Systemic PaO2 Oscillations Cause Mild Brain Injury in a Pig Model.

OBJECTIVE: Systemic PaO2 oscillations occur during cyclic recruitment and derecruitment of atelectasis in acute respiratory failure and might harm brain tissue integrity. DESIGN: Controlled animal study. SETTING: University research laboratory. SUBJECTS: Adult anesthetized pigs. INTERVENTIONS: Pigs were randomized to a control group (anesthesia and extracorporeal circulation for 20 hr with constant PaO2, n = 10) or an oscillation group (anesthesia and extracorporeal circulation for 20 hr with artificial PaO2 oscillations [3 cycles min⁻¹], n = 10). Five additional animals served as native group (n = 5). MEASUREMENTS AND MAIN RESULTS: Outcome following exposure to artificial PaO2 oscillations compared with constant PaO2 levels was measured using 1) immunohistochemistry, 2) real-time polymerase chain reaction for inflammatory markers, 3) receptor autoradiography, and 4) transcriptome analysis in the hippocampus. Our study shows that PaO2 oscillations are transmitted to brain tissue as detected by novel ultrarapid oxygen sensing technology. PaO2 oscillations cause significant decrease in NISSL-stained neurons (p < 0.05) and induce inflammation (p < 0.05) in the hippocampus and a shift of the balance of hippocampal neurotransmitter receptor densities toward inhibition (p < 0.05). A pathway analysis suggests that cerebral immune and acute-phase response may play a role in mediating PaO2 oscillation-induced brain injury. CONCLUSIONS: Artificial PaO2 oscillations cause mild brain injury mediated by inflammatory pathways. Although artificial PaO2 oscillations and endogenous PaO2 oscillations in lung-diseased patients have different origins, it is likely that they share the same noxious effect on the brain. Therefore, PaO2 oscillations might represent a newly detected pathway potentially contributing to the crosstalk between acute lung and remote brain injury.

Deviation of tracheal pressure from airway opening pressure during high-frequency oscillatory ventilation in a porcine lung model.

Oxygenation during high-frequency oscillatory ventilation is secured by a high level of mean airway pressure. Our objective was to identify a pressure difference between the airway opening of the respiratory circuit and the trachea during application of different oscillatory frequencies. Six female Pietrain pigs (57.1 ± 3.6 kg) were first ventilated in a conventional mechanical ventilation mode. Subsequently, the animals were switched to high-frequency oscillatory ventilation by setting mean airway opening pressure 5 cmH(2)O above the one measured during controlled mechanical ventilation. Measurements at the airway opening and at tracheal levels were performed in healthy lungs and after induction of acute lung injury by surfactant depletion. During high-frequency oscillatory ventilation, the airway opening pressure was set at a constant level. The pressure amplitude was fixed at 90 cmH(2)O. Starting from an oscillatory frequency of 3 Hz, the frequency was increased in steps of 3 Hz to 15 Hz and then decreased accordingly. At each frequency, measurements were performed in the trachea through a side-lumen of the endotracheal tube and the airway opening pressure was recorded. The pressure difference was calculated. At every oscillatory frequency, a pressure loss towards the trachea could be shown. This pressure difference increased with higher oscillatory frequencies (3 Hz 2.2 ± 2.1 cmH(2)O vs. 15 Hz 7.5 ± 1.8 cmH(2)O). The results for healthy and injured lungs were similar. Tracheal pressures decreased with higher oscillatory frequencies. This may lead to pulmonary derecruitment. This has to be taken into consideration when increasing oscillatory frequencies and differentiated pressure settings are mandatory.

Evaluating intra-abdominal pressures in a porcine model of acute lung injury by using a wireless motility capsule.

BACKGROUND: Intra-vesical pressure measurement as the reference standard for assessing intra-abdominal pressures is mainly indirect and discontinuous. We therefore evaluated a motility capsule for continuous intra-abdominal pressure measurement in an animal model with a high probability for capillary leakage and intestinal edema. MATERIAL/METHODS: Motility capsules were inserted into the stomachs of 8 anesthetized and ventilated pigs. Stomach pH, pressure, and temperature data were wirelessly transmitted to a recorder attached to each animal's abdomen. Intra-gastric pressures measured by the capsule were compared to intra-vesical pressures measured by a pressure transducer system. RESULTS: The intra-abdominal pressures ranged from 3 to 15 mmHg (7.8 ± 2.4 mmHg [mean ± SD]) measured via the bladder. The capsule pressure recordings ranged from 1 to 3 mmHg (1.7 ± 0.5 mmHg [mean ± SD]). Bland-Altman analysis revealed an unacceptable bias between the 2 methods. The test bias was 6.2 (± 1.4) mmHg and the limits of agreement were from 3.3 to 8.9 mmHg. CONCLUSIONS: Pressures in the stomach as measured by motility capsule underestimated the intra-vesical pressures. Discrepancies between gastric and intra-vesical pressures could be caused by gastric dilatation or different position of the 2 devices to the zero reference point.

Hepatic effects of lung-protective pressure-controlled ventilation and a combination of high-frequency oscillatory ventilation and extracorporeal lung assist in experimental lung injury.

BACKGROUND: Ventilation with high positive end-expiratory pressure (PEEP) can lead to hepatic dysfunction. The aim of this study was to investigate the hepatic effects of strategies using high airway pressures either in pressure-controlled ventilation (PCV) or in high-frequency oscillatory ventilation (HFOV) combined with an arteriovenous extracorporeal lung assist (ECLA). MATERIAL/METHODS: Pietrain pigs underwent induction of lung injury by saline lavage. Ventilation was continued for 24 hours either as PCV with tidal volumes of 6 ml/kg and PEEP 3 cmH2O above the lower inflection point of the pressure-volume curve or as HFOV (≥ 12 Hz) with a mean tracheal airway pressure 3 cmH2O above the lower inflection point combined with arteriovenous ECLA (HFOV+ECLA). Fluids and norepinephrine stabilized the circulation. The indocyanine green plasma disappearance rate, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, glutamate dehydrogenase, lactate dehydrogenase and creatine kinase were determined repeatedly. Finally, liver neutrophils were counted and liver cell apoptosis was assessed by terminal deoxynucleotidyl transferase nick end labeling (TUNEL). RESULTS: Aspartate aminotransferase increased in the PCV group about three-fold and in the HFOV+ECLA group five-fold (p<0.001). Correspondingly, creatine kinase increased about two-fold and four-fold, respectively (p<0.001). Lactate dehydrogenase was increased in the HFOV+ECLA group (p<0.028). The number of neutrophils infiltrating the liver tissue and the apoptotic index were low. CONCLUSIONS: High airway pressure PCV and HFOV with ECLA in the treatment of lavage-induced lung injury in pigs did not cause liver dysfunction or damage. The detected elevation of enzymes might be of extrahepatic origin.

Gastric pH and motility in a porcine model of acute lung injury using a wireless motility capsule.

BACKGROUND: Evaluation of gastric pH and motility in a porcine model of acute lung injury using a novel, wireless motility capsule. MATERIAL/METHODS: A motility capsule was applied into the stomach of 7 Pietrain pigs with acute lung injury induced by high volume saline lavage. Wireless transmission of pH, pressure and temperature data was performed by a recorder attached to the animal's abdomen. Gastric motility was evaluated using pH and pressure values, and capsule location was confirmed by autopsy. RESULTS: Gastric pH values were statistically significantly different (P<0.003) in the animals over time and ranged from 1.15 to 9.94 [5.73 ± 0.47 (mean ± SD)] with an interquartile range of 0.11 to 2.07. The capsule pressure recordings ranged from 2 to 4 mmHg [2.6 ± 0.5 mmHg (mean ± SD)]. There was no change in pressure patterns or sudden rise of pH >3 pH units during 24 hours. All animals had a gastroparesis with the capsules located in the stomach as indicated by the pressure and pH data and confirmed by necropsy. CONCLUSIONS: The preliminary data show that Pietrain pigs with acute lung injury have a high variability in gastric pH and severely disturbed gastric motility.

Acute respiratory distress induced by repeated saline lavage provides stable experimental conditions for 24 hours in pigs.

Surfactant depletion is most often used to study acute respiratory failure in animal models. Because model stability is often criticized, the authors tested the following hypotheses: Repeated pulmonary lavage with normal saline provides stable experimental conditions for 24 hours with a PaO2/FiO2 ratio < 300 mm Hg. Lung injury was induced by bilateral pulmonary lavages in 8 female pigs (51.5 +/- 4.8 kg). The animals were ventilated for 24 hours (PEEP: 5 cm H2O; tidal volume: 6 mL/kg; respiratory rate: 30/min). After 24 hours the animals were euthanized. For histopathology slides from all pulmonary lobes were obtained. Supernatant of the bronchoalveolar fluid collected before induction of acute respiratory distress syndrome (ARDS) and after 24 hours was analyzed. A total of 19 +/- 6 lavages were needed to induce ARDS. PaO2/FiO2 ratio and pulmonary shunt fraction remained significantly deteriorated compared to baseline values after 24 hours (P < .01). Slight to moderate histopathologic changes were detected. Significant increases of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were observed after 24 hours (P < .01). The presented surfactant depletion-based lung injury model was associated with increased pulmonary inflammation and fulfilled the criteria of acute ling injury (ALI) for 24 hours.

Arteriovenous Extracorporeal Lung Assist Allows For Maximization Of Oscillatory Frequencies: A Large-animal Model Of Respiratory Distress.

BACKGROUND: Although the minimization of the applied tidal volume (VT) during high-frequency oscillatory ventilation (HFOV) reduces the risk of alveolar shear stress, it can also result in insufficient CO2-elimination with severe respiratory acidosis. We hypothesized that in a model of acute respiratory distress (ARDS) the application of high oscillatory frequencies requires the combination of HFOV with arteriovenous extracorporeal lung assist (av-ECLA) in order to maintain or reestablish normocapnia. METHODS: After induction of ARDS in eight female pigs (56.5 ± 4.4 kg), a recruitment manoeuvre was performed and intratracheal mean airway pressure (mPaw) was adjusted 3 cmH2O above the lower inflection point (Plow) of the pressure-volume curve. All animals were ventilated with oscillatory frequencies ranging from 3-15 Hz. The pressure amplitude was fixed at 60 cmH2O. At each frequency gas exchange and hemodynamic measurements were obtained with a clamped and de-clamped av-ECLA. Whenever the av-ECLA was de-clamped, the oxygen sweep gas flow through the membrane lung was adjusted aiming at normocapnia. RESULTS: Lung recruitment and adjustment of the mPaw above Plow resulted in a significant improvement of oxygenation (p < 0.05). Compared to lung injury, oxygenation remained significantly improved with rising frequencies (p < 0.05). Normocapnia during HFOV was only maintained with the addition of av-ECLA during frequencies of 9 Hz and above. CONCLUSION: In this animal model of ARDS, maximization of oscillatory frequencies with subsequent minimization of VT leads to hypercapnia that can only be reversed by adding av-ECLA. When combined with a recruitment strategy, these high frequencies do not impair oxygenation.