Gli autori desiderano ringraziare Christine Guesdon (Abbott) per i doni dei Stentgrafts.

Metodi Il protocollo è stato approvato dal Comitato Etico Bichat-Debré (N ° 2012-15/698-0074). Il modello di perfusione elastasi è stata descritta la prima volta da Anidjar nel 1990 1: aneurisma dell&#39;aorta addominale è indotta dalla perfusione elastasi in ratti maschi Wistar, di età compresa tra 8-9 settimane 250-300 g. Due a 4 settimane dopo, un re-laparotomia viene eseguita, e una 3 mm di diametro ricoperta endoprotesi coronariche è utilizzato per escludere l&#39;aneurisma. L&#39;innesto, inserito attraverso un aortotomy distale, è distribuito sotto visione ingrandita. Due settimane più tardi, endoprotesi pervietà è confermata da un aortografia dalla carotide comune di sinistra prima del sacrificio. L&#39;aorta stented complesso e tessuti circostanti vengono poi raccolte e condizionati per l&#39;analisi. Protocollo 1. Fase 1: Aneurisma aortico addominale induzione (giorno 0) <ol><li> Anestetizzare l&#39;animale con isoflurano, e prestazionim un intra peritoneale iniezione penthobarbital. 0,1 ml/100 g di penthobarbitol è diluito in 0,1 ml di saline/100 g di peso dell&#39;animale. L&#39;anestesia è adeguato per la procedura. </li><li> Shave l&#39;addome, e pulire la pelle con l&#39;alcol. </li><li> Fai Xypho pubico incisione della pelle con una lama. Muscoli addominali strato poi peritoneo, evitando gli organi interni, sono aperti con le forbici. Mettere le crocette e avvolgere gli intestini in un impacco bagnato sul lato sinistro dell&#39;animale. </li><li> Aprire il peritoneo posteriore direttamente sopra l&#39;aorta, senza strapparla. L&#39;obiettivo è quello di prevenire future aderenze intestinali da dissezione economica. </li><li> Legare tutte collaterali dalla vena renale sinistra alla biforcazione iliaca con una sola legatura, all&#39;origine dell&#39;aorta. Se l&#39;aorta è bloccato per l&#39;intestino o la vena cava, c&#39;è un alto rischio di sanguinamento durante il secondo intervento, questo è spesso fatale per il ratto. </li><li> Passare una seta 4-0 due volte intorno al aorta 15 mm sotto la left vena renale. E &#39;importante per sezionare completamente l&#39;aorta, ca. 15 millimetri sotto la vena renale sinistra ed appena prossimale alla biforcazione iliaca per consentire l&#39;inserimento dei morsetti approssimatore Gilbert. </li><li> Dopo il bloccaggio prossimale dell&#39;aorta appena sotto la vena renale sinistra, e distalmente appena sopra la biforcazione iliaca, rimuovere l&#39;avventizia, ed eseguire una piccola aortotomy quanto prossimale possibile al morsetto distale. L&#39;aorta deve essere accuratamente lavata con soluzione salina e una cannula angolati e tutti i rimanenti sangue lavati per evitare l&#39;embolizzazione coagulo quando declamping. </li><li> Introdurre calore-conico tubo di polietilene (PE 10) uniformemente all&#39;interno dell&#39;aorta, e passare la seta 4-0 intorno l&#39;aorta (al passo 1.6) e legare per fissare il tubo ed evitare l&#39;espulsione pressione. </li><li> Iniettare elastasi in una lunghezza da 10 a 13 mm aorta (dal morsetto prossimale alla seta). </li><li> Infondere 725 microlitri della soluzione di elastasi è d a velocità costante-rate in 30 min. È importante attentamente survey l&#39;iniezione: durante l&#39;infusione, l&#39;aorta dovrebbe espandersi da 140-150% del suo diametro normale. </li><li> Al termine dell&#39;infusione, rimuovere il catetere, lavare l&#39;elastasi con soluzione salina, tagliare la seta e chiudere il aortotomy con circa 3 punti del 10-0 Prolene. Rimuovere i morsetti: distale poi prossimale. Cura deve essere presa per evitare di sutura trans-aortico. Con una pratica pochi e considerando la porzione ridotta di aortotomy, trombosi aorta è estremamente raro. </li><li> Chiudere parete addominale con una sutura assorbibile continuo, e la pelle con interrotti suture non assorbibili. Iniettare una dose mg / kg di Carprofen 5 sottocutanea per prevenire il dolore. Riportare i ratti a loro gabbia e dare il topo da laboratorio standard chow e acqua ad libidum. </li></ol> 2. Fase 2: Aneurisma aortico addominale Esclusione con un Coronarica PTFE (politetrafluoroetilene) endoprotesi coperto (giorno 15-30) <ol><li> Prima dell&#39;operazione, diluire Aspirina 1000 mg in 1 L di acqua. Quotidiano waassunzione ter stata stimata di 10-12 ml/100 g / di