Intestinal circulation, oxygenation and metabolism is not affected by oleic acid lung injury.

This study was performed to establish a platform for further studies on effects of ventilatory treatment modalities on the intestines during mechanical ventilation of acute lung injury (ALI). We tested the hypotheses that oleic acid (OA) infusion causes changes in intestinal circulation, oxygenation and metabolism, and that OA is distributed to tissues outside the lung. This was performed as an experimental, prospective and controlled study in an university animal research laboratory. Thirteen juvenile anaesthetized pigs were used in the main study, where seven were given an intravenous infusion of 0.1 ml kg(-1) OA and six served as control (surgery only). In a separate study, four animals were given an intravenous infusion of 0.1 ml kg(-1) (3)H-labelled OA. We measured systemic and mesenteric (portal venous blood flow, jejunal mucosal perfusion) haemodynamic parameters, mesenteric oxygenation (jejunal tissue oxygen tension) and systemic cytokines (tumour necrosis factor-alpha and interleukin-6). We calculated mesenteric lactate flux and mesenteric oxygen delivery, uptake and extraction ratio. In the animals given 3H-OA, we measured 3H-OA in different tissues (lungs, heart, liver, kidney, stomach, jejunum, colon and arterial blood). We found that OA given intravenously is distributed in small amounts to the intestines. This intestinal exposure to OA does not cause intestinal injury when evaluating mesenteric blood flow, metabolism or oxygenation. OA infusion induced a moderate increase in mean pulmonary arterial pressure and a decrease in PaO2/Fraction inspired O2 (P/F) ratio, giving evidence of severe lung injury. Consequently, the OA lung injury model is suitable for studies on intestinal effects of ventilatory treatment modalities during mechanical ventilation of ALI

Physiological relevance and performance of a minimal lung model -- an experimental study in healthy and acute respiratory distress syndrome model piglets

Background: Mechanical ventilation (MV) is the primary form of support for acute respiratory distress syndrome (ARDS) patients. However, intra- and inter- patient-variability reduce the efficacy of general protocols. Model-based approaches to guide MV can be patient-specific. A physiological relevant minimal model and its patient-specific performance are tested to see if it meets this objective above. Methods: Healthy anesthetized piglets weighing 24.0 kg [IQR: 21.0-29.6] underwent a step-wise PEEP increase manoeuvre from 5cmH2O to 20cmH2O. They were ventilated under volume control using Engstrom Care Station (Datex, General Electric, Finland), with pressure, flow and volume profiles recorded. ARDS was then induced using oleic acid. The data were analyzed with a Minimal Model that identifies patient-specific mean threshold opening and closing pressure (TOP and TCP), and standard deviation (SD) of these TOP and TCP distributions. The trial and use of data were approved by the Ethics Committee of the Medical Faculty of the University of Liege, Belgium.Results and discussions3 of the 9 healthy piglets developed ARDS, and these data sets were included in this study. Model fitting error during inflation and deflation, in healthy or ARDS state is less than 5.0% across all subjects, indicating that the model captures the fundamental lung mechanics during PEEP increase. Mean TOP was 42.4cmH2O [IQR: 38.2-44.6] at PEEP = 5cmH2O and decreased with PEEP to 25.0cmH2O [IQR: 21.5-27.1] at PEEP = 20cmH2O. In contrast, TCP sees a reverse trend, increasing from 10.2cmH2O [IQR: 9.0-10.4] to 19.5cmH2O [IQR: 19.0-19.7]. Mean TOP increased from average 21.2-37.4cmH2O to 30.4-55.2cmH2O between healthy and ARDS subjects, reflecting the higher pressure required to recruit collapsed alveoli. Mean TCP was effectively unchanged. Conclusion: The minimal model is capable of capturing physiologically relevant TOP, TCP and SD of both healthy and ARDS lungs. The model is able to track disease progression and the response to treatment

Estabilidade do modelo animal de lesão pulmonar aguda induzida por ácido oleico Stability of the animal model of oleic acid-induced acute lung injury

OBJETIVO: Avaliar a estabilidade das variáveis hemodinâmicas, da mecânica respiratória e de troca gasosa do modelo animal de lesão pulmonar aguda induzida por ácido oleico. MÉTODOS: Trata-se de um estudo experimental no qual foram utilizados 10 cães de raça indeterminada. As variáveis foram aferidas inicialmente e em 30, 60, 90 e 120 min após a administração do ácido oleico. Para analisar as medidas repetidas, foram testados efeitos lineares e quadráticos e foram utilizados ajustes de modelos lineares mistos com estruturas de variâncias e covariâncias diversificadas, dependendo da variável analisada. RESULTADOS: Observamos estabilidade da pressão arterial média aos 30 min, assim como da frequência cardíaca, da pressão arterial pulmonar e da pressão de capilar pulmonar aos 60 min. Frequência respiratória, volume corrente, volume minuto e trabalho respiratório estabilizaram aos 30 min. Quanto às variáveis de troca gasosa, PaO2, relação PaO2/FiO2 e fração de shunt pulmonar estabilizaram-se aos 30 min. As demais variáveis mantiveram-se em ascensão ou queda contínuas. CONCLUSÕES: O modelo de lesão pulmonar aguda induzida por ácido oleico é estável para algumas das variáveis testadas; porém, a estabilização se dá em momentos diferentes. As variáveis da mecânica respiratória e de troca gasosa estabilizaram em 30 min, e as hemodinâmicas, em 60 min.<br>OBJECTIVE: To evaluate the stability of hemodynamic, respiratory and gas exchange variables in an animal model of oleic acid-induced acute lung injury. METHODS: This was an experimental study involving 10 mongrel dogs. The variables were measured at baseline, as well as at 30, 60, 90 and 120 min after the administration of oleic acid. In order to analyze repeated measurements, linear and quadratic effects were tested. Mixed linear models with diversified variance and covariance structures were used, depending on the variable studied. RESULTS: We found that mean arterial blood pressure stabilized at 30 min, as did heart rate, pulmonary arterial pressure and pulmonary capillary pressure at 60 min. Respiratory rate, tidal volume, minute volume and respiratory work stabilized at 30 min. Regarding gas exchange variables, PaO2, PaO2/FiO2 ratio and pulmonary shunt fraction stabilized at 30 min. The remaining variables maintained a continuous rise or fall. CONCLUSIONS: This oleic acid-induced acute lung injury model is stable for some of the variables tested, although stabilization occurs at different times. The respiratory and gas exchange variables stabilized at 30 min, whereas the hemodynamic variables stabilized at 60 min