocardial isozyme were significantly reduced, but recovered in response to cell treatment. Thus, cell therapy results in improvement of BZ bioenergetic abnormality in hearts with postinfarction LV remodeling, which is accompanied by significantly improvements in BZ CK activity and CK isozyme expression. The fast 2D (31)P MR CSI mapping can reliably measure the heterogeneity of bioenergetics in hearts with post infarction LV remodeling.