Ventilation-induced lung injury in rats is associated with organ injury and systemic inflammation that is attenuated by dexamethasone

Nin, Nicolás; Peñuelas, Óscar; Paula, Marta de; Lorente, José A.; Fernández-Segoviano, Pilar; Esteban, Andrés

doi:10.1097/01.ccm.0000205663.92384.e7

Cited by 51 publications

(62 citation statements)

References 22 publications

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“…Research has shown that high tidal volume induces distal organ injury and systemic proinflammatory response, suggesting that inflammatory rather than purely hemodynamic alterations are involved in distal organ injury (19). In the present study, eNOS expression in the kidney was comparable for the two groups.…”

Section: Discussionsupporting

confidence: 61%

Glomerular filtration is reduced by high tidal volume ventilation in an in vivo healthy rat model

Luque

Shimizu

Andrade

et al. 2009

Braz J Med Biol Res

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Mechanical ventilation has been associated with organ failure in patients with acute respiratory distress syndrome. The present study examines the effects of tidal volume (V T) on renal function using two V T values (8 and 27 mL/kg) in anesthetized, paralyzed and mechanically ventilated male Wistar rats. Animals were randomized into two groups of 6 rats each: V T8 (V T, 8 mL/kg; 61.50 ± 0.92 breaths/min; positive end-expiratory pressure, 3.0 cmH2O; peak airway pressure (PAW), 11.8 ± 2.0 cmH2O), and V T27 (V T, 27 mL/kg; 33.60 ± 1.56 breaths/min; positive end-expiratory pressure, none, and PAW, 22.7 ± 4.0 cmH2O). Throughout the experiment, mean PAW remained comparable between the two groups (6.33 ± 0.21 vs 6.50 ± 0.22 cmH2O). For rats in the V T27 group, inulin clearance (mL·min-1·body weight-1) decreased acutely after 60 min of mechanical ventilation and even more significantly after 90 min, compared with baseline values (0.60 ± 0.05 and 0.45 ± 0.05 vs 0.95 ± 0.07; P < 0.001), although there were no differences between groups in mean arterial pressure or gasometric variables. In the V T8 group, inulin clearance at 120 min of mechanical ventilation remained unchanged in relation to baseline values (0.72 ± 0.03 vs 0.80 ± 0.05). The V T8 and V T27 groups did not differ in terms of serum thiobarbituric acid reactive substances (3.97 ± 0.27 vs 4.02 ± 0.45 nmol/mL) or endothelial nitric oxide synthase expression (94.25 ± 2.75 vs 96.25 ± 2.39%). Our results show that glomerular filtration is acutely affected by high tidal volume ventilation but do not provide information about the mechanism

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Section: Discussionsupporting

confidence: 61%

Glomerular filtration is reduced by high tidal volume ventilation in an in vivo healthy rat model

Luque

Shimizu

Andrade

et al. 2009

Braz J Med Biol Res

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“…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). Imai et al demonstrated that mechanical ventilation with high tidal volumes induces epithelial cell apoptosis in the kidney and small intestine (Imai et al, 2003).…”

Section: Local Versus Systemic Inflammationsupporting

confidence: 65%

“…We observed, however, that the potent anti-inflammatory agent dexamethasone did not prevent occurrence of the more crude parameters of VILI like the elevation in BALf protein level, the increase in pulmonary wet-to-dry ratio and the reduction in PaO 2 /FiO 2 ratio (Hegeman et al, 2011b). Our findings oppose previous studies describing protective effects of glucocorticoid therapy on lung injury (Nin et al, 2006;Ohta et al, 2001). In a rat model of VILI, dexamethasone was shown to restore pulmonary function after 75 minutes of mechanical ventilation as indicated by improved PaO 2 /FiO 2 ratios (Nin et al, 2006).…”

Section: Inhibition Of Ventilator-induced Lung Inflammation: Does It contrasting

confidence: 56%

“…Moreover, these authors showed that mechanical ventilation leads to elevated levels of serum markers such as creatinine indicative for renal failure (Imai et al, 2003). Ventilator-induced cardiovascular and hepatic injury has been described as well (Nin et al, 2006). It should be noted that these previous studies used animals with pre-existing lung injury whereas our study used healthy animals, suggesting that already existing inflammation is not a prerequisite for unveiling the negative effects of mechanical ventilation on distal organs.…”

Section: Local Versus Systemic Inflammationmentioning

confidence: 42%

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Ventilator-Induced Lung Injury: Mechanisms and Future Therapeutic Interventions

Hegeman¹,

Schultz²,

Heijnen³

et al. 2012

Front Lines of Thoracic Surgery

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“…Another potential confounding factor is the captopril-induced decrease in blood pressure. However, there is evidence that haemodynamic changes do not play a pivotal role in lung injury [21][22][23]. Correction of hypotension induced during high VT ventilation did not change microvascular leak in the lung [23].…”

Section: Discussionmentioning

confidence: 99%

ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin

Asperen¹,

Lutter²,

Haitsma³

et al. 2008

European Respiratory Journal

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Ventilator-induced lung injury is characterised by inflammation and apoptosis, but the underlying mechanisms are poorly understood. The present study proposed a role for angiotensin-converting enzyme (ACE) via angiotensin II (Ang II) and/or bradykinin in acute lung injury. The authors assessed whether ACE and, if so, Ang II and/or bradykinin are implicated in inflammation and apoptosis by mechanical ventilation.Rats were ventilated for 4 h with low-or high-pressure amplitudes in the absence or presence of the ACE inhibitor captopril. Nonventilated animals served as controls. ACE activity, Ang II and bradykinin levels, as well as inflammatory parameters (total protein, macrophage inflammatory protein-2 and interleukin-6) were determined. Apoptosis was assessed by the number of activated caspase-3 and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labelling)-positive cells.Bronchoalveolar lavage fluid ACE activity, levels of total protein, inflammatory parameters and the number of apoptotic cells were increased in the high-pressure amplitude group as compared with the control group. Blocking ACE activity by captopril attenuated inflammation and apoptosis in the latter group. Similar results were obtained by blocking Ang II receptors, but blocking bradykinin receptors did not attenuate the anti-inflammatory and anti-apoptotic effects of captopril.The current authors conclude that inflammation and apoptosis in ventilator-induced lung injury is, at least in part, due to angiotensin-converting enzyme-mediated angiotensin II production.

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Ventilation-induced lung injury in rats is associated with organ injury and systemic inflammation that is attenuated by dexamethasone

Cited by 51 publications

References 22 publications

Glomerular filtration is reduced by high tidal volume ventilation in an in vivo healthy rat model

Glomerular filtration is reduced by high tidal volume ventilation in an in vivo healthy rat model

Ventilator-Induced Lung Injury: Mechanisms and Future Therapeutic Interventions

ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin

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