Beneficial effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor in rats with heart failure following myocardial infarction.
Myocardial ischemia can cause myocardial infarction and as a consequence, heart failure. 3-(2,2,2-trimethylhydrazinium) propionate (MET-88) inhibits gamma-butyrobetaine hydroxylase and has cardioprotective effects on the ischemic heart. We now examined the effects of MET-88 in rats with congestive heart failure following myocardial infarction. Congestive heart failure was produced by left coronary artery ligation in rats. MET-88 at 100 mg/kg/day was orally administered from the 2nd day after surgery. We performed a survival study for 181 days, and measured ventricular remodeling, cardiac function, and myocardial high-energy phosphate levels after treatment for 20 days. MET-88 prolonged survival with a median 50% survival of 103 days compared to 79 days for the heart-failure control rats. The expansion of the left ventricular cavity (ventricular remodeling) in heart-failure rats was prevented by treatment with MET-88, and the effect of MET-88 was similar to that of captopril at 20 mg/kg. MET-88 attenuated the rise in right atrial pressure in heart-failure rats and augmented cardiac functional adaptability against an increased load. Also, MET-88 improved the myocardial energy state in heart-failure rats. The present results indicate that MET-88 improves the pathosis in rats with heart failure induced by myocardial infarction.
Hayashi
Y
Y
Pharmacology Research Laboratory, Taiho Pharmaceutical Co., Ltd., 224-2, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima, Japan. yucky@mail.netwave.or.jp
Kirimoto
T
T
Asaka
N
N
Nakano
M
M
Tajima
K
K
Miyake
H
H
Matsuura
N
N
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D006333:Heart Failure / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008763:Methylhydrazines / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D050563:gamma-Butyrobetaine Dioxygenase
D002317:Cardiovascular Agents; D008763:Methylhydrazines; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C050147:3-(2,2,2-trimethylhydrazine)propionate; D000255:Adenosine Triphosphate; D006899:Mixed Function Oxygenases; D050563:gamma-Butyrobetaine Dioxygenase