Strain-specific differences in lung tissue viscoelasticity of mechanically ventilated infant Sprague-Dawley and...

Rats are often used in ventilator-induced lung injury (VILI) models. However, strain-specific susceptibility for VILI has not been elucidated yet. The aim of this study was to demonstrate strain-specific differences in VILI in infant Sprague-Dawley and Wistar rats. VILI was compared in 2-wk-old pups after 8 h of protective or injurious ventilation. Pups were ventilated with tidal volumes (V_T) of ∼7 mL/kg and positive end-expiratory pressures (PEEP) of 6 cmH₂O (V_T7 PEEP6) or with V_T of ∼21 mL/kg and PEEP 2 cmH₂O (V_T21 PEEP2). Interleukin-6, macrophage inflammatory protein-2 (MIP-2), inflammatory cells, and albumin in bronchoalveolar lavage fluid (BALF); histology; and low-frequency forced oscillation technique (LFOT) and pressure-volume (PV) maneuvers were assessed. Alveolar macrophages, neutrophils, and MIP-2 derived from BALF revealed more pronounced VILI after V_T21 PEEP2 in both strains. LFOT and PV analyses demonstrated rat strain-specific differences both at baseline and particularly in response to V_T21 PEEP2 ventilation. Sprague-Dawley rats showed higher airway and tissue resistance and elastance values with no difference in hysteresivity between ventilation strategies. Wister rats challenged by V_T21 PEEP2 experienced significantly more energy dissipation when compared with V_T7 PEEP6 ventilation. In conclusion, both rat strains are useful for VILI models. The degree of VILI severity depends on ventilation strategy and selected strain. However, fundamental and time-dependent differences in respiratory system mechanics exist and reflect different lung tissue viscoelasticity. Hence, strain-specific characteristics of the respiratory system need to be considered when planning and interpreting VILI studies with infant rats.