Blondonnet Raiko, Paquette Bertille, Audard Jules, Guler Ridvan, Roman François-Xavier, Zhai Ruoyang, Belville Corinne, Blanchon Loïc, Godet Thomas, Futier Emmanuel, Bazin Jean-Etienne, Constantin Jean-Michel, Sapin Vincent, Jabaudon Matthieu
Department of Perioperative Medicine, CHU Clermont-Ferrand; GReD, CNRS, INSERM, Université Clermont Auvergne;
Department of Perioperative Medicine, CHU Clermont-Ferrand; GReD, CNRS, INSERM, Université Clermont Auvergne.
J Vis Exp. 2020 Sep 24(163). doi: 10.3791/61644.
Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent need to find effective therapies. Preclinical studies have shown that inhaled halogenated agents may have beneficial effects in animal models of ARDS. The development of new devices to administer halogenated agents using modern intensive care unit (ICU) ventilators has significantly simplified the dispensing of halogenated agents to ICU patients. Because previous experimental and clinical research suggested potential benefits of halogenated volatiles, such as sevoflurane or isoflurane, for lung alveolar epithelial injury and inflammation, two pathophysiologic landmarks of diffuse alveolar damage during ARDS, we designed an animal model to understand the mechanisms of the effects of halogenated agents on lung injury and repair. After general anesthesia, tracheal intubation, and the initiation of mechanical ventilation, ARDS was induced in piglets via the intratracheal instillation of hydrochloric acid. Then, the piglets were sedated with inhaled sevoflurane or isoflurane using an ICU-type device, and the animals were ventilated with lung-protective mechanical ventilation during a 4 h period. During the study period, blood and alveolar samples were collected to evaluate arterial oxygenation, the permeability of the alveolar-capillary membrane, alveolar fluid clearance, and lung inflammation. Mechanical ventilation parameters were also collected throughout the experiment. Although this model induced a marked decrease in arterial oxygenation with altered alveolar-capillary permeability, it is reproducible and is characterized by a rapid onset, good stability over time, and no fatal complications. We have developed a piglet model of acid aspiration that reproduces most of the physiological, biological, and pathological features of clinical ARDS, and it will be helpful to further our understanding of the potential lung-protective effects of halogenated agents delivered through devices used for inhaled ICU sedation.
急性呼吸窘迫综合征（ARDS）是危重症患者低氧性呼吸衰竭和死亡的常见原因，因此迫切需要找到有效的治疗方法。临床前研究表明，吸入卤化剂可能对ARDS动物模型有有益作用。利用现代重症监护病房（ICU）呼吸机开发的用于输送卤化剂的新设备，显著简化了向ICU患者输送卤化剂的操作。由于先前的实验和临床研究表明，卤化挥发物，如七氟醚或异氟醚，对肺泡上皮损伤和炎症（ARDS期间弥漫性肺泡损伤的两个病理生理标志）具有潜在益处，我们设计了一个动物模型，以了解卤化剂对肺损伤和修复作用的机制。在全身麻醉、气管插管并开始机械通气后，通过气管内滴注盐酸在仔猪中诱发ARDS。然后，使用ICU型设备用吸入的七氟醚或异氟醚使仔猪镇静，并在4小时期间用肺保护性机械通气对动物进行通气。在研究期间，采集血液和肺泡样本，以评估动脉氧合、肺泡-毛细血管膜通透性、肺泡液体清除率和肺部炎症。在整个实验过程中还收集机械通气参数。虽然该模型导致动脉氧合显著下降，肺泡-毛细血管通透性改变，但它具有可重复性，其特点是起效迅速、随时间稳定性好且无致命并发症。我们开发了一种酸吸入仔猪模型，该模型再现了临床ARDS的大多数生理、生物学和病理特征，这将有助于我们进一步了解通过用于ICU吸入镇静的设备输送卤化剂的潜在肺保护作用。
