Toma Ildiko, Kim Paul J, Dash Rajesh, McConnell Michael V, Nishimura Dwight, Harnish Phillip, Yang Phillip C
Department of Medicine, Stanford University, Stanford, CA, USA.
Department of Electrical Engineering, Stanford University, Stanford, CA, USA.
Cardiovasc Diabetol. 2016 Feb 5;15:24. doi: 10.1186/s12933-016-0348-y.
A novel MRI technique, employing dual contrast manganese-enhanced MRI (MEMRI) and delayed enhancement MRI (DEMRI), can evaluate the physiologically unstable peri-infarct region. Dual contrast MEMRI-DEMRI enables comprehensive evaluation of telmisartan to salvage the peri-infarct injury to elucidate the underlying mechanism of restoring the ischemic cardiomyopathy in the diabetic mouse model.
Dual contrast MEMRI-DEMRI was performed on weeks 1, 2, and 4 following initiation of telmisartan treatment in 24 left anterior descendent artery ligated diabetic mice. The MRI images were analyzed for core infarct, peri-infarct, left ventricular end-diastolic, end-systolic volumes, and the left ventricular ejection fraction (LVEF). Transmission electron microscopy (TEM) and real-time PCR were used for ex vivo analysis of the myocardium. Telmisartan vs. control groups demonstrated significantly improved LVEF at weeks 1, 2, and 4, respectively (33 ± 7 %*** vs. 19 ± 5 %, 29 ± 3 %*** vs. 22 ± 4 %, and 31 ± 2 %*** vs 18 ± 6 %, ***p < 0.001). The control group demonstrated significant differences in the scar volume measured by MEMRI and DEMRI, demonstrating peri-infarct injury. Telmisartan group significantly salvaged the peri-infarct injury. The myocardial effects were validated by TEM, which confirmed the presence of the injured but viable cardiomyocyte morphology in the peri-infarct region and by flow cytometry of venous blood, which demonstrated significantly increased circulating endothelial progenitor cells (EPCs).
The improved cardiac function in ischemic cardiomyopathy of diabetic mice by telmisartan is attributed to the attenuation of the peri-infarct injury by the angiogenic effects of EPCs to salvage the injured cardiomyocytes. Dual-contrast MEMRI-DEMRI technique tracked the therapeutic effects of telmisartan on the injured myocardium longitudinally.
一种采用双对比锰增强磁共振成像（MEMRI）和延迟增强磁共振成像（DEMRI）的新型磁共振成像技术，可评估生理上不稳定的梗死周边区域。双对比MEMRI-DEMRI能够全面评估替米沙坦对梗死周边损伤的挽救作用，以阐明在糖尿病小鼠模型中恢复缺血性心肌病的潜在机制。
对24只左前降支结扎的糖尿病小鼠在开始替米沙坦治疗后的第1、2和4周进行双对比MEMRI-DEMRI检查。对磁共振图像分析梗死核心、梗死周边、左心室舒张末期、收缩末期容积以及左心室射血分数（LVEF）。采用透射电子显微镜（TEM）和实时聚合酶链反应进行心肌的离体分析。替米沙坦组与对照组相比，在第1、2和4周时LVEF分别显著改善（分别为33±7%***对19±5%、29±3%***对22±4%、31±2%***对18±6%，***p<0.001）。对照组通过MEMRI和DEMRI测量的瘢痕容积有显著差异，表明存在梗死周边损伤。替米沙坦组显著挽救了梗死周边损伤。TEM验证了心肌效应，其证实梗死周边区域存在受损但存活的心肌细胞形态，静脉血的流式细胞术表明循环内皮祖细胞（EPC）显著增加。
替米沙坦改善糖尿病小鼠缺血性心肌病的心功能归因于EPC的血管生成作用减轻梗死周边损伤，从而挽救受损心肌细胞。双对比MEMRI-DEMRI技术纵向跟踪了替米沙坦对受损心肌的治疗效果。
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