Martínez-Falguera Daina, Aranyó Júlia, Ferrer-Curriu Gemma, Teis Albert, Revuelta-Lopez Elena, Diaz-Güemes Idoia, Monguió-Tortajada Marta, Fadeuilhe Edgar, Rodríguez-Leor Oriol, Poblador Francesc, Montejo Borja, Roura Santiago, Villuendas Roger, Sarrias Axel, Bazan Victor, Jorge Esther, Delgado Victoria, Jimenez-Trinidad Francisco Rafael, Rigol Montserrat, Martinez-Micaelo Neus, Amigó Núria, Bayes-Genis Antoni, Bisbal Felipe, Gálvez-Montón Carolina
ICREC Research Program Germans Trias i Pujol Research Institute (IGTP) Barcelona Spain.
Faculty of Medicine University of Barcelona (UB) Spain.
J Am Heart Assoc. 2025 Jun 3;14(11):e040214. doi: 10.1161/JAHA.124.040214. Epub 2025 May 26.
Empagliflozin and sacubitril/valsartan are established in heart failure treatment, but their effects after myocardial infarction (MI) are less clear. This study evaluated early empagliflozin initiation, with or without sacubitril/valsartan, on post-MI inflammation, oxidative stress, metabolism, fibrosis, cardiac function, and ventricular tachycardia (VT) risk in a pig model.
A total of 24 of 30 pigs survived the MI procedure and were subsequently randomized to receive beta-blocker treatment alone (control-MI), beta-blocker+empagliflozin, or beta-blocker+empagliflozin+sacubitril/valsartan. Immune response, metabolic profile, and cardiac function were monitored. At 30 days after MI, programmed electrical stimulation and high-density mapping were performed and VT inducibility was assessed. Tissue samples were collected for cardiac inflammation, oxidative stress, and metabolic analyses.
Empagliflozin reduced circulating leukocytes at 2 and 15 days after MI (=0.010 and =0.050, respectively) and decreased C-C chemokine receptor 2+ monocytes at 15 days (=0.049). Nitric oxide bioavailability increased in remote myocardium (=0.059), along with cardioprotective liver lipids and collagen III in the myocardial scar (=0.023). No effect on cardiac function or VT inducibility was observed at 30 days. With empagliflozin+sacubitril/valsartan, scar collagen I decreased (=0.082), left ventricular compliance improved (=0.029), electrophysiological remodeling improved (reduced border-zone corridors [=0.006] and deceleration zones [=0.008]), and VT inducibility decreased (=0.025).
In this pig model of nonreperfused MI treated with beta-blocker, early initiation of empagliflozin reduced inflammation, improved nitric oxide bioavailability, increased protective liver lipids, and modified scar composition without affecting cardiac function or VT risk. With empagliflozin+sacubitril/valsartan treatment, scar collagen I and VT inducibility declined and left ventricular remodeling was enhanced.
恩格列净和沙库巴曲缬沙坦已被用于心力衰竭治疗，但其在心肌梗死（MI）后的作用尚不清楚。本研究评估了在猪模型中，早期开始使用恩格列净联合或不联合沙库巴曲缬沙坦对心肌梗死后炎症、氧化应激、代谢、纤维化、心脏功能和室性心动过速（VT）风险的影响。
30头猪中共有24头在心肌梗死手术后存活，随后随机分为单独接受β受体阻滞剂治疗（对照-MI组）、β受体阻滞剂+恩格列净组或β受体阻滞剂+恩格列净+沙库巴曲缬沙坦组。监测免疫反应、代谢谱和心脏功能。在心肌梗死后30天，进行程序性电刺激和高密度标测，并评估室性心动过速的诱发性。收集组织样本进行心脏炎症、氧化应激和代谢分析。
恩格列净在心肌梗死后第2天和第15天减少了循环白细胞（分别为P=0.010和P=0.050），并在第15天减少了C-C趋化因子受体2+单核细胞（P=0.049）。远隔心肌中的一氧化氮生物利用度增加（P=0.059），同时心肌瘢痕中的心脏保护性肝脂质和Ⅲ型胶原增加（P=0.023）。在30天时未观察到对心脏功能或室性心动过速诱发性的影响。使用恩格列净+沙库巴曲缬沙坦时，瘢痕Ⅰ型胶原减少（P=0.082），左心室顺应性改善（P=0.029），电生理重塑改善（边界区通道减少[P=0.006]和减速区减少[P=0.008]），室性心动过速诱发性降低（P=0.025）。
在这个用β受体阻滞剂治疗的非再灌注心肌梗死猪模型中，早期开始使用恩格列净可减轻炎症，改善一氧化氮生物利用度，增加保护性肝脂质，并改变瘢痕组成，而不影响心脏功能或室性心动过速风险。使用恩格列净+沙库巴曲缬沙坦治疗时，瘢痕Ⅰ型胶原和室性心动过速诱发性降低，左心室重塑得到增强。
