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Published on: July 7, 2016
Cardiotonic agent SCH00013 prolongs survival of cardiomyopathic hamsters
Tadahito Narita1, Ryogo Yui, Yuji Koide
1Zenyaku Kogyo Co., Ltd., Tokyo, Japan. tadahito_narita@mail.zenyaku.co.jp
Insights
Long-term treatment with SCH00013, a novel cardiotonic agent, significantly improved survival rates in hereditary cardiomyopathic hamsters. This suggests SCH00013 may be a promising therapeutic candidate for chronic heart failure.
Area of Science:
- Cardiology
- Pharmacology
- Animal Models
Background:
- Hereditary cardiomyopathy in BIO 14.6 hamsters serves as a model for human heart failure.
- Novel cardiotonic agents with calcium-sensitizing properties are being investigated for therapeutic potential.
Purpose of the Study:
- To evaluate the long-term effects of SCH00013 on the survival of BIO 14.6 hamsters with hereditary cardiomyopathy.
- To determine if SCH00013 administration impacts the progression of cardiac fibrosis and calcification.
Main Methods:
- Sixty-nine male BIO 14.6 hamsters were divided into untreated, low-dose SCH00013, and high-dose SCH00013 groups.
- Survival curves were analyzed, and histomorphometric examinations were performed to assess cardiac pathology.
- Plasma concentrations of SCH00013 were measured in the high-dose group.
Main Results:
- The high-dose SCH00013 group exhibited significantly prolonged survival compared to the untreated group (P < 0.005).
- First deaths occurred later in both SCH00013-treated groups compared to controls.
- No significant differences in ventricular calcification or fibrosis were observed between treated and untreated hamsters.
Conclusions:
- SCH00013 demonstrates a beneficial effect on survival in a genetic model of cardiomyopathy.
- Despite not altering cardiac pathology, SCH00013's survival benefit suggests potential for chronic heart failure treatment.
Abstract:
The authors examined the effects of long-term treatment with SCH00013, a novel cardiotonic agent with calcium-sensitizing action, on survival of hereditary cardiomyopathic BIO 14.6 hamsters. Sixty-nine male hamsters at 223 days of age were divided into untreated, SCH00013-low (approximately 1 mg/kg/d), and SCH00013-high (approximately 10 mg/kg/d) groups. Survival curves were constructed in the three groups. The first deaths in the untreated, SCH00013-low, and SCH00013-high groups were found at 263, 290, and 314 days of age, respectively. A 50% mortality rate was observed at 392 days in the untreated group, 396 days in the SCH00013-low group, and 445 days in SCH00013-high group. The survival time distribution of the SCH00013-high group was significantly different from that of the untreated group (P < 0.005). However, histomorphometric examinations revealed that the degree of progression of calcification and fibrosis in the ventricular wall of the BIO 14.6 hamsters was not different between the untreated and SCH00013-treated groups. Plasma concentration of this agent was 2 microM at the end of the second week of continuous administration via drinking water in SCH00013-high group. Thus, SCH00013 was beneficial for the survival of cardiomyopathic hamsters, suggesting that this agent is a possible candidate for the treatment of chronic heart failure.
