Name: a rabbit model of durable transgene expression in jugular vein to common carotid artery interposition grafts
Uploaded: 2018-09-10T12:30:00.000+00:00
Duration: 13 min 58 s
Description: Watch this Scientific Journal Video about A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts at JoVE.com

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Bu iletişim kuralı kritik adımlarda anestezi yönetimi, arter/aşılı damar anticoagulation, cerrahi manipülasyon ve aşılı damarın hemodinamik ölçümleri içerir. İki nispeten uzun işlemleri (genellikle 3-3.5 bilateral ven greft için h ve ikili greft iletim için 1,5-2,5 h) içeren bu modelde birden çok hayatta kalma cerrahi anestezi düzgün yönetimi önemlidir. Biz anestezi ile bir nosecone ve endotrakeal entübasyon tarafından yönetilen ve entübasyon pozitif basınç havalandırma atelectasis engell...

Ateroskleroz lipid birikimi ve damar duvarındaki inflamasyon gemi lümen, kalp krizi, felç ve bacaklarda1,2kaybı daralma için kurşun Kronik iltihabi bir hastalıktır. Perkütan girişimler (Örn., anjiyoplasti ve stent uygulamaları) ve medikal tedavi (e.g., Statinler ve antiplatelet ajanlar) yararlı tedaviler için ateroskleroz; Ancak, koroner ve periferik dolaşımları ciddi obstrüktif hastalık her iki tedavisinde etkisiz çoğu zaman. Bypass greftleme, otojen damar parçalar, kullanarak şiddetli, diffüz koroner ve periferik damar hastalığı3,4olan hastalar tedavi için ortak bir yordam kalır. Ancak, her iki koroner yerleştirilen Greftler damar ve periferik dolaşımları zavallı uzun vadeli açıklık oranlarına sahip. Koroner dolaşım ven greft 1 yıl ve % 50 tıkandı yaklaşık % 10-20 10 yıl5,6tarafından tıkandı. Periferik dolaşım ven greft başarısızlık oranları 30-%50 5 yıl7de vardır.
Tam yerinde hastalığın bir tedavi gen ürünü teslim edebilirsiniz çünkü gen tedavisi damar grefti başarısızlık önlenmesi için çekici bir yaklaşımdır. Buna göre çok sayıda preklinik çalışmaları ven greft gen terapisi8,9test ettik. Ancak, aslında tüm bu çalışmaların erken zaman puan (2-12 hafta)10,11,12,13,14,15, etkinliğini inceledik 16 , 17. gen tedavisi müdahalelerin dayanıklı sağlayabilir bulgusuna farkındayız genellikle sonuçlar neointimal hiperplazi ve ateroskleroz4geç ven greft hatalarına karşı koruma (yıl). Aşılı damarlarında dayanıklı transgene ifade sağlar ve böylece gen tedavisi müdahalelerin geç gibi erken zaman noktalarda test sağlayan bir yöntem geliştirdik. Dayanıklı transgene ifade elde etmek için HDAd vektörler ve Gecikmeli İletim strateji yöntem içermektedir. HDAd vektörel çizimler sağlamak uzun süreli transgene ifade onlar viral genler tarafından bağışıklık sistemi18,19,transduced hücre tanıma (ve ret)20, önlenmesi, eksikliği nedeniyle 21. Ertelenen iletim (greft yerleştirme sonrası gerçekleştirilen 28 gün) erken aşılama22sonra oluşan arterialization işlemi sırasında transduced hücrelerinin kaybı önler.
Ven greft iletim greft yerleştirme10,11,12,15,16 zamanında tedavi transgene ifade ven greft duvardaki ulaşmak diğer yöntemleri itimat ,17. Seri olarak ölçülen zaman transgene ifade bu yaklaşım kullanarak hızlı bir şekilde iletim22,23sonra azalır. Buna göre bu yaklaşımı kullanarak çalışmalar ven, etkinlik 4 hafta ötesinde değerlendirilmesi ile en değil bir aşılama sonra 12 hafta ötesinde etkinliğini inceleyen değil. Buna ek olarak, bizim Yöntem damar grefti elde stably en az 24 hafta boyunca ve arterler büyük olasılıkla gerçekleştirilen benzer çalışmalar üzerinde tabanlı devam ederse transgene ifade devam ediyor uzun süre22,24. Biz kararlı transgene ifade, bu süre elde hiçbir diğer damar grefti gen terapisi müdahalesi farkındayız.
Bir tavşan modeli bizim yöntem geliştirmek için kullanılır. Diğerleri kemirgenler, tavşan, kullanmış ya da damar sınamak için daha büyük hayvanlar gen terapisi10,11,12,15,16,17,25grefti, 26. Kemirgen modellerle karşılaştırıldığında, adatavşanı are daha pahalı ve daha sıkı düzenleyici gereksinimlerine tabidir. Ancak, daha büyük hayvanlar için karşılaştırıldığında (Örn., domuzlar ve köpekler), adatavşanı are çok daha az pahalı satın almak ve ev ve işlemek daha kolay. Ayrıca, insan damarlarının fizyolojik tavşan damarları benzer27, onlar yeterince büyük perkütan girişimler28,29test etmek için kullanılabilir ve bu yeterli doku sağlar birden çok uç nokta (Örn., histoloji, protein, RNA) bir tek damar numune22,30kullanılarak incelenebilir. Ven greft tavşanlarla yüksek yağlı diyet ile beslenir, buna ek olarak, onlar ven greft ateroskleroz31,32, koroner arter bypass ven greft başarısızlık4,5 ortak bir neden olan geliştirmek . Bu aterosklerotik tavşan ven greft gen terapisi müdahaleler bu yöntemle teslim test etmek için bir substrat olarak hizmet verebilir. Sağlanan Protokolü tavşan ven greft dayanıklı transgene ifade ulaşmak için gerekli teknik becerileri Master müfettişler yardımcı olabilir.

