In Vivo Mapping of Myocardial Injury Outside the Infarct Zone: Tissue at an Intermediate Pathological State

Abstract

Background The goal was to determine the feasibility of mapping the injured‐but‐not‐infarcted myocardium using 99m Tc‐duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted. Methods and Results Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30‐minute ligation. In vivo single‐photon emission computed tomography was acquired after 3 hours (n=6) using 99m Tc‐duramycin, a phosphatidylethanolamine‐specific radiopharmaceutical. The 99m Tc‐duramycin + areas were compared with infarct and area‐at‐risk (n=8). Cardiomyocytes and endothelial cells were isolated for gene expression profiling. Cardiac function was measured with echocardiography (n=6) at 4 weeks. In vivo imaging with 99m Tc‐duramycin identified the infarct (3.9±2.4% of the left ventricle and an extensive area 23.7±2.2% of the left ventricle) with diffuse signal outside the infarct, which is pathologically between normal and infarcted (apoptosis 1.8±1.6, 8.9±4.2, 13.6±3.8%; VCAM‐1 [vascular cell adhesion molecule 1] 3.2±0.8, 9.8±4.1, 15.9±4.2/mm 2 ; tyrosine hydroxylase 14.9±2.8, 8.6±4.4, 5.6±2.2/mm 2 ), with heterogeneous changes including scattered micronecrosis, wavy myofibrils, hydropic change, and glycogen accumulation. The 99m Tc‐duramycin + tissue is quantitatively smaller than the area‐at‐risk (26.7% versus 34.4% of the left ventricle, P =0.008). Compared with infarct, gene expression in the 99m Tc‐duramycin + –noninfarct tissue indicated a greater prosurvival ratio (BCL2/BAX [B‐cell lymphoma 2/BCL2‐associated X] 7.8 versus 5.7 [cardiomyocytes], 3.7 versus 3.2 [endothelial]), and an upregulation of ion channels in electrophysiology. There was decreased contractility at 4 weeks (regional fractional shortening −8.6%, P <0.05; circumferential strain −52.9%, P <0.05). Conclusions The injured‐but‐not‐infarcted tissue, being an intermediate zone between normal and infarct, is mapped in vivo using phosphatidylethanolamine‐based imaging. The intermediate zone contributes significantly to cardiac dysfunction.