Name: oleic acid-injection in pigs as a model for acute respiratory distress syndrome
Uploaded: 2018-10-26T12:30:00
Description: Watch this Scientific Journal Video about Oleic Acid-Injection in Pigs As a Model for Acute Respiratory Distress Syndrome at JoVE.com

作者要感谢达格玛 Dirvonskis 的卓越技术支持。

这里描述的所有动物实验都已得到机构和国家动物护理委员会 (德国科布伦茨 Landesuntersuchungsamt 莱茵-普法尔茨) 的批准; 批准号 G14-1-077), 并按照该准则进行欧洲和德国实验室动物科学协会。实验在2-3 月龄的麻醉雄性猪 (sus 野猪家蝇) 中进行, 重27-29 公斤。
1. 麻醉、插管和机械通气
<ol><li>在麻醉前扣留6小时的食物, 以降低吸入的风险, 但允许免费使用水来减轻压力。</li>
	<li>对?...

<ol>
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P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ARDS:+clinical+lessons+from+the+oleic+acid+model+of+acute+lung+injury.">ARDS: clinical lessons from the oleic acid model of acute lung injury.</a> American Journal of Respiratory and Critical Care Medicine. 149 (1), 245-260 (1994).</li><li>Goncalves-de-Albuquerque, C. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oleic+acid+induces+lung+injury+in+mice+through+activation+of+the+ERK+pathway.">Oleic acid induces lung injury in mice through activation of the ERK pathway.</a> Mediators of Inflammation. 2012, 956509 (2012).</li><li>Ballard-Croft, C., Wang, D., Sumpter, L. R., Zhou, X., Zwischenberger, J. 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S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Basic+surgical+techniques+in+the+Gottingen+minipig:+intubation,+bladder+catheterization,+femoral+vessel+catheterization,+and+transcardial+perfusion.">Basic surgical techniques in the Gottingen minipig: intubation, bladder catheterization, femoral vessel catheterization, and transcardial perfusion.</a> Journal of Visualized Experiments. (52), 2652 (2011).</li><li>Russ, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lavage-induced+Surfactant+Depletion+in+Pigs+As+a+Model+of+the+Acute+Respiratory+Distress+Syndrome+(ARDS).">Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS).</a> Journal of Visualized Experiments. (115), 53610 (2016).</li><li>Brower, R. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Higher+versus+lower+positive+end-expiratory+pressures+in+patients+with+the+acute+respiratory+distress+syndrome.">Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.</a> The New England Journal of Medicine. 351 (4), 327-336 (2004).</li><li>Hartmann, E. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+respiratory+rate+and+end-expiratory+pressure+variation+on+cyclic+alveolar+recruitment+in+an+experimental+lung+injury+model.">Influence of respiratory rate and end-expiratory pressure variation on cyclic alveolar recruitment in an experimental lung injury model.</a> Critical Care. 16 (1), (2012).</li><li>Hartmann, E. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhalation+therapy+with+the+synthetic+TIP-like+peptide+AP318+attenuates+pulmonary+inflammation+in+a+porcine+sepsis+model.">Inhalation therapy with the synthetic TIP-like peptide AP318 attenuates pulmonary inflammation in a porcine sepsis model.</a> BMC Pulmonary Medicine. 15, 7 (2015).</li><li>Julien, M., Hoeffel, J. M., Flick, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oleic+acid+lung+injury+in+sheep.">Oleic acid lung injury in sheep.</a> Journal of Applied Physiology. 60 (2), 433-440 (1986).</li><li>Wiener-Kronish, J. 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本文介绍了一种油酸致肺损伤的方法, 作为研究重症 ARDS 各个方面的模型。另外还有不同乳液、不同注射部位和不同温度的乳液23、24、25、26、27、28 的其他协议 ,29。我们的方法提供了可重现和稳定的肺功能恶化。由于油酸...