<table><tbody><tr><td>&lt;strong&gt;Disposables&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>3mL syringe with 24G needle</td><td>Becton Dickinson</td><td>309571</td><td>2x for vein graft surgery; 2x for gene transfer&amp;nbsp; surgery</td></tr><tr><td>1 mL syringe with 27G needle</td><td>Becton Dickinson</td><td>309623</td><td>2x for vein graft surgery, 5x for gene transfer surgery</td></tr><tr><td>19G needle</td><td>Becton Dickinson</td><td>305187</td><td>Gene transfer surgery</td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>20 mL syringe, luer lock</td><td>Nipro Medical Corp</td><td>JD+20L</td><td></td></tr><tr><td>Catheters, 24Ga x 3/4&amp;rdquo;</td><td>Terumo Medical Products</td><td>SROX2419V</td><td></td></tr><tr><td>21G needle</td><td>Becton Dickinson</td><td>305165</td><td>Gene transfer surgery and for 20 mL syringe of saline</td></tr><tr><td>Gauze 4&amp;rdquo; x 4&amp;rdquo;</td><td>Dynarex</td><td>3242</td><td>~10-15 per surgery</td></tr><tr><td>3-0 silk suture</td><td>Covidien Ltd.</td><td>S-244</td><td></td></tr><tr><td>5-0 silk suture</td><td>Covidien Ltd.</td><td>S-182</td><td></td></tr><tr><td>7-0 polypropylene suture</td><td>CP Medical</td><td>8703P</td><td>Vein graft surgery</td></tr><tr><td>7-0 polypropylene suture</td><td>CP Medical</td><td>8648P</td><td>Gene transfer surgery</td></tr><tr><td>5-0 polyglycolic acid suture</td><td>CP Medical</td><td>421A</td><td></td></tr><tr><td>3-0 polyglycolic acid suture</td><td>CP Medical</td><td>398A</td><td></td></tr><tr><td>Alcohol swabs</td><td>Covidien Ltd.</td><td>6818</td><td>For the placement of I.V. line</td></tr><tr><td>Catheter plug</td><td>Vetoquinol</td><td>411498</td><td></td></tr><tr><td>Ketamine HCl, 100 mg/mL</td><td>Vedco Inc.</td><td>5098916106</td><td></td></tr><tr><td>Xylazine, 100 mg/mL</td><td>Akorn Inc.</td><td>4821</td><td></td></tr><tr><td>Lidocaine, 20 mg/mL</td><td>Pfizer</td><td>409427702</td><td></td></tr><tr><td>Marcaine 0.5%</td><td>Pfizer</td><td>409161050</td><td></td></tr><tr><td>Beuthanasia D-Special</td><td>Intervet Inc.</td><td>NDC 00061047305</td><td>Harvest surgery only</td></tr><tr><td>Buprenorphine HCl, 0.3 mg/mL</td><td>Patterson Veterinary</td><td>12496075705</td><td></td></tr><tr><td>Saline IV bag, 0.9% sodium chloride</td><td>Baxter</td><td>2B1309</td><td></td></tr><tr><td>Heparin&amp;nbsp; (5000 U/mL)</td><td>APP Pharmaceuticals</td><td>NDC 63323-047-10</td><td></td></tr><tr><td>Papaverine (3.5 mg/ml)</td><td>American Reagent Inc.</td><td>NDC 0517-4002-25</td><td>Diluted from 30mg/mL stock; Use 1 mL maximum</td></tr><tr><td>Fentanyl patch, 25 mcg/h</td><td>Apotex Corp.</td><td>NDC 60505-7006-2</td><td></td></tr><tr><td>Isoflurane</td><td>Multiple vendors</td><td>Catalog number not available</td><td></td></tr><tr><td>&amp;nbsp;Viral vector</td><td></td><td></td><td>Gene transfer surgery only</td></tr><tr><td>&lt;strong&gt;Surgical Instruments&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Metzenbaum needle holder 7&quot; straight</td><td>Roboz</td><td>RS-7900</td><td></td></tr><tr><td>Operating scissors 6.5&quot; straight