All authors disclose no financial or any other conflicts of interests.
GRANTS:
This study was supported by a grant from the Deutsche Forschungsgemeinschaft to P. Pickerodt and W. Boemke (Pi795/2-2).

<ol>
	<li>Rubenfeld, G. D., 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=Incidence+and+Outcomes+of+Acute+Lung+Injury.">Incidence and Outcomes of Acute Lung Injury.</a> N Engl J Med. 353 (16), 1685-1693 (2005).</li><li>Ballard-Croft, C., Wang, D., Sumpter, L. R., Zhou, X., Zwischenberger, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Large-animal+models+of+acute+respiratory+distress+syndrome.">Large-animal models of acute respiratory distress syndrome.</a> Ann Thorac Surg. 93 (4), 1331-1339 (2012).</li><li>Lachmann, B., Robertson, B., Vogel, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+lung+lavage+as+an+experimental+model+of+the+respiratory+distress+syndrome.">In vivo lung lavage as an experimental model of the respiratory distress syndrome.</a> Acta Anaesthesiol Scand. 24 (3), 231-236 (1980).</li><li>Donaubauer, B., 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=Low-dose+inhalation+of+an+endothelin-A+receptor+antagonist+in+experimental+acute+lung+injury:+ET-1+plasma+concentration+and+pulmonary+inflammation.">Low-dose inhalation of an endothelin-A receptor antagonist in experimental acute lung injury: ET-1 plasma concentration and pulmonary inflammation.</a> Exp Biol Med (Maywood). 231 (6), 960-969 (2006).</li><li>Theisen, M. 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=Ventral+recumbency+is+crucial+for+fast+and+safe+orotracheal+intubation+in+laboratory+swine.">Ventral recumbency is crucial for fast and safe orotracheal intubation in laboratory swine.</a> Lab Anim. 43 (1), 96-101 (2009).</li><li>Kelly, C. R., Rabbani, L. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Videos+in+clinical+medicine.+Pulmonary-artery+catheterization.">Videos in clinical medicine. Pulmonary-artery catheterization.</a> N Engl J Med. 369 (25), 35 (2013).</li><li>Forrester, J. 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=Thermodilution+cardiac+output+determination+with+a+single+flow-directed+catheter.">Thermodilution cardiac output determination with a single flow-directed catheter.</a> Am Heart J. 83 (3), 306-311 (1972).</li><li>Deja, 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=The+inhaled+ET(A)+receptor+antagonist+LU-135252+acts+as+a+selective+pulmonary+vasodilator.">The inhaled ET(A) receptor antagonist LU-135252 acts as a selective pulmonary vasodilator.</a> Clin Sci (Lond). 103, 21-24 (2002).</li><li>Matute-Bello, G., Frevert, C. W., Martin, T. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+acute+lung+injury.">Animal models of acute lung injury.</a> Am J Physiol Lung Cell Mol Physiol. 295 (3), 379-399 (2008).</li><li>Kloot, T. E., 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=Recruitment+maneuvers+in+three+experimental+models+of+acute+lung+injury.+Effect+on+lung+volume+and+gas+exchange.">Recruitment maneuvers in three experimental models of acute lung injury. Effect on lung volume and gas exchange.</a> Am J Respir Crit Care Med. 161 (5), 1485-1494 (2000).</li></ol>

We gratefully acknowledge the help of Prof. Burkhard Lachmann when contemplating the intricacies of PEEP settings during surfactant washout and the excellent technical assistance of Birgit Brandt and Sabine Molling.

מאמר זה מתאר צעד אחר צעד הדרכה כדי לגרום פגיעת ריאות חריפה חזירים בשל כישלון פעיל שטח על ידי lavages ריאות חוזרים ונשנה. שיטה ספציפית זו מאפשרת הידרדרות לשחזור דומה בתפקוד הריאות והתנגדות בכלי הדם הריאתיים. זה הכרחי כדי שטיפה החזירים עד P עיגול 2 / F אני O <...