急性呼吸窘迫综合征 (ARDS) 是一种重症监护综合征, 自50年前的第一次描述以来, 已广泛研究1。这一研究机构使人们更好地了解病理生理学, 并导致 ARDS 的发展, 从而改善患者护理和结果2,3。然而, 患有 ARDS 的患者的死亡率仍然很高, 约 35-40%4,5,6。事实上, 大约10% 的 icu 录取和23% 的 icu 病人谁需要机械通气是由于 ARDS 强调了在这一领域的进一步研究的相关性。
动物模型被广泛应用于研究, 以检查不同类型疾病的病理生理变化和潜在的治疗方式。由于 ARDS 的复杂性, 没有单一的动物模型来模拟这种疾病, 但不同的模型代表不同的方面7。一种成熟的模型是油酸注射液 (OAI) 所致肺损伤。该模型已被广泛应用于各种动物, 包括小鼠8、大鼠9、猪10、狗11和绵羊12。油酸是一种不饱和脂肪酸和最常见的脂肪酸在身体的健康人类13。它是存在于人血浆, 细胞膜和脂肪组织13。在生理上, 它是必然的白蛋白, 而它是通过血液13进行。血液中脂肪酸含量的增加与不同的病症相关, 某些疾病的严重性与血清脂肪酸水平13有关。建立了油酸 ARDS 模型, 试图重现14例外伤患者脂栓塞引起的 ards。油酸直接影响在肺部的固有免疫受体13和触发中性粒细胞积累15, 炎症介质生产16, 和细胞死亡13。在生理上, 油酸诱发快速的低氧血症, 增加肺动脉压力和血管外肺积水的积累。此外, 它还诱发动脉低血压和心肌凹陷7。这种模式的缺点是中心静脉通路的必要性, 有问题的机械相关性和快速低氧血症和心脏抑郁症导致的潜在致命进展。与其他模型相比, 该模型的优势在于小动物和大鼠的可用性、ards 中的病理生理学机制的有效重现性、油酸注射液后急性发作以及研究孤立 ards 的可能性。没有系统性炎症像在许多其他脓毒症模型7。本文对油酸致猪肺损伤进行了详细的描述, 为表征肺功能损害的稳定性提供了代表性的数据。OAI 引起的肺损伤有不同的实验方案。这里提供的协议能够可靠地诱发急性肺损伤。