blunt/blunt</td><td>Roboz</td><td>RS-6828</td><td></td></tr><tr><td>Needle holder /w suture scissors</td><td>Miltex</td><td>8-14-IMC</td><td></td></tr><tr><td>Castroviejo scissors</td><td>Roboz</td><td>RS-5658</td><td></td></tr><tr><td>Castroviejo needle holder, 5.75&quot; straight with lock</td><td>Roboz</td><td>RS-6412</td><td></td></tr><tr><td>Stevens scissors 4.25&quot; curved blunt/blunt</td><td>Roboz</td><td>RS-5943</td><td></td></tr><tr><td>Alm retractor 4&quot; 4X4 5mm blunt prongs</td><td>Roboz</td><td>RS-6514</td><td>2x</td></tr><tr><td>Backhaus towel clamp 3.5&quot;</td><td>Roboz</td><td></td><td>4x</td></tr><tr><td>Micro clip setting forceps 4.75&quot;</td><td>Roboz</td><td>RS-6496</td><td></td></tr><tr><td>Micro vascular clips, 11 mm</td><td>Roboz</td><td></td><td></td></tr><tr><td>Surg-I-Loop</td><td>Scanlan International</td><td>1001-81M</td><td>5 cm length</td></tr><tr><td>Bonaccolto forceps, 4&amp;rdquo; (10 cm) long longitudinal serrations, cross serrated tip, 1.2mm tip width</td><td>Roboz</td><td>RS-5210</td><td></td></tr><tr><td>Dumont #3 forceps Inox tip size .17 &amp;times; .10 mm</td><td>Roboz</td><td>RS-5042</td><td></td></tr><tr><td>Graefe forceps, 4&amp;rdquo; (10 cm) long serrated straight, 0.8 mm tip</td><td>Roboz</td><td>RS-5280</td><td></td></tr><tr><td>Halstead mosquito forceps,&amp;nbsp; 5&quot; straight, 1.3 mm tips</td><td>Roboz</td><td>RS-7110</td><td>2x</td></tr><tr><td>Halstead mosquito forceps,&amp;nbsp; 5&quot; curved, 1.3mm tips</td><td>Roboz</td><td>RS-7111</td><td></td></tr><tr><td>Jacobson mosquito forceps 5&quot; curved extra delicate, 0.9 mm tips</td><td>Roboz</td><td>RS-7117</td><td></td></tr><tr><td>Kantrowitz forceps, 7.25&quot; 90 degree delicate, 1.7 mm tips</td><td>Roboz</td><td>RS-7305</td><td></td></tr><tr><td>Tissue forceps 5&quot;, 1X2 teeth, 2 mm tip width</td><td>Roboz</td><td>RS-8162</td><td></td></tr><tr><td>Allis-Baby forceps, 12 cm, 4x5 teeth, 3 mm tip width</td><td>Fine Science Tools</td><td>11092-12</td><td>2x</td></tr><tr><td>Adson forceps, 12 cm, serrated, straight</td><td>Fine Science Tools</td><td>11006-12</td><td></td></tr><tr><td>Veterinary electrosurgery handpiece and electrode</td><td>MACAN Manufacturing</td><td>HPAC-1; R-F11</td><td></td></tr><tr><td>&lt;strong&gt;Surgical Suite Equipment&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Circulating warm water blanket and pump</td><td>Multiple vendors</td><td>Catalog number not available</td><td></td></tr><tr><td>Bair hugger warming unit</td><td>3M</td><td>Model 505</td><td></td></tr><tr><td>IV infusion pump</td><td>Heska</td><td>Vet IV 2.2</td><td></td></tr><tr><td>Isoflurane vaporizer and scavenger</td><td>Multiple vendors</td><td>Catalog number not available</td><td></td></tr><tr><td>Veterinary multi-parameter monitor</td><td>Surgivet</td><td>Surgivet Advisor</td><td></td></tr><tr><td>Veterinary electrosurgery unit</td><td>MACAN Manufacturing</td><td>MV-9</td><td></td></tr><tr><td>Surgical microscope</td><td>D.F. Vasconcellos</td><td>M900</td><td>25X magnification for vein graft surgery; 16X magnification for gene transfer surgery</td></tr></tbody></table>

