Influence of natural seawater variables on the corrosion behaviour of aluminium-magnesium alloy.

Corrosion is an important issue for alloys in natural seawater, where microorganisms can accelerate or mitigate corrosion. Al-Mg alloys are used for marine activities and various associated technologies. Here, the behaviour of AA5083 alloy was investigated in natural seawater with marine exposure lasting up to 50 days and detailing the first 8 days in two experimental series. Experimental work was carried out, including semi-field tests in natural seawater (biotic conditions) compared with abiotic conditions. The open circuit potential (OCP) measurements, during the immersion time, exhibited significantly different behaviours: an OCP downward displacement occurred under abiotic conditions, while, in biotic conditions OCP remained generally stable since the beginning of the immersion, revealing an inhibiting effect of the biological activity on the Al-Mg corrosion. This was accompanied by different surface modifications under biotic conditions: surface and cross-section characterization, performed by scanning electron microscopy with energy dispersive X-ray spectroscopy, showed less corrosion developed on the surface after 8-day immersion and formation of a protective layer during 50-day immersion. The present study shows that marine biological activity positively influences the Al alloy corrosion process, with surface modifications resulting in a protective effect counteracting the aggressiveness of chloride ions.

Deterioration of Lung Function in a Pig Model of Uncontrolled Cardiac Death.

INTRODUCTION: Uncontrolled donors after circulatory determination of death (uDCDD) represent a yet unexplored pool of organs potentially available for transplantation. The aims of this study were to validate a protocol of cardiac death in the pig and to investigate lung function during the process. MATERIALS AND METHODS: Cardiac death was induced in preanesthetized animals with an injection of 600 mg propofol; once systolic blood pressure was <50 mm Hg (Agonal Phase), a 20 mEq bolus of KCl was given and, after asystolia was documented, cardiopulmonary resuscitation (CPR) started, followed by 5 minutes no touch (end-CPR). Invasive blood pressure (BP) and heart rate (HR) were recorded; blood samples taken at baseline, 15 minutes after CPR, and after the no touch period (end-CPR). Computed tomography (CT) scans were taken at baseline and at end-CPR. RESULTS: Agonal phase was reached in 6 ± 1 minutes and lasted 3 ± 1 minutes; average HR was 49 ± 16 beats/min, and BP was 41 ± 12 mm Hg. CPR lasted 35 ± 3 minutes; average HR and BP were 113 ± 32 beats/min and 86 ± 63 mm Hg, respectively. PaO2/FiO2 decreased from 442 ± 31 mm Hg at baseline to 63 ± 36 at end-CPR (P < .001). pH decreased from 7.378 ± 0.045 to 6.931 ± 0.042 (P < .001), with a corresponding increase of lactate from 0.9 ± 0.2 to mmol/L to 12.8 ± 2.1 (P < .001). As assessed using CT scan, total lung volume decreased (baseline vs end-CPR 1107 ± 106 mL vs 617 ± 95; P < .001), whereas noninflated tissue (ie, atelectasis) significantly increased (46 ± 10 g vs 131 ± 89; P = .008). CONCLUSIONS: Lung function greatly deteriorated after cardiac death. The model we set may constitute a reproducible platform for future investigations on lung uDCDD.

Successful Transplantation of Lungs From an Uncontrolled Donor After Circulatory Death Preserved In Situ by Alveolar Recruitment Maneuvers and Assessed by Ex Vivo Lung Perfusion.

We developed a protocol to procure lungs from uncontrolled donors after circulatory determination of death (NCT02061462). Subjects with cardiovascular collapse, treated on scene by a resuscitation team and transferred to the emergency room, are considered potential donors once declared dead. Exclusion criteria include unwitnessed collapse, no-flow period of >15 min and low flow >60 min. After death, lung preservation with recruitment maneuvers, continuous positive airway pressure, and protective mechanical ventilation is applied to the donor. After procurement, ex vivo lung perfusion (EVLP) is performed. From November 2014, 10 subjects were considered potential donors; one of these underwent the full process of procurement, EVLP, and transplantation. The donor was a 46-year-old male who died because of thoracic aortic dissection. Lungs were procured 4 h and 48 min after death, and deemed suitable for transplantation after EVLP. Lungs were then offered to a rapidly deteriorating recipient with cystic fibrosis (lung allocation score [LAS] 46) who consented to the transplant in this experimental setting. Six months after transplantation, the recipient is in good condition (forced expiratory volume in 1 s 85%) with no signs of rejection. This protocol allowed procurement of lungs from an uncontrolled donor after circulatory determination of death following an extended period of warm ischemia.

