Belenichev Igor, Goncharov Olexiy, Bukhtiyarova Nina, Kuchkovskyi Oleh, Ryzhenko Victor, Makyeyeva Lyudmyla, Oksenych Valentyn, Kamyshnyi Oleksandr
Department of Pharmacology and Medical Formulation with Course of Normal Physiology, Zaporizhzhia State Medical and Pharmaceutical University, 69035 Zaporizhzhia, Ukraine.
Department of Clinical Laboratory Diagnostics, Zaporizhzhia State Medical and Pharmaceutical University, 69035 Zaporizhzhia, Ukraine.
Biomedicines. 2024 Aug 28;12(9):1957. doi: 10.3390/biomedicines12091957.
Beta-blockers are first-line drugs in the treatment of chronic heart failure (CHF). However, there is no consensus on the specific effects of the beta-blockers of the I-III generation on energy metabolism in CHF. The aim of this study is to conduct a study of beta-blockers of different generations on myocardial energy metabolism in experimental CHF. CHF was modeled in white outbred rats by administering doxorubicin. The study drugs were administered intragastrically-new drug Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide)-3.5 mg/kg, Metoprolol-15 mg/kg, Nebivolol -10 mg/kg, Carvedilol 50 mg/kg, and Bisoprolol, 10 mg/kg. In the myocardium, the main indices of energy metabolism were determined-ATP, ADP, AMP, malate, lactate, pyruvate, succinate dehydrogenase (SDH) activity, and NAD-dependent malate dehydrogenase (NAD-MDH) activity. Traditional second-generation beta-blockers (Metoprolol and Bisoprolol) did not affect the studied indices of energy metabolism, and third-generation beta-blockers with additional properties-Carvedilol and, especially, Nebivalol and Hypertril-improved myocardial energy metabolism. The obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF.
β受体阻滞剂是治疗慢性心力衰竭(CHF)的一线药物。然而,关于第一代至第三代β受体阻滞剂对CHF能量代谢的具体影响尚无共识。本研究的目的是对不同代的β受体阻滞剂在实验性CHF中的心肌能量代谢进行研究。通过给予阿霉素在白色远交系大鼠中建立CHF模型。研究药物通过胃内给药——新药Hypertril(1-(β-苯乙基)-4-氨基-1,2,4-三唑溴化物)——3.5毫克/千克、美托洛尔——15毫克/千克、奈必洛尔——10毫克/千克、卡维地洛50毫克/千克和比索洛尔10毫克/千克。在心肌中,测定能量代谢的主要指标——三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)、苹果酸、乳酸、丙酮酸、琥珀酸脱氢酶(SDH)活性和烟酰胺腺嘌呤二核苷酸依赖性苹果酸脱氢酶(NAD-MDH)活性。传统的第二代β受体阻滞剂(美托洛尔和比索洛尔)不影响所研究的能量代谢指标,而具有额外特性的第三代β受体阻滞剂——卡维地洛,尤其是奈必洛尔和Hypertril——改善了心肌能量代谢。所得结果将有助于扩展我们对用于治疗心血管疾病的不同代β受体阻滞剂对能量代谢影响的理解,也是这些药物在CHF综合治疗中实际选择的实验依据。