Partial Liquid Ventilation Reduces Release of Leukotriene B4 and Interleukin-6 in Bronchoalveolar Lavage in Surfactant-Depleted Newborn Pigs

Abstract

Perfluorocarbons have been shown to reduce the inflammatory process generated by alveolar macrophages in vitro. The aim of this study was to evaluate the impact of different ventilator modalities such as partial liquid ventilation (PLV), conventional ventilation (CV), and high-frequency oscillatory ventilation (HFOV) on the release of inflammatory mediators in vivo. Acute lung injury was induced in 30 male piglets by repeated saline lavage (arterial oxygen tension, Ͻ60 mm Hg; fraction of inspired oxygen, 1.0). Thereafter, animals were randomly assigned to one of five groups of six animals each: 1) 24 h of CV; 2) 24 h of CV plus surfactant therapy (SϩCV); 3) 24 h of HFOV plus surfactant therapy (SϩHFOV); 4) 1 h of PLV followed by 23 h of CV (PLV); and 5) 24 h of CV without previous lung injury (control group). Piglets randomized to SϩCV or SϩHFOV received natural surfactant (100 mg/kg). PLV with FC-77 was started in an initial dose of 30 mL/kg over 30 min followed by 0.5 mL·kg Ϫ1 ·min Ϫ1 for another 30 min. After 1 h of PLV the animals were conventionally ventilated for 23 h. Before acute lung injury and after 24 h the number of inflammatory cells and the levels of IL-6, leukotriene B 4 , and tumor necrosis factor-␣ were measured in the bronchoalveolar lavage fluid. Additionally, the oxygenation index and the histopathologic damage were evaluated. Before acute lung injury, the number of inflammatory cells and the levels of mediators in bronchoalveolar lavage fluid were not different among the groups. After 24 h, the number of granulocytes in the PLV group was as low as in the control group. leukotriene B 4 and IL-6 levels were found to be elevated in all groups except the control group (p Ͻ 0.01). The release of leukotriene B 4 and IL-6 was lowest in the PLV group when compared with SϩHFOV, SϩCV, or CV (p Ͻ 0.05). No differences among the groups were detected for tumor necrosis factor-␣. Although the concentrations of leukotriene B 4 and IL-6 after PLV were lowest in the PLV group, histopathologic evidence of damage and the oxygenation index in the PLV group did not differ from that found in the SϩCV or SϩHFOV groups. In conclusion, PLV with perfluorocarbons may protect the lung from acute pulmonary inflammation more effectively than CV or HFOV does. Mechanical ventilation of the S-deficient lung may cause ALI in children and adults (1). Despite the widespread use of S, preferentially extremely premature infants are at high risk to develop chronic lung disease as result of the ALI (2, 3). Although the pathogenesis of chronic lung disease is very complex, pulmonary inflammation seems to play a major role in the development of this disease (4, 5). The severity of the ALI and the subsequent process of pulmonary inflammation can be modified by improved ventilation strategies.

Anti-inflammatory effects of perfluorocarbon compounds

“…By contrast, the effect of PLV with a PFC on TNF-α levels did not follow a consistent trend in the various animal studies [71,83,[88][89][90][91] and may depend on where TNF-α levels were assessed. For example, Kawamae and coworkers investigated the effect of PLV on TNF-α levels in an hydrochloric acid-induced rat lung-injury model [91].…”

“…By contrast, studies in different lung-injury models generally showed a decrease in expression of several cytokines, such as IL-1β [23,25,27], IL-6 [27,71,73,74] and IL-8 [23,27,28,73,[85][86][87], in the PLVtreatment group compared with the respective GV-treatment group. By contrast, the effect of PLV with a PFC on TNF-α levels did not follow a consistent trend in the various animal studies [71,83,[88][89][90][91] and may depend on where TNF-α levels were assessed.…”

Effects of therapeutic bronchoalveolar lavage and partial liquid ventilation on meconium-aspirated newborn piglets

“…The pulmonary conditions were not completely the same as with neonatal patients. Since fixed ventilatory settings, high FIO 2 , different PEEP and inspiratory time, and deep anesthesia are commonly used in animal studies with MAS (7,12,16,28,29), some atelectasis before lung injury would be expected. Therefore, the preinjury alveolar-arterial oxygen difference might be worse than for a normal infant breathing spontaneously with room air (10,17,18,28).…”

Pathogenetic Significance of Biological Markers of Ventilator-Associated Lung Injury in Experimental and Clinical Studies

“…15 In preterm pigs, conventional tidal volume ventilation induced greater increases in leukotriene-B 4 and IL-6 than high-frequency oscillatory ventilation or partial liquid ventilation; however, BAL levels of TNF-α were not different among the groups. 28 Altemeier and colleagues 29 pretreated rabbits with endotoxin before mechanical ventilation with a tidal volume of 15 mL/kg without PEEP for 8 h and found that endotoxin combined with mechanical ventilation resulted in significant increases in BAL levels of TNF-α, IL-8, growth-related oncogene-α, and MIP-1. Endotoxin or mechanical ventilation alone did not increase these cytokines.…”