התמותה של תסמונת מצוקה אנושית חריפה בדרכי הנשימה (ARDS) נותר גבוה עם ערכים בין 40 ל 50% 1 למרות יותר מ -4 עשורים של מחקר אינטנסיבי. במודלים של בעלי החיים של פציעת ריאות לשחק תפקיד מרכזי בחקירת pathomechanisms המורכב או שיטות טיפוליות חדשניות להפחתת תמותה ולהגביל מוגבלויות לטווח ארוכות. מודלים שונים הוקמו כדי לגרום פגיעה ריאות המדמה היבטים של ARDS האדם או גדול (חזירים למשל) או חיות קטנות (למשל מכרסמים). שיטות שונות מאוד, כולל עירוי דם ריאתי של חומצה אולאית, תוך ורידי (iv) עירוי של חיידקים, ו אנדוטוקסינים או קשירת cecal ו לנקב (CLP) מודלים גרימת ARDS הנגרמת אלח דם. בנוסף, פציעות ריאות ישירות בשל כרכים גאים גדולים ולחצי inspiratory שיא גבוה (פציעת ריאות נגרמת הנשמה; וילי), עשן / לשרוף פציעות או איסכמיה ריאות / reperfusion (I / R) מודלים משמשים לעתים קרובות2. חסרון עיקרי אחד דגמי CLP, וכן דגמי עבודה עם אנדוטוקסינים, היא הדלקת הבסיסית אשר מעכבת את ניתוח biotrauma כתוצאה מפגיעת ריאות לבד. יתר על כן, זה עלול לקחת שעות עד ימים כדי לגרום לפציעת ריאות, כפי שנהוג עבור Vili בחיות גדולות. האינדוקציה של פציעת ריאות ידי סחף פעיל שטח עם lavages ריאות חוזרים ונשנה, כפי שתואר לראשונה על ידי ואח &#39;לכמן. ב שרקנים 3, היא שיטה יעילה זמן כדי לגרום פגיעת ריאות עם פשרות פונקציונליות מכאניות לשחזור, כמו גם שינויים בתנגודת בכלי דם הריאתיים. Adaption את המודל הזה כדי מאוורר חזירים מכאניים של כ 30-60 קילו משקל גוף תומך במחקר בסיסי במאווררים מכאניים בשימוש קליני, צנתרים וצגים, בעוד פשרות חילוף גזים ופרמטרים המודינמיים הן מאוד לשחזור בעת ובעונה אחת 4. בנוסף, אינדוקציה של פציעה ריאות ידי lavages לאדורש ציוד ספציפי שאינו זמין נפוץ במעבדות נשימה המיועדות ניסויים בבעלי חיים גדולים. המודל המוצג במאמר זה הוא מתאים ציוד בדרישת מחקר (למשל מאווררים) אשר נועד לשימוש בבני אדם, ויתר על כן מבטיח שחזור גבוה של deteriorations המתרחש בתפקוד ריאות. תקינה של מודל זה מסייעת להבטיח השוואתי בין ניסויים ולצמצם את מספר בעלי החיים הנדרשים. Recruitability הפוטנציאל של אזורי ריאות atelectatic עם תמרוני גיוס מכוונים או לא ידועים הוא מגבלה חמורה של הדגם הספציפי הזה. במאמר הבא אנו לתת תיאור מפורט של מודל שטיפת האינדוקציה של פציעת ריאות ולספק נתונים נציג לאפיין את היציבות של הפשרות בתפקוד ריאות.

