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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	<li>Libby, P., Bornfeldt, K. E., Tall, A. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atherosclerosis:+Successes,+Surprises,+and+Future+Challenges.">Atherosclerosis: Successes, Surprises, and Future Challenges.</a> Circ Res. 118, 531-534 (2016).</li><li>Fowkes, F. G., 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=Comparison+of+global+estimates+of+prevalence+and+risk+factors+for+peripheral+artery+disease+in+2000+and+2010:+a+systematic+review+and+analysis.">Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis.</a> Lancet. 382, 1329-1340 (2013).</li><li>Mohr, F. 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H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vein+graft+failure:+from+pathophysiology+to+clinical+outcomes.">Vein graft failure: from pathophysiology to clinical outcomes.</a> Nat Rev Cardiol. 13 (8), 451-470 (2016).</li><li>Harskamp, R. E., Lopes, R. D., Baisden, C. E., de Winter, R. J., Alexander, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Saphenous+vein+graft+failure+after+coronary+artery+bypass+surgery:+pathophysiology,+management,+and+future+directions.">Saphenous vein graft failure after coronary artery bypass surgery: pathophysiology, management, and future directions.</a> Ann Surg. 257, 824-833 (2013).</li><li>Sabik, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+saphenous+vein+graft+patency.">Understanding saphenous vein graft patency.</a> Circulation. 124 (3), 273-275 (2011).</li><li>Owens, C. D., Ho, K. J., Conte, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lower+extremity+vein+graft+failure:+a+translational+approach.">Lower extremity vein graft failure: a translational approach.</a> Vasc Med. 13, 63-74 (2008).</li><li>Robertson, K. E., McDonald, R. A., Oldroyd, K. G., Nicklin, S. A., Baker, A. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevention+of+coronary+in-stent+restenosis+and+vein+graft+failure:+does+vascular+gene+therapy+have+a+role.">Prevention of coronary in-stent restenosis and vein graft failure: does vascular gene therapy have a role.</a> Pharmacol Ther. 136, 23-34 (2012).</li><li>Yla-Herttuala, S., Baker, A. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiovascular+Gene+Therapy:+Past,+Present,+and+Future.">Cardiovascular Gene Therapy: Past, Present, and Future.</a> Mol Ther. 25, 1095-1106 (2017).</li><li>Schwartz, L. 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このプロトコルの重要なステップには、麻酔の管理、動脈/グラフト静脈の抗凝固、手術操作、グラフト静脈の血行動態の測定が含まれます。2 つの比較的長い操作 (二国間静脈グラフトの通常 3 〜 3.5 h および二国間移植伝達の 1.5 〜 2.5 h) を含む複数この生存手術モデルの麻酔の適切な管理が欠かせません。両方、粗野で、気管内挿管による麻酔を投与し、挿管を考える肯定的な圧力換気、無...

