Pulmonary effects of expiratory-assisted small-lumen ventilation during upper airway obstruction in pigs.

Novel devices for small-lumen ventilation may enable effective inspiration and expiratory ventilation assistance despite airway obstruction. In this study, we investigated a porcine model of complete upper airway obstruction. After ethical approval, we randomly assigned 13 anaesthetised pigs either to small-lumen ventilation following airway obstruction (n = 8) for 30 min, or to volume-controlled ventilation (sham setting, n = 5). Small-lumen ventilation enabled adequate gas exchange over 30 min. One animal died as a result of a tension pneumothorax in this setting. Redistribution of ventilation from dorsal to central compartments and significant impairment of the distribution of ventilation/perfusion occurred. Histopathology demonstrated considerable lung injury, predominantly through differences in the dorsal dependent lung regions. Small-lumen ventilation maintained adequate gas exchange in a porcine airway obstruction model. The use of this technique for 30 min by inexperienced clinicians was associated with considerable end-expiratory collapse leading to lung injury, and may also carry the risk of severe injury.

Ventilation/perfusion ratios measured by multiple inert gas elimination during experimental cardiopulmonary resuscitation.

BACKGROUND: During cardiopulmonary resuscitation (CPR) the ventilation/perfusion distribution (VA /Q) within the lung is difficult to assess. This experimental study examines the capability of multiple inert gas elimination (MIGET) to determine VA /Q under CPR conditions in a pig model. METHODS: Twenty-one anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0, 0.7 or 0.21). VA/ Q by micropore membrane inlet mass spectrometry-derived MIGET was determined at baseline and during CPR following induction of ventricular fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical impedance tomography and return of spontaneous circulation were assessed. Intergroup differences were analysed by non-parametric testing. RESULTS: MIGET measurements were feasible in all animals with an excellent correlation of measured and predicted arterial oxygen partial pressure (R(2) = 0.96, n = 21 for baseline; R(2) = 0.82, n = 21 for CPR). CPR induces a significant shift from normal VA /Q ratios to the high VA /Q range. Electrical impedance tomography indicates a dorsal to ventral shift of the ventilation distribution. Diverging pulmonary shunt fractions induced by the three inspired oxygen levels considerably increased during CPR and were traceable by MIGET, while 100% oxygen most negatively influenced the VA /Q. Return of spontaneous circulation were achieved in 52% of the animals. CONCLUSIONS: VA /Q assessment by MIGET is feasible during CPR and provides a novel tool for experimental purposes. Changes in VA /Q caused by different oxygen fractions are traceable during CPR. Beyond pulmonary perfusion deficits, these data imply an influence of the inspired oxygen level on VA /Q. Higher oxygen levels significantly increase shunt fractions and impair the normal VA /Q ratio.

PaO2 oscillations caused by cyclic alveolar recruitment can be monitored in pig buccal mucosa microcirculation.

BACKGROUND: Cyclic alveolar recruitment and derecruitment play a role in the pathomechanism of acute lung injury and may lead to arterial partial pressure of oxygen (PaO(2) ) oscillations within the respiratory cycle. It remains unknown, however, if these PaO(2) oscillations are transmitted to the microcirculation. The present study investigates if PaO(2) oscillations can be detected in the pig buccal mucosa microcirculation. METHODS: Respiratory failure was induced by surfactant depletion in seven pigs. PaO(2) oscillations caused by cyclic recruitment and derecruitment were measured in the thoracic aorta by fast fluorescence quenching of oxygen technology. Haemoglobin oxygen saturation, haemoglobin amount and blood flow in the buccal mucosa microcirculation were determined by combined fast white light spectrometry and laser Doppler flowmetry additionally to systolic arterial pressure. Measurements were performed during baseline conditions and during cyclic recruitment and derecruitment. RESULTS: Measurements remained stable during baseline. Respiratory-dependent oscillations occurred in the systemic circulation [PaO(2) oscillations 92 (69-172) mmHg; systolic arterial pressure oscillations 33 (13-35) %] and were related to the respiratory rate (5.0 ± 0.2/min) as confirmed by Fourier analysis. Synchronised oscillations were detected to the pig buccal mucosa microcirculation [haemoglobin oxygen saturation oscillations 3.4 (2.7-4.9) %; haemoglobin amount oscillations 8.5 (2.3-13.3) %; blood flow oscillations 66 (18-87) %]. The delay between PaO(2) -\ and microcirculatory oxygen oscillations was 7.2 ± 2.8 s. CONCLUSION: The present study suggests that PaO(2) oscillations caused by cyclic recruitment and derecruitment were transmitted to the buccal mucosa microcirculation. This non-invasive approach of measuring oxygen waves as a surrogate parameter of cyclic recruitment and derecruitment could be used to monitor PaO(2) oscillations at the bedside.