peso corporeo al giorno. </li><li> Dopo anestesia come precedentemente descritto, eseguire una re-laparotomia, evitando accuratamente potenziali organi interni aderenti alla parete addominale. Aneurisma è stato definito da un aumento del 50% almeno dell&#39;aorta rispetto al diametro dell&#39;aorta prossimale misurata sotto visione diretta. Sulla base della nostra esperienza, la percentuale di successo è del 90%, comprese le morti precoci, soprattutto a causa aorta scoppio (dati non pubblicati) </li><li> Sezionare il aorta alla biforcazione aortica e anche al colletto prossimale. L&#39;aneurisma dovrebbe sorgere alcuni millimetri sotto la vena renale sinistra, ciò permette una lunghezza soddisfacente tra il collo distale e il morsetto distale per inserire il catetere, e suturare l&#39;aorta. Lunghezza endoprotesi dipende dalle dimensioni dell&#39;aneurisma. Colli sia prossimale e distale dovrebbero essere coperte da almeno 2 millimetri. </li><li> Avvolgere un doppio anello di seta intorno al collo prossimale. Bloccare l&#39;aorta prossimale sopra l&#39;aneurisma e Below dell&#39;arteria renale sinistra, e distalmente sopra della biforcazione aortica. </li><li> Di eseguire una grande aortotomy appena sopra la aortotomy precedente per evitare di strappare la parete aortica, quando l&#39;introduzione del endoprotesi. Non risciacquare l&#39;aorta di preservare l&#39;integrità del trombo. Spingere l&#39;endoprotesi verso il morsetto prossimale. Rimuovere la pinza è e controllare la tensione della seta per permettere progressione innesto. Adattare la tensione intorno al catetere consegna per consentire progressione endoprotesi finché il bordo prossimale della endoprotesi raggiunge il colletto prossimale, ma anche questo impedirà massiccia emorragia dopo la rimozione morsetto prossimale. Il palloncino e l&#39;estremità prossimale del catetere consegna possono coprire le arterie renali, ma non l&#39;endoprotesi che deve essere distribuito sotto le arterie renali. </li><li> Distribuire l&#39;endoprotesi sotto controllo visivo diretto utilizzando una siringa di gonfiaggio a 8 atm di pressione. Sgonfiare il palloncino mentre stringendo la seta e rimuovere l&#39;albero palloncino. </li><li> Lavare il stentgraft con soluzione fisiologica. Posizionare un morsetto appena sotto la parte distale del aneurisma, aorta e chiudere con suture interrotte 10-0 Prolene. </li><li> Chiudere la ferita, iniettare per via sottocutanea carprofene e lasciare che gli animali ritornano alla loro gabbia. Dare il cibo standard di laboratorio e acqua ad libidum. </li></ol> 3. Fase 3: Controllo di endoprotesi pervietà (30 Giorni) 15 giorni dopo l&#39;inserimento endoprotesi, svolgono una arteriografia per controllare la pervietà dell&#39;innesto <ol><li> Dopo l&#39;anestesia, eseguire un gomito a gomito incisione trasversale. L&#39;arteria carotide comune di sinistra si trova sotto le ghiandole sottomandibolari e sottolinguale e sotto il muscolo sternocleidomastoideo. Si raccomanda due centimetri esposizione lunghezza. </li><li> Legare l&#39;arteria distale con una seta 4-0. Dopo il bloccaggio prossimale, inserire un catetere 18G retrograda e fissare con una seta 4-0 superato due volte intorno alla carotide e legato. Di lunghezza sufficiente permette l&#39;inserimento e fissaggio del catetere siaribalta morsetto prossimale viene rimosso. Se è difficile per esporre due centimetri di arteria, il tubo, bloccato dopo aver riempito con soluzione salina può essere spinto in posizione prossimale, mentre la rimozione della pinza prossimale. </li><li> Iniettare contrasto attraverso il catetere sotto fluoroscopia diretta. Eseguire un controllo angiografico endoprotesi sia per confermare l&#39;assenza di endoleak che potrebbe risultare di una distribuzione inadeguata del endoprotesi, e confermare la pervietà endoprotesi. Questo passaggio è importante perché l&#39;alto numero di vasi collaterali consentono un&#39;adeguata perfusione gamba anche con una endoprotesi trombosi. Non abbiamo provato ad eseguire l&#39;ecografia duplex: postuliamo che la struttura in acciaio endoprotesi impedisce una corretta valutazione della pervietà endoprotesi e endoleak. </li><li> Sacrifica il ratto per dissanguamento secondo le raccomandazioni 18 e l&#39;aneurisma, endoprotesi, trombo e la parete aortica sono raccolte per gli studi istologici o biochimici. </li></ol>