<table><tbody><tr><td>Evita Infinity V500</td><td>Dr&amp;auml;ger</td><td></td><td>intensive care ventilator</td></tr><tr><td>Vigilance I&amp;nbsp;</td><td>Edwards</td><td></td><td>monitor</td></tr><tr><td>Vasofix Braun&amp;uuml;le 20G</td><td>B Braun</td><td>4268113B</td><td>peripheral vein catheter</td></tr><tr><td>Mallinckrodt Tracheal Tube Cuffed</td><td>Covidien</td><td>107-80</td><td>&amp;nbsp;8.0 mm ID</td></tr><tr><td>MultiCath3</td><td>Vygon</td><td>157,300</td><td>3 lumen central venous catheter, 20 cm length</td></tr><tr><td>Leader Cath Set</td><td>Vygon</td><td>115,805</td><td>arterial catheter</td></tr><tr><td>Percutaneus Sheath Introducer Set</td><td>Arrow</td><td>SI-09600</td><td>introducer sheath for pulmonary artery catheter of 4-6 Fr., 10 cm length</td></tr><tr><td>Swan-Ganz True Size Thermodilution Catheter</td><td>Edwards</td><td>132F5</td><td>pulmonary artery catheter, 75 cm length</td></tr><tr><td>Flow through chamber thermistor</td><td>Baxter</td><td>93-505</td><td>for measuring cardiac output</td></tr><tr><td>urinary catheter</td><td></td><td></td><td>no specific model requiered</td></tr></tbody></table>

lavage-induced surfactant depletion in pigs as a model of the acute respiratory distress syndrome (ards)

במודלים של בעלי חיים שונים של פגיעת ריאות קיימים כדי ללמוד את pathomechanisms המורכב של תסמונת מצוקה נשימתית חריפת אדם (ARDS) ולהעריך טיפולים עתידיים. פציעה ריאות חמורה עם הידרדרות לשחזור של חילוף הגזים ריאתי ופרמטרים המודינמיים יכול להיגרם חזירים מורדם באמצעות lavages ריאות חוזרות ונשנות עם מי מלח 0.9% מחוממים (50 מ&quot;ל / ק&quot;ג משקל גוף). כולל ניטור נשימה המודינמי רגילות עם התקנים הוחלו קליני במודל זה מאפשר ההערכה של אסטרטגיות טיפוליות חדשניות (תרופות, מאווררים מודרניים, oxygenators הממברנה extracorporeal, ECMO), ומגשר על הפער בין הספסל שליד המיטה. יתר על כן, אינדוקציה של פציעה ריאות עם lavages ריאות אינו מחייב הזרקה של פתוגנים / אנדוטוקסינים כי ההשפעה על מדידות של ציטוקינים פרו ואנטי דלקתיים. החיסרון של מודל הוא recruitability גבוהה של רקמת הריאה atelectatic. התקינה של המודל עוזר להימנע ממכשולים, כדי להבטיח גomparability בין הניסויים, וכדי להקטין את מספר בעלי החיים הנדרשים.

P עיגול 2 / F אני O 2 -ratio ירידות במהלך ריאות lavages, אבל ההשפעה המדויקת של שטיפה אחת קשה לנבא. אנו מתחילים לקחת דגימות גז דם עורקים מן השטיפה השלישית ואילך לזהות ירידת P עיגול 2 / F אני O 2 -ratio מתחת ל -100 מ&quot;מ כספי. ...

Watch this Scientific Journal Video about Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome ARDS at JoVE.com

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

lavages ריאתי חוזר בחזירים הרדימו לגרום לפציעת ריאות דומה היבטים מרכזיים של תסמונת מצוקה נשימתית חריפת אדם (ARDS). לשם כך הריאות lavaged שוב ושוב עם מי מלח 0.9% ב 37 מעלות צלזיוס. מטרת הפרוטוקול היא הקלה לשחזור של חילוף גזים ופרמטרים המודינמיים למחקר ARDS.

דלדול פעילי שטח הנגרמת שטיפה בחזירים כמודל של תסמונת מצוקה נשימתית חריפה (ARDS)

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

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

11.2K Views.  Charité - Universitätsmedizin, Berlin.  lavages ריאתי חוזר בחזירים הרדימו לגרום לפציעת ריאות דומה היבטים מרכזיים של תסמונת מצוקה נשימתית חריפת אדם (ARDS). לשם כך הריאות lavaged שוב ושוב עם מי מלח 0.9% ב 37 מעלות צלזיוס. מטרת הפרוטוקול היא הקלה לשחזור של חילוף גזים ופרמטרים המודינמיים למחקר ARDS...

