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Combination therapy has been shown to improve cardiovascular outcomes in hypertensive, diabetic patients. Amlodipine demonstrates beneficial pleiotropic effects including improved endothelial function and enhanced angiogenesis. Amlodipine with telmisartan may provide a synergistic benefit. We used dual contrast CMR, using manganese-enhanced MRI (MEMRI) and gadolinium (delayed-enhanced MRI; DEMRI), to evaluate the viable myocardium and myocardial scar, respectively, and investigate the underlying mechanism of combination therapy.
Db/db mice underwent permanent LAD ligation and were allocated to two groups: (1) tap water (n = 17) and (2) telmisartan (10 mg/kg/day) and amlodipine (10 mg/kg/day) in the tap water following 1 week of convalescence after AMI (n = 23). MEMRI and DEMRI were performed weekly to obtain LVEF and assess viable myocardium and scar. Pressure-volume loop analysis, flow cytometry of venous blood and real-time PCR of the explanted myocardium were performed at the end of the study.
We demonstrate significantly improved LVEF at weeks 1, 2, and 4 following combined telmisartan and amlodipine therapy (32.0% ± 4.8%*, 31.8% ± 3.9%*, and 35.3% ± 2.3%*) compared to control (18.9% ± 1.5%, 21.8% ± 1.3%, and 15.7% ± 3.4%, *p < .05). Pressure-volume loop analysis corroborated improved systolic and diastolic parameters. MEMRI demonstrates significantly increased viable myocardial volumes in the treated mice (87.2% ± 0.92%*, 90.2% ± 1.3%*, and 91.4% ± 1.1%*) compared to control (80.5% ± 7.6%, 79.9% ± 3.1%, and 79.9% ± 3.1%, *p<0.05). DEMRI scar volumes demonstrate a significantly decreased scar at 4 weeks post treatment. The measurement of endothelial progenitor cells shows a dramatic increase in the treated compared to control (98.1% ± 0.25%* vs. 5.0% ± 2.6%, *p<0.05). No differential expression of fibrotic genes is observed.
This study provides potential evidence of salvage of the injured myocardium by combined telmisartan and amlodipine therapy, which could underlie the mechanism of myocardial restoration after ischemic injury. Dual contrast CMR accurately identifies the dynamic effects on both the viable myocardium and myocardial scar.
Poster Sessions, Expo North
Saturday, March 09, 2013, 3:45 p.m.-4:30 p.m.
Session Title: Imaging: MRI Ill – CMR in Myocardial Disease and Dysfunction
Abstract Category: 19. Imaging: MRI
Presentation Number: 1184-372
- 2013 American College of Cardiology Foundation