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Non ho nulla da rivelare.

Due modelli di AAA sono stati già descritti nel nostro laboratorio: xenotrapianto 19 e modelli indotti elastasi 1 modello elastasi è il più simile al aneurismi aortici umani:. Un grande trombo endoluminale circolare viene quindi escluso dalla riparazione endovascolare dell&#39;aneurisma. Endoleak sono un abituale complicanza di EVAR 14,15. Molte questioni rimangono ancora irrisolti: rottura AAA sono stati descritti con bassi endoleak, e talvolta senza sacc...

Competenze endovascolari hanno progredito da quando il primo endovascolare aneurisma riparazione (EVAR) da Parodi nel 1991 3, quasi la metà di tutti gli aneurismi addominali sono ora trattati con EVAR 4. A differenza di chirurgia, EVAR lascia il trombo, escludendolo dalla circolazione sanguigna sistemica. Gli aneurismi sono caratterizzati da un trombo ricco di emoglobina più strati, un sottile media e una avventizia fibrosed e infiammato. Il ruolo cruciale nella progressione proteolisi 5 aneurisma è stata dimostrata trent&#39;anni fa 6, 7: aneurisma sac trombo è associato ad una parete sottile aortica, lisi di elastina, bassa densità di cellule muscolari lisce in media, e un alto livello di immuno -infiammatori reazione avventiziale 8,9. Questi cambiamenti suggeriscono che l&#39;attività proteolitica enzimatica si verifica all&#39;interno del trombo, piuttosto che direttamente nella parete aortica. Inoltre, lo strato luminale del trombo è ricco di agglutinato rosso sangue ceLLS rilasciando emoglobina. Essi sono coinvolti principalmente in formazione di fibrina, l&#39;attivazione piastrinica e indurre la formazione di trombina. Infine, trombo induce anche t-PA e plasminogeno di ritenzione, che sono coinvolti nella fibrinolisi e di reclutamento dei leucociti, soprattutto neutrofili. Questi sono 12 volte più importante nel trombo che nel sangue 10. La loro presenza è associata ad un alto tasso di metalloproteinasi della matrice di tipo 8 (MMP-8), MMP-9 e elastasi: rilasciano serina proteasi granulari e agenti ossidanti pro portano alla degradazione della matrice fibrillare, e in ultima analisi parete aortica rottura 9,11 -13. Intervento di aneurisma elettivo mira a prevenire la rottura. EVAR lascia sia a parete dell&#39;aneurisma e trombo intatto. Così, aneurisma perfusione da collaterali aortici (arterie lombari, mesenterica inferiore ...), è chiamato endoleak, ed è una specifica complicanza del trattamento endovascolare 14,15, a volte porta alla rottura vigilian con endoleak di bassa pressione. Inoltre, in alcuni pazienti, non vi è alcun aumento di diametro dell&#39;aneurisma 16. Interazione tra sangue circolante e parete aneurismatica mantiene il citato intra luminale attività biologica trombo. Quindi, Type V endoleak, definita come l&#39;espansione della sacca aneurismatica senza endoleak identificati, possono essere spiegati con l&#39;attività enzimatica all&#39;interno del trombo aneurisma. Né l&#39;imaging radiologico (scan 18FDG-PET, scintigrafia attivazione piastrinica, ferro ossido contrasto MRI17), né il prelievo di sangue periferico (MMP-9, microparticelle derivati ​​piastrinici, plasmina / complessi anti-plasmina) utilizzati per esplorare l&#39;impatto endovascolare su aneurismi dell&#39;aorta nell&#39;uomo direttamente valutare vie biochimiche. A nostra conoscenza, non vi è alcun sperimentali modelli animali di esclusione dell&#39;aneurisma riproducibili ed economico. Questo permette aneurisma esclusione modificazioni biologiche ed istologiche pre e post da esplorare.

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 <td>Animals </td>
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 <td>Wistar rats</td>
 <td></td>
 <td></td>
 <td>aged from 8 to 9 weeks. Weight range from 350 to 400 g</td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Instruments</td>
 </tr>
 <tr>
 <td>Isoflurane anesthesic system</td>
 <td></td>
 <td></td>
 <td>4,5% at the beginning, then 2%</td>
 </tr>
 <tr>
 <td>Penthobarbital</td>
 <td>Ceva sante animale, Libourne, France</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Dissection stereomicroscope</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Steriles gloves</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Microsurgical Steriles instruments</td>
 <td>Moria, Antony, France</td>
 <td></td>
 <td>Needle holder,	Forceps, Scissors,Gilbert approximator
o	3 Micro clamps</td>
 </tr>
 <tr>
 <td>N&deg;40 Silk string</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Prolen 9-0 and 10-0</td>
 <td>Ethicon, Johnson &amp; Johnson, Auneau, France</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Heat-tapered polyethylene tubing</td>
 <td>PE 10</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Syringe infusion pump</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Porcine pancreatic elastase</td>
 <td>Sigma, St. Louis, Mo., USA</td>
 <td></td>
 <td>550 &mu;l of salin is mixed with 175 &mu;l of elastase</td>
 </tr>
 <tr>
 <td>Indeflator</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>9 to 16 mm length, 3 mm diameter coronary PTFE covered stentgraft</td>
 <td>Abbott, Abbott Park, Illinois, USA</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>C-Arm OEC 9800</td>
 <td>GE Medical Systems, Milwaukee, WI</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Aspegic 1000 mg</td>
 <td>Aspirin, Sanofi-Aventis, Paris, France</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Reagent</td>
 </tr>
 <tr>
 <td>Aerane isoflurane 100ML</td>
 <td>Baxter</td>
 <td>Aerane</td>
 <td></td>
 </tr>
 <tr>
 <td>Penthobarbital</td>
 <td>Centravet</td>
 <td>053pen203</td>
 <td></td>
 </tr>
 <tr>
 <td>Silk Suture 4-0</td>
 <td>Fine Science</td>
 <td>18020-40</td>
 <td></td>
 </tr>
 <tr>
 <td>Microsurgical steriles instruments</td>
 <td>Moria</td>
 <td>9980-9983-9987-204/A-204/D-8148-4877A-4878A</td>
 <td></td>
 </tr>
 <tr>
 <td>Prolen 9-0 and 10-0</td>
 <td>Ethicon</td>
 <td>W2829 &ndash; NS2850</td>
 <td></td>
 </tr>
 <tr>
 <td>Heat tapered Polyethylene tubing : PE 10</td>
 <td>Bioseb</td>
 <td>MRE-010</td>
 <td></td>
 </tr>
 <tr>
 <td>Infusion pump</td>
 <td>World precision instrument</td>
 <td>AL-1000</td>
 <td></td>
 </tr>
 <tr>
 <td>Porcine pancreatic elastase</td>
 <td>Sigma</td>
 <td>E1250-100MG</td>
 <td></td>
 </tr>
 <tr>
 <td>Indeflator</td>
 <td>Longreal</td>
 <td>KY025 25 100</td>
 <td></td>
 </tr>
 <tr>
 <td>Aspegic 1000mg (Aspirin)</td>
 <td>Sanofi-Aventis</td>
 <td>3400931898191</td>
 <td></td>
 </tr>
 <tr>
 <td>C-Arm OEC 9800</td>
 <td>General electric.</td>
 <td>OEC 9800</td>
 <td></td>
 </tr>
 <tr>
 <td>Stentgraft : Jostent</td>
 <td>Abbott</td>
 <td>210CG1230 
 210CG1630</td>
 <td></td>
 </tr>
</tbody>
</table>

