Abstract 9472: Pretreatment with Novel Angiotensin type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-Induced Cardiac Toxicity and Improves Survival
Background: Cardiac toxicity are important complications of Doxorubicin-based chemotherapy. Protective effect of angiotensin receptor blockers (ARBs) in heart failure been established; however efficacy of ARB on prevention of doxorubicin induced cardiomyopathy and the survivals were not been investigated. We performed a preclinical study to evaluate the preventive effect of a novel ARB, fimasartan, in doxorubicin-induced cardiomyopathy.
Method: All animals (n=63) were randomly assigned into 3 groups; daily treated with vehicle (Dox-only), 5mg/Kg (Low-fima), and 10mg/Kg of fimasartan (High-fima). Doxorubicin (3mg/kg) was injected intravenously once a week for 6 weeks. Fimasartan were administered daily for 8 weeks via gastric gavage. Echocardiography was performed in baseline, 6th and 8th week. Hemodynamic assessment was performed at 9th week using the miniaturized conductance catheter system.
Result: 8-wk survival rate in High-Fima was higher (100%), than those in Low-fima (75%), and in Dox-only group (50%, p<0.05). Echocardiography showed preserved LV systolic function in in High-Fima after 8weeks of treatment (LV EF=72±7%), but not in Dox-only group (54.6±8.4%, p=0.002). LV end-systolic and end-diastolic dimension increased progressively in Dox-only group; however remodeling was attenuated in Low-fima and High-fima group. Hemodynamic study showed higher positive (5931±1354 mmHg/sec) and negative dP/dt (-5410.3±1338.2) in High-fima group, than Dox-only group. (3425±947, -3123±1127 mmHg/sec, p<0.001). Animals in Dox-only group looked very sick and showed severe anorexia, rat shedding, eye discharge and ascites compared to Low- and High-fima group.
Conclusion: A novel ARB, fimasartan, prevents doxorubicin-induced cardiomyopathy and improves survivals in dose-dependent manner in doxorubin-induced cardiomyopathy. It shows possibility of fimasartan as a treatment option to prevent doxorubicin-induced cardiomyopathy.
- © 2012 by American Heart Association, Inc.