Ventilator-induced mediator release: role of PEEP and surfactant

Lung protective ventilation such as the ARDSnet low tidal volumes strategy can reduce mortality in ARDS patients. The lmowledge that an essential therapy such as mechanical ventilation on the intensive care influences patient outcome has given rise to the re-evaluation of current ventilation practices. This review addresses the current state of lung protective strategies and their physiological rationale. Latest knowledge on the instigation and progression of lung injury by mechanical ventilation is explored, particularly the interaction between ventilation and the inflammatmy response occun·ing in an ARDS lung. Furthennore, the role of tidal volume, PEEP, recruitment maneuvers and surfactant on lung injury is discussed. Finally, we discuss results from clinical studies on mechanical ventilation and elucidate these results with data acquired in experimental studies. Guidelines for future strategies and/or investigations are presented

Partial liquid ventilation improves lung function in ventilation-induced lung injury

Disturbances in lung function and lung mechanics are present after ventilation with high peak inspiratory pressures (PIP) and low levels of positive end-expiratory pressure (PEEP). Therefore, the authors investigated whether partial liquid ventilation can re-establish lung function after ventilation-induced lung injury. Adult rats were exposed to high PIP without PEEP for 20 min. Thereafter, the animals were randomly divided into five groups. The first group was killed immediately after randomization and used as an untreated control. The second group received only sham treatment and ventilation, and three groups received treatment with perfluorocarbon (10 mL x kg(-1), 20 mL x kg(-1), and 20 ml x kg(-1) plus an additional 5 mL x kg(-1) after 1 h). The four groups were maintained on mechanical ventilation for a further 2-h observation period. Blood gases, lung mechanics, total protein concentration, minimal surface tension, and small/large surfactant aggregates ratio were determined. The results show that in ventilation-induced lung injury, partial liquid ventilation with different amounts of perflubron improves gas exchange and pulmonary function, when compared to a group of animals treated with standard respiratory care. These effects have been observed despite the presence of a high intra-alveolar protein concentration, especially in those groups treated with 10 and 20 mL of perflubron. The data suggest that replacement of perfluorocarbon, lost over time, is crucial to maintain the constant effects of partial liquid ventilation

Effect of SP-B peptides on the uptake of liposomes by alveolar cells

Background: Exogenous surfactant has been accepted worldwide as a therapy of RDS in premature and term infants. Exogenous surfactant is usually derived from lung extracts containing phospholipids and the surfactant proteins SP-B and SP-C. Synthetic peptides of SP-B and SP-C are being tested with the aim to develop a completely synthetic surfactant preparation. Nevertheless, the effects of these peptides on the endogenous surfactant metabolism remain unknown. Objectives: The effect of synthetic SP-B peptides on uptake of surfactant-like liposomes was investigated in alveolar cells. Native SP-B and seven SP-B peptides were included: monomeric and dimeric SP-B1-25(Cys-11 → Ala-11), SP-B63-78and Ala-SP-B63-78(Cys-71 → Ala-71;Cys-77 → Ala-77)and their serine mutants. Methods: In vitro, alveolar macrophages (AM) and alveolar type II cells (ATII) were incubated with liposomes containing SP-B or one of its peptides. In vivo, rats received intratracheally various SP-B peptides (SP-B/lipid ratio 1:33 w/w) incorporated in fluorescent surfactant-like liposomes. One hour after instillation, AM and ATII were isolated and cell-associated fluorescence was determined using flow cytometry. Confocal laser microscopy was performed to ensure internalization of the liposomes. Results: In vitro uptake by AM or ATII was not influenced by the SP-B peptides. In vivo, SP-B1-25and Ser-SP-B1-25increased the uptake by AM whereas dSP-B1-25decreased the uptake. Neither SP-B1-25nor dSP-B1-25affected total uptake by ATII. The overall uptake by SP-B63-78variants was not changed. Conclusions: Surface-active synthetic SP-B peptides do not interfere with the normaluptake of surfactant by ATII. Copyrigh

The effect of open lung ventilation on right ventricular and left ventricular function in lung-lavaged pigs

INTRODUCTION: Ventilation according to the open lung concept (OLC) consists of recruitment maneuvers, followed by low tidal volume and high positive end-expiratory pressure, aiming at minimizing atelectasis. The minimization of atelectasis reduces the right ventricular (RV) afterload, but the increased intrathoracic pressures used by OLC ventilation could increase the RV afterload. We hypothesize that when atelectasis is minimized by OLC ventilation, cardiac function is not affected despite the higher mean airway pressure. METHODS: After repeated lung lavage, each pig (n = 10) was conventionally ventilated and was ventilated according to OLC in a randomized cross-over setting. Conventional mechanical ventilation (CMV) consisted of volume-controlled ventilation with 5 cmH2O positive end-expiratory pressure and a tidal volume of 8-10 ml/kg. No recruitment maneuvers were performed. During OLC ventilation, recruitment maneuvers were applied until PaO2/FiO2 > 60 kPa. The peak inspiratory pressure was set to obtain a tidal volume of 6-8 ml/kg. The cardiac output (CO), th

Improvement of lung mechanics by exogenous surfactant: effect of prior application of high positive end-expiratory pressure

The use of a ventilation strategy with high positive end-expiratory pressure (PEEP) that is intended to recruit collapsed alveoli and to prevent recurrent collapse can reduce alveolar protein influx in experimental acute lung injury (ALI). This could affect the pulmonary response to treatment with surfactant, since plasma proteins inhibit surfactant function. We studied the effect of exogenous surfactant on lung mechanics after 4 h of mechanical ventilation with high or low PEEP. Twenty-two adult male Sprague-Dawley rats were anaesthetized, tracheotomized and submitted to pressure-controlled mechanical ventilation with 100% oxygen. One group served as healthy controls (n = 6). In the remaining animals acute lung injury was induced by repeated lung lavages to obtain a PaO2 < 13 kPa during ventilation with a peak inspiratory pressure (PIP) of 26 cm H2O and a PEEP of 6 cm H2O. These animals were allocated randomly to ventilation with high PEEP (n = 8; 100 breaths min-1, I:E = 1:1 PIP 35 cm H2O, PEEP 18 cm H2O) or to conventional mechanical ventilation (PIP 28 cm H2O, PEEP 8 cm H2O; n = 8; ventilated control group). After 4 h of ventilation, all animals were given surfactant (120 mg kg-1) via the trachea and ventilation was continued for 15 min. At the end of the study, pressure-volume curves were constructed to measure total lung capacity at 35 cm H2O (TLC35) and maximal compliance (Cmax), and bronchoalveolar lavage was then used to measure alveolar protein influx. After lavage, PaO2, remained around 13 kPa in the ventilated control group and was > 66 kPa in the high-PEEP group. After surfactant treatment, PaO2 increased to > 53 kPa in both groups. In the ventilated control group alveolar protein influx was greater and TLC35 and Cmax were lower than in the high-PEEP group. We conclude that the pulmonary response to exogenous surfactant after mechanical ventilation in experimental ALI is improved when a ventilation strategy with high PEEP is used

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

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. Copyrigh