a new murine model of endovascular aortic aneurysm repair

Endovascolare dell&#39;aneurisma esclusione è una tecnica validata per evitare la rottura di aneurisma. Risultati a lungo termine evidenziano limitazioni di tecnica e nuovi aspetti di aneurisma dell&#39;aorta addominale (AAA) fisiopatologia. Non vi è alcun aneurisma aortico addominale endoprotesi esclusione modello economico e riproducibile, che consentirebbe indagini profonde di AAA prima e dopo il trattamento. Con la presente descriviamo come indurre, e quindi di escludere con una endoprotesi coronariche coperta di un aneurisma aortico addominale in un topo. L&#39;elastasi modello indotta AAA noto fu riportata nel 1990 1 in un ratto, poi descritto nei topi 2. Elastina degradazione porta alla dilatazione dell&#39;aorta con infiltrazione infiammatoria della parete addominale e intra trombo endoluminale, corrispondente con AAA umana. Esclusione endovascolare con endoprotesi piccolo coperto viene quindi eseguita, escluse eventuali interazioni tra la circolazione del sangue e il trombo aneurisma. Esclusione del caso ed endoprotesi pervietà èconfermato prima di eutanasia da parte di un angiografia pensiero la carotide sinistra. Controllo parziale di elastasi diffusione rende aneurisma forma diversa per ciascun animale. È difficile creare un aneurisma, che consentirà un periodo adeguato aorta sotto dell&#39;aneurisma per una introduzione endoprotesi facile e con un&#39;adeguata colletto prossimale e distale per evitare endoleak. Un sacco di fallimento può portare alla introduzione endoprotesi, che a volte portano alla aorta lacrima di dolore e guai a punto, e danno endoteliale con trombosi aortica post operatorio. Dare l&#39;aspirina ai ratti prima dell&#39;impianto endoprotesi diminuisce tasso di fallimento senza emorragia maggiore. Momento di serraggio attiva i neutrofili, endotelio e piastrine, e può interferire con analisi biologiche.

<html> Aneurisma è fissato in una soluzione di paraformaldeide al 4% durante 24 ore, poi in una Soluzione tampone fosfato fino fissazione in un blocco di resina. Usiamo un HPS (ematossilina Floxina Safran) (Figura 1) colorazione, mostrando guarigione cellule proliferative di tutto il PTFE (Figura 2). Cellule mesenchimali vengono quindi caratterizzati da α-actina colorazione (Figura 3). <img src="/files/f...

Watch this Scientific Journal Video about A New Murine Model of Endovascular Aortic Aneurysm Repair at JoVE.com

A New Murine Model of Endovascular Aortic Aneurysm Repair

Modificazioni istologiche e biochimiche dopo aneurisma endograft esclusione sono ancora poco chiari. Descriviamo un nuovo modello di impianto endograft su un aneurisma murino. Attraverso l&#39;analisi trombo con e senza persistente circolazione interfaccia flusso sanguigno, e nuova valutazione biomateriali endovascolare, questo modello vi aiuterà a comprendere meglio endovascolare dell&#39;aneurisma esclusione patobiologia.

Un nuovo modello murino di endovascolare aneurisma dell&#39;aorta riparazione

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of ...

a-new-murine-model-of-endovascular-aortic-aneurysm-repair

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Medicine

14.3K Views.  Hôpital X. Bichat, AP-HP, Paris. Modificazioni istologiche e biochimiche dopo aneurisma endograft esclusione sono ancora poco chiari. Descriviamo un nuovo modello di impianto endograft su un aneurisma murino. Attraverso l'analisi trombo con e senza persistente circolazione interfaccia flusso sanguigno, e nuova valutazione biomateriali endovascolare, questo modello vi aiuterà a comprendere meglio endovascolare dell'aneurisma esclusione patobiologia.