Early outcome of liver transplantation performed with organs procured from brain death donors with transient or sustained cardio-circulatory collapse.

BACKGROUND: Aim of this study was to compare early graft function after transplantation of recipients transplanted with livers procured from donors after brain death who experienced transient or sustained cardio-circulatory collapse. METHODS: We retrospectively analysed patients who underwent liver transplantation (LTx) at our Institution from January 2010 to May 2012. Recipients were divided into 3 groups: those who received livers from brain death donors who experienced reversible cardio-circulatory arrest before organ procurement (RCA); those who experienced sustained cardio-circulatory collapse, treated with extra-corporeal membrane oxygenation support as rescue therapy of refractory cardiogenic shock (ECMO). Standard donors were considered as reference group (REF). Postoperative graft function, Primary Non-Function (PNF), and complications during the first 30 days were analysed. RESULTS: 102 LTx were analysed (76 REF, 22 RCA and 4 ECMO). The main cause of donor's death was post-anoxic coma in RCA and ECMO, cerebrovascular accident in REF. SGOT in REF, RCA, and ECMO donors were 27 [17-43], 54 [34-92], 716 [190-962] respectively, SGPT 17 [12-34], 46 [27-73], 84 [51-175] UI/L respectively, both P<0.01. All recipients had similar SGOT (P=0.48), SGPT (P=0.75) and Model for End-Stage Liver Disease scores (P=0.98) before LTx; similar graft cold and warm ischemia time and serum lactate levels at the end of surgery. After LTx, Intensive Care Unit stay and the incidence of PNF were similar. CONCLUSION: The use of livers procured from donors after brain death that experienced transient or sustained cardio-circulatory collapse was associated with early graft function comparable to that of standard donors.

Graft downsizing during ex vivo lung perfusion: case report and technical notes.

Among patients with respiratory insufficiency awaiting lung transplantation, small adult patients have a lower opportunity of receiving size-matched pulmonary grafts, because of the shortage of donors, particularly those of small size. Reducing the size of an oversized graft is one of the methods to increase the donor pool; similarly, ex vivo lung perfusion is an emerging technique aimed toward the same purpose. We describe how we combined the 2 techniques (lobar transplantation plus contralateral nonanatomic graft reduction during ex vivo lung perfusion) to overcome graft shortage in a clinical case. For the 1st time, this case report demonstrates that surgical manipulation during ex vivo lung perfusion does not affect the functional improvement in a lung previously judged to be not suitable for transplantation. The 6-month follow-up results are similar to those of standard bilateral lung transplantation.

Preoperative changes of forced vital capacity due to body position do not correlate with postoperative respiratory function in obese subjects.

BACKGROUND: Obese patients are at risk of developing postoperative pulmonary complications. We hypothesized that preoperative changes in dynamic spirometry due to body posture would correlate with the drop of forced vital capacity (FVC) measured early after surgery. METHODS: Thirty consecutive morbidly obese patients undergoing gastric banding were investigated. All subjects were studied the day before surgery (T0) and on postoperative day one (T1). Forced Vital Capacity (FVC) was measured, together with heart rate, mean arterial pressure and respiratory rate. At T0 measurements were taken in a random fashion with subjects in upright and in supine position. Subjects were then investigated after surgery in the supine position (T1). Postoperative pain was assessed at T1 using visual analogue scale. Intraoperative variables were also collected. RESULTS: Body Mass Index (BMI) of the investigated subjects was 43.9 ± 5.7 Kg/m2 (range 33.8-60); their age was 40 ± 8 years. All dynamic spirometric data decreased significantly from upright to supine position (P<0.05) and after surgery from 3.07 L (2.77-3.71) to 1.50 (1.15-2.12) (FVC T0 supine vs. T1, P<0.05). Changes of FVC due to body position did not correlate with changes of FVC occurring after surgery (R2=0.105, P=0.081). When subjects were stratified by the median postoperative drop of FVC (45.74%), preoperative (anthropometric and spirometric data), intraoperative (ventilatory settings and hemodynamics) and postoperative (FVC and pain) parameters were similar between groups. The duration of pneumoperitoneum was correlated with the drop of FVC (R2=0.551, P<0.05). CONCLUSION: The derangement of FVC that occurs in obese subjects after gastric banding is not predictable before surgery from anthropometric or spirometric data. The duration of pneumoperitoneum significantly contributes to postoperative impairment of respiratory function.

