A Novel Angiotensin Type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats.
10.3346/jkms.2015.30.5.559
- Author:
Sung A CHANG
1
;
Byung Kwan LIM
;
You Jung LEE
;
Mi Kyung HONG
;
Jin Oh CHOI
;
Eun Seok JEON
Author Information
1. Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. eunseok.jeon@samsung.com
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Angiotensin Receptor Blocker;
Doxorubicin-induced Cardiomyopathy
- MeSH:
Angiotensin Receptor Antagonists/*therapeutic use;
Animals;
Biphenyl Compounds/*therapeutic use;
Cardiomyopathies/chemically induced/mortality/*prevention & control;
Doxorubicin/*toxicity;
Echocardiography;
Hemodynamics;
Pyrimidines/*therapeutic use;
Rats;
Rats, Sprague-Dawley;
Receptor, Angiotensin, Type 1/chemistry/*metabolism;
Survival Rate;
Tetrazoles/*therapeutic use;
Ventricular Function, Left/physiology
- From:Journal of Korean Medical Science
2015;30(5):559-568
- CountryRepublic of Korea
- Language:English
-
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.