動脈硬化は、脂質蓄積と血管壁の炎症で血管内腔、心臓発作、ストロークおよび手足1,2の損失の縮小につながる慢性炎症性疾患です。経皮的介入 (e.g、血管形成術とステント留置術) と薬物療法 (e.g。、スタチン系薬剤と抗血小板薬のエージェント); アテローム性動脈硬化症の治療は、。ただし、彼らはしばしば冠動脈および末梢循環に重度の閉塞性疾患の両方の治療に効果的です。バイパス術、自家静脈セグメントを使用して深刻なびまん性冠動脈および末梢血管疾患3,4の患者を治療するための一般的な手順のままです。ただし、両方の冠は、移植を静脈し、末梢循環悪い長期開存率があります。冠循環の静脈グラフトが 1 年間で 50% 遮蔽の約 10-20% は 10 年5,6に遮蔽されました。末梢循環の静脈グラフト故障率、5 年間7時 30-50% です。
病気のサイトに正確に治療遺伝子産物を配信できるため、遺伝子治療は静脈グラフト障害の防止のための魅力的なアプローチです。したがって、多くの前臨床研究は静脈グラフト遺伝子療法8,9をテストしています。ただし、本質的にこれらの研究のすべては、早い時間 (2-12 週) のポイント10、11,12,13,14,15,の有効性を調べられます16,17. 遺伝子療法の介入が耐久性を提供できるという証拠はないと意識しております (年) 通常起因する新生内膜過形成や動脈硬化4後半の静脈グラフト障害に対する保護。グラフト静脈で耐久性のある遺伝子発現をでき、後半と初期の時点で遺伝子治療介入のテストによりメソッドを開発しました。耐久性のある遺伝子発現を成し遂げるためには、メソッドには、HDAd ベクトルと遅延伝達戦略が組み込まれています。HDAd ベクトル免疫18,19,によって導入された細胞の認識 (と拒絶)20,を防止するウイルスの遺伝子がないために長期の遺伝子発現を提供する21. 遅延伝達 (グラフト留置後実行される 28 日) は22移植後早期に発生する大量の処理中に導入された細胞の損失を防ぐことができます。
移植配置10、11,12,15,16 時静脈グラフトの伝達に依存して静脈の血管壁における治療導入遺伝子発現を達成する他の方法 ,17。連続的に測定したとき遺伝子発現のこのアプローチを使用してすばやく伝達22,23後低下します。したがって、このアプローチを用いた研究がほとんどない 4 週間を超えて有効性を評価すると、グラフト静脈後 12 週を超えて有効性を検討していません。これに対し、本方式による静脈グラフトと-同じような研究に基づいて動脈可能性がありますで実行される、少なくとも 24 数週間安定持続する遺伝子発現のはるかに長い22,24を続けています。その他静脈グラフト遺伝子療法の介入なしこの期間の遺伝子発現の安定を実現すると意識しております。
家兎モデルを使用して、本手法を開発しました。他の齧歯動物、ウサギ、使用したまたは静脈をテストするより大きい動物移植遺伝子療法10、11,12,15,16,17,25、 26。齧歯動物モデルと比較して、ウサギはより高くより厳格な規制要件が適用されます。しかしより大きい動物に比較 (e.g。、ブタおよび犬)、ウサギを購入し家にはるかに高価な、はるかに扱いやすい。ウサギ血管生理人間の血管のようにまた、27、彼らが経皮的介入28,29をテストするため使用することができます、彼らは十分な組織を提供する十分に大きい複数のエンドポイント (e.g。、組織学、タンパク質、RNA) 単一の血管標本22,30を使用して調べることができます。さらに、静脈グラフトのウサギは、高脂肪食にうんざりした、彼ら開発静脈移植動脈硬化31,32, 冠動脈バイパス静脈グラフト障害4,5 の一般的な原因であります。.これらの動脈硬化家兎静脈グラフトは、遺伝子治療の介入は、この方法をテストするための基板として使用できます。指定されたプロトコルは、ウサギ静脈グラフトにおける遺伝子発現の耐久性を達成するために必要な技術的なスキルを習得する捜査官を助けることができます。

<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

静脈グラフト バイパス手術は、閉塞性動脈疾患の一般的な治療法ただし、長期的な成功は、血栓症、肥厚、動脈硬化など血管障害によって制限されます。この記事の目標は、ウサギの二国間静脈移植を配置し、遺伝子発現の耐久性を実現する遺伝子の転送ベクトルと移植を伝達する方法を示すことです。メソッドは、通常静脈グラフトの恒常性の遺伝子とその蛋白質製品の生物学的役割の調査をことができます。例えば静脈グラフト障害を防ぐことができる活動のための遺伝子のテストを実行できます、transgene の式に新生内膜増殖を防ぐかどうかは、血管の炎症を軽減メソッドまたは家兎動脈硬化を軽減供給。高脂肪食。初期生残手術中に右と左の外頚静脈のセグメントは摘出、逆側の端に一般的な頚動脈移植として両側に配置されます。28 日後を実行、2 番目の生存手術中にグラフトのそれぞれは血管クリップで循環から隔離され、ルーメンがヘルパー依存 (HDAd) アデノウイルスベクターを含むソリューション (すなわち) 経由で満ちています。20 分インキュベーション後ベクトル ソリューションを吸気、切開を修理し、流れを復元します。静脈は、個々 の実験的プロトコルによって決まります時点で収穫されます。移植配置と情報伝達系の 28 日間の遅延は動脈循環の静脈グラフトの適応を確保するため必要です。この適応は、静脈グラフト導入前に、または直後移植で発生する遺伝子発現の急速な損失を回避できます。メソッドは、耐久性、安定した遺伝子発現によりグラフト静脈を達成するためにその能力でユニークです。ウサギ他動物大静脈血管モデルと比較して、低コストと簡単な処理の利点があります。ウサギ齧歯動物の静脈グラフトのモデルと比較して、解析のための豊富な組織を提供する大きく、操作が簡単の血管があります。

オペレーターは、実験データを生成するこのメソッドを使用できます前に、new 演算子の技術的な習熟度を検証する必要があります。New 演算子を実現する必要があります最初のマイルス トーンは、一貫性のある静脈グラフトの開存を初回血管移植手術とその後の遅延伝達手術後です。以上手術のそれぞれが望ましいと達成した後 90% 開存性。開存は、我々 は通常術後 ...

