This work was supported by a Wisconsin Partnership Program New Investigator Award (ID 2832), a National Heart, Lung, Blood Institute R01 Grant (HL-068673) and a T32 training Grant (HL-110853). We thank Dr. Melina Kibbe&#8217;s group at Northwestern University for providing helpful information.

NOT: Etik Açıklama: Tüm işlemler Wisconsin Üniversitesi Kurumsal Hayvan Bakım ve Kullanım Kurulu tarafından onaylanan Laboratuvar Hayvanları Bakım ve Kullanımı Kılavuzu (Ulusal Akademiler Press, 8. baskı, 2011), ve protokollere uygun. Tüm ameliyatlar (oran 2 ml / dak akış, teneffüs yoluyla) izofluran anestezi altında, ve tüm çabalar acı en aza indirmek için yapılmıştır. Hayvanlar kademeli CO2 ile doldurulmuş bir odacığm içine kurban edilmiştir. Genel Anestezi ve Cilt Kesiden 1. İndüksiyon <ol><li> 23-28 g bir 12-16 haftalık yaş ve vücut ağırlığı, erkek C57BL / 6 fareleri kullanın. Kapalı-devre anestezi aparatı ile izofluran ile hayvan anestezisi. Onun ayak kısma doğru anesthetization onaylayın. Kuruluğunu önlemek için gözlerin bazı yapay gözyaşı merhemi sürün. </li><li> Biraz kaçırılan sol arka bacak ve diz eklem sl ile yatar pozisyonda fare yerleştirinightly gerdi. Sol üst uyluk yöresinde saç tıraş ve klorheksidin ile cilt dezenfekte, steril pamuk uçlu aplikatörler kullanarak üç kez uygulandı. Ameliyat sırasında sterilize aletler tutmak için sıcak bir boncuk sterilizatör kullanın. </li><li> Sol bacak üzerinde bir sterilize gazlı bez örtü yerleştirin. Kasık (Şekil 1A) diz ekleminin sol medial uyluk üzerinde 1.5 cm düz, uzunlamasına deri kesi yapmak. </li></ol> Femoral Arter ve Şube 2. Pozlama NOT: Şekil 1B üst uyluk brüt damar anatomisini gösterir. cilt kesi düzgün medial uyluk orta hat boyunca yapıldığında yüzeyel femoral arter (SFA) bir mikroskop aracılığıyla görülebilir. <ol><li> Ince cımbız ve daha sonra döngü 9-0 naylon sütür ile SFA ile SFA örten ince fasya açın. NOT: Bu süreçte, femoral sinir kolayca konuronun duvara kolayca deler ve kanamaları çok ince olduğu için ide, ancak bitişik femoral ven yakın ilgi gerektirir. anahtar teknik arter kendisine odaklanmak; sürece diseksiyon yakın arterin yürütülen olarak, herhangi bir kaza sonucu damar hasarı önlenebilir. </li><li> SFA döngüye sonra, sivrisinek forseps ile dikiş tutun ve hafifçe aşağı doğru çekin. Bu manevra kolay daha diseksiyon yapar, ama çok zorla çekmeyin arter zarar vermemek için. </li><li> Proksimale 9-0 naylon sütür ile femoral arter (CFA) ortaya çıkarmak ve döngü arter diseksiyon devam edin. NOT: Genellikle, epigastrik arter (Şekil 1B) bir nokta distalinde CFA döngü tel yerleştirilmesi için yeterli. Aynı şekilde sivrisinek forseps ile CFA dikiş döngü tutun. </li><li> Yukarı CFA sütür döngü çekin ve SFA sütür döngü aşağı SFA ve derin femoral arter (DFA) çatallaşmayı ortaya çıkarmak. DFA, CFA büyük şube,uyluk kas (Şekil 1B) doğru gider. NOT: tel sonra DFA&#39;dan eklenecektir. </li><li> Ekstra dikkatli Döngü DFA bitişik ven arterin altında karışık çünkü. Venden kanama durumunda, gazlı bez ile bir 30- ila 60 sn, basit bir sıkıştırma genellikle hemostaz üretmek için yeterlidir. </li><li> DFA 9-0 naylon sütür ile döngüye sonra, her üç dikiş döngüler (Şekil 2A) onların doğru pozisyonlarda olduğundan emin olun. </li><li> Distale mümkün olduğunca