Published ahead of print on April 27, 2006, doi:10.1164/rccm.200507-1178OC Am. J. Respir. Crit. Care Med., Volume 174, Number 2, July 2006, 178-186 A more recent version of this article appeared on July 15, 2006
Submitted on July 29, 2005 Ischemia and Reperfusion Increases Susceptibility to Ventilator-induced Lung Injury in RatsEttore Crimi1,1 Departments of Anaesthesia, Critical Care Medicine and Physiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Departments of Anesthesiology and Critical Care Medicine, University of Eastern Piedmont, Eastern Piedmont, Novara, Italy, 2 Departments of Anaesthesia, Critical Care Medicine and Physiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada, 3 Department of Cardiology, St. Michael's Hospital, Toronto, Ontario, Canada, 4 Dipartimento di discipline Medico-Chirurgiche, Sezione di Anestesiologia e Rianimazione, Universita di Torino, Ospedale S. Giovanni Battista, Torino, Italy * To whom correspondence should be addressed. E-mail: arthur.slutsky{at}utoronto.ca.
Objectives: Hemorrhagic shock followed by resuscitation (HSR) commonly triggers an inflammatory response that leads to acute respiratory distress syndrome (ARDS). Hypothesis: HSR exacerbates mechanical stress-induced lung injury by rendering the lung more susceptible to ventilator-induced lung injury. Methods: Rats were subjected to hemorrhagic shock followed by resuscitation, and were randomized into a HSR + High tidal volume with zero positive end-expiratory pressure (PEEP) or a HSR + Low tidal volume with 5 cm H2O PEEP. A Sham operated rat + High tidal volume and zero PEEP served as a control. Results: HSR increased susceptibility to ventilator-induced lung injury with an increase in lung elastance and the wet-dry ratio, and a reduction in PaO2 as compared to the other groups. The lung injury observed in the HSR + High tidal volume group was associated with a higher level of IL-6 in the lung and blood, increased epithelial cell apoptosis in the kidney and small intestine villi, and a tendency toward high levels of ALT, AST, LDH and creatinine in plasma. Conclusions: HSR priming renders the lung and kidney more susceptible to mechanical ventilation-induced organ injury. Key words: Inflammation, multiple organ failure, lung mechanic
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