Abstract
Figures and Tables
Fig. 1
Study design. After baseline echocardiography (EchoCG), animals were randomly assigned into two groups: negative control (NC) and DOX (DOX-only; 3 mg/kg of DOX intravenously once a week for six weeks) groups. The DOX-only group was divided into three groups as follows: non-treated (DOX-only), low-dose fimasartan (Low-fima), and high-dose fimasartan (High-fima). Echocardiography and NIBP was performed in all the study animals at weeks six and eight from baseline, and hemodynamic evaluation was performed at week nine from baseline.
![jkms-30-559-g001](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-g001.jpg)
Fig. 2
Changes in blood pressure, body weight, and echocardiographic findings. (A) Mean blood pressure was significantly decreased in the fimasartan-treated group (High-fima and Low-fima) compared with the normal control group at week eight from baseline. (B) Body weight increased in all animals until week three from baseline, and then decreased in all animals administered with DOX. At eight weeks, the DOX-only group showed the lowest body weight. (C) LVEF also decreased in the DOX-only group at eight weeks. In contrast, body weight and LVEF were preserved in High-fima and Low-fima groups. (D) LV end-systolic dimension (ESD) progressively increased in the DOX-only group; however, LV dilatation was attenuated in Low-fima and High-fima groups (*P < 0.05 compared to NC group, †P < 0.05 compared to DOX-only group).
![jkms-30-559-g002](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-g002.jpg)
Fig. 3
Survival curves and general features of study animals. Eight-week survival rate of the High-fima group is greater (100%) than that of Low-fima (75%) and DOX-only groups (50%, P < 0.05).
![jkms-30-559-g003](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-g003.jpg)
Fig. 4
General feature of treated animals. (A) Rats in Dox-only group show severe shedding and ascites. (B) In contrast, rats in the High-fima group show no shedding or ascites.
![jkms-30-559-g004](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-g004.jpg)
Fig. 5
Left ventricular pressure-volume loop by microminiaturized press-volume catheterization. End-systolic pressure volume relation (ESPVR) slopes was significantly decreased in DOX-only and Low-fima groups, whereas slope values was similar to normal control in the High-fima group.
![jkms-30-559-g005](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-g005.jpg)
Fig. 6
ERK and AKT activity in week nine heart lysates by Western blot analysis. Decreased ERK phosphorylation is reversed by high-dose fimasartan treatment (A, C). However, AKT phosphorylation is not affected, suggesting that fimasartan may activate cell survival signaling under DOX-induced cardiotoxicity (B, D). *P < 0.05. NS, not significant.
![jkms-30-559-g006](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-g006.jpg)
Table 1
Baseline characteristics of study animals
![jkms-30-559-i001](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-i001.jpg)
Table 2
Echocardiographic data after 6 and 8 weeks of treatment
![jkms-30-559-i002](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-i002.jpg)
Table 3
General conditions of study animals
![jkms-30-559-i003](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-i003.jpg)
Table 4
Hemodynamic result at 9 weeks
![jkms-30-559-i004](/upload/SynapseData/ArticleImage/0063jkms/jkms-30-559-i004.jpg)
*P value<0.05 by ANOVA among doxorubicin injected group; †P value<0.05 by post poc analysis compared to Dox-only group; ‡P value<0.05 by post poc analysis compared to low-fima group. LV, left ventricular; ESV, end systolic volume; EDV, end-diastolic volume; τ, tau; Ees, end-systolic pressure-volume relation; Emax, maximum elastance; EDPVR, end-diastolic pressure volume relation; PRSW, preload recruitable stroke work.
Notes
This study was supported by an investigator initiative research grant from Boryung Pharmaceutical, Inc., and by grants (Jeon ES, Lee YS) from the Korea Samsung Biomedical Research Institute (SBRI GL1-B2-271-1) (Jeon ES, Lim BK).
DISCLOSURE The authors have no potential conflicts of interest to declare in relation to this article.
AUTHOR CONTRIBUTION Conceived and designed the study: Chang SA, Lim BK, Jeon ES. Data collection: Chang SA, Lee YJ, Hong MK, Lim BK. Analyzed the data: Chang SA, Lim BK, Choi JO. Statistical analysis: Chang SAS, Lim BK. Manuscript preparation: Chang SA, Lim BK, Choi JO, Jeon ES. Manuscript approval: all authors.