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.
A computational model to support the welfare-based management of a laboratory colony of common marmosets
Here, a computational model to forecast the population dynamics of a laboratory colony of common marmosets (Callithrix jacchus) is presented. This tool supports decision-making that seeks to maximize welfare and maintain a healthy and genetically diverse colony. The model considers the population in terms of three compartments: breeding adults, their offspring and nonbreeding adults. Natural events are explicitly represented, including births, deaths and the transfer of mature offspring from family housing to adult housing. These events are simulated using rates based on historical data extracted from the colony record-keeping system. Multi-year forecasts of population dynamics are generated, taking full account of interventions such as the implementation of breeding controls, the usage of animals by a portfolio of research projects and relocation to external primate facilities. Model forecasts are validated against real data. Uncertainties in animal usage are propagated through the model. The resulting forecasts provide a realistic range of future stock levels to support colony management and decision-making. The model outputs provide evidence to help assess the impacts of making interventions in the system, for example, breeding control strategies. This evidence-based approach to colony management serves to enhance animal welfare and accountability to regulatory bodies and stakeholders. The model can be adapted to simulate the dynamics of other nonhuman primate colonies.
Differential effects of anesthetics and sex on supraventricular electrophysiology and atrial fibrillation substrate in rats
Rodents are increasingly used in atrial electrophysiology research, yet such studies are often performed under anesthesia owing to technical challenges. Here we developed an implantable device for comprehensive atrial studies in ambulatory rats and investigated the effects of commonly used anesthetics on supraventricular electrophysiology and arrhythmic substrate, comparing them with the unanesthetized state (UAS). Adult rats were evaluated 4 weeks after implantation. Studies were conducted in the UAS under 2% isoflurane (ISO) and under 40 mg/kg pentobarbital (PEN). Pacing protocols determined various parameters, including sinoatrial node recovery time, atrioventricular node effective refractory period and atrial effective refractory period. Arrhythmic substrate was assessed after 20 triggering bursts per condition, and arrhythmic tendency was analyzed manually and through the complexity ratio, an unbiased measure recently developed by our group. PEN mildly increased heart rate in both sexes, while ISO did not affect heart rate but prolonged the corrected sinus node recovery time in males. PEN increased atrioventricular node effective refractory period in both sexes, while ISO affected males only. Both ISO and PEN prolonged atrial effective refractory period compared with UAS in both sexes. Arrhythmic measures were higher in males and were attenuated by ISO and, to a lesser extent, by PEN in males only. The dominant frequency of arrhythmic events was reduced by both anesthetics in both sexes. These findings demonstrate a significant impact of commonly used anesthetics on rat supraventricular electrophysiology, with sex-based differences, highlighting the importance of methodologies that enable cardiac electrophysiology studies in unanesthetized rodents.
Parent-of-origin of alleles: an essential variable in in vivo experiments