Cardioprotection of Ischemic Myocardium

Abstract

Aim. Cardioprotective effect of precursors in the synthesis of the uridine-5ʼ-diphosphate (UDP) - the mitochondrial ATP-dependent potassium channels (mitoKATP channels) endogenous activator - uridine and uridine-5ʼ-monophosphate (UMP) and the relation between there mechanism of action and activity of mitoKATP channels were studied. Methods. The experiments were performed on the male Wistar rats weighing 300-350 g. Acute myocardial ischemia (MI) lasting 60 min was produced by occlusion of the descending branch of the left coronary artery (LCA) under artificial pulmonary ventilation. Animals were anesthetized with sodium ethaminal (50 mg/kg). Uridine or UMP in the dose of 30 mg/kg was injected intravenously 5 min prior to LCA occlusion. A selective blocker of these channels 5-hydroxydecanoate (5-HD, 5 mg/kg intravenously 5 min prior to injection of uridine or UMP) was used to detect the involvement of mitoKATP channels in the effects of drugs. ATP and creatine phosphate (CP) was determined in the heart homogenates. The intensity of lipid peroxidation (LPO) was estimated by the content of lipid hydroperoxides (LHP) and the state of the antioxidant system (AOS) by superoxidedismutase (SOD) activity and the reduced glutathione (GH) content. Results. Occlusion of the LCA during 60 min led to the decrease of ATP and CP content in the myocardium by 35% and 59% respectively. At the same time changes in LPO and AOS were observed. The amount of LHP increased by 97%, the activity of SOD was reduced by 28% and the content of GH decreased by 30%. Uridine and UMP given 5 minutes prior to LCA occlusion prevented the development of these metabolic disorders in the ischemic myocardium. Selective blocker of mitoKATP channels 5-HD eliminated the protective effect of both drugs. Conclusion. Uridin and UMP have the evident cardioprotective effect in the acute MI, stabilizing the miocardium energy metabolism, preventing the AOS function depression and excessive activation of LPO. The mechanism of protective action of the drugs is associated with the activation of mitoKATP channels. (For citation: Bulion VV, Krylova IB, Selina EN. Cardioprotection of ischemic myocardium. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):13-17. doi: 10.17816/RCF16213-17).