<table >
	<tbody>
		<tr >
			<td >3-way-stopcock blue</td>
			<td >Becton Dickinson Infusion Therapy AB Helsingborg, Sweden</td>
			<td >394602</td>
			<td ></td>
		</tr>
		<tr >
			<td >3-way-stopcock red</td>
			<td >Becton Dickinson Infusion Therapy AB Helsingborg, Sweden</td>
			<td >394605</td>
			<td ></td>
		</tr>
		<tr >
			<td >Atracurium</td>
			<td >Hikma Pharma GmbH , Martinsried</td>
			<td>4262659</td>
			<td ></td>
		</tr>
		<tr >
			<td >Canula 20 G</td>
			<td >Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td >301300</td>
			<td ></td>
		</tr>
		<tr >
			<td >Datex Ohmeda S5</td>
			<td >GE Healthcare Finland Oy, Helsinki, Finland</td>
			<td></td>
			<td ></td>
		</tr>
		<tr >
			<td >Desinfection</td>
			<td >Sch&#252;lke &#38; Mayr GmbH, Germany</td>
			<td>104802</td>
			<td ></td>
		</tr>
		<tr >
			<td >Endotracheal tube</td>
			<td >Teleflex Medical Sdn. Bhd, Malaysia</td>
			<td >112482</td>
			<td ></td>
		</tr>
		<tr >
			<td >Endotracheal tube introducer</td>
			<td >R&#252;sch</td>
			<td>5033062</td>
			<td ></td>
		</tr>
		<tr >
			<td >Engstr&#246;m Carestation</td>
			<td >GE Heathcare, Madison USA</td>
			<td ></td>
			<td ></td>
		</tr>
		<tr >
			<td >Fentanyl</td>
			<td >Janssen-Cilag GmbH, Neuss</td>
			<td ></td>
			<td ></td>
		</tr>
		<tr >
			<td >Gloves</td>
			<td >Paul Hartmann, Germany</td>
			<td>9422131</td>
			<td ></td>
		</tr>
		<tr >
			<td >Incetomat-line 150 cm</td>
			<td >Fresenius, Kabi Germany GmbH</td>
			<td >9004112</td>
			<td ></td>
		</tr>
		<tr >
			<td >Ketamine</td>
			<td >Hameln Pharmaceuticals GmbH</td>
			<td ></td>
			<td ></td>
		</tr>
		<tr >
			<td >Laryngoscope</td>
			<td >Teleflex Medical Sdn. Bhd, Malaysia</td>
			<td >671067-000020</td>
			<td ></td>
		</tr>
		<tr >
			<td >Logical pressure monitoring system</td>
			<td >Smith- Medical Germany GmbH</td>
			<td>MX9606</td>
			<td ></td>
		</tr>
		<tr >
			<td >Logicath 7 Fr 3-lumen 30cm</td>
			<td >Smith- Medical Germany GmbH</td>
			<td>MXA233x30x70-E</td>
			<td ></td>
		</tr>
		<tr >
			<td >Masimo Radical 7</td>
			<td >Masimo Corporation Irvine, Ca 92618 USA</td>
			<td ></td>
			<td ></td>
		</tr>
		<tr >
			<td >Mask for ventilating dogs</td>
			<td >Henry Schein, Germany</td>
			<td >730-246</td>
			<td ></td>
		</tr>
		<tr >
			<td >Neofox Kit</td>
			<td >Ocean optics Largo, FL USA</td>
			<td>NEOFOX-KIT-PROBE</td>
			<td ></td>
		</tr>
		<tr >
			<td >Norepinephrine</td>
			<td >Sanofi- Aventis, Seutschland GmbH</td>
			<td >73016</td>
			<td ></td>
		</tr>
		<tr >
			<td >Oleic acid</td>
			<td >Applichem GmbH Darmstadt, Germany</td>
			<td>1,426,591,611</td>
			<td ></td>
		</tr>
		<tr >
			<td >Original Perfusor syringe 50ml Luer Lock</td>
			<td >B.Braun Melsungen AG, Germany</td>
			<td>8728810F</td>
			<td ></td>
		</tr>
		<tr >
			<td >PA-Katheter Swan Ganz 7,5 Fr 110cm</td>
			<td >Edwards Lifesciences LLC, Irvine CA, USA</td>
			<td>744F75</td>
			<td ></td>
		</tr>
		<tr >
			<td >Percutaneous sheath introducer set 8,5 und 9 Fr, 10 cm with integral haemostasis valve/sideport</td>
			<td >Arrow international inc. Reading, PA, USA</td>
			<td>AK-07903</td>
			<td ></td>
		</tr>
		<tr >
			<td >Perfusor FM Braun</td>
			<td >B.Braun Melsungen AG, Germany</td>
			<td>8713820</td>
			<td ></td>
		</tr>
		<tr >
			<td >Potassium chloride</td>
			<td >Fresenius, Kabi Germany GmbH</td>
			<td>6178549</td>
			<td ></td>
		</tr>
		<tr >
			<td >Propofol 2%</td>
			<td >Fresenius, Kabi Germany GmbH</td>
			<td ></td>
			<td ></td>
		</tr>
		<tr >
			<td >Saline</td>
			<td >B.Braun Melsungen AG, Germany</td>
			<td ></td>
			<td ></td>
		</tr>
		<tr >
			<td >Sonosite Micromaxx Ultrasoundsystem</td>
			<td >Sonosite Bothell, WA, USA</td>
			<td ></td>
			<td ></td>
		</tr>
		<tr >
			<td >Stainless Macintosh Size 4</td>
			<td >Teleflex Medical Sdn. Bhd, Malaysia</td>
			<td >670000</td>
			<td ></td>
		</tr>
		<tr >
			<td >Sterofundin</td>
			<td >B.Braun Melsungen AG, Germany</td>
			<td ></td>
			<td ></td>
		</tr>
		<tr >
			<td >Stresnil 40mg/ml</td>
			<td >Lilly Germany GmbH, Abteilung Elanco Animal Health</td>
			<td ></td>
			<td ></td>
		</tr>
		<tr >
			<td >Syringe 10 mL</td>
			<td >Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td>309110</td>
			<td ></td>
		</tr>
		<tr >
			<td >Syringe 2 mL</td>
			<td >Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td>300928</td>
			<td ></td>
		</tr>
		<tr >
			<td >Syringe 20 mL</td>
			<td >Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td >300296</td>
			<td ></td>
		</tr>
		<tr >
			<td >Syringe 5 mL</td>
			<td >Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td>309050</td>
			<td ></td>
		</tr>
		<tr >
			<td >venous catheter 22G</td>
			<td >B.Braun Melsungen AG, Germany</td>
			<td>4269110S-01</td>
			<td ></td>
		</tr>
	</tbody>
</table>

