A Novel Angiotensin Type I Receptor Antagonist,Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats |
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| Authors: | Sung-A Chang Byung-Kwan Lim You Jung Lee Mi-Kyung Hong Jin-Oh Choi Eun-Seok Jeon |
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| Affiliation: | 1.Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.;2.Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.;3.Department of Biomedical Science, Jungwon University, Goesan-gun, Korea. |
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| Abstract: | ![]()
Angiotensin receptor blockers (ARBs) have organ-protective effects in heart failure and may be also effective in doxorubicin-induced cardiomyopathy (DOX-CMP); however, the efficacy of ARBs on the prevention of DOX-CMP have not been investigated. We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP. All animals underwent echocardiography and were randomly assigned into three groups: treated daily with vehicle (DOX-only group, n=22), 5 mg/kg of fimasartan (Low-fima group, n=22), and 10 mg/kg of fimasartan (High-fima group, n=19). DOX was injected once a week for six weeks. Echocardiography and hemodynamic assessment was performed at the 8th week using a miniaturized conductance catheter. Survival rate of the High-fima group was greater (100%) than that of the Low-fima (75%) and DOX-only groups (50%). Echocardiography showed preserved left ventricular (LV) ejection fraction in the High-fima group, but not in the DOX-only group (P=0.002). LV dimensions increased in the DOX-only group; however, remodeling was attenuated in the Low-fima and High-fima groups. Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group. A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.Graphical Abstract | |
| Keywords: | Angiotensin Receptor Blocker Doxorubicin-induced Cardiomyopathy |
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