1. Telmisartan in the diabetic murine model of acute myocardial infarction: dual contrast manganese-enhanced and delayed enhancement MRI evaluation of the peri-infarct region
- Author
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Toma, Ildiko, Kim, Paul J, Dash, Rajesh, McConnell, Michael V, Nishimura, Dwight, Harnish, Phillip, and Yang, Phillip C
- Subjects
Heart Disease ,Biomedical Imaging ,Cardiovascular ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Angiotensin II Type 1 Receptor Blockers ,Animals ,Apoptosis ,Benzimidazoles ,Benzoates ,Contrast Media ,Diabetes Mellitus ,Type 2 ,Disease Models ,Animal ,Endothelial Progenitor Cells ,Fibrosis ,Flow Cytometry ,Gadolinium DTPA ,Magnetic Resonance Imaging ,Manganese ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Microscopy ,Electron ,Transmission ,Myocardial Infarction ,Myocardium ,Myocytes ,Cardiac ,Predictive Value of Tests ,Recovery of Function ,Stroke Volume ,Telmisartan ,Time Factors ,Tissue Survival ,Ventricular Function ,Left ,Manganese-enhanced MRI ,Delayed-enhanced MRI ,Peri-infarct injury ,Diabetes mellitus ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology - Abstract
BackgroundA 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.Methods and resultsDual 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).ConclusionThe 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.
- Published
- 2016