Rats surviving injurious mechanical ventilation show reversible pulmonary, vascular and inflammatory changes

Abstract

Objective: To describe the time course of the changes in pulmonary and vascular function, and systemic inflammation induced by injurious mechanical ventilation. Design: Experimental study in an animal model of ventilator-induced lung injury. Setting: Animal research laboratory. Methods: Anesthetized male adult Sprague-Dawley rats were ventilated with VT 9 ml/kg and PEEP 5 cm H2O, or VT 35 ml/kg and zero PEEP for 1 h, and were killed. Other rats received ventilation for 1 h with high VT, to observe survival (n = 36), or to be monitored and killed at different points in time (24, 72 and 168 h; n = 7 in each group). Blood samples for measuring biochemical parameters were obtained. Post-mortem, a bronchoalveolar lavage (BAL) was performed, the aorta and pulmonary microvessels were isolated to examine ex-vivo vascular responses and pulmonary slices were examined (light microscopy). Measurements and results: Mortality in rats ventilated with high VT was 19 of 36 (54%). Mechanical ventilation was associated with hypotension, hypoxaemia and membrane hyaline formation. AST, ALT, IL-6, MIP-2 serum and BAL fluid concentrations, as well as VEGF BAL fluid concentration, were increased in rats ventilated with high VT. Lung injury score was elevated. Aortic vascular responses to acetylcholine and norepinephrine, and microvascular responses to acetylcholine, were impaired. These changes resolved by 24-72 h. Conclusions: Injurious ventilation is associated with respiratory and vascular dysfunction, accompanied by pulmonary and systemic inflammation. The survival rate was about 50%. In survivors, most induced changes completely normalized by 24-72 h after the insult. © 2008 Springer-Verlag.