oleic acid-injection in pigs as a model for acute respiratory distress syndrome

急性呼吸窘迫综合征是一种相关的重症监护疾病, 发病率介于2.2% 至19% 的重症监护病房患者之间。尽管在过去的几十年治疗进展, ARDS 患者仍然遭受死亡率在35和40% 之间。仍然需要进一步的研究, 以改善患者的结果, 患有 ARDS。一个问题是, 没有单一的动物模型可以模仿急性呼吸窘迫综合征的复杂病理机制, 但有几个模型来研究它的不同部分。油酸注射液 (OAI) 诱发肺损伤是研究动物通气策略、肺力学和通气/灌注分布的良好模式。OAI 导致气体交换严重受损, 肺力学的恶化和 alveolo 毛细管屏障的破坏。这个模型的缺点是这个模型有争议的机械相关性和中心静脉通路的必要性, 这是挑战, 特别是在较小的动物模型。总之, OAI 引起的肺损伤可使小动物和大鼠产生重现性结果, 因此是研究 ARDS 的一个非常适合的模型。然而, 进一步的研究是必要的, 以找到一个模型, 模仿 ARDS 的所有部分, 缺乏与现有的不同模型相关的问题。

2/FiO2-油酸分馏应用后的比值降低 (图 1)。在本文的研究中, 0.185 ±0.01 毫升千克-1油酸是必要的诱导肺损伤。在肺损伤后, 所有动物均表现为氧合受损, 并在进一步的时间过程中出现了变种。在动物1和 3, 它保持在一个水平, 很少波动;在动物2中, 我们观察到最初的增加, 其次是末端的减少, 而动物4显示恒定的上升。然而, 在6小时后...

Watch this Scientific Journal Video about Oleic Acid-Injection in Pigs As a Model for Acute Respiratory Distress Syndrome at JoVE.com

Oleic Acid-Injection in Pigs As a Model for Acute Respiratory Distress Syndrome

油酸注射液在猪急性呼吸窘迫综合征模型中的研究

本文提出一种通过中心静脉注射油酸诱导猪急性肺损伤的方案。这是一个建立的动物模型, 用于研究急性呼吸窘迫综合征 (ARDS)。

The acute respiratory distress syndrome is a relevant intensive care disease with an incidence ranging between 2.2% and 19% of intensive care unit ...

此方法可以帮助回答有关 ARDS 期间发生的病理生理变化的关键问题，以便开发和评估此病的新治疗方案。该技术的主要优点是，它再现了人类ARDS中观察到的基本病理变化。对于超声波制导仪器，在实验猪的右内侧韧带上放置一个超声波探针，并扫描股骨血管。转动探头 90 度以完全可视化长轴中的股动脉，并使用 Seldinger 的针头在在线超声波可视化下将右股动脉拉大。当脉动明亮的血液流出时，引入导丝并缩回针头。检查，以确保通过超声波可视化塞尔丁格导线的位置是正确的。可视化股骨静脉，用针头连续吸气，在线超声成像下将静脉进行。当静脉血能够吸气时，插入塞尔丁格的电线并缩回针头。使用塞尔丁格的技术插入一个5-法国动脉介绍护套和必要的静脉导管，并扭转相应的三向停止。在插入肺动脉导管之前，检查其是否正常工作，并通过左静脉导管插入。当肺动脉导管通过引入器护套时，用一毫升空气充气气球，并在监测典型波形的同时推进肺动脉导管。然后放气气球，检查血液是否能通过肺动脉导管的所有端口吸气。然后插入探针，通过右动脉引入器护套进行超快测量部分氧压。为了诱发肺部损伤，将一个20毫升注射器装上每公斤油酸0.1毫升，再装一个20毫升注射器，再装两毫升新鲜抽血。用血液将盐水加入注射器，在两个注射器中的总体积为 20 毫升，并将两个注射器连接到三向止血球。将去甲肾上腺素注射器泵连接到中央静脉导管的一个端口，然后开始超快的部分氧压测量。记录所有相关参数的基线值，并设置受启发氧的分数为 1.0。进行肺招募操作，将三向止损口连接到肺动脉导管的近位端口。然后注射油和血盐混合物，反复从一个注射器到另一个，通过三向停止，彻底混合溶液。当达到均匀乳液时，将乳液的两毫升注入中央静脉导管，并继续混合。注射后密切监测血流动力学，必要时给予去甲肾上腺素10至100微克的玻利瓦尔注射，以保持平均动脉压力超过60毫米汞。每三分钟重复两毫升油酸溶液注射，直到动脉部分压力的氧分数的受启发比低于200毫米汞。等待30分钟，重新评估受启发比氧分的部分压力。如果汞的比例仍然超过200毫米，重复注射，直到受启发比例的氧部分部分压力低于200毫米汞。然后根据急性呼吸窘迫综合症网络的建议设置通风。在油酸分馏应用后，激发氧比的部分氧压分数降低。尽管在肺部损伤诱导后，氧化损伤的典型损伤，但在整个损伤时间段，动物之间观察到氧气损伤的频繁变化。在输送油酸的同时，需要密切监测受启发氧比的部分氧压分数。激发氧比的部分氧压分数的降低与肺动脉压力的增加同时发生，在实验的其余部分中，肺动脉压力通常保持升高，动物之间也观察到一些波动。肺损伤在肺损伤诱导后6小时采集的肺部可视觉上检测，组织学分析显示肺水肿和出血。看完这段视频后，你应该对如何通过必要的静脉注射油酸来诱发猪急性肺损伤有一个良好的理解。不要忘记，使用油酸可能非常危险，并采取预防措施，如戴手套，在执行此过程时应始终采取安全课程。