Extracorporeal lung perfusion and ventilation to improve donor lung function and increase the number of organs available for transplantation.

INTRODUCTION: Ex vivo lung perfusion (EVLP) has been validated as a valuable technique to increase the pool of organs available for lung transplantation. MATERIAL AND METHODS: After a preclinical experience, we obtained permission from the Ethics Committee of our institution to transplant lungs after EVLP reconditioning. ABO compatibility, size match, and donor arterial oxygen pressure (PaO(2))/fraction of inspired oxygen (FiO(2)) ≤ 300 mm Hg were considered to be inclusion criteria, whereas the presence of chest trauma and lung contusion, evidence of gastric content aspiration, pneumonia, sepsis, or systemic disease were exclusion criteria. We only considered subjects on an extra corporeal membrane oxygenation (ECMO) bridge to transplantation with rapid functional deterioration. Using Steen solution with packed red blood cells oxygenated with 21% O(2), 5% to 7% CO(2) was delivered, targeted with a blood flow of approximately 40% predicted cardiac output. Once normothermic, the lungs were ventilated with a tidal volume of 7 mL/kg a PEEP of 5 cmH(2)O and a respiratory rate of 7 bpm. Lungs were considered to be suitable for transplantation if well oxygenated [P(v-a) O(2) > 350 mm Hg on FiO(2) 100%], in the absence of deterioration of pulmonary vascular resistance and lung mechanics over the perfusion time. RESULTS: From March to September 2011, six lung transplantations were performed, including two with EVLP. The functional outcomes were similar between groups: at T72 posttransplantation, the median PaO(2)/FiO(2) were 306 mm Hg (range, 282 to 331 mm Hg) and 323 mm Hg (range, 270 to 396 mm Hg) (P = 1, EVLP versus conventional). Intensive care unit ICU and hospital length of stay were similar (P = .533 and P = .663, respectively) with no mortality at 60 days in both groups. EVLP donors were older (49 ± 6 y versus 21 ± 7 y, P < .05), less well oxygenated (184 ± 6 mm Hg versus 570 ± 30, P < .05), displaying higher Oto scores (9.5 ± 0.7 versus 1.7 ± 1.5, P < .05). CONCLUSIONS: The first 6 months of the EVLP program allowed us to increase the number of organs available for transplantation with short-term outcomes comparable to conventional transplantations.

Use of the Oto lung donor score to analyze the 2010 donor pool of the Nord Italia Transplant program.

INTRODUCTION: The feasibility and utility of a lung donor score that has been recently proposed was tested among a pool of lung donors referred to the Nord Italia Transplant program (NITp) organ procurement organization. MATERIAL AND METHODS: Each lung donor was assigned an Oto score including, age, smoking history, chest X-ray, secretions and ratio of arterial oxygen tension to inspired oxygen fraction (PaO(2)/FiO(2)). Based on clinical compromise, each variable received a score between 0 and 3, except for PaO(2)/FiO(2), which was scored between 0 and 6 given its overall relevance. RESULTS: Throughout 2010, 201 multiorgan donors were initially considered to be potential lung donors. Among these, 59 (29.4%) eventually yielded 67 lung transplantations (named "Used group"). Among the 142 (70.6%) refused lungs, 28 were not used due to logistic or medical problems ("general exclusion" group, GE) and 114, because of poor lung function ("lung exclusion" group, LE). Median lung donor scores were 1 (range, 0 to 3), 4 (range, 2.5 to 6.5), and 7 (range, 5 to 9) in the Used, GE, and LE groups, respectively (one-way analysis of variance, P < .001). Some donors with Oto scores ≤7 worsened over time so that the score had significantly increased by the time of organ retrieval. Overall, subjects who died after lung transplantation were characterized by higher lung donor scores, (2 [1-4] versus 0.5 [0-3], P = .003). CONCLUSION: Our analysis suggested that the use of a donor score as a dynamic tool over the donation process was of great utility to describe and analyze a pool of lung donors.

Lipomatous muscular 'dystrophy' of Piedmontese cattle.

Lipomatous myopathy is a degenerative muscle pathology characterized by the substitution of muscle cells with adipose tissue, sporadically reported in cattle, pigs, and rarely in sheep, horses and dogs. This study investigated the pathology of this myopathy in 40 muscle samples collected from regularly slaughtered Piedmontese cattle living in Piedmont region (Italy). None of the animals showed clinical signs of muscular disease. Muscle specimens were submitted to histological and enzymatic investigations. Gross pathology revealed a different grade of infiltration of adipose tissue, involving multiple or single muscles. The most affected regions were the ventral abdomen and the shoulders, especially the cutaneous muscles and the muscles of the thoracic group. Morphological staining revealed an infiltration of adipose tissue varying in distribution and severity, changes in muscle fibre size and increased number of fibres with centrally located nuclei, suggesting muscle degeneration-regeneration. Necrosis and non-suppurative inflammatory cells were also seen. Furthermore, proliferation of connective tissue and non-specific myopathic changes were present. Chemical and physical characteristics of the affected tissue were also evaluated. The authors discuss about the aetiopathogenesis and classification of this muscle disorder whose histological lesions were similar to those reported in human dystrophies.

The consumption of glucose during ex vivo lung perfusion correlates with lung edema.

INTRODUCTION: Ex vivo lung perfusion (EVLP) has been recently proposed to recondition organs before transplantation from donors with marginal or unacceptable features. The aim of our investigation was to explore glucose consumption during EVLP. MATERIALS AND METHODS: We investigated 8 domestic pigs (mean weight, 21 ± 0.8 kg). After perfusion with Perfadex, retrieval, and back table surgery, we initiated EVLP. The lungs were perfused with Steen solution with added methylprednisolone, cefazoline, and heparin. The blood flow was gradually increased with a target of 40% of the estimated cardiac output (or less if the pulmonary artery pressure was >15 mm Hg), while keeping the left atrial pressure between 3 and 5 mm Hg. The temperature of the perfusate was increased from 25 °C to 37 °C. Once the temperature of the lung outflow was >32 °C, we began gas flow (4 L/min, 5%-8% CO(2) in air) and mechanical ventilation. EVLP parameters and blood gases were measured throughout the experiment; glucose consumption was calculated as (glucose initial-glucose final)/time. The wet to dry ratio was also calculated as an index of lung edema. RESULTS: When stratified by median glucose consumption (0.237 mg/min), high glucose consumers (0.588 ± 0.17) were characterized by worse lung function, as assessed by oxygenation (partial pressure of oxygen/inspiratory fraction of oxygen [PaO(2)/FiO(2)] 326 ± 63 mm Hg vs 218 ± 84; P=.083 low vs high, respectively), and lung edema (wet/dry ratio 6.5 ± 0.7 vs 8.6 ± 0.9; P=.012). Glucose consumption correlated with wet to dry ratio (R(2)=0.663; P=.014). CONCLUSIONS: We found that the worse the lung function, the greater the consumption of glucose during EVLP. This observation suggests the need to explore lung metabolism during EVLP to possibly obtain metrics for evaluation.

The rule regulating pH changes during crystalloid infusion.

PURPOSE: To define the rule according to which crystalloid solutions characterized by different strong ion difference (SID) modify the acid-base variables of human plasma. METHODS: With a previously validated software, we computed the effects of diluting human plasma with crystalloid solutions ([SID] 0-60, 10 mEq/l stepwise). An equation was derived to compute the diluent [SID] required to maintain the baseline pH unchanged, at constant PCO2 and at every dilution fraction. The results were experimentally tested using fresh frozen plasma, re-warmed at 37°C, equilibrated at PCO2 35 and 78 mmHg, at baseline and after the infusion of crystalloid solutions with 0, 12, 24, 36, 48 mEq/l [SID]. RESULTS: The mathematical analysis showed that the diluent [SID] required to maintain unmodified the baseline pH equals the baseline bicarbonate concentration, [HCO3⁻], assuming constant PCO2 throughout the process. The experimental data confirmed the theoretical analysis. In fact, at the baseline [HCO3⁻] of 18.3 ± 0.3 mmol/l (PCO2 35 mmHg) the pH was 7.332 ± 0.004 and remained 7.333 ± 0.003 when the diluting [SID] was 18.5 ± 0.0 mEq/l. At baseline [HCO3⁻] of 19.5 ± 0.3 mmol/l (PCO2 78 mmHg) the pH was 7.010 ± 0.003 and remained 7.004 ± 0.003 when the diluting [SID] was 19.1 ± 0.1 mEq/l. At both PCO2 values infusion with [SID] lower or greater than baseline [HCO3⁻] led pH to decrease or increase, respectively. CONCLUSIONS: The baseline [HCO3⁻] dictates the pH response to crystalloid infusion. If a crystalloid [SID] equals baseline [HCO3⁻], pH remains unchanged at constant PCO2, whereas it increases or decreases if the [SID] is greater or lower, respectively.

