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

Abstract

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.

• Authors: Y Hayashi, T Kirimoto, N Asaka, M Nakano, K Tajima, H Miyake, N Matsuura
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 395 Issue 3 Pg. 217-24 (May 03 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10812052 (Publication Type: Journal Article)

Chemical References

• Cardiovascular Agents
• Methylhydrazines
• Lactic Acid
• Adenosine Monophosphate
• Adenosine Diphosphate
• 3-(2,2,2-trimethylhydrazine)propionate
• Adenosine Triphosphate
• Mixed Function Oxygenases
• gamma-Butyrobetaine Dioxygenase

Topics

• Adenosine Diphosphate (metabolism)
• Adenosine Monophosphate (metabolism)
• Adenosine Triphosphate (metabolism)
• Animals
• Body Weight (drug effects)
• Cardiovascular Agents (pharmacology)
• Heart Failure (etiology, mortality, prevention & control)
• Heart Ventricles (drug effects, pathology, physiopathology)
• Hemodynamics (drug effects)
• Lactic Acid (metabolism)
• Male
• Methylhydrazines (pharmacology)
• Mixed Function Oxygenases (antagonists & inhibitors)
• Myocardial Infarction (complications)
• Rats
• Rats, Sprague-Dawley
• Survival Rate
• gamma-Butyrobetaine Dioxygenase