bifurkasyonundan bir noktada arter bağlanması için DFA diseksiyonu ile devam edin. Ekstra dikiş kesin ama iki ucu DFA tel ekleme yapma kolay stabilize sivrisinek forseps ile tutulabilir, böylece belli bir uzunluğa bırakın. </li></ol> 3. Tel Yaralanması oluşturma <ol><li> DFA aracılığıyla Tel takın <ol><li> Geçici hemostat kurmak için CFA, SFA ve DFA sütür süzün. </li><li> DF küçük bir delik açınMicroscissors için uygun değildir. Bir 0.015 inç çaplı bir tel için yeterince büyük bir delik genişletmek için kavisli microtweezers ipuçlarını yerleştirin (Şekil 2B arter ve tel arasındaki boyut farkı gösterir). <ol><li> DFA&#39;da bir delik yapmadan önce, CFA sütür döngü gevşetin ve hafifçe kelepçe / donuk uçlu microtweezers ile DFA birkaç kez sıkın. Bu manevra tel ekleme kolaylaştırmak için son derece arteriyel çapını genişletir. PBS ile iyice tel Rutubet zamanda yumuşak sokulması için önemlidir. </li><li> DFA&#39;da bir delik yaparken, arter duvarı kırpmak, ama küçük bir v şekilli nip yapmak ve manipülasyon için keskin uçlu microtweezers ile flep çimdik yok. </li></ol></li><li> DFA üzerinde yeterince-genişlemiş delikten teli takın. CFA etrafında dikiş döngü gevşeterek ederken yavaşça iliak arter doğru tel ilerlemek. 5-8 mm çoğu durumda tüm CFA uzunluğu karşılamak için yeterli olduğunu (Şekil 2C </strong&gt;). Arteriyel perforasyon genellikle fare kaybına neden olduğu gibi zorla tel sokmayın. Uzunluğu yaklaşık 15 mm tel kısaltılması işleme yardımcı olur. </li></ol></li><li> Min 1 için içeride Tel bırakın <ol><li> Optimal uzunlukta tel taktıktan sonra, arter duvarı daraltabilir 1 dakika bırakın. Kurumasını önlemek için PBS ile tel ve arterler ıslatın. Başka bir 9-0 naylon dikiş bu bekleme süresi boyunca kablo ekleme noktasına DFA proksimal çevresinde yerleştirilebilir. Bu dikiş tel çıkarılmasını takiben DFA delik kapatmak için daha sonra kullanılacaktır. </li></ol></li><li> Tel Al ve Kan Akışı Devam <ol><li> Damar kanülasyon forseps ile tel tutun ve onu nazikçe geri çekin; Tel sorunsuz alınabilir olmalıdır. Nazik rotasyon ile tel geri çekerek, genellikle arter duvarına tel bağlılık kaynaklanan herhangi bir direnç, üstesinden gelmek için yardımcı olur. Yine, güçlü bir manevra hayvan kaybına neden olabilir. </li><li> Birtel almak fter, 9-0 naylon sütür ile çatallanma noktasında DFA Arter. SFA kan çıkışı tehlikeye atacağını bifürkasyonun, çok yakın Arter etmeyin. </li><li> Normal kan akışını sürdürmek için SFA ve CFA dikiş döngüler gevşetin. CFA tel yerleştirme (Şekil 2B) tarafından iyi genişletilmiş olduğunu unutmayın. </li></ol></li></ol> 4. Cilt Kapatma ve Ameliyat Sonrası Bakım <ol><li> Kontrol kanar. Küçük sızıntı basit sıkıştırma durdurulabilir; bazı büyük arter kanamaları bir 11-0 naylon sütür ile dikiş gerektirir. Bu dikildi arterler sonunda arter tıkanıklığına neden olur. </li><li> Cilt Zımbalar (genellikle 3-4 zımba) ile yara cilt kapatın. Klorheksidin cerrahi çözüm uygulayarak sterilize yara alan tutun. </li><li> Ameliyat sonrası tedavileri uygulayın. Buprenorfin subkutan enjeksiyonu ile fare ağrıyı kontrol. Bu suf kavuşana kadar ısınma pad üzerinde fare tutmaksternum yatma korumak için bilinç ficient. Diğer hayvanların şirket olmadan temiz bir kafes içinde Evi onu tamamen iyileşene kadar. </li></ol>

