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The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury.

Puntorieri V, Hiansen JQ, McCaig LA, Yao LJ, Veldhuizen RA, Lewis JF - BMC Pulm Med (2013)

Bottom Line: Instillation of exogenous surfactant did not influence the development of lung injury.Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology & Pharmacology, Western University, London, Ontario, Canada. vpuntori@uwo.ca.

ABSTRACT

Background: Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation.

Methods: Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours).

Results: For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.

Conclusions: The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

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Related in: MedlinePlus

Experiment 2: Peak Inspiratory Pressure (PIP) was measured over the course of MV. Values are expressed as mean ± SEM. +p > 0.05 versus Air No Treatment at the specific time point indicated, *p < 0.05 versus the respective Air control at each time point; n = 6 per group.
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Figure 3: Experiment 2: Peak Inspiratory Pressure (PIP) was measured over the course of MV. Values are expressed as mean ± SEM. +p > 0.05 versus Air No Treatment at the specific time point indicated, *p < 0.05 versus the respective Air control at each time point; n = 6 per group.

Mentions: In experiment 2, the effect of exogenous surfactant on systemic inflammation during MV was assessed in the presence of a pre-existing acid-induced lung injury/inflammation. Physiological parameters such as peak inspiratory pressure and perfusion pressure were monitored throughout ventilation as in experiment 1, and PIP values are shown in Figure 3. Although all experimental groups were exposed to the same ventilation strategy, the peak inspiratory pressure was significantly higher in Acid injured mice compared to the respective Air groups (Acid No Treatment vs Air No Treatment; Acid bLES vs Air bLES). Exogenous surfactant administration led to a significant increase in PIP values during the first hour of MV (10 to 75 min) in the Air bLES group compared to Air No Treatment group and, importantly, did not reduce PIP values in the Acid bLES group compared to Acid No Treatment group at any time point. Perfusion pressure was monitored during MV and maintained between 5 and 7 mmHg for all groups (data not shown).


The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury.

Puntorieri V, Hiansen JQ, McCaig LA, Yao LJ, Veldhuizen RA, Lewis JF - BMC Pulm Med (2013)

Experiment 2: Peak Inspiratory Pressure (PIP) was measured over the course of MV. Values are expressed as mean ± SEM. +p > 0.05 versus Air No Treatment at the specific time point indicated, *p < 0.05 versus the respective Air control at each time point; n = 6 per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222563&req=5

Figure 3: Experiment 2: Peak Inspiratory Pressure (PIP) was measured over the course of MV. Values are expressed as mean ± SEM. +p > 0.05 versus Air No Treatment at the specific time point indicated, *p < 0.05 versus the respective Air control at each time point; n = 6 per group.
Mentions: In experiment 2, the effect of exogenous surfactant on systemic inflammation during MV was assessed in the presence of a pre-existing acid-induced lung injury/inflammation. Physiological parameters such as peak inspiratory pressure and perfusion pressure were monitored throughout ventilation as in experiment 1, and PIP values are shown in Figure 3. Although all experimental groups were exposed to the same ventilation strategy, the peak inspiratory pressure was significantly higher in Acid injured mice compared to the respective Air groups (Acid No Treatment vs Air No Treatment; Acid bLES vs Air bLES). Exogenous surfactant administration led to a significant increase in PIP values during the first hour of MV (10 to 75 min) in the Air bLES group compared to Air No Treatment group and, importantly, did not reduce PIP values in the Acid bLES group compared to Acid No Treatment group at any time point. Perfusion pressure was monitored during MV and maintained between 5 and 7 mmHg for all groups (data not shown).

Bottom Line: Instillation of exogenous surfactant did not influence the development of lung injury.Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology & Pharmacology, Western University, London, Ontario, Canada. vpuntori@uwo.ca.

ABSTRACT

Background: Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation.

Methods: Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours).

Results: For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.

Conclusions: The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

Show MeSH
Related in: MedlinePlus