Video: A New Murine Model of Endovascular Aortic Aneurysm Repair

Reproducable Paraplegia by Thoracic Aortic Occlusion in a Murine Model of Spinal Cord Ischemia-reperfusion

Background 
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury.&#160;The current model demonstrates reproducible lower&#160;extremity paralysis following thoracic aortic occlusion.
Methods 
Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery.&#160; Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr.
Results 
Mice that underwent sham surgery showed no observable hind&#160;limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post&#160;operative mortality.
Conclusion 
Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.

The lack of mechanistic understanding of spinal cord ischemia-reperfusion injury has hindered further adjuncts to prevent paraplegia following high risk aortic operations. Thus, the development of animal models is imperative. This manuscript demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion in a murine model.

Riproducibile Paraplegia da Toracica aortica occlusione in un modello murino di Spinal Cord ischemia-riperfusione

Background
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered ...

Ricerca

Medicina

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.

Aprire tracheostomia gastrico acido aspirazione Modello murino di lesioni polmonari acute Risultati in massima acuta non letale 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 ...

Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model

Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These complications can be attributed to impairments in re-endothelialization within the wound margins. Yet, the cellular and molecular mechanisms of re-endothelialization remain to be defined. While several animal models to study re-endothelialization after arterial denudation are available, few are performed in the mouse because of surgical limitations. This undermines the opportunity to exploit transgenic mouse lines and investigate the contribution of specific genes to the process of re-endothelialization. Here, we present a step-by-step protocol for creating a highly reproducible murine model of arterial denudation injury in the infrarenal abdominal aorta using external vascular clamping. Immunocytochemical staining of injured aortas for fibrinogen and &#946;-catenin demonstrate the exposure of a pro-thrombotic surface and the border of intact endothelium, respectively. The method presented here has the advantages of speed, excellent overall survival rate, and relative technical ease, creating a uniquely practical tool for imposing arterial denudation injury in transgenic mouse models. Using this method, investigators may elucidate the mechanisms of re-endothelialization under normal or pathological conditions.

Understanding the cellular and molecular mechanisms of re-endothelialization following arterial denudation injury is of paramount importance in preventing thrombosis and restenosis of arteries. Here we describe a protocol for reproducible arterial denudation injury of the infrarenal abdominal aorta. The procedure was developed to investigate the underlying mechanisms that regulate endothelial regeneration using mouse models.

Riproducibile arteriosa Denudation Lesioni da infrarenale aortico addominale di serraggio in un modello murino

Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These ...

Creation of a Rodent Model of Abdominal Aortic Aneurysm by Blocking Adventitial Vasa Vasorum Perfusion

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic aneurysms (AAAs). This article introduces and describes a standard protocol used to induce AAAs through adventitial VV hypoperfusion created with a combination of polyurethane catheter insertion into the aortic lumen and suture ligation of the infrarenal abdominal aorta.
The protocol involves the use of male rats weighing 300-400 g, which are provided food and water ad libitum. After laparotomy with a ventral midline abdominal incision, exfoliation of the aorta is performed, which blocks blood flow from the perivascular tissue. Aortotomy involving a small incision adjacent to the renal artery branches is performed, and a polyurethane catheter is inserted using an 18-gauge indwelling needle. After repairing the incision, tight ligation of the aorta over the catheter blocks VV blood flow from the proximal direction through the aortic wall without disturbing the aortic blood flow. This technique can induce an AAA with progressive aortic dilatation.
The greatest benefit of this model is that VV hypoperfusion causes tissue hypoxia and the development of an infrarenal AAA, which has morphological and pathological characteristics similar to those of a human AAA.

Polyurethane catheter insertion into the aortic lumen and suture ligation of the aorta induce chronic hypoxia due to hypoperfusion of the adventitial vasa vasorum. This article describes a novel animal model of abdominal aortic aneurysm (AAA) with characteristics similar to those of AAA in humans.

Creazione di un modello del roditore del Aneurysm aortico addominale bloccando Adventitial Vasa Vasorum perfusione

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic ...

