Tidal volume drives inflammation during mechanical ventilation for viral respiratory infection

Objective: Respiratory syncytial virus lower respiratory tract infection is the most frequent cause of respiratory insufficiency necessitating mechanical ventilation in infants during the winter season. Recently, we presented a new animal model to show that mechanical ventilation aggravates respiratory syncytial virus-induced pulmonary inflammation by distinct mechanisms. We now use this model to study whether low tidal volume mechanical ventilation causes less ventilator-induced lung injury in the presence of respiratory syncytial virus lower respiratory tract infection. Design: Randomized controlled experimental study. Setting: University Medical Center animal laboratory. Subjects: Male BALB/c mice, 6-8 weeks old and weighing 20-28 g. Interventions: Mice were inoculated with respiratory syncytial virus or mock virus on day 0 and ventilated on day 1 or 5 with high (12mL/kg) or low (6mL/kg) tidal volume for 5 hours. Measurements and Main Results: Total and differential cell counts as well as cytokine concentrations were determined in bronchoal-veolar lavage fluid. Compared with nonventilated respiratory syncytial virus-infected mice, high tidal volume ventilation of respiratory syncytial virus-infected mice on day 5 enhanced bronchoalveolar lavage fluid total cell count (0.35 vs 0.99× 10e6/mL; p < 0.01), neutrophils (0.02 vs 0.17 × 10e6/mL; p< 0.01), interleukin-6 (58 vs 250 pg/mL; p<0.01), and keratinocyte-derived chemokine (95 vs 335 pg/mL; p < 0.01) levels. In low tidal volume ventilation of respiratory syncytial virus-infected mice, no significant difference in cell counts or cytokine concentrations was observed compared with spontaneous breathing respiratory syncytial virus-infected controls on both days. Conclusions: Low tidal volume mechanical ventilation causes less ventilation-induced cellular and cytokine influx into the bronchoal-veolar space during respiratory syncytial virus lower respiratory tract infection.