Abstract

IntroductionIn acute lung injury (ALI), elevation of procollagen type III (PC III) occurs early and has an adverse impact on outcome. We examined whether different high-inflation strategies of mechanical ventilation (MV) in oleic acid (OA) ALI alter regional expression of PC III.MethodsWe designed an experimental, randomized, and controlled protocol in which rats were allocated to two control groups (no injury, recruited [alveolar recruitment maneuver after tracheotomy without MV; n = 4 rats] and control [n = 5 rats]) or four injured groups (one exposed to OA only [n = 10 rats] and three OA-injured and ventilated). The three OA-injured groups were ventilated for 1 hour according to the following strategies: LVHP-S (low volume-high positive end-expiratory pressure [PEEP], supine; n = 10 rats, tidal volume [VT] = 8 ml/kg, PEEP = 12 cm H2O), HVLP-S (high volume-low PEEP, supine; n = 10 rats, VT = 20 ml/kg, PEEP = 5 cm H2O), and HVLP-P (high volume-low PEEP, prone; n = 10 rats). Northern blot analysis for PC III and interleukin-1-beta (IL-1β) and polymorphonuclear infiltration index (PMI) counting were performed in nondependent and dependent regions. Regional differences between groups were assessed by two-way analysis of variance after logarithmic transformation and post hoc tests.ResultsA significant interaction for group and region effects was observed for PC III (p = 0.012) with higher expression in the nondependent region for HVLP-S and LVHP-S, intermediate for OA and HVLP-P, and lower for control (group effect, p < 0.00001, partial η2 = 0.767; region effect, p = 0.0007, partial η2 = 0.091). We found high expression of IL-1β (group effect, p < 0.00001, partial η2 = 0.944) in the OA, HVLP-S, and HVLP-P groups without regional differences (p = 0.16). PMI behaved similarly (group effect, p < 0.00001, partial η2 = 0.832).ConclusionPC III expression is higher in nondependent regions and in ventilatory strategies that caused overdistension. This response was partially attenuated by prone positioning.

Highlights

  • In acute lung injury (ALI), elevation of procollagen type III (PC III) occurs early and has an adverse impact on outcome

  • In healthy rat lungs submitted to injurious ventilation either with high or low tidal volume (VT) values, extracellular matrix (ECM) reacted with an increased synthesis of mRNA for procollagen type III (PC III), which was more pronounced in nondependent regions of the lungs [10]

  • The animals were similar in regard to weight, doses of anesthetic agents and volume of saline infused, PAW, and VT and positive end-expiratory pressure (PEEP)

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Summary

Introduction

In acute lung injury (ALI), elevation of procollagen type III (PC III) occurs early and has an adverse impact on outcome. In healthy rat lungs submitted to injurious ventilation either with high or low tidal volume (VT) values, ECM reacted with an increased synthesis of mRNA for procollagen type III (PC III), which was more pronounced in nondependent regions of the lungs [10]. This suggests an effect of regional transpleural forces that emerged due to lung heterogeneity in the context of ventilatorinduced lung injury [11]

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