Effect of ventilatory rate on airway cytokine levels and lung injury

BACKGROUND: Controversy exists regarding the effect of large-volume mechanical ventilation (MV), as a sole stimulus, on the pulmonary cytokine milieu. We used a well described experimental model of ventilator-induced lung injury (VILI) to examine the impact of large volume ventilation on pulmonary cytokines in vivo and to study the effect of respiratory rate (RR) variation on these levels. MATERIALS AND METHODS: Sixty rats (410 +/- 47 g) were randomized to: 1) non ventilated control; 2) V(t) = 40 ml/kg, RR = 40 bpm; 3) V(t) = 40 ml/kg, RR = 20 bpm; 4) V(t) = 7 ml/kg, RR = 40 bpm; or 5) V(t) = 7 ml/kg, RR = 20 bpm. After 1 h of MV, bronchoalveolar lavage (BAL) and serum were collected. BAL was analyzed for urea, protein, lactate dehydrogenase (LDH), tumor necrosis factor (TNF)alpha and interleukin (IL)-6. Epithelial lining fluid volume (ELF) was calculated. RESULTS: Regardless of RR, animals ventilated at 7 ml/kg did not differ from control in any outcome. In contrast, MV at 40 ml/kg V(t) with 40 bpm produced lung injury characterized by significant elevations of BAL TNFalpha, IL-6, protein, ELF, and LDH. At 40 ml/kg V(t), RR reduction (20 bpm) significantly reduced all injury measures. CONCLUSION: This study confirms that large-volume MV, as a sole stimulus, produces lung injury and cytokine release. Whereas increasing RR at low V(t) has little impact on injury parameters, RR reduction under VILI-promoting conditions significantly limits lung injury.