Impact of obesity on infarct size, circulating biomarkers, mitochondrial function and mortality in a Göttingen minipig myocardial infarct model.

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.