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A Novel Angiotensin Type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats.

Chang SA, Lim BK, Lee YJ, Hong MK, Choi JO, Jeon ES - J. Korean Med. Sci. (2015)

Bottom Line: We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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Figure 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.

Mentions: Hemodynamic data acquired using a micro-conductance catheter are summarized in Table 4 and Fig. 5. The absolute values of positive and negative dP/dt were highest in the High-fima group (5,931±1,354 mmHg/sec and -5,410±1,338 mmHg/sec) compared with the Low-fima (4,241±888 mmHg/sec and -3,502±1,088 mmHg/sec) and DOX-only groups (3,425±947 mmHg/sec and -3,121±1,127 mmHg/sec, P<0.001 by ANOVA, respectively). However, other parameters such as Ea, Ees, Emax, and PRSW did not show statistically significant differences between the groups. dP/dt-EDV was significantly higher in the High-fima group, with similar values to normal controls. The end-systolic pressure volume relation (ESPVR) slopes were significantly decreased in the DOX-only and Low-fima groups, whereas slope values were similar to normal control in the High-fima group (Fig. 5).


A Novel Angiotensin Type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats.

Chang SA, Lim BK, Lee YJ, Hong MK, Choi JO, Jeon ES - J. Korean Med. Sci. (2015)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414639&req=5

Figure 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.
Mentions: Hemodynamic data acquired using a micro-conductance catheter are summarized in Table 4 and Fig. 5. The absolute values of positive and negative dP/dt were highest in the High-fima group (5,931±1,354 mmHg/sec and -5,410±1,338 mmHg/sec) compared with the Low-fima (4,241±888 mmHg/sec and -3,502±1,088 mmHg/sec) and DOX-only groups (3,425±947 mmHg/sec and -3,121±1,127 mmHg/sec, P<0.001 by ANOVA, respectively). However, other parameters such as Ea, Ees, Emax, and PRSW did not show statistically significant differences between the groups. dP/dt-EDV was significantly higher in the High-fima group, with similar values to normal controls. The end-systolic pressure volume relation (ESPVR) slopes were significantly decreased in the DOX-only and Low-fima groups, whereas slope values were similar to normal control in the High-fima group (Fig. 5).

Bottom Line: We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus