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Harmful effects of mechanical ventilation with large tidal volumes, volutrauma, may contribute much to diffuse acute lung injury. Extracellular vesicles have been noted in the context of vital organ injury. We hypothesized that extracellular vesicles from acutely injured lung can be found in both lung and blood. In a two-hit experimental porcine model, we tested if extracellular vesicles could be detected in bronchoalveolar lavage fluid and in plasma over a six-hour period of large tidal volume ventilation after surfactant depletion. After 2 hours of volutrauma, bronchoalveolar lavage fluid showed increased levels of extracellular vesicles containing nucleic acids (stained by SYTO 13) and those positive for both SYTO 13 and HMGB1. No such increase was detected in plasma at any timepoint during the six-hour experiments. This shows that nucleic acid-containing extracellular vesicles appear to be involved in progression of lung injury, possibly indicating cellular damage, but their potential to serve as diagnostic biomarkers of acute lung injury progression, based on plasma sampling, and in the very early phase, is not confirmed by these findings.

Pharmacological inhibition of soluble epoxide hydrolase has been shown to attenuate lung injury development in rodents exposed to bacterial lipopolysaccharide. To investigate if these effects can be reproduced in larger animals, we tested soluble epoxide hydrolase (sEH) inhibition using an sEH inhibitor 1-adamantanyl-3-{5-[2-(ethylethoxy)ethoxy]pentyl}urea (AEPU) in a porcine model of lipopolysaccharide-induced acute lung injury. AEPU was selected from 23 sEH inhibitors based on IC50 values and metabolic stability profiles established by a fluorescent based activity assay and porcine liver microsomal test, respectively. Hydrolysis of fatty acid epoxides to their corresponding diols is catalyzed by sEH. Inhibition of sEH reduces this conversion, leading to an accumulation of epoxides relative to diols. Hence, AEPU-treated subjects (n = 9) showed metabolic signs of effective in vivo inhibition of the target enzyme reflected in an increased epoxide/diol ratio of 12 (13)-epoxyoctadecenoic acid to 12,13-dihydroxyoctadecenoic acid compared to placebo-treated controls (p = 0.026). However, there was no difference in lung injury development or survival in subjects treated with the rapidly metabolized AEPU compared to placebo-treated controls (n = 10). In conclusion, administration of the soluble epoxide hydrolase inhibitor AEPU did not attenuate endotoxin induced lung injury with lipopolysaccharide in pigs under the severe conditions tested here.

Inflammatory signaling pathways involving eicosanoids and other regulatory lipid mediators are a subject of intensive study, and a role for these in acute lung injury is not yet well understood. We hypothesized that oxylipin release from lung injury could be detected in bronchoalveolar lavage fluid and in plasma. In a porcine model of surfactant depletion, ventilation with hyperinflation was assessed. Bronchoalveolar lavage and plasma samples were analyzed for 37 different fatty acid metabolites (oxylipins). Over time, hyperinflation altered concentrations of 4 oxylipins in plasma (TXB₂, PGE₂, 15-HETE and 11-HETE), and 9 oxylipins in bronchoalveolar lavage fluid (PGF_2α, PGE₂, PGD₂, 12,13-DiHOME, 11,12-DiHETrE, 13-HODE, 9-HODE, 15-HETE, 11-HETE). Acute lung injury caused by high tidal volume ventilation in this porcine model was associated with rapid changes in some elements of the oxylipin profile, detectable in lavage fluid, and plasma. These oxylipins may be relevant in the pathogenesis of acute lung injury by hyperinflation.

BACKGROUND: Although mechanical ventilation is often lifesaving, it can also cause injury to the lungs. The lung injury is caused by not only high pressure and mechanical forces but also by inflammatory processes that are not fully understood. Heparin-binding protein (HBP), released by activated granulocytes, has been indicated as a possible mediator of increased vascular permeability in the lung injury associated with trauma and sepsis. We investigated if HBP levels were increased in the bronchoalveolar lavage fluid (BALF) or plasma in a pig model of ventilator-induced lung injury (VILI). We also investigated if HBP was present in BALF from healthy volunteers and in intubated patients in the intensive care unit (ICU).

METHODS: Anaesthetized pigs were randomized to receive ventilation with either tidal volumes of 8 ml/kg (controls, n = 6) or 20 ml/kg (VILI group, n = 6). Plasma and BALF samples were taken at 0, 1, 2, 4, and 6 h. In humans, HBP levels in BALF were sampled from 16 healthy volunteers and from 10 intubated patients being cared for in the ICU.

RESULTS: Plasma levels of HBP did not differ between pigs in the control and VILI groups. The median HBP levels in BALF were higher in the VILI group after 6 h of ventilation compared to those in the controls (1144 ng/ml (IQR 359-1636 ng/ml) versus 89 ng/ml (IQR 33-191 ng/ml) ng/ml, respectively, p = 0.02). The median HBP level in BALF from healthy volunteers was 0.90 ng/ml (IQR 0.79-1.01 ng/ml) as compared to 1959 ng/ml (IQR 612-3306 ng/ml) from intubated ICU patients (p < 0.001).

CONCLUSIONS: In a model of VILI in pigs, levels of HBP in BALF increased over time compared to controls, while plasma levels did not differ between the two groups. HBP in BALF was high in intubated ICU patients in spite of the seemingly non-harmful ventilation, suggesting that inflammation from other causes might increase HBP levels.

Pigs are used for long-term biomedical experiments requiring repeated injections, infusions and collections of blood samples. Thus, it is necessary for vascular catheters to be indwelling to avoid undue stress to the animals and the use of restraints. We propose a refined model of percutaneous insertion of long-term central venous catheters to minimize the surgical trauma and postoperative complications associated with catheter insertion. Different sizes of needles (18 Ga versus 21 Ga) for initial puncture of the veins were compared. In conventional pigs weighing less than 30 kg, catheter insertion may be facilitated by using a microintroducer set with a 21 Ga needle. In pigs weighing 50 kg, a standard 18 Ga needle may be preferable.

Objectives: To report and evaluate a complex touch massage intervention according to the British Medical Research Council framework. This study aimed to evaluate the effects of touch massage on levels of anxiety and physiological stress in patients scheduled for elective aortic surgery.

Background: The use of touch massage has increased during the past decade but no systematic studies have been implemented to investigate the effectiveness of such treatment. It is important to conduct multidisciplinary investigations into the effects of complex interventions such as touch massage. For this, the British Medical Research Council has provided a useful framework to guide the development, piloting, evaluation and reporting of complex intervention studies.

Method: A pilot study with a randomized controlled design including 20 patients (10 + 10) scheduled for elective aortic surgery. Selected outcome parameters included; self-reported anxiety, measured by the State-Trait Anxiety Inventory Form Y instrument, and physiological stress, measured by heart rate variability, blood pressure, respiratory frequency, oxygen saturation and concentrations of cortisol, insulin and glucose in serum.

Results: There were significant differences in self-reported anxiety levels before and after touch massage (p = 0·007), this was not observed in the control group (p = 0·833). There was a significant difference in self-reported anxiety levels between the touch massage group and the control group after touch massage and rest (p = 0·001). There were no significant differences in physiological stress-related outcome parameters between patients who received touch massage and controls.

Conclusion: In our study, touch massage decreased anxiety levels in patients scheduled for elective aortic surgery, and the British Medical Research Council framework was a useful guideline for the development, evaluation and reporting of a touch massage intervention.

Relevance to clinical practice: Touch massage can reduce patients' anxiety levels and is thus an important nursing intervention in intensive and post-operative care.

Touch massage (TM) is a form of pleasant touch stimulation used as treatment in clinical settings and found to improve well-being and decrease anxiety, stress, and pain. Emotional responses reported during and after TM have been studied, but the underlying mechanisms are still largely unexplored. In this study, we used functional magnetic resonance (fMRI) to test the hypothesis that the combination of human touch (i.e. skin-to-skin contact) with movement is eliciting a specific response in brain areas coding for pleasant sensations. The design included four different touch conditions; human touch with or without movement and rubber glove with or without movement. Force (2.5N) and velocity (1.5cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale) and human touch was rated as most pleasant, particularly in combination with movement. The fMRI results revealed that TM stimulation most strongly activated the pregenual anterior cingulate cortex (pgACC). These results are consistent with findings showing pgACC activation during various rewarding pleasant stimulations. This area is also known to be activated by both opioid analgesia and placebo. Together with these prior results, our finding furthers the understanding of the basis for positive TM treatment effects.

OBJECTIVES: To evaluate effects of touch massage (TM) on stress responses in healthy volunteers.

METHODS: A crossover design including twenty-two (mean age=28.2) healthy volunteers (11 male and 11 female) cardiac autonomic tone was measured by heart rate (HR) and heart rate variability (HRV). Stress hormone levels (cortisol) were followed in saliva. We also measured blood glucose and serum insulin. Extracellular (ECV) levels of glucose, lactate, pyruvate and glycerol were followed using the microdialysis technique (MD). TM was performed on hands and feet for 80min, during control, participants rested in the same setting. Data were collected before, during, and after TM and at rest. Saliva cortisol, serum glucose, and serum insulin were collected before, immediately following, and 1h after intervention or control, respectively.

RESULTS: After 5min TM, HR decreased significantly, indicating a reduced stress response. Total HRV and all HRV components decreased during intervention. Saliva cortisol and insulin levels decreased significantly after intervention, while serum glucose levels remained stable. A similar, though less prominent, pattern was seen during the control situation. Only minor changes were observed in ECV levels of glucose (a decrease) and lactate (an increase). No significant alterations were observed in glycerol or pyruvate levels throughout the study. There were no significant differences between groups in ECV concentrations of analyzed substances.

CONCLUSIONS: In healthy volunteers, TM decreased sympathetic nervous activity, leading to decreased overall autonomic activity where parasympathetic nervous activity also decreased, thereby maintaining the autonomic balance.

To test the hypotheses that repeated brief intestinal ischemic insults would elicit an intestinal preconditioning response to a subsequent intestinal I/R injury and that a similar response would be elicited by repeated lung recruitment maneuvers (RMs). Randomized experimental controlled animal study. University hospital animal laboratory. Eighteen anesthetized pigs. Animals were randomized to one of three groups, with six animals in each group. Control group 75-min superior mesenteric artery (SMA) occlusion followed by 60-min reperfusion. Ischemic preconditioning group, three 5-min-long SMA occlusions preceding 75-min SMA occlusion and 60-min reperfusion. Recruitment maneuver (RM) group, three 2-min-long RMs preceding 75-min SMA occlusion and 60-min reperfusion. We measured systemic and mesenteric hemodynamic parameters, jejunal mucosal perfusion, net mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygenation. Every 15 min, jejunal microdialysate samples were collected and analyzed for glucose, lactate, and glycerol. Jejunal tissue samples were collected postmortem. After occlusion of SMA, regional parameters in all groups indicated abolished perfusion and gradually increasing intraluminal microdialysate lactate and glycerol levels. At reperfusion, regional parameters indicated mesenteric hyperperfusion, whereas microdialysis markers of mucosal anaerobic metabolism and cell injury decreased, although not reaching baseline. Histological examination revealed severe mucosal injury in all groups. There were no significant differences between groups in the observed parameters. No protective preconditioning response could be observed when performing repeated brief intestinal ischemic insults or repeated lung RMs before an intestinal I/R injury.