a rabbit model of durable transgene expression in jugular vein to common carotid artery interposition grafts

Ven greft bypass cerrahisi tıkayıcı damar hastalığı için ortak bir tedavidir; Ancak, uzun vadeli başarı greft hatası nedeniyle kan pıhtılaşması, intimal hiperplazi ve ateroskleroz ile sınırlıdır. Bu makalenin amacı iki taraflı venöz interpozisyonu Greftler giyen bir tavşan..... yerleştirerek, sonra Greftler dayanıklı transgene ifade elde bir gen transferi vektör ile transducing bir yöntem göstermektir. Yöntemi normal ven greft homeostazı, genler ve protein ürünleri biyolojik rollerinin incelenmesi sağlar. Ayrıca transgenes ven greft başarısızlık, e.gengelleyebilir faaliyetleri için test sağlar., ister bir transgene ifade neointimal büyüme engeller, damar iltihabı azaltır veya ateroskleroz tavşanların azaltır beslenen yüksek yağlı diyet ile. Bir ilk hayatta kalma ameliyat sırasında sağ ve sol dış juguler ven parçalarını çıkardım ve bilateral ters uç-yan ortak karotid arter interpozisyonu greft yerleştirilir. 28 gün sonra gerçekleştirilen ikinci bir hayatta kalma ameliyat sırasında her greft dolaşımı damar klipleri ile yalıtılmış ve lümen (bir arteriotomy) yardımcı bağlı adenoviral (HDAd) vektör içeren bir çözüm ile doldurulur. 20-min kuluçka sonra vektör çözüm emişli, arteriotomy tamir ve akış geri yüklenir. Damarları bireysel deneysel iletişim kuralları tarafından dikte zaman noktalarda hasat. Greft yerleştirme ve iletim arasında 28 günlük gecikmeye arteriyel dolaşımı için ven greft adaptasyon sağlamak gereklidir. Bu adaptasyon hızlı önce veya hemen sonra aşılama transduced ven greft oluşur transgene ifade kaybı önler. Sağlam, dayanıklı transgene ifade aşılı damarlarında elde etmek için onun yetenek benzersiz bir yöntemdir. Diğer büyük hayvan ven greft modellerle karşılaştırıldığında, tavşan düşük maliyetli ve kolay kullanım avantajları var. Kemirgen ven greft modellerle karşılaştırıldığında, tavşan bol doku analizi için sağlamak daha büyük ve daha kolay manipüle kan damarları var.

