Beneficial effects of MET-88, a γ-butyrobetaine hydroxylase inhibitor in rats with heart failure following myocardial infarction

• Published in: European journal of pharmacology 2000-05, Vol.395 (3), p.217-224
• Main Authors: Hayashi, Yukio, Kirimoto, Tsukasa, Asaka, Naomasa, Nakano, Motoko, Tajima, Kiyotaka, Miyake, Hidekazu, Matsuura, Naosuke
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Monophosphate - metabolism; Adenosine Triphosphate - metabolism; Animals; Biological and medical sciences; Body Weight - drug effects; Cardiac functional adaptability; Cardiotonic agents; Cardiovascular Agents - pharmacology; Cardiovascular system; gamma-Butyrobetaine Dioxygenase; Heart failure; Heart Failure - etiology; Heart Failure - mortality; Heart Failure - prevention & control; Heart Ventricles - drug effects; Heart Ventricles - pathology; Heart Ventricles - physiopathology; Hemodynamics - drug effects; High-energy phosphate; Lactic Acid - metabolism; Male; Medical sciences; Methylhydrazines - pharmacology; Mixed Function Oxygenases - antagonists & inhibitors; Myocardial Infarction - complications; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Survival Rate; Ventricular remodeling; γ-Butyrobetaine hydroxylase inhibitor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00098-4

Myocardial ischemia can cause myocardial infarction and as a consequence, heart failure. 3-(2,2,2-trimethylhydrazinium) propionate (MET-88) inhibits γ-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.