Assessing Aerobic Capacity in Rat and Mouse Models: A Critical Narrative Review

Aerobic capacity reflects pulmonary ventilation, oxygen transport, cardiovascular performance, skeletal-muscle perfusion, and mitochondrial oxygen utilization. In rodents, V̇O₂max, V̇O₂peak, running speed, time to exhaustion, critical speed, lactate-derived thresholds, and voluntary activity are often grouped as aerobic capacity despite representing distinct constructs. This review aims to critically examine the physiological foundations, experimental modalities, outcome measures, methodological determinants, and translational challenges of aerobic-capacity assessment in rats and mice. A structured search of PubMed, Web of Science Core Collection, and Scopus was conducted from database inception to August 6, 2026. Studies addressing aerobic and endurance capacity, oxygen uptake, exercise performance, treadmill running, voluntary wheel running, swimming, indirect calorimetry, and methodological issues were synthesized narratively. Directly measured V̇O₂max, or V̇O₂peak when maximal criteria are not fulfilled, provides the strongest index of aerobic capacity. Running speed, distance, and time to exhaustion are performance outcomes influenced by running economy, anaerobic capacity, neuromuscular function, motivation, and test tolerance. Lactate-derived thresholds and critical speed provide complementary information on sustainable exercise intensity. Treadmill running with indirect calorimetry offers control for maximal oxygen-uptake assessment, whereas voluntary wheel running reflects self-selected activity and swimming is useful for lactate-based models. Validity depends on biological, procedural, environmental, and technical factors. Reliable assessment requires alignment among physiological construct, exercise modality, outcome measure, and experimental population. Model-specific validation, objective maximality and exhaustion criteria, appropriate oxygen-uptake normalization, calibrated systems, refined motivational procedures, and transparent reporting are essential for reproducibility, animal welfare, and translational interpretation.