Işleç deneysel verileri oluşturmak için bu yöntemi kullanmadan önce yeni bir işleç teknik yeterlilik doğrulanması gerekir. Yeni bir işleç elde etmek gerekir ilk kilometre taşı tutarlı ven greft açıklık ven-aşılama ameliyat ve sonraki Gecikmeli İletim ameliyattan sonra olmuştur. Her ameliyat bir arzu ve ulaşılabilir sonra bitti % 90 açıklık. Açıklık olmayan invaziv genellikle ameliyat sonrası günlük 5-7 gerçekleştirmek Transkutanöz ultrason kullanarak te...

Watch this Scientific Journal Video about A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts at JoVE.com

A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts

Tavşan manken dayanıklı Transgene ifade juguler ven ortak karotid arter interpozisyonu Greftler için

Bu yöntem interpozisyonu ven greft tavşanların yerleşimini, greft iletim ve dayanıklı transgene ifade ulaşılmasına anlatılmaktadır. Bu soruşturma transgenes ve protein ürünlerini aşılı damarlarında fizyolojik ve patolojik rolleri ve gen terapileri ven greft hastalığı için test sağlar.

Vein graft bypass surgery is a common treatment for occlusive arterial disease; however, long-term success is limited by graft failure due to thrombosis, ...

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Research

JoVE Journal

Medicine

10.3K Görüntüleme.  University of Washington School of Medicine. Bu yöntem interpozisyonu ven greft tavşanların yerleşimini, greft iletim ve dayanıklı transgene ifade ulaşılmasına anlatılmaktadır. Bu soruşturma transgenes ve protein ürünlerini aşılı damarlarında fizyolojik ve patolojik rolleri ve gen terapileri ven greft hastalığı için test sağlar.

Video: A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts

Training a Sophisticated Microsurgical Technique: Interposition of External Jugular Vein Graft in the Common Carotid Artery in Rats

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in peripheral arterial bypass surgery as well as in arteriovenous fistulas.1-5 The experimental procedure of vein graft interposition in the common carotid artery by using the cuff-technique has been applied in several research projects to examine the aetiology of neointimal hyperplasia and therapeutic options to address it. 6-8 The cuff prevents vessel anastomotic remodeling and induces turbulence within the graft and thereby the development of neointimal hyperplasia.
Using the superior caval vein graft is an established small-animal model for venous arterialization experiment.9-11 This current protocol refers to an established jugular vein graft interposition technique first described by Zou et al., 9 as well as others.12-14 Nevertheless, these cited small animal protocols are complicated.
To simplify the procedure and to minimize the number of experimental animals needed, a detailed operation protocol by video training is presented. This video should help the novice surgeon to learn both the cuff-technique and the vein graft interposition. Hereby, the right external jugular vein was grafted in cuff-technique in the common carotid artery of 21 female Sprague Dawley rats categorized in three equal groups that were sacrificed on day 21, 42 and 84, respectively. Notably, no donor animals were needed, because auto-transplantations were performed. The survival rate was 100 % at the time point of sacrifice. In addition, the graft patency rate was 60 % for the first 10 operated animals and 82 % for the remaining 11 animals. The blood flow at the time of sacrifice was 8&plusmn;3 ml/min. In conclusion, this surgical protocol considerably simplifies, optimizes and standardizes this complicated procedure. It gives novice surgeons easy, step-by-step instruction, explaining possible pitfalls, thereby helping them to gain expertise fast and avoid useless sacrifice of experimental animals.

Neointimal hyperplasia is the primary cause of stenosis in arterialized veins. We propose a new protocol whereby the right external jugular vein is grafted using the cuff technique in the common carotid artery of Sprague Dawley rats. The survival rate was 100 % at the time point of sacrifice.

