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

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 similar to 7 mL/kg and positive end-expiratory pressures (PEEP) of 6 cmH(2)O (V(T)7 PEEP6) or with V-T of similar to 21mL/kg and PEEP 2 cmH(2)O (V(T)21 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(T)21 PEEP2 in both strains. LFOT and PV analyses demonstrated rat strain-specific differences both at baseline and particularly in response to V(T)21 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(T)21 PEEP2 experienced significantly more energy dissipation when compared with V(T)7 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.

Automated summary

This study demonstrated strain-specific differences in ventilator-induced lung injury (VILI) in infant Sprague-Dawley and Wistar rats. The severity of VILI depends on ventilation strategy and selected strain, with fundamental and time-dependent differences in respiratory system mechanics. Hence, strain-specific characteristics of the respiratory system should be considered in VILI studies with infant rats.