Yazarlar Stentgrafts en hediyeler için Christine Guesdon (Abbott) teşekkür etmek istiyorum.

Yöntemler Protokol Bichat-Debre Etik Komitesi (N ° 2012-15/698-0074) tarafından onaylanmıştır. Elastaz perfüzyon modeli, ilk kez 1990 yılında 1 Anidjar tarafından tarif edilmiştir: abdominal aortik anevrizma 8-9 haftalık, 250-300 g arası, erkek Wistar sıçanları elastaz perfüzyon ile indüklenir. İki ile 4 hafta sonra, yeniden laparotomi ve 3 mm çapında koroner stentgraft anevrizma dışlamak için kullanılır kaplıdır. Distal aortotomy içine yerleştirilen greft, büyütülmüş görüş altında konuşlanmıştır. İki hafta sonra, stentgraft açıklık kurban önce sol karotis arter tarafından aortografi ile onaylanır. Bütün stentli aort ve çevre dokulara daha sonra hasat ve analiz için koşuluna bağlıdır. Protokol 1. Adım 1: Abdominal Aort Anevrizması indüksiyon (Gün 0) <ol><li> Izofluran ile hayvan uyutmak ve performansm içi periton pentobarbital enjekte. Penthobarbitol 0.1 ml/100 gr hayvan ağırlığının saline/100 g 0.1 ml olarak seyreltilir. Anestezi işlemi için yeterli. </li><li> Karın Tıraş ve alkol ile cilt temizleyin. </li><li> Bir bıçak ile Xypho kasık cilt kesi yapmak. Sonra periton karın kasları katman, iç organları kaçınarak, makasla açıktır. Serpme yerleştirin ve hayvanın sol tarafında bir ıslak kompres olarak bağırsak sarın. </li><li> Yırtmadan, doğrudan aort üzerinde posterior periton açın. Amaç ekonomik diseksiyon ile ileride bağırsak yapışıklıkları önlemek içindir. </li><li> Aort kökeni de, sol renal ven sadece bir bağ ile iliak bifurkasyon tüm teminatlar Arter. Aort bağırsakları veya vena kava yapışmış ise, ikinci müdahale sırasında kanama riski yüksek var, bu genellikle fare için ölümcüldür. </li><li> Iki kez aort etrafında 4-0 ipek, lef altında 15 mm past renal ven. Bu tamamen aort, yaklaşık incelemek önemlidir. Sol renal ven ve Gilbert Approximator kelepçeler ekleme izin vermek için iliak bifurkasyon sadece proksimal altında 15 mm. </li><li> Sadece sol renal ven altında proksimal aort sıkma sonra, ve distal sadece iliak çatallanma üzerinde, adventisya kaldırmak ve distal kelepçe mümkün olduğunca proksimal sıra küçük aortotomy gerçekleştirin. Aort dikkatle tuzlu ve açılı kanül ve klempin zaman pıhtı embolizasyon önlemek için yıkanmış kalan tüm kan ile yıkanmalıdır zorundadır. </li><li> Aort içinde sorunsuz ısı-konik polietilen boru (PE 10) tanıtmak ve aort etrafındaki 4-0 ipek (adım 1.6 de) geçmek ve tüp güvenli ve basınç sınır dışı önlemek için bağlayacağım. </li><li> Aort bir 10 ila 13 mm uzunluğunda (proksimal kelepçe gelen ipek) içine elastaz enjekte edilir. </li><li> Elastaz çözüm aşılamak 725 ul 30 dakika hız-hız sabiti d olduğunu. Bu dikkatle s önemlidirurvey enjeksiyon: infüzyon sırasında, aort normal çapının 140-150% tarafından genişletmek gerekir. </li><li> Infüzyon sonunda, kateter kaldırmak tuzlu su ile elastaz yıkayın, ipek kesme ve 10-0 Prolen yaklaşık 3 dikiş ile aortotomy kapatın. Kelepçeleri çıkarın: distal sonra proksimal. Bakım trans-aort dikiş önlemek için alınması gereken. Birkaç uygulama ve aortotomy küçük uzunluğunu dikkate alınarak, aort tromboz son derece nadirdir. </li><li> Sürekli emilebilir sütür ve kesintiye olmayan emilebilir dikişlerle deri ile karın duvarı kapatın. Ağrı önlemek için subkutan Carprofen bir 5 mg / kg dozda enjekte edilir. Kendi kafesine fareler dönün ve standart sıçan laboratuvar yemi ve su ad libidum verir. </li></ol> 2. Adım 2: Koroner PTFE (Politetrafloroetilen) Kapalı Stentgraft ile Abdominal Aort Anevrizması Dışlama (Gün 15-30) <ol><li> Önceki çalışma için, suyun 1 L &#39;aspirin 1000 mg seyreltin. Günlük waTer alımı günde 10-12 ml/100 g / vücut ağırlığının tahmin edilmiştir. </li><li> Daha önce açıklandığı gibi anestezi sonra, dikkatli bir şekilde karın duvarına yapışık potansiyel iç organları kaçınarak, yeniden laparotomi gerçekleştirin. Anevrizma en az direk görüş altında ölçülen proksimal aort çapı göre aort% 50 artış olarak tanımlandı. Bizim deneyime dayalı, başarı oranı aort patlama çoğunlukla nedeniyle erken ölüm, (yayınlanmamış veri) dahil olmak üzere,% 90 </li><li> Aort bifürkasyonunda ve proksimal boyun aort parçalara ayır. Bu distal boyun ve kateter eklemek için distal kelepçe arasında tatmin edici bir uzunluk sağlar ve aort dikiş, anevrizma sol renal ven altında birkaç milimetre doğması halinde. Stentgraft uzunluğu anevrizma boyutuna bağlıdır. Proksimal ve distal hem boyun en az 2 milimetre ile örtülmelidir. </li><li> Proksimal boynuna bir çift döngü ipek sarın. Anevrizma ve b yukarıda proksimal aort KelepçeSol renal arter elow ve distal aort çatallanma üzerinde. </li><li> Sadece stentgraft tanıtan zaman aort duvar yırtılmasını önlemek için önceki aortotomy üzerinde büyük bir aortotomy gerçekleştirin. Trombüs bütünlüğünü korumak için aort durulama yapmayın. Proksimal kelepçe doğru stentgraft itin. Kelepçe olduğu çıkarın ve greft ilerleme sağlamak için ipek gerginliği kontrol. Stentgraft proksimal kenarı proksimal boyun ulaşır, aynı zamanda bu proksimal kelepçe çıkarıldıktan sonra büyük kanama engelleyecek kadar stentgraft ilerleme sağlamak için teslim kateter etrafında gerilim uyarlayın. Balon ve teslim kateterin proksimal ucu renal arterler değil, renal arterlerin altında konuşlandırılacak olan stentgraft kapsayabilir. </li><li> 8 atm basınçta bir şişirme şırınga kullanarak doğrudan görsel kontrol altında stentgraft dağıtın. Ipek sıkma iken balon deflate ve balon mili çıkarın. </li><li> S yıkayıntuzlu su ile tentgraft. Adil bir anevrizmanın distal kısmını aşağıya kelepçe ve kesintili 10-0 Prolen dikişlerle yakın aort yerleştirin. </li><li> Yara kapatmak, cilt altına enjekte Carprofen ve hayvanlar kafes geri dönelim. Standart laboratuar yemi ve su ad libidum verin. </li></ol> 3. Adım 3: Stentgraft Patensisi Kontrolü (Gün 30) Stentgraft takıldıktan sonra 15 gün, greft açıklığı kontrol etmek için anjiyografi gerçekleştirmek <ol><li> Anestezi sonra, dirsek kesi bir enine dirsek gerçekleştirin. Sol karotis arter submandibuler ve sublingual bezler altında ve sternomastoid kas altında yer almaktadır. 2 cm uzunluğunda maruz tavsiye edilir. </li><li> 4-0 ipek ile distal arter Arter. Sıkma proksimal sonra, retrograd bir 18G kateter yerleştirin ve karotis arter etrafında iki kez geçti ve bağlı 4-0 ipek ile sabitleyin. Yeterli bir uzunluğa izin yerleştirilmesi ve kateter sabitlemeön plana proksimal kelepçe kaldırılır. Bu arter 2cm ortaya çıkarmak için zor ise, tüp, tuzlu su ile doldurulur sonra kelepçeli proksimal kelepçe çıkarmadan iken proksimal itilebilir. </li><li> Doğrudan floroskopi altında kateter ile kontrast enjekte edilir. Her iki stentgraft uygun olmayan bir dağıtım neden ve stentgraft açıklığı onaylamak olabilir Kaçak olup olmaması onaylamak için bir stentgraft anjiografik kontrolü yapın. Teminat gemilerin yüksek sayıda bile tromboze stentgraft ile yeterli bacak perfüzyon izin bu adım önemlidir. Biz Dubleks ultrasonografi gerçekleştirmek için deneyin vermedi: Biz stentgraft çelik yapı stentgraft açıklığı ve kaçak doğru değerlendirilmesi engeller önerme. </li><li> Önerileri 18 göre kesilmesi ile sıçan Kurban ve anevrizma, stentgraft, trombüs ve aort duvarı histolojik veya biyokimyasal çalışmalar için hasat edilir. </li></ol>

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Ben ifşa hiçbir şey yok.