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

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

אוטם שריר לב והערכת תוצאה תפקודית בחזירים

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As such, primary or &#39;neuronal-like&#39; cell culture systems are commonly utilized. While&#160;these systems are relatively easy to work with, and are useful model systems in which various functional outcomes (such as cell death) can be readily quantified, the examined outcomes and pathways in cultured immature neurons (such as excitotoxicity-mediated cell death pathways) are not necessarily the same as those observed in mature brain, or in intact tissue. Therefore, there is the need to develop models in which cellular mechanisms in mature neural tissue can be examined. We have developed an in vitro technique that can be used to investigate a variety of molecular pathways in intact nervous tissue. The technique described herein utilizes rat cortical tissue, but this technique can be adapted to use tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken) or brain regions (for example, hippocampus, striatum, etc.). Additionally, a variety of stimulations/treatments can be used (for example, excitotoxic, administration of inhibitors, etc.). In conclusion, the brain slice model described herein can be used to examine a variety of molecular mechanisms involved in excitotoxicity-mediated brain injury.

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

We have developed a brain slice model which can be used to examine molecular mechanisms involved in excitotoxicity-mediated brain injury.&#160;This technique generates viable mature brain tissue and reduces animal numbers required for experimentation, whilst keeping the neuronal circuitry, cellular interactions, and postsynaptic compartments partly intact.

הפעלת יתר רעיל גירוי של המוח כMicroslices<em&gt; במבחנה</em&gt; דגם של שבץ

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As ...

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

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 shown to effectively induce humoral and cellular responses at systemic and mucosal sites, namely the lungs and urogenital tract. Sublingual vaccination can promote protection against infections at the lower and upper respiratory tract; it can also promote tolerance to allergens and ameliorate asthma symptoms. Modulation of lung&#8217;s immune response by sublingual immunotherapy (SLIT) is safer than direct administration of formulations by intranasal route because it does not require delivery of potentially harmful molecules directly into the airways. In contrast to intranasal delivery, side effects involving brain toxicity or facial paralysis are not promoted by SLIT. The immune mechanisms underlying SLIT remain elusive and its use for the treatment of acute lung infections has not yet been explored. Thus, development of appropriate animal models of SLIT is needed to further explore its potential advantages. 
This work shows how to perform sublingual administration of therapeutic agents in mice to evaluate their ability to protect against acute pneumococcal pneumonia. Technical aspects of mouse handling during sublingual inoculation, precise identification of sublingual mucosa, draining lymph nodes and isolation of tissues, bronchoalveolar lavage and lungs are illustrated. Protocols for single cell suspension preparation for FACS analysis are described in detail. Other downstream applications for the analysis of the immune response are discussed. Technical aspects of the preparation of Streptococcus pneumoniae inoculum and intranasal challenge of mice are also explained.
SLIT is a simple technique that allows screening of candidate molecules to modulate lungs&#8217; immune response. Parameters affecting the success of SLIT are related to molecular size, susceptibility to degradation and stability of highly concentrated formulations.

The present work illustrates the convenience of using sublingual immunotherapy to boost the innate immune response in the lungs and confer protection against acute pneumococcal pneumonia in mouse.

אימונותרפיה תת לשונית כחלופה ללהשרות הגנה מפני זיהומים בדרכי הנשימה חריפים

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 ...

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are therefore required to confine cardiac damage, promote survival and reduce the disease burden of heart failure. Large animal experiments are an essential part in the translational process from experimental to clinical therapies. To optimize clinical translation, robust and representative outcome measures are mandatory. The present manuscript aims to address this need by describing the assessment of three clinically relevant outcome modalities in a pig acute myocardial infarction (AMI) model: infarct size in relation to area at risk (IS/AAR) staining, 3-dimensional transesophageal echocardiography (TEE) and admittance-based pressure-volume (PV) loops. Infarct size is the main determinant driving the transition from AMI to heart failure and can be quantified by IS/AAR staining. Echocardiography is a reliable and robust tool in the assessment of global and regional cardiac function in clinical cardiology. Here, a method for three-dimensional transesophageal echocardiography (3D-TEE) in pigs is provided. Extensive insight into cardiac performance can be obtained by admittance-based pressure-volume (PV) loops, including intrinsic parameters of myocardial function that are pre- and afterload independent. Combined with a clinically feasible experimental study protocol, these outcome measures provide researchers with essential information to determine whether novel therapeutic strategies could yield promising targets for future testing in clinical studies.