Parenchymal and vascular lesions in ageing equine brains: histological and immunohistochemical studies.

Many age-related changes are described in the nervous system of different species, but detailed studies of brain lesions in ageing horses are lacking. The aim of the present study was to systematically characterize lesions in the brains of 60 horses aged from 7 to 23 years. No gross changes were present in any brain. Microscopically, spongiform changes, lipofuscin storage, corpora amylacea, gliosis and satellitosis were common, together with axonal and neuronal swellings. The most important findings were the presence of pseudocalcium-calcium (pCa-Ca) deposits and arterial wall degeneration. Scanning electron microscopical examination of two cases with vascular mineralization revealed marked deposition of an amorphous substance in the vessel walls that was probably formed by a polyanionic protein matrix and a mineral component. Immunohistochemically, numerous axonal spheroids were positively labelled for ubiquitin. No PrPsc was detected in sections with neuronal vacuolation. Neuronal swelling, corpora amylacea, hippocampal Tau-positive neurons and methenamine-positive diffuse (preamyloid) plaques were also detected. Congo red staining failed to detect amyloid deposition. The characterization of age-related lesions in the brains of these horses will allow these changes to be discriminated from pathological processes in future studies. Some lesions described here, including some vascular changes, the presence of diffuse plaques and tau accumulation in hippocampal neurons, have not been described previously in the horse.

Immunofluorescence staining for the detection of immunoglobulins and complement (C3) in dogs with renal disease.

Renal cortical biopsies from 74 dogs with different degrees of renal failure were studied by immunofluorescence to assess the frequency and extent of the deposition of immunoglobulins G, M and A (IgG, IgM, IgA) and complement C3. The dogs were divided into two groups on the basis of their clinical signs, and standard histological and electron microscopical examinations, according to whether their disease was an immune-mediated nephropathy (IMN) or a non-immune-mediated nephropathy (NIMN). In the dogs with an imn there was strong immunofluorescence due to IgG in the mesangium and the glomerular basement membrane and to IgM in the mesangium. The mechanism of immune complex trapping in the glomerulus also resulted in positive reactions to IgM in the dogs with an NIMN.

Abdomino-thoracic transmission during ACS: facts and figures.

Elevated intra-abdominal pressure (IAP) exerts effects not only on intra-abdominal organs, but also on organs distant to the abdominal compartment. Abdomino-thoracic interaction during intra-abdominal hypertension (IAH) or abdominal compartment syndrome (ACS) interferes with pulmonary, cardiovascular and cerebral function. In accordance with recent guidelines, IAH is defined as IAP above 12 mmHg and ACS as IAP more than 20 mmHg with one or more new organ failures. In this review we will first discuss the effects of elevated IAP on pulmonary dynamics and the relevance for interpreting airway pressures and adjusting ventilator settings. We will then discuss the interaction between abdomino-thoracic pressure transmission and global haemodynamics, the knowledge of which is necessary for correct assessment of cardiac preload and to optimize fluid therapy in the setting of IAH/ACS. A discussion on the relationship between increased IAP, increased intracranial pressure (ICP) and decreased cerebral perfusion pressure (CPP) will follow. Finally, we will review ventilator-induced thoracic pressure swings and their transmission to the abdominal compartment.

Canine necrotizing encephalitis associated with anti-glomerular basement membrane glomerulonephritis.

A 2-year-old male West Highland white terrier with a 4-month history of seizures was referred for investigation. Depressed mentation, proprioceptive deficit and decreased menace response were noted at neurological examination. Post-mortem examination of the brain revealed multifocal lesions located principally in the left side of the diencephalon and mesencephalon. The lesions consisted of non-suppurative inflammation and large areas of cavitation. The clinical evaluation and histopathological findings were consistent with a diagnosis of necrotizing meningoencephalitis (NME). Immunofluorescence performed on frozen sections of kidney revealed strong smooth linear labelling of the glomerular basement membrane with anti-IgG serum as well as weaker linear labelling with anti-IgM serum. This histomorphological pattern was consistent with anti-glomerular basement membrane glomerulonephritis. The association of this type of glomerulonephritis with a necrotizing encephalitis would support the hypothesis of an immune-mediated aetiology for NME.

