Why does lung injury occur after the use of higher tidal volumes?
In humans and mice, NLRP3 inflammasome gene expression was up-regulated for those who received higher tidal volumes. (Image source: Thinkstock)
Mechanical ventilation can be life saving. For patients with acute lung injury, lower rather than higher tidal volumes can reduce lung injury and decrease mortality. What is the basis for this finding? Damage and pathogen-associated molecular patterns are activated by injured tissue and then form the NLRP3 inflammasone. In the study “Ventilator-induced Lung Injury Is Mediated by the NLRP3 Inflammasome,” Dr. Maria T. Kuipers (Research Fellow, Laboratory of Experimental Intensive Care and Anesthesiology [LEICA], and Center of Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands) and colleagues proposed that NLRP3 inflammasome signaling produces an inflammatory response that is responsible for ventilator-induced lung injury.
Experiments were performed in humans and mice. Bronchial brush samples and bronchoalveolar lavage fluid from mechanically ventilated patients undergoing surgery for more than 5 h without preexisting lung injury were obtained from 40 patients. The patients were divided into lung protective (6 ml/kg ideal body and 10 cm H20 PEEP) and standard ventilation (12 ml/kg ideal body weight and no PEEP) groups. In mice, both normal and NLRP3 inflammasome deficient and adaptor apoptosis-associated speck-like protein deficient mice were randomized to receive either high (inspiratory pressure of 18 cm H20) or low tidal volume (inspiratory pressure of 10 cm H20) for 5 h.
In humans and mice, NLRP3 inflammasome gene expression was up-regulated for those who received higher tidal volumes. In mice, end-products of NLPR3 inflammasone activation were also up-regulated. Ventilator-induced lung injury was reduced in NLRP3 and adaptor apoptosis-associated speck-like protein deficient mice. Also, in mice with pharmacologic inhibition of the IL-1β and NLRP3 inflammasome pathway, e.g., with interleukin-1 receptor antagonist, or glibenclamide, ventilator-induced lung injury was reduced.
Whether treatment in humans with ventilator-induced lung injury, particularly for patients who are more susceptible to lung injury such as those who are obese, by using inhibitors of ventilator-induced lung injury would improve outcome is unclear. Indeed, glibenclamide, a sulphonylurea, is used also used to treat diabetes.