Short-term exposure to high-pressure ventilation leads to pulmonary biotrauma and systemic inflammation in the rat.

Though often lifesaving, mechanical ventilation itself bears the risk of lung damage [ventilator-induced lung injury (VILI)]. The underlying molecular mechanisms have not been fully elucidated, but stress-induced mediators seem to play an important role in biotrauma related to VILI. Our purpose was to evaluate an animal model of VILI that allows the observation of pathophysiologic changes along with parameters of biotrauma. For VILI induction, rats (n=16) were ventilated with a peak airway pressure (pmax) of 45 cm H2O and end-expiratory pressure (PEEP) of 0 for 20 min, followed by an observation time of 4 h. In the control group (n=8) the animals were ventilated with a pmax of 20 cm H2O and PEEP of 4. High-pressure ventilation resulted in an increase in paCO2 and a decrease in paO2 and mean arterial pressure. Only 4 animals out of 16 survived 4 h and VILI lungs showed severe macroscopic and microscopic damage, oedema and neutrophil influx. High-pressure ventilation increased the cytokine levels of macrophage inflammatory protein-2 and IL-1beta in bronchoalveolar lavage and plasma. VILI also induced pulmonary heat shock protein-70 expression and the activity of matrix metalloproteinases. The animal model used enabled us to observe the effect of high-pressure ventilation on mortality, lung damage/function and biotrauma. Thus, by combining barotrauma with biotrauma, this animal model may be suitable for studying therapeutical approaches to VILI.