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

耐久性のある遺伝子発現により一般的な頚動脈移植に頸静脈の家兎モデル

このメソッドでは、ウサギの介在静脈グラフトの配置、移植の伝達と遺伝子発現の耐久性の達成をについて説明します。これは遺伝子とグラフト静脈でタンパク質製品の生理学的および病理学的役割と静脈グラフト病に対する遺伝子治療のテストの調査をことができます。

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

a-rabbit-model-durable-transgene-expression-jugular-vein-to-common

Research

JoVE Journal

Medicine

10.3K ビュー.  University of Washington School of Medicine. このメソッドでは、ウサギの介在静脈グラフトの配置、移植の伝達と遺伝子発現の耐久性の達成をについて説明します。これは遺伝子とグラフト静脈でタンパク質製品の生理学的および病理学的役割と静脈グラフト病に対する遺伝子治療のテストの調査をことができます。

ビデオ: 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.

ラットの総頚動脈で外頚静脈グラフトの介在：洗練された顕微鏡下手術の訓練

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

医学

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.

変更されたカフ法を用いたマウス子宮頸心臓移植モデル

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.

マウスにおける異子宮頸心臓移植

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.

静脈介在モデル：バイパスグラフト開存を研究するための適切なモデル

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.

生体内でウサギの一般的な頚動脈内皮細胞への遺伝子導入

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.

改変非縫合カフ技術を用いたマウス子宮頸動脈大動脈移植モデル

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.

静脈移植を用いた血管形成術を模したウサギ静脈間位置モデルによる動脈血圧下の内膜過形成の評価

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.

カフ法 による マウス頸動脈への組織改変血管移植片の移植

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

生物工学

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.

げっ歯類におけるヘテロトピック心臓弁移植のための簡略モデル

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.

ウサギモデルからの頸静脈移植片の収穫:ex vivo研究のためのウサギ頸静脈の一部を切除する外科的処置

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

耐久性のある遺伝子発現により一般的な頚動脈移植に頸静脈の家兎モデル

要約

さらに動画を探す

この動画の章

ラットの総頚動脈で外頚静脈グラフトの介在：洗練された顕微鏡下手術の訓練

変更されたカフ法を用いたマウス子宮頸心臓移植モデル

マウスにおける異子宮頸心臓移植

静脈介在モデル：バイパスグラフト開存を研究するための適切なモデル

生体内でウサギの一般的な頚動脈内皮細胞への遺伝子導入

改変非縫合カフ技術を用いたマウス子宮頸動脈大動脈移植モデル

静脈移植を用いた血管形成術を模したウサギ静脈間位置モデルによる動脈血圧下の内膜過形成の評価

カフ法によるマウス頸動脈への組織改変血管移植片の移植

げっ歯類におけるヘテロトピック心臓弁移植のための簡略モデル

ウサギモデルからの頸静脈移植片の収穫:ex vivo研究のためのウサギ頸静脈の一部を切除する外科的処置

耐久性のある遺伝子発現により一般的な頚動脈移植に頸静脈の家兎モデル

要約

さらに動画を探す

この動画の章

ラットの総頚動脈で外頚静脈グラフトの介在：洗練された顕微鏡下手術の訓練

変更されたカフ法を用いたマウス子宮頸心臓移植モデル

マウスにおける異子宮頸心臓移植

静脈介在モデル：バイパスグラフト開存を研究するための適切なモデル

生体内でウサギの一般的な頚動脈内皮細胞への遺伝子導入

改変非縫合カフ技術を用いたマウス子宮頸動脈大動脈移植モデル

静脈移植を用いた血管形成術を模したウサギ静脈間位置モデルによる動脈血圧下の内膜過形成の評価

カフ法 による マウス頸動脈への組織改変血管移植片の移植

げっ歯類におけるヘテロトピック心臓弁移植のための簡略モデル

ウサギモデルからの頸静脈移植片の収穫:ex vivo研究のためのウサギ頸静脈の一部を切除する外科的処置

カフ法によるマウス頸動脈への組織改変血管移植片の移植