Abdomino-thoracic transmission during acs: facts and figures.

Elevated intra-abdominal pressure (IAP) exerts effects not only on intra-abdominal organs, but also on organs distant to the abdominal compartment. Abdomino-thoracic interaction during intra-abdominal hypertension (IAH) or abdominal compartment syndrome (ACS) interferes with pulmonary, cardiovascular and cerebral function. In accordance with recent guidelines, IAH is defined as IAP above 12 mmHg and ACS as IAP more than 20 mmHg with one or more new organ failures. In this review we will first discuss the effects of elevated IAP on pulmonary dynamics and the relevance for interpreting airway pressures and adjusting ventilator settings. We will then discuss the interaction between abdomino-thoracic pressure transmission and global haemodynamics, the knowledge of which is necessary for correct assessment of cardiac preload and to optimize fluid therapy in the setting of IAH/ACS. A discussion on the relationship between increased IAP, increased intracranial pressure (ICP) and decreased cerebral perfusion pressure (CPP) will follow. Finally, we will review ventilator-induced thoracic pressure swings and their transmission to the abdominal compartment.

Positive end-expiratory pressure applied to the dependent lung during one-lung ventilation improves oxygenation and respiratory mechanics in patients with high FEV1.

BACKGROUND AND OBJECTIVE: The aim of this study was to test the efficacy of positive end-expiratory pressure (PEEP) to the dependent lung during one-lung ventilation, taking into consideration underlying lung function in order to select responders to PEEP. METHODS: Forty-six patients undergoing open-chest thoracic surgical procedures were studied in an operating room of a university hospital. Patients were randomized to receive zero end-expiratory pressure (ZEEP) or 10 cmH2O of PEEP to the dependent lung during one-lung ventilation in lateral decubitus. The patients were stratified according to preoperative forced expiratory volume in 1 s (FEV1) as an indicator of lung function (below or above 72%). Oxygenation was measured in the supine position, in the lateral decubitus with an open chest, and after 20 min of ZEEP or PEEP. The respiratory system pressure-volume curve of the dependent hemithorax was measured in supine and open-chest lateral decubitus positions with a super-syringe. RESULTS: Application of 10 cmH2O of PEEP resulted in a significant increase in PaO2 (P < 0.05). This did not occur in ZEEP group, considered as a time matched control. PEEP improved oxygenation only in patients with high FEV1 (from 11.6+/-4.8 to 15.3+/-7.1 kPa, P < 0.05). There was no significant change in the low FEV1 group. Dependent hemithorax compliance decreased in lateral decubitus, more in patients with high FEV1 (P < 0.05). PEEP improved compliance to a greater extent in patients with high FEV1 (from 33.6+/-3.6 to 48.4+/-3.9 mLcmH2O(-1), P < 0.05). CONCLUSIONS: During one-lung ventilation in lateral decubitus, PEEP applied to the dependent lung significantly improves oxygenation and respiratory mechanics in patients with rather normal lungs as assessed by high FEV1.

Physical and biological triggers of ventilator-induced lung injury and its prevention.

Ventilator-induced lung injury is a side-effect of mechanical ventilation. Its prevention or attenuation implies knowledge of the sequence of events that lead from mechanical stress to lung inflammation and stress at rupture. A literature review was undertaken which focused on the link between the mechanical forces in the diseased lung and the resulting inflammation/rupture. The distending force of the lung is the transpulmonary pressure. This applied force, in a homogeneous lung, is shared equally by each fibre of the lung's fibrous skeleton. In a nonhomogeneous lung, the collapsed or consolidated regions do not strain, whereas the neighbouring fibres experience excessive strain. Indeed, if the global applied force is excessive, or the fibres near the diseased regions experience excessive stress/strain, biological activation and/or mechanical rupture are observed. Excessive strain activates macrophages and epithelial cells to produce interleukin-8. This cytokine recruits neutrophils, with consequent full-blown inflammation. In order to prevent initiation of ventilator-induced lung injury, transpulmonary pressure must be kept within the physiological range. The prone position may attenuate ventilator-induced lung injury by increasing the homogeneity of transpulmonary pressure distribution. Positive end-expiratory pressure may prevent ventilator-induced lung injury by keeping open the lung, thus reducing the regional stress/strain maldistribution. If the transpulmonary pressure rather than the tidal volume per kilogram of body weight is taken into account, the contradictory results of the randomised trials dealing with different strategies of mechanical ventilation may be better understood.