Sıçanlarda Common Karotid Arter interpozisyon Harici Juguler Ven Greft: Gelişmiş Mikrocerrahi Tekniği Eğitimi

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in ...

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Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique

Mouse models are of special interest in research since a wide variety of monoclonal antibodies and commercially defined inbred and knockout strains are available to perform mechanistic in vivo studies. While heart transplantation models using a suture technique were first successfully developed in rats, the translation into an equally widespread used murine equivalent was never achieved due the technical complexity of the microsurgical procedure. In contrast, non-suture cuff techniques, also developed initially in rats, were successfully adapted for use in mice1-3. This technique for revascularization involves two major steps I) everting the recipient vessel over a polyethylene cuff; II) pulling the donor vessel over the formerly everted recipient vessel and holding it in place with a circumferential tie. This ensures a continuity of the endothelial layer, short operating time and very high patency rates4.
Using this technique for vascular anastomosis we performed more than 1,000 cervical heart transplants with an overall success rate of 95%. For arterial inflow the common carotid artery and the proximal aortic arch were anastomosed resulting in a retrograde perfusion of the transplanted heart. For venous drainage the pulmonary artery of the graft was anastomosed with the external jugular vein of the recipient5.
Herein, we provide additional details of this technique to supplement the video.

The murine cervical heart transplantation model is well suited for immunological as well as ischemia reperfusion injury studies. We modified the procedure using a non-suture cuff technique and performed more than 1,000 successful transplants with this approach.
Herein, we provide additional details of this technique to supplement the video.

Modifiye Manşet Tekniği Sıçangiller Servikal Kalp Nakli Modeli

Mouse models are of special interest in research since a wide variety of monoclonal antibodies and commercially defined inbred and knockout strains are ...

Heterotopic Cervical Heart Transplantation in Mice

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies this model by avoiding challenging suture anastomoses of small vessels thereby reducing warm ischemia time. In comparison to abdominal graft implantation the cervical model is less invasive and the implanted graft is easily accessible for further follow-up examinations. Anastomoses are performed by pulling the ascending aorta of the graft over the cuff with the recipient&#8217;s common carotid artery and by pulling the main pulmonary artery over the cuff with the external jugular vein. Selection of appropriate cuff size and complete mobilization of the vessels are important for successful revascularization. Ischemia-reperfusion (I/R) injury can be minimized by perfusing the graft with a cardioplegic solution and by hypothermia. In this article, we provide technical details for a simplified and improved cuff technique, which should allow surgeons with basic microsurgical skills to perform the procedure with a high success rate.

The cuff technique shortens and facilitates the model of heterotopic cervical heart transplantation in mice by avoiding technically challenging suture anastomoses of small vessels. The technical details shown in this video paper should allow researches to establish this model in their laboratories.

Farelerde Heterotopik Servikal Kalp Nakli

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies ...

Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. Research models for bypass graft failure are essential for a better understanding of pathobiological and pathophysiological processes during graft patency loss. Large animal models, such as pigs or sheep, resemble human anatomical structures but require special facilities and equipment. This video describes a rat vein interposition model to investigate vein graft patency loss. Rats are inexpensive and easy to handle. Compared to mouse models, the convenient size of rats permits better operability and enables a sufficient amount of material to be obtained for further diverse analysis. In brief, the inferior epigastric vein of a donor rat is harvested and used to replace a segment of the femoral artery. Anastomosis is conducted via single stitches and sealed with fibrin glue. Graft patency can be monitored non-invasively using duplex sonography. Myointimal hyperplasia, which is the main cause for graft patency loss, develops progressively over time and can be calculated from histological cross sections.

This video demonstrates a model to study the development of myointimal hyperplasia after venous interposition surgery in rats.

Ven interpozisyonu Model: baypas açıklığının Eğitim için uygun bir model

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. ...

