The use of pharmacological agents to trigger preconditioning mechanisms may improve the prevention and treatment of coronary heart disease. The aim of this study was to evaluate the ability of a structural analog of apelin-12 ((NαMe)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH, metilin) to reproduce the effect of ischemic preconditioning (IP) of rat hearts in vivo. Control rats were exposed to 40-min occlusion of the left descending coronary artery (LDCA) followed by 60-min restoration of coronary blood flow (reperfusion). IP was modeled by three cycles of 5-min occlusion/5-min reperfusion of the LDCA before prolonged regional myocardial ischemia and reperfusion. Metilin (5 mg/kg) was administered to rats intravenously by bolus injection 30 min before LDCA occlusion. IP or metilin had a significant impact on the studied parameters. The size of necrotic damage to the left ventricle, expressed as the percentage ratio of myocardial infarction/myocardial area at risk (MI/AAR, %), at the end of reperfusion was 26.9±2.0% and 29.3±2.6%, respectively, compared with 43.8±1.2% in the control (p < 0.01). The activity of creatine kinase-MB (CK-MB) in blood plasma decreased to 1026.1±93.9 IU/ml and 1195.2±142.0 IU/ml, respectively, compared with 1986.3±193.7 IU/ml in the control (p < 0.02). Administration of metilin, as well as IP, increased the reduced content of ATP, total adenine nucleotide pool (ΣAN) and phosphocreatine (PCr) in the AAR at the end of reperfusion compared to the control (p < 0.05–0.01). In the metilin group, the content of total creatine (ΣCr) in AAR was higher than in the control (p < 0.05). Intravenous administration of 5 mg/kg 5-hydroxydecanoate (5HD), an inhibitor of mitochondrial ATP-dependent K+ channels (mitoKATP), abolished the preconditioning effect of metilin, and increased the MI/AAR, %, and plasma CK-MB activity to values that insignificantly differed from the control (39.4±2.8% and 2258.2±179.1 IU/ml, respectively). Simultaneously, 5HD significantly reduced the ATP and ΣAN levels in AAR compared to those in the metilin group and the ATP, ΣAN, and PCr levels compared to the IP group. The results indicate that pharmacological preconditioning by metilin reduced cardiac ischemia/reperfusion injury via the involvement of mitoKATP in the mechanism of metilin action.
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Keywords: metilin, rat heart, preconditioning, myocardial infarction, creatine kinase-MB, energy state of the myocardial area at risk
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Veselova O.M., Serebryakova L.I., Studneva I.M., Azmuko A.A., Avdeev A.V., Sidorova M.V., Pisarenko O.I. (2025) The preconditioning effect of a structural analogue of apelin-12 in a rat model of acute myocardial infarction. Biomeditsinskaya Khimiya, 71(5), 342-350.
Veselova O.M. et al. The preconditioning effect of a structural analogue of apelin-12 in a rat model of acute myocardial infarction // Biomeditsinskaya Khimiya. - 2025. - V. 71. -N 5. - P. 342-350.
Veselova O.M. et al., "The preconditioning effect of a structural analogue of apelin-12 in a rat model of acute myocardial infarction." Biomeditsinskaya Khimiya 71.5 (2025): 342-350.
Veselova, O. M., Serebryakova, L. I., Studneva, I. M., Azmuko, A. A., Avdeev, A. V., Sidorova, M. V., Pisarenko, O. I. (2025). The preconditioning effect of a structural analogue of apelin-12 in a rat model of acute myocardial infarction. Biomeditsinskaya Khimiya, 71(5), 342-350.
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