Reliable and accurate outcome assessment is the key for translation of preclinical therapies into clinical treatment. The current paper describes how to assess three clinically relevant primary outcome parameters of cardiac performance and damage in a pig acute myocardial infarction model.

הערכת התוצאה העיקרית במודל חזיר של באוטם שריר הלב

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are ...

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

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms. Unfortunately, difficulties determining the etiology of ARDS, as well as a wide range of pathophysiology have resulted in a lack of critical information that could be useful in developing therapeutic strategies.
Translational animal models are valuable when their pathogenesis and pathophysiology accurately reproduce a concept proven in both in vitro and clinical settings. Although large animal models (e.g., sheep) share characteristics of the anatomy of human trachea-bronchial tree, murine models provide a host of other advantages including: low cost; short reproductive cycle lending itself to greater data acquisition; a well understood immunologic system; and a well characterized genome leading to the availability of a variety of gene deletion and transgenic strains. A robust model of low pH induced ARDS requires a murine ALI that targets mainly the alveolar epithelium, secondarily the vascular endothelium, as well as the small airways leading to the alveoli. Furthermore, a reproducible injury with wide differences between different injurious and non-injurious insults is important.
The murine gastric acid aspiration model presented here using hydrochloric acid employs an open tracheostomy and recreates a pathogenic scenario that reproduces the low pH pneumonitis injury in humans. Additionally, this model can be used to examine interaction of a low pH insult with other pulmonary injurious entities (e.g., food particles, pathogenic bacteria).

This protocol induces acute lung injury in a mouse that has close fidelity to the pathogenesis of acid pneumonitis observed in humans. We generate a maximal acute nonlethal low pH lung injury and account for differences in rodent-human anatomic respiratory structure using an open tracheostomy coupled with circumferential pressure release.

להרחיב הנשמת קיבת חומצה שאיפת Murine הדגם של פגיעה החריפה ריאות תוצאות ב מקסימלי חריפה קטלנית פגיעת ריאות

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

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

The acute respiratory distress syndrome is a relevant intensive care disease with an incidence ranging between 2.2% and 19% of intensive care unit patients. Despite treatment advances over the last decades, ARDS patients still suffer mortality rates between 35 and 40%. There is still a need for further research to improve the outcome of patients suffering from ARDS. One problem is that no single animal model can mimic the complex pathomechanism of the acute respiratory distress syndrome, but several models exist to study different parts of it. Oleic acid injection (OAI)-induced lung injury is a well-established model for studying ventilation strategies, lung mechanics and ventilation/perfusion distribution in animals. OAI leads to severely impaired gas exchange, deterioration of lung mechanics and disruption of the alveolo-capillary barrier. The disadvantage of this model is the controversial mechanistic relevance of this model and the necessity for central venous access, which is challenging especially in smaller animal models. In summary, OAI-induced lung injury leads to reproducible results in small and large animals and hence represents a well-suited model for studying ARDS. Nevertheless, further research is necessary to find a model that mimics all parts of ARDS and lacks the problems associated with the different models existing today.

In this article, we present a protocol to induce acute lung injury in pigs by central-venous injection of oleic acid. This is an established animal model for studying the acute respiratory distress syndrome (ARDS).

הזרקת חומצה אולאית חזירים כמודל עבור תסמונת מצוקה נשימתית חריפה

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

Bronchoalveolar Lavage and Oleic Acid-Injection in Pigs as a Double-Hit Model for Acute Respiratory Distress Syndrome (ARDS)

