Антиишемические и цитопротективные эффекты триметазидина (экспериментальное исследование)

Anti-ischemic and cytoprotective effects of trimetazidme (experimental research)

Trimetazidine is an anti-ischemic drug whose cytoprotective mechanisms are not yet fully understood (but until now mainly related to the trimetazidine-induced "metabolic shift" from lipid beta-oxidation to glucose aerobic oxidation). Trimetazidine is a drug with cardioprotective properties. Its effect has been attributed to the inhibition of the long chain fatty acids intramitochondrial transport via carnitine-palmitoyl-transferase-1. Antianginal drugs that exert their anti-ischaemic effects primarily by altering myocardial metabolism have recently attracted attention. These drugs increase glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Whilst they have been demonstrated to reduce ischaemia in several clinical trials, their use remains limited. Clinical evidence supports the possibility that trimetazidine is able to improve the fasting glycemia in diabetic patients. For this reason, the objective of the present study was to determine the effect of trimetazidine on serum glucose of rabbits with fasting hyperglycemia. All animals received water and food "ad libitum. " Blood glucose was measured weekly to confirm fasting hyperglycemia in rabbits. The rabbits were treated for 1 month with trimetazidine (1 mg/kg), and blood samples were collected (in the fasting period) on the last day of treatment (the 30th day); and then on the 15th day posttreatment, measurements of plasma glucose were taken. Fasting plasma levels after 30 days of trimetazidine administration decreased significantly from 144.2 ± 3.4 mg/dL (pre-drug) to 121.9 ± 5.7 mg/dL (P < 0.01). 15 days after the end of treatment, fasting plasma glucose levels (137.1 ± 7.1 mg/dL) were close to the pretreatment levels but significantly different (P<0. 05) from levels on day 30 of treatment. These data suggest that trimetazidine improved blood glucose utilization in rabbits with fasting hyperglycemia. The potential of these metabolic agents may extend beyond the treatment of ischaemia secondary to coronary artery disease. They offer significant promise for the treatment of symptoms occurring due to metabolic syndrome, hypertonic heart, hypertrophic cardiomyopathy, and chronic heart failure. Trimetazidine, which is widely used clinically, acts by inhibiting long chain 3-ketoacyl CoA thiolase (3-KAT), a key fatty acid beta-oxidation enzyme. 11 is the first of a promising new class of metabolic agents that act by optimising energy metabolism in the heart.