Cardiotonic agent SCH00013 prolongs survival of cardiomyopathic hamsters.
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.
Narita
Tadahito
T
Zenyaku Kogyo Co., Ltd., Tokyo, Japan. tadahito_narita@mail.zenyaku.co.jp
Yui
Ryogo
R
Koide
Yuji
Y
Sakato
Mitsuo
M
Kawashima
Seiichiro
S
D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002316:Cardiotonic Agents / Q000097:blood / Q000627:therapeutic use*; D006224:Cricetinae; D004095:Dihydropyridines / Q000097:blood / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D011724:Pyridazines / Q000097:blood / Q000627:therapeutic use*; D015996:Survival Rate
D002316:Cardiotonic Agents; D004095:Dihydropyridines; D011724:Pyridazines; C115124:Sch 00013