Flethøj Mette, Debes Karina Poulsdóttir, Larsen Cecilie, de Blanck Caroline, Ludvigsen Trine Pagh, Kirchhoff Jeppe, Møller Jacob Eifer, Larsen Steen, Gøtze Jens P, Jespersen Thomas, Olsen Lisbeth Høier
Research and Early Development, Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Lab Anim (NY). 2025 Apr;54(4):103-111. doi: 10.1038/s41684-025-01533-4. Epub 2025 Mar 27.
Obesity is a risk factor for the development of coronary artery disease and myocardial infarction (MI). However, most large animal studies of MI are performed in lean animals. Here we assessed the impact of obesity on echocardiographic findings, infarct size, circulating biomarkers, mitochondrial respiratory capacity and mortality in a closed-chest minipig model of MI. The initial study population consisted of 20 obese (median 60.0 kg [interquartile range 55.9-64.6 kg]) and 18 lean (25.0 kg [23.4-36.5 kg]) female Göttingen minipigs. The duration of obesity induction using a western-style diet was up to approximately 6 months (156 days [24-162 days]) before the induction of MI. The induction of MI by 120-min balloon occlusion of the left anterior descending coronary artery was feasible in 17 lean and 17 obese animals. Mortality was higher in obese compared with lean animals (53% versus 12%), driven primarily by refractory ventricular fibrillation during occlusion. Electrocardiographic findings showed longer QRS and QT intervals and more extensive ST-segment elevation in obese animals compared with lean animals during occlusion. Plasma concentrations of pro-atrial natriuretic peptide, pro-C-type natriuretic peptide and cardiac troponin T were significantly lower in obese compared with lean animals. Infarct size estimated 8 weeks after MI was significantly smaller in obese (10% [9-11%]) compared with lean animals (13% [13-15%]). Finally, mitochondrial-complex-I-linked respiratory capacity was overall significantly higher in obese animals; however, no group difference was found in intrinsic mitochondrial respiratory capacity.
肥胖是冠状动脉疾病和心肌梗死（MI）发生发展的一个危险因素。然而，大多数关于MI的大型动物研究是在瘦动物身上进行的。在此，我们评估了肥胖对MI闭胸小型猪模型的超声心动图表现、梗死面积、循环生物标志物、线粒体呼吸能力和死亡率的影响。初始研究群体包括20只肥胖（中位数60.0千克[四分位间距55.9 - 64.6千克]）和18只瘦（25.0千克[23.4 - 36.5千克]）的雌性哥廷根小型猪。采用西式饮食诱导肥胖的时间长达MI诱导前约6个月（156天[24 - 162天]）。通过对左前降支冠状动脉进行120分钟球囊闭塞诱导MI，在17只瘦动物和17只肥胖动物中是可行的。肥胖动物的死亡率高于瘦动物（53%对12%），主要原因是闭塞期间难治性室颤。心电图表现显示，与瘦动物相比，肥胖动物在闭塞期间QRS和QT间期更长，ST段抬高更广泛。与瘦动物相比，肥胖动物血浆中的心钠素原、C型利钠肽原和心肌肌钙蛋白T浓度显著更低。MI后8周估计的梗死面积，肥胖动物（10%[9 - 11%]）显著小于瘦动物（13%[13 - 15%]）。最后，肥胖动物中线粒体复合物I相关的呼吸能力总体上显著更高；然而，在内在线粒体呼吸能力方面未发现组间差异。