Quantitative Micro-CT Analysis of Aortopathy in a Mouse Model of &#946;-aminopropionitrile-induced Aortic Aneurysm and Dissection

Aortic aneurysm and dissection is associated with significant morbidity and mortality in the population and can be highly lethal. While animal models of aortic disease exist, in vivo imaging of the vasculature has been limited. In recent years, micro-computerized tomography (micro-CT) has emerged as a preferred modality for imaging both large and small vessels both in vivo and ex vivo. In conjunction with a method of vascular casting, we have successfully used micro-CT to characterize the frequency and distribution of aortic pathology in &#946;-aminopropionitrile-treated C57/Bl6 mice. Technical limitations of this method include variations in the quality of the perfusion introduced by poor animal preparation, the application of proper methodologies for vessel size quantification, and the non-survivability of this procedure. This article details a methodology for the intravascular perfusion of a lead-based radiopaque silicone rubber for the quantitative characterization of aortopathy in a mouse model of aneurysm and dissection. In addition to visualizing aortic pathology, this method may be used for examining other vascular beds in vivo or vascular beds removed post-mortem.

Quantitative Micro-CT Analysis of Aortopathy in a Mouse Model of &amp;#946;-aminopropionitrile-induced Aortic Aneurysm and Dissection

This article describes a detailed methodology of using a radiopaque lead-based silicone rubber to perfuse the murine vasculature for aortic diameter quantification in a mouse model of aortic aneurysm and dissection.

Analisi quantitativa di Micro-CT di Aortopathy in un modello murino di indotta da β-aminopropionitrile aneurisma e dissezione

Aortic aneurysm and dissection is associated with significant morbidity and mortality in the population and can be highly lethal. While animal models of ...

Murine Cervical Aortic Transplantation Model using a Modified Non-Suture Cuff Technique

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. However, only minor improvement in the long-term results of transplanted solid organs could be observed over the past decades. In this context, chronic allograft vasculopathy (CAV) still represents the leading cause of late organ failure in cardiac, renal and pulmonary transplantation.
Thus far, the underlying pathogenesis of CAV development remains unclear, explaining why effective treatment strategies are presently missing and emphasizing a need for relevant experimental models in order to study the underlying pathophysiology leading to CAV formation. The following protocol describes a murine heterotopic cervical aortic transplantation model using a modified non-suture cuff technique. In this technique, a segment of the thoracic aorta is interpositioned in the right common carotid artery. With the use of the non-suture cuff technique, an easy to learn and reproducible model can be established, minimizing the possible heterogeneity of sutured vascular micro anastomoses.

Here, we present a protocol of heterotopic aortic transplantation in mice using the non-suture cuff technique in a cervical murine model. This model can be used to study the underlying pathology of chronic allograft vasculopathy (CAV) and can help evaluate new therapeutic agents in order to prevent its formation.

Modello di trapianto aortico cervicale murine utilizzando una tecnica di manette non sutura modificata

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. ...

Murine Surgical Model of Topical Elastase Induced Descending Thoracic Aortic Aneurysm

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. An aneurysm forms as a result of progressive weakening and eventual dilation of the aorta, which can rupture or tear once it reaches a critical diameter. Aneurysms of the descending aorta in the chest, called descending thoracic aortic aneurysms (dTAA), make up a large proportion of aneurysm cases in the United States. Uncontained dTAA rupture is almost universally lethal, and elective repair has a high rate of morbidity and mortality. The purpose of our model is to study dTAA specifically, to elucidate the pathophysiology of dTAA and to search for molecular targets to halt the growth or reduce the size of dTAA. By having a murine model to study thoracic pathology precisely, targeted therapies can be developed to specifically test dTAA. The method is based on the placement of porcine pancreatic elastase (PPE) directly on the outer murine aortic wall after surgical exposure. This creates a destructive and inflammatory reaction, which weakens the aortic wall and allows for aneurysm formation over weeks to months. Though murine models possess limitations, our dTAA model produces robust aneurysms of predictable size. Furthermore, this model can be used to test genetic and pharmaceutical targets which may arrest dTAA growth or prevent rupture. In human patients, interventions such as these could help avoid aneurysm rupture, and difficult surgical intervention.

We describe a surgical protocol to consistently induce robust descending thoracic aortic aneurysms in mice. The procedure involves left thoracotomy, thoracic aorta exposure, and placement of a sponge soaked in porcine pancreatic elastase on the aortic wall.

Modello chirurgico murine dell'elastasi topica indotta decrescente all'aneurtica toracica

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. ...