The treatment of ARDS continues to pose major challenges for intensive care physicians in the 21st century with mortality rates still reaching up to 50% in severe cases. Further research efforts are needed to better understand the complex pathophysiology of this disease. There are different well-established animal models to induce acute lung injury but none has been able to adequately mimic the complex pathomechanisms of ARDS. The most crucial factor for the development of this condition is the damage to the alveolar capillary unit. The combination of two well-established lung injury models allow us to mimic in more detail the underlying pathomechanism. Bronchoalveolar lavage (BAL) leads to surfactant depletion as well as alveolar collapse. The repeated instillation of fluid volumes causes subsequent hypoxemia. Surfactant depletion is a key factor of ARDS in humans. BAL is often combined with other lung injury approaches, but not with a second hit followed by oleic acid injection (OAI) yet. Oleic acid injection leads to severely impaired gas exchange, a deterioration of lung mechanics and disruption of the alveolo-capillary barrier. The OAI mimics most of the expected effects of ARDS consisting of extended inflammation of lung tissue with an increase of alveolar leakage and gas exchange impairment. A disadvantage of the combination of different models is the difficulty to determine the influence to the lung injury caused by BAL alone, OAI alone or both together. The model presented in this report represents the combination of BAL and OAI as a new double-hit lung injury model. This new model is easy to implement and an alternative to study different therapeutic approaches in ARDS in the future.

<meta charset="utf8"></head><body>שטיפת סימפונות והזרקת חומצה אולאית בחזירים כמודל מכה כפולה לתסמונת מצוקה נשימתית חריפה ARDS

Different, complex animal models exist to study the pathophysiology of acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage and oleic acid injection induced lung injury is suitable as a new double-hit animal model for studying the acute respiratory distress syndrome.

שטיפת סימפונות והזרקת חומצה אולאית בחזירים כמודל פגיעה כפולה לתסמונת מצוקה נשימתית חריפה (ARDS)

The treatment of ARDS continues to pose major challenges for intensive care physicians in the 21st century with mortality rates still reaching up to 50% ...

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

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.

We describe a model of hydrochloric acid-induced acute respiratory distress syndrome (ARDS) in piglets receiving sedation with halogenated agents, isoflurane and sevoflurane, through a device used for inhaled intensive care sedation. This model can be used to investigate the biological mechanisms of halogenated agents on lung injury and repair.

משלוח סוכן הלוגני במודל חזירי של תסמונת מצוקה נשימתית חריפה באמצעות מכשיר מסוג יחידת טיפול נמרץ

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

Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome (ARDS)

Various animal models exist to study the complex pathomechanisms of the acute respiratory distress syndrome (ARDS). These models include pulmo-arterial infusion of oleic acid, infusion of endotoxins or bacteria, cecal ligation and puncture, various pneumonia models, lung ischemia/reperfusion models and, of course, surfactant depletion models, among others. Surfactant depletion produces a rapid, reproducible deterioration of pulmonary gas exchange and hemodynamics and can be induced in anesthetized pigs using repeated lung lavages with 0.9% saline (35 mL/kg body weight, 37 &#176;C). The surfactant depletion model supports investigations with standard respiratory and hemodynamic monitoring with clinically applied devices. But the model suffers from a relatively high recruitability and ventilation with high airway pressures can immediately reduce the severity of the injury by reopening atelectatic lung areas. Thus, this model is not suitable for investigations of ventilator regimes that use high airway pressures. A combination of surfactant depletion and injurious ventilation with high tidal volume/low positive end-expiratory pressure (high Tv/low PEEP) to cause ventilator induced lung injury (VILI) will reduce the recruitability of the resulting lung injury. The advantages of a timely induction and the possibility to perform experimental research in a setting comparable to an intensive care unit are preserved.

Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome ARDS

A combination of surfactant washout using 0.9% saline (35 mL/kg body weight, 37 &#176;C) and high tidal volume ventilation with low PEEP to cause moderate ventilator induced lung injury (VILI) results in experimental acute respiratory distress syndrome (ARDS). This method provides a model of lung injury with low/limited recruitability to study the effect of various ventilation strategies for extended periods.

דלדול פעילי שטח בשילוב עם אוורור מזיק גורם למודל רבייה של תסמונת מצוקה נשימתית חריפה (ARDS)

Various animal models exist to study the complex pathomechanisms of the acute respiratory distress syndrome (ARDS). These models include pulmo-arterial ...

דלדול פעילי שטח הנגרמת שטיפה בחזירים כמודל של תסמונת מצוקה נשימתית חריפה (ARDS)

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