An inhaled tumor necrosis factor-alpha-derived TIP peptide improves the pulmonary function in experimental lung injury.

INTRODUCTION: The lectin-like domain of TNF-α enhances the fluid clearance across the alveolar barrier. For experimental purposes, the lectin-like domain can be mimicked by a synthetic peptide representing the TIP-motif of TNF-α. The present study aims to assess the acute effect of TIP on the pulmonary function in a porcine model of acute respiratory distress syndrome (ARDS). METHODS: Lung injury was induced in 16 pigs (25-27 kg) by bronchoalveolar lavage followed by injurious ventilation. Following randomisation, either nebulised TIP (1 mg/kg; AP301, APEPTICO, Vienna, Austria) or water for injection (control group) was administered. During 5 h of monitoring, the extravascular lung water index (EVLWI), the quotient of partial pressure of oxygen and inspired oxygen concentration (PaO(2) /FiO(2) ) and the pulmonary shunt fraction were repetitively assessed. The data were evaluated by an analysis of variance including Bonferroni-Holm correction. RESULTS: Comparable baseline conditions in both groups were achieved. Ventilatory parameters were standardised in both groups. In the TIP group, a significant reduction of the EVLWI and a simultaneous increase in the PaO(2) /FiO(2) ratio was shown (each P < 0.0001). No changes in the control group were observed (EVLWI: P = 0.43, PaO(2) /FiO(2) : P = 0.60). The intergroup comparison demonstrates a significant advantage of TIP inhalation over placebo (EVLWI: P < 0.0001, PaO(2) /FiO(2) : P = 0.004, shunt fraction: P = 0.0005). CONCLUSIONS: The inhalation of TIP induces an amelioration of clinical surrogate parameters of the lung function in a porcine lung injury model. By mimicking the lectin-like domain, the synthetic TIP peptide AP301 is an innovative approach as supportive therapy in ARDS.

Transmission of arterial oxygen partial pressure oscillations to the cerebral microcirculation in a porcine model of acute lung injury caused by cyclic recruitment and derecruitment.

BACKGROUND: Cyclic recruitment and derecruitment (R/D) play a key role in the pathomechanism of acute lung injury (ALI) leading to respiration-dependent oscillations of arterial partial pressure of oxygen (Pa(O(2))). These Pa(O(2)) oscillations could also be forwarded to the cerebral microcirculation. METHODS: In 12 pigs, partial pressure of oxygen was measured in the thoracic aorta (Pa(O(2))) and subcortical cerebral tissue (Pbr(O(2))). Cerebral cortical haemoglobin oxygen saturation (Sbr(O(2))), cerebral blood flow (CBF), and peripheral haemoglobin saturation (Sp(O(2))) were assessed by spectroscopy and laser Doppler flowmetry. Measurements at different fractions of inspired oxygen (F(I(O(2)))) were performed at baseline and during cyclic R/D. STATISTICS: frequency domain analysis, the Mann-Whitney test, linear models to test the influence of Pa(O(2)) and systolic arterial pressure (SAP) oscillations on cerebral measurements. RESULTS: Parameters [mean (SD)] remained stable during baseline. Pa(O(2)) oscillations [10.6 (8) kPa, phase(reference)], systemic arterial pressure (SAP) oscillations [20 (9) mm Hg, phase(Pa(O(2))-SAP) -33 (72)°], and Sp(O(2))oscillations [1.9 (1.7)%, phase(Pa(O(2))-Sp(O(2))) 264 (72)°] were detected during lung R/D at 1.0. Pa(O(2)) oscillations decreased [2.7 (3.5) kPa, P=0.0008] and Sp(O(2)) oscillations increased [6.8 (3.9)%, P=0.0014] at F(I(O(2))) 0.3. In the brain, synchronized Pbr(O(2)) oscillations [0.6 (0.4) kPa, phase(Pa(O(2))-Pbr(O(2))) 90 (39)°], Sbr(O(2)) oscillations [4.1 (1.5)%, phase(Pa(O(2))-Sbr(O(2))) 182 (54)°], and CBF oscillations [198 (176) AU, phase(Pa(O(2))-CBF) 201 (63)°] occurred that were dependent on Pa(O(2)) and SAP oscillations. CONCLUSIONS: Pa(O(2)) oscillations caused by cyclic R/D are transmitted to the cerebral microcirculation in a porcine model of ALI. These cyclic oxygen alterations could play a role in the crosstalk of acute lung and brain injury.