AAA iki model zaten bizim laboratuvarda tanımlanmıştır: ksenogreft 19 ve elastaz kaynaklı modelleri 1 Elastaz modeli insan aort anevrizması için en benzer:. Büyük bir çevresel intraluminal trombüs sonra endovasküler anevrizma tamiri ile hariçtir. Kaçak EVAR 14,15 bir olağan komplikasyonudur. Bir sürü soru çıkmıştır: AAA rüptürü anevrizma kesesi büyümesi 16 olmadan bazen düşük kaçak tarif edilmiş ve. Kaçak kan dolaş...

Endovasküler becerileri hemen hemen tüm abdominal anevrizmaların yarısı şimdi EVAR 4 ile tedavi edilir 1.991 3 Parodi tarafından ilk endovasküler aort anevrizma onarımı (EVAR), yana ilerlemiştir. Cerrahinin aksine, EVAR sistemik kan onu hariç trombüs bırakır. Anevrizma bir hemoglobin zengin çok katmanlı trombüs, ince bir medya ve bir fibrosed ve iltihaplı adventisya ile karakterizedir. Anevrizma ilerlemesinde proteoliz 5 önemli rol otuz yıl önce gösterilmiştir 6, 7: anevrizma kesesi trombüs ince aort duvar, elastin lizis, medyada düz kas hücrelerinin düşük yoğunluklu ve immün yüksek düzeyde ilişkili -inflamatuar adventisyal reaksiyon 8,9. Bu değişiklikler, proteolitik enzim aktivitesi trombüs yerine, doğrudan aort duvarında içinde gerçekleşir olduğunu göstermektedir. Buna ek olarak, trombüs lümen tabaka aglutinant kavkılı kırmızı kan ce zenginlls hemoglobin serbest. Onlar öncelikle fibrin oluşumu, trombosit aktivasyonu ve trombin oluşumu neden olarak katılıyor. Son olarak, trombüs da fibrinoliz ve işe lökositler, özellikle nötrofil katılan t-PA ve plazminojen tutma, neden olur. Bunlar, kan akışı 10 daha trombüs 12 kat daha önemlidir. Onların varlığı matriks metalloproteinaz tipi 8 (MMP-8) yüksek bir oranda bir ilişki olduğunu, MMP-9 ve elastaz: Onlar kopma 9,11 fibriler matriks bozulmasına sebep taneli serin proteazlar ve profesyonel oksidatif maddeleri bırakın, ve sonuçta aort duvar -13. Seçmeli anevrizma müdahale rüptürü önlemek amaçlamaktadır. EVAR anevrizma duvar ve trombüs hem olduğu gibi bırakır. Bu nedenle, aort teminat (lomber arterler, inferior mezenterik arter ...) ile anevrizma perfüzyon, kaçak adlı ve endovasküler tedavi 14,15 belirli bir komplikasyonudur, bazen rüptür arifesinde yol açmaktadırdüşük basınçlı kaçak ile n. Ayrıca, bazı hastalarda, anevrizma çapı 16 bir artış yoktur. Dolaşan kan ve anevrizmal duvar arasındaki etkileşim söz konusu içi luminal trombüs biyolojik aktivite tutar. Bu nedenle, Tip V kaçak, tespit endoleak olmadan anevrizma kesesi genişlemesi olarak tanımlanan, anevrizma trombüs içindeki enzimatik aktivite ile açıklanabilir. Ne radyolojik görüntüleme (18FDG-PET taraması, trombosit aktivasyonu sintigrafisi, demir oxyde kontrast MRI17) ne de periferik kan örneklemesi (MMP-9, trombosit kaynaklı mikro, plazmin / anti-plazmin kompleks) doğrudan insanlarda aort anevrizması üzerindeki endovasküler etkisini keşfetmek için kullanılan biyokimyasal yollar değerlendirmek. Bildiğimiz kadarıyla, herhangi bir tekrarlanabilir ve ucuz deneysel anevrizma dışlanma hayvan modellerinde yoktur. Bu bir öncesi ve sonrası anevrizma dışlama biyolojik ve histolojik değişiklikler keşfedilmeyi sağlar.