Porcine Model of Infrarenal Abdominal Aortic Aneurysm

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called &#946;-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease.
Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone.
Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% &#177; 47.4% at day 7, 105.4% &#177; 58.1% at day 14, and 113.5% &#177; 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p &#60; 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease.
Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.&#160;

This novel model creates robust infrarenal abdominal aortic aneurysms in swine using a combination of balloon angioplasty, elastase/collagenase perfusion, topical elastase application, and oral compound &#946;-aminopropionitrile administration, which interferes with collagen cross-linking.

Modello porcinario dell'aneurisma aortico addominale a infrarosso

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal ...

A Murine Model of Hemodialysis Access-Related Hand Dysfunction

Chronic kidney disease is a major public health problem, and the prevalence of end-stage renal disease (ESRD) requiring chronic renal replacement therapies such as hemodialysis continues to increase. Autogenous arteriovenous fistula (AVF) placement remains a primary vascular access option for ESRD patients. Unfortunately, approximately half of the hemodialysis patients experience dialysis access-related hand dysfunction (ARHD), ranging from subtle paresthesia to digital gangrene. Notably, the underlying biologic drivers responsible for ARHD are poorly understood, and no adequate animal model exists to elucidate the mechanisms and/or develop novel therapeutics for the prevention/treatment of ARHD. Herein, we describe a new mouse model in which an AVF is created between the left common iliac artery and vein, thereby facilitating the assessment of limb pathophysiology. The microsurgery includes vessel isolation, longitudinal venotomy, creation of arteriovenous anastomosis, and venous reconstruction. Sham surgeries include all the critical steps except for AVF creation. Iliac AVF placement results in clinically relevant alterations in central hemodynamics, peripheral ischemia, and impairments in hindlimb neuromotor performance. This novel preclinical AVF model provides a useful platform that recapitulates common neuromotor perturbations reported by hemodialysis patients, allowing researchers to investigate the mechanisms of ARHD pathophysiology and test potential therapeutics.

This protocol details the surgical steps of murine common iliac arteriovenous fistula creation. We developed this model to study hemodialysis access-related limb pathophysiology.

Un modello murino di disfunzione della mano correlata all'accesso all'emodialisi

Chronic kidney disease is a major public health problem, and the prevalence of end-stage renal disease (ESRD) requiring chronic renal replacement ...

Drug Treatment by Central Venous Catheter in a Mouse Model of Angiotensin II Induced Abdominal Aortic Aneurysm and Monitoring by 3D Ultrasound

Since pharmaceutical treatment options are lacking in the clinical management of abdominal aortic aneurysm (AAA), animal models, in particular mouse models, are applied to advance the understanding of the disease pathogenesis and to identify potential therapeutic targets. Testing novel drug candidates to block AAA growth in these models generally requires repeated drug administration during the time course of the experiment. Here, we describe a compiled protocol for AAA induction, insertion of an intravenous catheter to facilitate prolonged therapy, and serial AAA monitoring by 3D ultrasound. Aneurysms are induced in apolipoprotein E (ApoE) deficient mice by angiotensin II release over 28 days from osmotic mini-pumps implanted subcutaneously into the mouse back. Subsequently, the surgical procedure for external jugular vein catheterization is conducted to allow for daily intravenous drug treatment or repeated blood sampling via a subcutaneous vascular access button. Despite the two dorsal implants, the monitoring of AAA development is readily facilitated by sequential semi-automated 3D ultrasound analysis, which yields comprehensive information on the expansion of aortic diameter and volume and on aneurysm morphology, as illustrated by experimental examples.

This protocol describes the consecutive implantation of an osmotic pump to induce abdominal aortic aneurysm by angiotensin II release in apolipoprotein E (ApoE) deficient mice and of a vascular access port with a jugular vein catheter for repeated drug treatment. Monitoring of aneurysm development by 3D ultrasound is effectively conducted despite dorsal implants.

Trattamento farmacologico mediante catetere venoso centrale in un modello murino di aneurisma dell'aorta addominale indotto da angiotensina II e monitoraggio mediante ecografia 3D

Since pharmaceutical treatment options are lacking in the clinical management of abdominal aortic aneurysm (AAA), animal models, in particular mouse ...