<ol>
	<li>Dzau, V. J., Braun-Dullaeus, R. C., Sedding, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vascular+proliferation+and+atherosclerosis:+new+perspectives+and+therapeutic+strategies.">Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies.</a> Nat Med. 8 (11), 1249-1256 (2002).</li><li>Hui, D. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intimal+hyperplasia+in+murine+models.">Intimal hyperplasia in murine models.</a> Curr Drug Targets. 9 (3), 251-260 (2008).</li><li>Ferns, G. A., Avades, T. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+mechanisms+of+coronary+restenosis:+insights+from+experimental+models.">The mechanisms of coronary restenosis: insights from experimental models.</a> Int J Exp Pathol. 81 (2), 63-88 (2000).</li><li>Sata, 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=A+mouse+model+of+vascular+injury+that+induces+rapid+onset+of+medial+cell+apoptosis+followed+by+reproducible+neointimal+hyperplasia.">A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia.</a> J Mol Cell Cardiol. 32 (11), 2097-2104 (2000).</li><li>Xu, Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+models+of+arteriosclerosis:+from+arterial+injuries+to+vascular+grafts.">Mouse models of arteriosclerosis: from arterial injuries to vascular grafts.</a> Am J Pathol. 165 (1), 1-10 (2004).</li><li>Lv, L., Meng, Q., Ye, M., Wang, P., Xue, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=STAT4+deficiency+protects+against+neointima+formation+following+arterial+injury+in+mice.">STAT4 deficiency protects against neointima formation following arterial injury in mice.</a> J Mol Cell Cardiol. 74C, 284-294 (2014).</li><li>Zhu, B., Kuhel, D. G., Witte, D. P., Hui, D. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Apolipoprotein+E+inhibits+neointimal+hyperplasia+after+arterial+injury+in+mice.">Apolipoprotein E inhibits neointimal hyperplasia after arterial injury in mice.</a> Am J Pathol. 157 (6), 1839-1848 (2000).</li><li>Fu, Y., Duru, E. A., Davies, M. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+metabolic+syndrome+on+the+response+to+arterial+injury.">Effect of metabolic syndrome on the response to arterial injury.</a> J Surg Res. , (2014).</li><li>Kuhel, D. G., Zhu, B., Witte, D. P., Hui, D. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinction+in+genetic+determinants+for+injury-induced+neointimal+hyperplasia+and+diet-induced+atherosclerosis+in+inbred+mice.">Distinction in genetic determinants for injury-induced neointimal hyperplasia and diet-induced atherosclerosis in inbred mice.</a> Arterioscler Thromb Vasc Biol. 22 (6), 955-960 (2002).</li><li>Cooley, B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+strain+differential+neointimal+response+in+vein+grafts+and+wire-injured+arteries.">Mouse strain differential neointimal response in vein grafts and wire-injured arteries.</a> Circ J. 71 (10), 1649-1652 (2007).</li><li>Ishigami, N., 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=Deficiency+of+CuZn+superoxide+dismutase+promotes+inflammation+and+alters+medial+structure+following+vascular+injury.">Deficiency of CuZn superoxide dismutase promotes inflammation and alters medial structure following vascular injury.</a> J Atheroscler Thromb. 18 (11), 1009-1017 (2011).</li></ol>

The authors declare no competing financial interests.

tel yaralanma prosedürü, biz 12-16 haftalık bir yaş erkek C57BL / 6 fareler kullanıldı sürece onların anatomik yapıları benzer olarak. 4 Bu yazıda farelerin tüm suşları için geçerlidir. Bizim ön çalışmalardan öğrendiğimiz gibi, 10 haftadan küçük farelerin femoral arter genellikle tel ekleme oldukça zorlu olduğunu çok küçük. Diğer yandan, 16 haftadan daha yaşlı farelerin tel ekleme teknik olarak daha kolay olan, ancak çok büyük bir çeşitlilik neointimal hiperplazi neden ...