In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium

The goal of this method is to introduce a transgene into the endothelium of isolated segments of both rabbit common carotid arteries. The method achieves focal endothelial-selective transgenesis, thereby allowing an investigator to determine the biological roles of endothelial-expressed transgenes and to quantify the in vivo transcriptional activity of DNA sequences in large artery endothelial cells. The method uses surgical isolation of rabbit common carotid arteries and an arteriotomy to deliver a transgene-expressing viral vector into the arterial lumen. A short incubation period of the vector in the lumen, with subsequent aspiration of the lumen contents, is sufficient to achieve efficient and durable expression of the transgene in the endothelium, with no detectable transduction or expression outside of the isolated arterial segment. The method allows assessment of the biological activities of transgene products both in normal arteries and in models of human vascular disease, while avoiding systemic effects that could be caused either by targeting gene delivery to other sites (e.g. the liver) or by the alternative approach of delivering genetic constructs to the endothelium by germ line transgenesis. Application of the method is limited by the need for a skilled surgeon and anesthetist, a well-equipped operating room, the costs of purchasing and housing rabbits, and the need for expertise in gene-transfer vector construction and use. Results obtained with this method include: transgene-related alterations in arterial structure, cellularity, extracellular matrix, or vasomotor function; increases or reductions in arterial inflammation; alterations in vascular cell apoptosis; and progression, retardation, or regression of diseases such as intimal hyperplasia or atherosclerosis. The method also allows measurement of the ability of native and synthetic DNA regulatory sequences to alter transgene expression in endothelial cells, providing results that include: levels of transgene mRNA, levels of transgene protein, and levels of transgene enzymatic activity.

In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium

This method is to introduce a transgene into the endothelium of rabbit carotid arteries. Introduction of the transgene allows the assessment of the biological role of the transgene product either in normal arteries or disease models. The method is also useful for measuring activity of DNA regulatory sequences.

Vivo Gen transferi için tavşan ortak Karotid arter endotel

The goal of this method is to introduce a transgene into the endothelium of isolated segments of both rabbit common carotid arteries. The method achieves ...

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. ...

A Rabbit Venous Interposition Model Mimicking Revascularization Surgery using Vein Grafts to Assess Intimal Hyperplasia under Arterial Blood Pressure

Although vein grafts have been commonly used as autologous grafts in revascularization surgeries for ischemic diseases, the long-term patency remains poor because of the acceleration of intimal hyperplasia due to the exposure to arterial blood pressure. The present protocol is designed for the establishment of experimental venous intimal hyperplasia by interposing rabbit jugular veins to the ipsilateral carotid arteries. The protocol does not require surgical procedures deep in the body trunk and the extent of the incision is limited, which is less invasive for the animals, allowing long-term observation after implantation. This simple procedure enables researchers to investigate strategies to attenuate the progression of intimal hyperplasia of the implanted vein grafts. Using this protocol, we reported the effects transduction of microRNA-145 (miR-145), which is known to control the phenotype of vascular smooth muscle cells (VSMCs) from the proliferative to the contractile state, into harvested vein grafts. We confirmed the attenuation of intimal hyperplasia of vein grafts by transducing miR-145 before implantation surgery through the phenotype change of the VSMCs. Here we report a less invasive experimental platform to investigate the strategies that can be used to attenuate intimal hyperplasia of vein grafts in revascularization surgeries.

The present protocol aims to experimentally create venous intimal hyperplasia by subjecting veins to arterial blood pressure for developing strategies to attenuate venous intimal hyperplasia following revascularization surgery using vein grafts.

Arteriyel Kan Basıncı Altında İntimal Hiperplazi değerlendirmek için Ven Greftleri kullanarak Revaskülarizasyon Cerrahisi Taklit Bir Tavşan Venöz Interposition Modeli

Although vein grafts have been commonly used as autologous grafts in revascularization surgeries for ischemic diseases, the long-term patency remains poor ...