<table border="1">
<tbody>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Animals </td>
 </tr>
 <tr>
 <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

Endovasküler anevrizma dışlama anevrizma rüptürü önlemek için geçerli bir tekniktir. Uzun dönem sonuçları teknik sınırlamalar ve Abdominal aort anevrizması (AAA) patofizyolojisi yeni yönlerini vurgulayın. Tedavi öncesi ve sonrası AAA derin araştırmalar sağlayacak ucuz ve tekrarlanabilir bir abdominal aort anevrizması endogreft dışlama modeli vardır. Burada, ikna etmek için nasıl açıklar ve sonra kapalı bir koroner stentgraft bir sıçan bir abdominal aort anevrizması ile dışlamak için. Iyi bilinen kaynaklı elastaz AAA tipinde olanlar daha sonra farenin 2&#39;de anlatılan bir sıçan, 1990 1 &#39;de rapor edilmiştir. Elastin bozulması insan AAA ile eşleşen, karın duvarı ve içi luminal trombüs inflamatuvar infiltrasyonu ile aort dilatasyon yol açar. Küçük kapalı stentgraft ile endovasküler sonra dolaşan kan ve anevrizma trombüs arasındaki etkileşimleri hariç gerçekleştirilir. Uygun dışlanma ve stentgraft açıklığı olanbir anjiyografi ile ötenazi önce teyit sol karotis arter düşündüm. Elastaz difüzyon kısmi kontrolü her bir hayvan için anevrizma şekli farklı kılan. Bu kolay bir stentgraft giriş için anevrizma altında aort bir uygun uzunlukta sağlayacak bir anevrizma, oluşturmak zordur, ve yeterli proksimal ve distal boyun ile kaçak önlemek için. Başarısızlık çok bazen dikiş ona acı ve sıkıntılar ile aort gözyaşı yol stentgraft giriş, ve post op aort trombozu ile endotel hasarı neden olabilir. Stentgraft implantasyon önce sıçanlara aspirin verilmesi büyük kanama olmadan başarısızlık oranı azalır. Zaman sıkma nötrofil, endotel ve trombosit aktive, ve biyolojik analiz engel olabilir.

<html> Anevrizma sonra, reçine bloğun tespit kadar tamponlu tuz çözeltisi, fosfat, içine 24 saat boyunca bir% 4 paraformaldehit ile tespit edilir. Biz PTFE etrafında iyileşme proliferatif hücreleri (Şekil 2) gösteren bir HPS (Hematoksilen Phloxin Safran) (Şekil 1) boyama, kullanın. Mezenkimal hücreler daha sonra α-aktin boyama (Şekil 3) ile karakterize edilmektedir. <img src="/files/ftp_uplo...

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

Anevrizma endogreft dışlama sonra histolojik ve biyokimyasal değişiklikler hala belirsiz. Bir fare anevrizma üzerinde endogreft implantasyon yeni bir model tarif. Kalıcı dolaşan kan akışı arayüzü ve yeni endovasküler biyomalzemeler değerlendirme olan ve olmayan trombüs analizi sayesinde, bu model daha iyi endovasküler anevrizma dışlama patobiyolojisi anlamanıza yardımcı olacaktır.

Endovasküler Aort Anevrizma Onarımı Yeni Bir murin Modeli

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

Research

JoVE Journal

Medicine

14.3K Görüntüleme.  Hôpital X. Bichat, AP-HP, Paris. Anevrizma endogreft dışlama sonra histolojik ve biyokimyasal değişiklikler hala belirsiz. Bir fare anevrizma üzerinde endogreft implantasyon yeni bir model tarif. Kalıcı dolaşan kan akışı arayüzü ve yeni endovasküler biyomalzemeler değerlendirme olan ve olmayan trombüs analizi sayesinde, bu model daha iyi endovasküler anevrizma dışlama patobiyolojisi anlamanıza yardımcı olacaktır.

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.

Spinal Kord İskemi-reperfüzyon bir Mürin Modelinde Torasik Aort Tıkanıklığı tarafından tekrarlanabilir Parapleji

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

Tıp

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.

Akut Akciğer Hasarı Açık Trakeostomi Gastrik Asit Aspirasyon Fare Modeli Maksimal Akut Ölümcül olmayan Akciğer Hasarı Sonuçlar

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.

Bir Fare Modelinde İnfrarenal Abdominal Aort Bağlama Ekipmanları tarafından tekrarlanabilir Arter denüdasyon Yaralanma

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.

Abdominal aort anevrizması Adventitial Vasa Vasorum perfüzyon engelleyerek kemirgen bir Model oluşturulması

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.

Aortopathy aort anevrizması β-aminopropionitrile-indüklenen ve diseksiyon, fare modeli nicel mikro-CT Analizi

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.

Modifiye Dikişsiz Manşet Tekniği Kullanılarak Murine Servikal Aort Transplantasyon Modeli

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.

Topikal Elastaz Indüklenen İndüklenen Torasik Aort Anevrizması Murine Cerrahi Modeli

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.

İnfrarenal Abdominal Aort Anevrizması Porcine Modeli

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.

Hemodiyaliz Erişimi ile İlişkili El Disfonksiyonunun Bir Murine Modeli

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.

Anjiyotensin II İndüklü Abdominal Aort Anevrizmasının Bir Fare Modelinde Santral Venöz Kateter ile İlaç Tedavisi ve 3D Ultrason ile İzleme

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