In the era of expanded application of endovascular treatments for various cardiovascular diseases, restenosis after angioplasty is one of the major problems for patients undergoing such treatments. Damage to the vascular endothelium at the time of angioplasty, in concert with the atherosclerotic background, induces excessive smooth muscle cell proliferation in the medial layer, resulting in neointimal hyperplasia.1,2 A viable animal model that recapitulates post-angioplasty neointimal hyperplasia is, thus, important not only for the investigation of disease mechanisms but also for the development of effective therapeutics to treat this pathology.
Mice represent an excellent model animal to recapitulate neointimal hyperplasia for the following reasons: the genetic backgrounds of experimental mice are well established; a wide variety of genetically-modified strains are available;2 obtaining littermates of the same background is easy; and the cost of the animals is relatively low. Arterial ligation model and wire injury model are the two most common mouse models of mechanically-induced neointimal hyperplasia. The arterial ligation model is easy to create, but physiologically dissimilar to the actual angioplasty procedure. The wire injury model closely mimics actual angioplasty procedures but is technically difficult due to the small size of mouse arteries.2,3 Sata et al. first described a wire injury method for mouse femoral arteries based on the anatomical structure of the vasculature and the use of proper-sized flexible wire. Utilizing this technique, they succeeded in reproducibly inducing neointimal hyperplasia in various strains of mice.4
Although femoral wire injury is a well-established model, some of the technical aspects of the technique are highly challenging compared to other models such as ligation.5 The purpose of this paper is to describe our mouse wire injury model procedures in detail, which is a modified version of Sata&#8217;s original method. We have made two main modifications: 1) Looping only the arteries, and 2) No lidocaine use.

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a murine model of arterial restenosis: technical aspects of femoral wire injury

Ateroskleroz neden Kardiyovasküler hastalık gelişmiş dünyada önde gelen ölüm nedenidir. Nedeniyle aterosklerotik plak gelişimi veya kurulmuş plakların çatlaması, damar lümeninin daralması gibi miyokard enfarktüsü ve inme gibi çeşitli hastalıklar giden normal kan akışını keser. Anjiyoplasti gibi klinik endovasküler işlemlerde yaygın lümen yeniden açmak için yapılır. Bununla birlikte, bu tedaviler, kaçınılmaz olarak bir fazla iyileşme yanıtı ve damar restenozu (yeniden daralma) neden olan lümen içine uzanan bir neointimal plak gelişimini tetikleme, damar duvarı hem de vasküler endotel hasar. Restenoz ateroskleroz için endovasküler tedavi başarısızlığı önemli bir nedenidir. Böylece, restenoz preklinik hayvan modelleri öteleme vasküler müdahalelere yaklaşımları yanı sıra patofizyolojik mekanizmaları araştırmak için hayati önem taşımaktadır. Bir çok murin experime arasındayakından endotel ve damar duvarını hem yaralı anjiyoplasti işlemi benzer çünkü ntal modelleri, femoral arter tel yaralanması yaygın anjiyoplasti sonrası restenoz çalışmaları için en uygun olarak kabul edilir. Ancak, birçok araştırmacı nedeniyle teknik zorluk yüksek derecede bu modeli kullanan zorluk. Bu, bir metal tel belirgin neointima indüklemek için yeterli darbe üretmek için, yaklaşık olarak tel üç kat daha incedir femoral arter içine takılması gerekir öncelikle çünkü. Burada, biz etkili bu modelin önemli teknik zorlukların üstesinden gelmek için gerekli cerrahi ayrıntıları açıklar. , Sunulan prosedürleri takip gerçekleştirerek fare femoral arter tel yaralanması kolaylaşır. Aşina sonra, bütün işlem 20 dakika içinde tamamlanabilir.

Ameliyatı takiben dört hafta, tel yaralı femoral arter hasat ve neointima oluşumunu analiz etmek için bir parafin blok örneği olun. Yukarıda tarif edilen genel anestezi neden. Hemen göğüs açın ve sol ventrikül bir 20-gauge kelebek iğne takın. Bir infüzyon şişe hattını bağlayın. % 4 paraformaldehid (genellikle 10-20 ml, her biri), ardından PBS damla infüzyon yoluyla perfüzyon fiksasyon gerçekleştirin. Hayvan daha sonra tel yaralı CFA çıkar ve 4 ° C&#39;de gece boyunca% 4 paraforma...

Watch this Scientific Journal Video about A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury at JoVE.com

A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury

restenoz fare femoral arter yaralanması tel modeli teknik olarak zordur. Bu protokolde başarıyla restenoz çalışmaları için tutarlı neointima ikna etmek tel yaralanması gerçekleştirmek için anahtar teknik detaylar önemlidir göstermektedir.

Arter Restenozun bir fare modeli: Femur Tel Yaralanma Teknik Yönleri

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to ...

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19.9K Görüntüleme.  University of Wisconsin School of Medicine and Public Health.  restenoz fare femoral arter yaralanması tel modeli teknik olarak zordur. Bu protokolde başarıyla restenoz çalışmaları için tutarlı neointima ikna etmek tel yaralanması gerçekleştirmek için anahtar teknik detaylar önemlidir göstermektedir. 

Video: A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury

Microsurgical Venous Pouch Arterial-Bifurcation Aneurysms in the Rabbit Model: Technical Aspects

For ruptured human cerebral aneurysms endovascular embolization has become an equivalent alternative to aneurysm clipping.1 However, large clinical trials have shown disappointing long-term results with unacceptable high rates of aneurysm recanalization and delayed aneurysm rupture.2 To overcome these problems, animal experimental studies are crucial for the development of better endovascular devices.3-5
Several animal models in rats, rabbits, canines and swine are available.6-8 Comparisons of the different animal models showed the superiority of the rabbit model with regard to hemodynamics and comparability of the coagulation system and cost-effectiveness.9-11 
The venous pouch arterial bifurcation model in rabbits is formed by a venous pouch sutured into an artificially created true bifurcation of both common carotid arteries (CCA). The main advantage of this model are true bifurcational hemodynamics.12 The major drawbacks are the sofar high microsurgical technical demands and high morbidity and mortality rates of up to 50%.13 These limitations have resulted in less frequent use of this aneurysm model in the recent years. These shortcomings could be overcome with improved surgical procedures and modified peri- and postoperative analgetic management and anticoagulation.14-16 Our techniques reported in this paper demonstrate this optimized technique for microsurgical creation of arterial bifurcation aneurysms.

An optimized technique for the microsurgical creation of arterial bifurcation aneurysms mimicking bifurcation human cerebral aneurysms is described. A venous pouch is sutured into an artificially created true bifurcation of both common carotid arteries. Facilitated microsurgical techniques and aggressive postoperative anticoagulation and analgesia lead to minimized morbidity rates and high aneurysm patency rates.

Tavşan Modelinde Mikrocerrahi Venöz Kılıfı Arter Bifurkasyon Anevrizmalarının: Teknik Yönleri

For ruptured human cerebral aneurysms endovascular embolization has become an equivalent alternative to aneurysm clipping.1 However, large clinical trials ...

Tıp

Femoral Arterial and Venous Catheterization for Blood Sampling, Drug Administration and Conscious Blood Pressure and Heart Rate Measurements

In multiple fields of study, access to the circulatory system in laboratory studies is necessary. Pharmacological studies in rats using chronically implanted catheters permit a researcher to effectively and humanely administer substances, perform repeated blood sampling and assists in conscious direct measurements of blood pressure and heart rate. Once the catheter is implanted long-term sampling is possible. Patency and catheter life depends on multiple factors including the lock solution used, flushing regimen and catheter material. This video will demonstrate the methodology of femoral artery and venous catheterization of the rat. In addition the video will demonstrate the use of the femoral venous and arterial catheters for blood sampling, drug administration and use of the arterial catheter in taking measurements of blood pressure and heart rate in a conscious freely-moving rat. A tether and harness attached to a swivel system will allow the animal to be housed and have samples taken by the researcher with minimal disruption to the animal. To maintain patency of the catheter, careful daily maintenance of the catheter is required using lock solution (100 U/ml heparinized saline), machine-ground blunt tip syringe needles and the use of syringe filters to minimize potential contamination. With careful aseptic surgical techniques, proper catheter materials and careful catheter maintenance techniques, it is possible to sustain patent catheters and healthy animals for long periods of time (several weeks).

Chronic catheterization of blood vessels in the rat is often required for administration of substances, obtain blood sample over a period of time or for direct conscious blood pressure measurements. Femoral arterial catheterization of the rat and corresponding measurements of blood pressure in the conscious animal will be demonstrated.

Kan Örnekleme, İlaç İdaresi ve Bilinçli Kan Basıncı ve Nabız ölçümleri Femoral Arter ve Venöz Kateterizasyon

In multiple fields of study, access to the circulatory system in laboratory studies is necessary. Pharmacological studies in rats using chronically ...

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.

A model of stent implantation in mouse carotid artery is described. Compared to other similar methods, this procedure is very rapid, simple and accessible, offering the possibility to study in a convenient way the vascular wall reaction to different drug-eluting stents and the molecular mechanisms of restenosis.

Restenoz Çalışmaları Karotis Arter Stent İmplantasyonu bir murin Modeli

Despite  the considerable progress made in the stent development in the last decades,  cardiovascular diseases remain the main cause of death in western ...

Technical Aspects of the Mouse Aortocaval Fistula

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta and inferior vena cava (IVC) are exposed. The proximal infrarenal aorta and the distal aorta are dissected for clamp placement and needle puncture, respectively. Special attention is paid to avoid dissection between the aorta and the IVC. After clamping the aorta, a 25 G needle is used to puncture both walls of the aorta into the IVC. The surrounding connective tissue is used for hemostatic compression. Successful creation of the AVF will show pulsatile arterial blood flow in the IVC. Further confirmation of successful AVF can be achieved by post-operative Doppler ultrasound.

The goal is to produce an arteriovenous fistula that is simple and reproducible. This method does not use sutures or glue adhesive. Therefore the samples can be used with the least amount of foreign materials for analysis.

Fare Aortocaval Fistül Teknik Yönleri

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta ...

The Rabbit Blood-shunt Model for the Study of Acute and Late Sequelae of Subarachnoid Hemorrhage: Technical Aspects

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and controllable animal models that simulate both conditions are presently uncommon. Therefore, new models are needed in order to mimic human pathophysiological conditions resulting from SAH.
This report describes the technical nuances of a rabbit blood-shunt SAH model that enables control of intracerebral pressure (ICP). An extracorporeal shunt is placed between the arterial system and the subarachnoid space, which enables examiner-independent SAH in a closed cranium. Step-by-step procedural instructions and necessary equipment are described, as well as technical considerations to produce the model with minimal mortality and morbidity. Important details required for successful surgical creation of this robust, simple and consistent ICP-controlled SAH rabbit model are described.

The experimental intracranial pressure-controlled blood shunt subarachnoid hemorrhage (SAH) model in the rabbit combines the standard procedures &#8212; subclavian artery cannulation and transcutaneous cisterna magna puncture, which enables close mimicking of human pathophysiological conditions after SAH. We present step-by-step instructions and discuss key surgical points for successful experimental SAH creation.

Subaraknoid Kanama Akut ve Geç sekeli Çalışmaları Tavşan Kan şant Modeli: Teknik Yönleri

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and ...

A Simple Critical-sized Femoral Defect Model in Mice

While bone has a remarkable capacity for regeneration, serious bone trauma often results in damage that does not properly heal. In fact, one tenth of all limb bone fractures fail to heal completely due to the extent of the trauma, disease, or age of the patient. Our ability to improve bone regenerative strategies is critically dependent on the ability to mimic serious bone trauma in test animals, but the generation and stabilization of large bone lesions is technically challenging. In most cases, serious long bone trauma is mimicked experimentally by establishing a defect that will not naturally heal. This is achieved by complete removal of a bone segment that is larger than 1.5 times the diameter of the bone cross-section. The bone is then stabilized with a metal implant to maintain proper orientation of the fracture edges and allow for mobility. 
Due to their small size and the fragility of their long bones, establishment of such lesions in mice are beyond the capabilities of most research groups. As such, long bone defect models are confined to rats and larger animals. Nevertheless, mice afford significant research advantages in that they can be genetically modified and bred as immune-compromised strains that do not reject human cells and tissue.
Herein, we demonstrate a technique that facilitates the generation of a segmental defect in mouse femora using standard laboratory and veterinary equipment. With practice, fabrication of the fixation device and surgical implantation is feasible for the majority of trained veterinarians and animal research personnel. Using example data, we also provide methodologies for the quantitative analysis of bone healing for the model.

Animal models are frequently employed to mimic serious bone injury in biomedical research. Due to their small size, establishment of stabilized bone lesions in mice are beyond the capabilities of most research groups. Herein, we describe a simple method for establishing and analyzing experimental femoral defects in mice.

Farelerde Basit Kritik ölçekli Femoral Hata Modeli

While bone has a remarkable capacity for regeneration, serious bone trauma often results in damage that does not properly heal. In fact, one tenth of all ...

Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. While these therapies lead to the rapid restoration of blood flow, these technologies remain limited by restenosis in the case of bare metal stents and angioplasty, or reduced healing and possibly enhanced risk of thrombosis in the case of drug eluting stents. A key pathophysiological mechanism in the formation of restenosis is intimal hyperplasia caused by the activation of vascular smooth muscle cells and inflammation due to arterial stretch and injury. Surgeries that induce arterial injury in genetically modified mice are useful for the mechanistic study of the vascular response to injury but are often technically challenging to perform in mouse models due to the their small size and lack of appropriate sized devices. We describe two approaches for a surgical technique that induces endothelial denudation and arterial stretch in the femoral artery of mice to produce robust neointimal hyperplasia. The first approach creates an arteriotomy in the muscular branch of the femoral artery to obtain vascular access. Following wire injury this arterial branch is ligated to close the arteriotomy. A second approach creates an arteriotomy in the main femoral artery that is later closed through localized cautery. This method allows for vascular access through a larger vessel and, consequently, provides a less technically demanding procedure that can be used in smaller mice. Following either method of arterial injury, a degradable drug delivery patch can be placed over or around the injured artery to deliver therapeutic agents.

We describe a surgical technique that produces wire injury in the femoral artery of mice to induce neointimal hyperplasia to serve as a model testing system for the perivascular delivery of therapeutic compounds for the inhibition of restenosis.

Bir Perivasküler Drug Delivery Patch İmplantasyonunda ile Femoral Arter Tel Yaralanma sıçan Modeli

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. ...

Murine Model of Intestinal Ischemia-reperfusion Injury

Intestinal ischemia is a life-threatening condition associated with a broad range of clinical conditions including atherosclerosis, thrombosis, hypotension, necrotizing enterocolitis, bowel transplantation, trauma and chronic inflammation. Intestinal ischemia-reperfusion (IR) injury is a consequence of acute mesenteric ischemia, caused by inadequate blood flow through the mesenteric vessels, resulting in intestinal damage. Reperfusion following ischemia can further exacerbate damage of the intestine. The mechanisms of IR injury are complex and poorly understood. Therefore, experimental small animal models are critical for understanding the pathophysiology of IR injury and the development of novel therapies.
Here we describe a mouse model of acute intestinal IR injury that provides reproducible injury of the small intestine without mortality. This is achieved by inducing ischemia in the region of the distal ileum by temporally occluding the peripheral and terminal collateral branches of the superior mesenteric artery for 60 min using microvascular clips. Reperfusion for 1 hr, or 2 hr after injury results in reproducible injury of the intestine examined by histological analysis. Proper position of the microvascular clips is critical for the procedure. Therefore the video clip provides a detailed visual step-by-step description of this technique. This model of intestinal IR injury can be utilized to study the cellular and molecular mechanisms of injury and regeneration.

Here we describe the detailed procedure of intestinal ischemia-reperfusion in mice which results in reproducible injury without mortality to encourage the standardization of this technique across the field. This model of intestinal ischemia-reperfusion injury can be utilized to study the cellular and molecular mechanisms of injury and regeneration.

Bağırsak İskemi-reperfüzyon Hasarı Murin Modeli

Intestinal ischemia is a life-threatening condition associated with a broad range of clinical conditions including atherosclerosis, thrombosis, ...

Induction of Accelerated Atherosclerosis in Mice: The "Wire-Injury" Model

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. Moreover, by rupture of the defective vascular wall, atherosclerosis induces occlusive thrombus formation, which represents the main cause of myocardial infarction or stroke and the most frequent cause of death. Despite the advances in the cardiovascular field, many questions remain unanswered, and additional basic research is essential to improve our understanding of the molecular mechanisms during atherosclerosis and its effects. Due to limited clinical studies, there is a need for representative animal models recreating atherosclerotic conditions such as neointima formation after stent implantation, balloon angioplasty, or endarterectomy. Since the mouse presents many advantages and is the most frequently used model for studying molecular processes, the current study proposes an invasive procedure of endothelial denudation, also known as the wire-injury model, which is representative of the human condition of neointima formation in arteries after revascularization procedures.

Induction of Accelerated Atherosclerosis in Mice: The &quot;Wire-Injury&quot; Model

This study describes an invasive procedure for the induction of accelerated atherosclerosis in mice. In comparison to other methods using electric- or cryo-induced injury, mechanical-induced injury mimics the human condition of restenosis after revascularization therapies and is ideal for the study of the molecular mechanisms involved.

Farelerde Hızlandırılmış Ateroskleroz Indüksiyonu: "Tel-Yaralanma" Modeli

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. ...

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 ...