Implantation of Tissue-Engineered Vascular Graft in Mouse Carotid Artery via Cuff Technique

The development of small-diameter vascular grafts has been a global endeavor, with numerous research groups contributing to this field. Animal experimentation plays a pivotal role in assessing the efficacy and safety of vascular grafts, particularly in the absence of clinical applications. Compared to alternative animal models, the mouse implantation model offers several advantages, including a well-defined genetic background, a mature method for disease model construction, and a straightforward surgical procedure. Based on these advantages, the present study devised a simple cuff technique for the implantation of tissue-engineered vascular grafts in the mouse carotid artery. This technique began with the fabrication of polycaprolactone (PCL) small-diameter vascular grafts via electrostatic spinning, followed by the seeding of macrophages onto the grafts through perfusion adsorption. Subsequently,&#160;the cellularized tissue-engineered vascular grafts were transplanted into the mouse carotid artery using the cuff technique to evaluate patency and regenerative capability. After 30 days of in vivo implantation, vascular patency was found to be satisfactory, with evidence of neo-tissue regeneration and the formation of an endothelial layer within the lumen of the grafts. All data were analyzed using statistical and graphing software. This study successfully established a mouse carotid artery implantation model that can be used to explore the cellular sources of vascular regeneration and the mechanisms of action of active substances. Furthermore, it provides theoretical support for the development of novel small-diameter vascular grafts.

Here, a protocol is presented for the implantation of a tissue-engineered vascular graft into the mouse carotid artery using the cuff technique, providing a suitable animal model for investigating vascular tissue regeneration mechanisms.

Fare Karotis Arterine Manşet Tekniği ile Doku Mühendisliği Yapılmış Vasküler Greft İmplantasyonu

The development of small-diameter vascular grafts has been a global endeavor, with numerous research groups contributing to this field. Animal ...

Biyomühendislik

A Simplified Model for Heterotopic Heart Valve Transplantation in Rodents

There is an urgent clinical need for heart valve replacements that can grow in children. Heart valve transplantation is proposed as a new type of transplant with the potential to deliver durable heart valves capable of somatic growth with no requirement for anticoagulation. However, the immunobiology of heart valve transplants remains unexplored, highlighting the need for animal models to study this new type of transplant. Previous rat models for heterotopic aortic valve transplantation into the abdominal aorta have been described, though they are technically challenging and costly. For addressing this challenge, a renal subcapsular transplant model was developed in rodents as a practical and more straightforward method for studying heart valve transplant immunobiology. In this model, a single aortic valve leaflet is harvested and inserted into the renal subcapsular space. The kidney is easily accessible, and the transplanted tissue is securely contained in a subcapsular space that is well vascularized and can accommodate a variety of tissue sizes. Furthermore, because a single rat can provide three donor aortic leaflets and a single kidney can provide multiple sites for transplanted tissue, fewer rats are required for a given study. Here, the transplantation technique is described, providing a significant step forward in studying the transplant immunology of heart valve transplantation.

This protocol describes a simple and efficient method for the transplantation of aortic valve leaflets under the renal capsule to allow for the study of alloreactivity of heart valves.

Kemirgenlerde Heterotopik Kalp Kapağı Transplantasyonu için Basitleştirilmiş Bir Model

There is an urgent clinical need for heart valve replacements that can grow in children. Heart valve transplantation is proposed as a new type of ...

Jugular Vein Graft Harvest From a Rabbit Model: A Surgical Procedure to Excise a Segment of Rabbit Jugular Vein for Ex Vivo Studies

Source: Nishio, H., et al. <a href="https://www.jove.com/v/60931">A Rabbit Venous Interposition Model Mimicking Revascularization Surgery using Vein Grafts to Assess Intimal Hyperplasia under Arterial Blood Pressure</a> J. Vis. Exp. (2020).
In this video, we demonstrate a procedure for surgically harvesting a segment of the jugular vein from a rabbit model. The resected segment can be used as an autologous vein graft to study intimal hyperplasia that develops due to arterial blood pressure.

Bir tavşan modelinden juguler ven grefti hasadı: ex vivo çalışmalar için tavşan juguler veninin bir segmentini eksize etmek için cerrahi bir prosedür

Source: Nishio, H., et al. A Rabbit Venous Interposition Model Mimicking Revascularization Surgery using Vein Grafts to Assess Intimal Hyperplasia under ...