Ventilator-induced endothelial activation and inflammation in the lung and distal organs

Abstract

IntroductionResults from clinical studies have provided evidence for the importance of leukocyte-endothelial interactions in the pathogenesis of pulmonary diseases such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), as well as in systemic events like sepsis and multiple organ failure (MOF). The present study was designed to investigate whether alveolar stretch due to mechanical ventilation (MV) may evoke endothelial activation and inflammation in healthy mice, not only in the lung but also in organs distal to the lung.MethodsHealthy male C3H/HeN mice were anesthetized, tracheotomized and mechanically ventilated for either 1, 2 or 4 hours. To study the effects of alveolar stretch in vivo, we applied a MV strategy that causes overstretch of pulmonary tissue i.e. 20 cmH2O peak inspiratory pressure (PIP) and 0 cmH20 positive end expiratory pressure (PEEP). Non-ventilated, sham-operated animals served as a reference group (non-ventilated controls, NVC).ResultsAlveolar stretch imposed by MV did not only induce de novo synthesis of adhesion molecules in the lung but also in organs distal to the lung, like liver and kidney. No activation was observed in the brain. In addition, we demonstrated elevated cytokine and chemokine expression in pulmonary, hepatic and renal tissue after MV which was accompanied by enhanced recruitment of granulocytes to these organs.ConclusionsOur data implicate that MV causes endothelial activation and inflammation in mice without pre-existing pulmonary injury, both in the lung and distal organs.

Ventilator-Induced Lung Injury: Mechanisms and Future Therapeutic Interventions

“…In addition, increased cytokine and chemokine mRNA levels were found in the lung and distal organs after mechanical ventilation (figures 1b-c, f-g, j-k) accompanied by enhanced granulocyte infiltration (figures 1d, h, l). Our data imply that ventilator-induced endothelial activation in the lung, liver and kidney facilitates migration and adhesiveness of activated immune cells to inflamed tissue, which in turn may lead to tissue injury in these organs (Hegeman et al, 2009). Since we observed increased endothelial activation and inflammation after mechanical ventilation in the lung and distal organs, it seems plausible that mechanical ventilation plays a significant role in the development of both VILI and MOF (Hegeman et al, 2009).…”

“…Our data imply that ventilator-induced endothelial activation in the lung, liver and kidney facilitates migration and adhesiveness of activated immune cells to inflamed tissue, which in turn may lead to tissue injury in these organs (Hegeman et al, 2009). Since we observed increased endothelial activation and inflammation after mechanical ventilation in the lung and distal organs, it seems plausible that mechanical ventilation plays a significant role in the development of both VILI and MOF (Hegeman et al, 2009). Supporting this hypothesis, earlier experimental research provided evidence that mechanical ventilation evokes detrimental effects in distal organs (Imai et al, 2003;Nin et al, 2006).…”

“…Although there is quite some evidence that inflammatory mediators will be released from inflamed pulmonary tissue into the systemic environment, a causal relationship between ventilator-induced spill-over and the pathogenesis of MOF has not been confirmed yet. Our experimental data indicate that ventilator-induced changes in de novo expression of adhesion molecules, cytokines and chemokines occur simultaneously in the lung, liver and kidney (Hegeman et al, 2009). Moreover, granulocyte recruitment to the liver and kidney was already observed after 1 hour of mechanical ventilation (Hegeman et al, 2009).…”

“…Moreover, they found a positive correlation between the number of organ systems failing and ICU mortality stressing the importance of MOF in the clinical outcome of critically ill patients (Vincent et al, 2006). Reprinted with permission of Critical Care (Hegeman et al, 2009). To investigate whether alveolar stretch may cause endothelial activation and inflammation in the lung and distal organs, healthy mice were mechanically ventilated for 1, 2 or 4 hours with high pressures (i.e.…”

“…It has been proposed that an elevation of adhesion molecule expression might contribute to tissue injury and ultimately to MOF by facilitating leukocyte activation and migration (Bone, 1991;Parrillo, 1993). In this regard, we examined whether alveolar stretch due to mechanical ventilation results in endothelial activation and inflammation in healthy mice, not only in the lung but also in organs distal to the lung (Hegeman et al, 2009). We observed that 4 hours of mechanical ventilation with high pressures, i.e.…”