Research

JoVE Journal

Medicine

Bronchoalveolar Lavage (BAL) for Research; Obtaining Adequate Sample Yield

Bronchoalveolar Lavage BAL for Research; Obtaining Adequate Sample Yield

支气管肺泡灌洗（BAL）的研究，获得适当的采样率

We describe a research technique for fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) using manual hand held suction in order to remove ...

科研

医学

A Research Method For Detecting Transient Myocardial Ischemia In Patients With Suspected Acute Coronary Syndrome Using Continuous ST-segment Analysis

研究方法检测疑似急性冠脉综合征患者短暂心肌缺血的连续ST段分析

Each year, an estimated 785,000 Americans will have a new coronary attack, or acute coronary syndrome (ACS). The pathophysiology of ACS involves rupture ...

The In ovo CAM-assay as a Xenograft Model for Sarcoma

The In ovo CAM-assay as a Xenograft Model for Sarcoma

该<em&gt;在OVO</em&gt; CAM作为一个肉瘤Xenograftmodel的检测

Sarcoma is a very rare disease that is heterogeneous in nature, all hampering the development of new therapies. Sarcoma patients are ideal candidates for ...

Sublingual Immunotherapy as an Alternative to Induce Protection Against Acute Respiratory Infections

舌下免疫治疗作为一种替代起到保护作用对急性呼吸道感染

Sublingual route has been widely used to deliver small molecules into the bloodstream and to modulate the immune response at different sites. It has been ...

Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS)

Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome ARDS

灌洗诱发的表面活性剂耗尽猪一样的急性呼吸窘迫综合征模型（ARDS）

Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future ...

Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury

急性肺损伤开放气管切开胃酸吸入小鼠模型结果在急性最大非致命性肺损伤

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute ...

A Component-resolved Diagnostic Approach for a Study on Grass Pollen Allergens in Chinese Southerners with Allergic Rhinitis and/or Asthma

中国南方与过敏性鼻炎和/或哮喘的花粉过敏原研究的成分分析诊断方法

Sensitization to grass pollen imposes a global risk for allergic airway diseases. Although prevention relies on local investigation of the pollen ...

Corneal Epithelial Abrasion with Ocular Burr As a Model for Cornea Wound Healing

眼毛刺角膜上皮磨损与角膜创面愈合的模型研究

The murine cornea provides an excellent model to study wound healing. The cornea is the outermost layer of the eye, and thus is the first defense to ...

Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology

毛利精密切肝片作为肝脏生物学的Ex Vivo模型

Understanding the mechanisms of liver injury, hepatic fibrosis, and cirrhosis that underlie chronic liver diseases (i.e., viral hepatitis, non-alcoholic ...

Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device

重症监护病房型装置在猪模型急性呼吸窘迫综合征中的卤化剂递送

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent ...