Injurious Mechanical Ventilation and End-Organ Epithelial Cell Apoptosis and Organ Dysfunction in an Experimental Model of Acute Respiratory Distress Syndrome

Abstract

HE ACUTE RESPIRATORY DIStress syndrome (ARDS) is a serious form of acute lung injury and has a mortality rate of at least 30%. 1,2 Although the most obvious clinical abnormalities are referable to the lung, the most common cause of death is dysfunction of other organs, termed multiple organ dysfunction syndrome (MODS). [1][2][3] Multiple organ dysfunction syndrome is often irreversible, with mortality ranging from 60% to 98%. [4][5][6] To date, there is neither an effective treatment for MODS nor an effective means for preventing its onset.Mechanical ventilation is essential for patients with ARDS. However, animal and clinical studies have shown that mechanical ventilation can worsen preexisting lung injury and produce ventilator-induced lung injury (VILI). The spectrum of VILI includes not only air leaks and increases in endothelial and epithelial permeability, but also includes increases in pulmonary and systemic inflammatory mediators. [7][8][9] The importance of VILI has recently been highlighted by clinical trials demonstrating that protective ventilatory strategies were associated with decreased serum cytokine and chemokine levels, 10,11 decreased levels of organ dysfunction, 11,12 and decreased mortality in patients with Author Affiliations are listed at the end of this article.

Neurally adjusted ventilatory assist decreases ventilator-induced lung injury and non-pulmonary organ dysfunction in rabbits with acute lung injury

“…Our results are different from those we observed in a previous study in which an injurious ventilatory strategy led to epithelial cell apoptosis in non-pulmonary organs such as the kidney [6]. We are unsure of the exact reason(s) for the difference in results, but it may be related to differences in length of the experiments and/or severity of injury in the two studies.…”

“…Our data support previous studies with respect to the development of biotrauma [5,6,10]. There was a profound increase in plasma IL-8 levels as well as in tissue IL-8 concentration in spleen, kidney, and heart, but not in the liver and small intestines.…”

Tidal volume in animal models of hemorrhagic and endotoxic shock

“…The current data were in agreement with the study by Imai et al , in which rabbits were exposed to two bouts of acid aspiration and VALI (8) with the hypothesis that milder injury may result in a greater degree of apoptosis in the lungs.…”

Lung and 'end organ' injury due to mechanical ventilation in animals: comparison between the prone and supine positions

“…Our results show that injurious mechanical ventilation increases the apoptosis in the lungs as well as in 'end organs'. These findings are consistent with those of Imai and colleagues [ 6 ], who demonstrated that the injurious mechanical ventilation can lead to epithelial cell apoptosis in organs distal to the lung, such as the kidneys. There is some evidence that increased apoptosis is accompanied by biochemical changes suggesting organ failure [ 6 , 7 ].…”

“…These findings are consistent with those of Imai and colleagues [ 6 ], who demonstrated that the injurious mechanical ventilation can lead to epithelial cell apoptosis in organs distal to the lung, such as the kidneys. There is some evidence that increased apoptosis is accompanied by biochemical changes suggesting organ failure [ 6 , 7 ]. This could be an explanation for the high rates of multiple organ failure in patients with ARDS and the decrease in mortality when lung protective strategy is applied [ 5 , 6 ].…”