Department of Cardiology, The Eighth Hospital of Guangzhou City, Guangzhou, PR China; The Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Biomed Pharmacother. 2021 Jan;133:110824. doi: 10.1016/j.biopha.2020.110824. Epub 2020 Dec 8.
LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNi), is reported to play a cardioprotective role after acute myocardial infarction (AMI). Angiotensin-converting enzyme inhibitors(ACEIs) have similar roles. However, it is unclear whether the combination of the two drugs has a better protective effect. The purpose of this study was to investigate the effect of this combination therapy after AMI.
Male C57BL/6 J mice subjected to ligation of left anterior descending artery were treated for 4 weeks with LCZ696, ACEI(benazepril), or both(combination therapy) after induction of MI. Cardiac function, hemodynamics, and inflammatory factors were evaluated at 1 st day, 14th day, and 28th day. Heart weight and myocardial fibrosis were measured at the end of the experiment.
Blood pressure was lower in all treatment groups than in the control group. The combination therapy group had the strongest antihypertensive effect. Compared with LCZ696 or benazepril, treatment with combination therapy increased ejection fraction, fractional shortening, and cardiac output and decreased N-terminal pro-B-type natriuretic peptide(NT-proBNP). The ratios of heart weight to body weight in all treatment groups were less than that in the control group. Compared with the control and LCZ696 group, the fibrotic area in the combination therapy group was suppressed and had a lower level of TGF-β1 in the left ventricle. The plasma concentration of bradykinin and renin in the combination therapy group were highest among groups at 14th and 28th day.
LCZ696 in combination with benazepril showed better positive effects in modulating heart failure and myocardial fibrosis after acute AMI in mice and affect some inflammatory markers.
LCZ696，一种血管紧张素受体-脑啡肽酶抑制剂（ARNi），据报道在急性心肌梗死（AMI）后具有心脏保护作用。血管紧张素转换酶抑制剂（ACEI）也具有类似的作用。然而，尚不清楚这两种药物的联合使用是否具有更好的保护作用。本研究旨在探讨这种联合治疗在 AMI 后的效果。
雄性 C57BL/6 J 小鼠结扎左前降支诱导 AMI 后，用 LCZ696、ACEI（贝那普利）或两者联合（联合治疗）治疗 4 周。在第 1 天、第 14 天和第 28 天评估心功能、血流动力学和炎症因子。实验结束时测量心脏重量和心肌纤维化。
与对照组相比，所有治疗组的血压均较低。联合治疗组的降压效果最强。与 LCZ696 或贝那普利相比，联合治疗可增加射血分数、缩短分数和心输出量，降低 N 端脑啡肽前体（NT-proBNP）。所有治疗组的心脏重量与体重的比值均小于对照组。与对照组和 LCZ696 组相比，联合治疗组的纤维化面积得到抑制，左心室中 TGF-β1 的水平降低。在第 14 天和第 28 天，联合治疗组的血管紧张素Ⅱ和肾素的血浆浓度在各组中最高。
LCZ696 联合贝那普利在调节急性 AMI 后小鼠心力衰竭和心肌纤维化方面表现出更好的积极作用，并影响一些炎症标志物。
