Time course of physiologic variables in response to ventilator-induced lung injury.
BACKGROUND
The time course of the physiological derangements that result from ventilator-induced lung injury has not been adequately described. Similarly, the regional topographies of pleural pressure and tissue edema have not been carefully mapped for this injury process.


METHODS
Lung injury was induced in 9 normal pigs by ventilating for 6 hours at a transpulmonary pressure of 35 cm H(2)O, with the animals in the supine position. Eight additional normal pigs received right thoracotomy to place pleural-surface-pressure sensors prior to an identical period and intensity of injurious ventilation. Gas exchange and lung mechanics were tracked in all the animals. Cytokines (tumor necrosis factor alpha, interleukin 6, and interleukin 8) in peripheral blood were assayed at 2 hour intervals, beginning at the onset of mechanical ventilation, from all the animals.


RESULTS
After a brief "induction" period, P(aO(2)) and tidal volume declined steadily in the animals that were ventilated to induce lung injury. The rate of decline was greater in the animals that received thoracotomy. The pleural pressure gradient steadily increased from ventral to dorsal. The serum cytokine levels did not evolve with developing injury, but cytokines were elevated at the onset of ventilation. Tissue edema, as assessed by the ratio of wet weight to dry weight, was greater in the thoracotomized animals than in the nonthoracotomized animals, and tissue edema tended to be greater in the caudal lung regions than in the cephalad lung regions.


CONCLUSIONS
Following the induction period, the development of ventilator-induced lung injury progressed steadily and then plateaued, as assessed by quantitative physiology variables during 6 hours of ventilation at a transpulmonary pressure of 35 cm H(2)O. Greater injury developed in animals that had a coexisting potential insult (thoracotomy). Injury development was not paralleled by bloodborne inflammatory cytokines.
Dries
David J
DJ
Pulmonary Research Laboratory, Regions Hospital, St Paul, Minnesota, USA.
Adams
Alexander B
AB
Marini
John J
JJ
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D035422:Pleural Cavity / Q000503:physiopathology*; D011312:Pressure; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000503:physiopathology*; D015656:Respiratory Mechanics / Q000502:physiology*; D012720:Severity of Illness Index; D013552:Swine