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Rats surviving after high tidal volume ventilation show marked and reversible pulmonary and systemic changes


High tidal volume (VT) ventilation (HTVV) induces pulmonary inflammation. The time course of pulmonary and systemic HTVV-induced vascular dysfunction is unknown. We tested whether rats receiving HTVV survive the insult, and we describe the time-course of the HTVV-induced vascular changes.


Normal anesthetized Sprague-Dawley rats were tracheostomized and ventilated for 1 hour with either VT = 9 ml/kg + PEEP 5 cmH2O, or VT = 35 ml/kg + ZEEP. After the HTVV period, the tracheostomy was closed, and rats were sent back to their cages breathing room air. Other rats were sacrificed at this point in time (t = 1 hour). Rats surviving the acute period of HTVV were again intubated, monitored and then sacrificed at different points in time (24 hours, 72 hours, 168 hours). We measured the mean arterial pressure, aortic blood flow (QAo), arterial blood gases, and total protein, AST, ALT, IL-6, and VEGF serum and BAL fluid concentrations. Aortic segments and pulmonary micro vessels were mounted in myographs, and responses to acetylcholine in norepinehrine-precontracted rings were tested. Histological lung changes were studied.


All lungs showed diffuse alveolar damage after HTVV at 1 and 24 hours, but histology was completely normal at t = 72 hours. HTVV induced hypotension, decreased QAo, hypoxemia, increased protein, AST, ALT, IL-6, and VEGF BAL fluid/serum concentration ratio. Acetylcholine and norephineprine-induced responses were impaired after HTVV in aortic rings. Moreover acetylcholine-induced responses in pulmonary microvessels were impaired. All these biochemical and vascular function changes normalized at t = 168 hours.


About half the rats receiving for a short period of time ventilation using very high VT survive. HTVV induces in a reversible fashion pulmonary and systemic inflammation and vascular dysfunction.


Funded by FIS CO3/11, GO3/063.

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Peñuelas, O., Nin, N., De Paula, M. et al. Rats surviving after high tidal volume ventilation show marked and reversible pulmonary and systemic changes. Crit Care 10 (Suppl 1), P6 (2006).

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