著者はStentgraftsの贈り物のためにクリスティンGuesdon（アボット）に感謝したいと思います。

方法プロトコルはビシャ-のDebre倫理委員会（N°2012-15/698-0074）によって承認されている。 エラスターゼ灌流モデルは、1990年1にAnidjarによって記載されている：腹部大動脈瘤、8〜9週、250〜300グラム熟成、雄Wistarラットにおいてエラスターゼ灌流により誘発される。二つ〜4週間後、再手術を施行し、直径3mmは、冠状動脈瘤がstentgraftを除外するために使用されて覆われている。遠位大動脈切開を通して挿入移植は、拡大されたビジョンの下に展開されます。二週間後、stentgraft開存性は犠牲前に左総頸動脈によって大動脈造影で確認されています。全体ステント大動脈と周囲の組織は、その後、収穫し、分析のために調整されています。 プロトコル 1。手順1：腹部大動脈瘤インダクション（0日目） <ol><li>イソフルランで動物を麻酔し、性能mは、腹腔内penthobarbital注射。 penthobarbitol 0.1 60ml/100gでは、動物の体重saline/100グラム0.1mlの中で希釈される。麻酔は、手続きのために十分である。 </li><li>腹部を剃る、とアルコールで皮膚を洗浄してください。 </li><li>ブレードXypho恥骨皮膚切開を行います。その後腹膜腹部の筋肉層は、内臓を避けて、ハサミで開いています。スプレッダーを置き、動物の左側に湿布で腸を包む。 </li><li>それを引き裂くことなく、直接、大動脈上記後部腹膜を開きます。目標は、経済の解剖によって将来腸癒着を防ぐためです。 </li><li>大動脈の原点に、一字で左腎静脈から腸骨分岐へのすべての担保を連結。大動脈は、腸や大静脈に付着されている場合は、第二の介入時の出血の危険性が高いがあり、これは多くの場合、ラットのために致命的である。 </li><li> LEF以下15ミリメートル、大動脈の周囲に二回4-0絹を渡すT腎静脈。それは完全に大動脈、約を解剖することが重要です。左腎静脈とギルバート近似クランプの挿入を可能にする腸骨分岐のすぐ近位下15ミリメートル。 </li><li>ただ左腎静脈下、および遠位だけ腸骨分岐上記近位大動脈をクランプした後、外膜を除去し、遠位クランプにできるだけ近限り小さく大動脈切開を行います。大動脈は慎重に生理食塩水と角張っカニューレとクランプ解除時血栓塞栓を避けるために洗浄し、残りのすべての血でフラッシュする必要があります。 </li><li>スムーズ大動脈内部熱テーパーポリエチレンチューブ（PE 10）を紹介し、大動脈周囲4-0絹（ステップ1.6で）渡すとチューブを固定し、圧力追放を避けるためにタイアップ。 </li><li>大動脈の10〜さ13 mm長さ（近クランプからシルクまで）にエラスターゼを注入する。 </li><li>エラスターゼ溶液を注入725μlを、30分でスピード速度定数でdです。それは慎重にsに重要ですurvey注入：注入中、大動脈は通常直径140から150パーセントで展開する必要があります。 </li><li>点滴の終わりに、カテーテルを取り外し、生理食塩水でエラスターゼをフラッシュし、絹をカットし、10-0 PROLENE約3ステッチで大動脈切開を閉じます。クランプを取り外します。遠その後近。ケアトランス大動脈縫合糸を避けるように注意する必要があります。少数の実践と大動脈切開の小さな長さを考慮し、大動脈血栓症は非常にまれです。 </li><li>連続的な吸収性縫合糸、および中断の非吸収性縫合糸で皮膚と腹壁を閉じます。痛みを防ぐために、皮下にカルプロフェンの5 mg / kgを投与量を注入します。彼らのケージにラットを返し、標準ラット実験餌と水を広告libidumを与える。 </li></ol> 2。ステップ2：冠動脈PTFE（ポリテトラフルオロエチレン）カバードStentgraft（日15-30）と腹部大動脈瘤の除外<ol><li>以前は操作に、水1Lにアスピリン1,000 mgのを希釈。毎日のWATERの摂取量は10〜12日60ml/100gでの/体重推定した。 </li><li>前述のように麻酔した後、慎重に腹壁に​​付着潜在内臓を避け、再開腹を行う。動脈瘤は、少なくとも直接的なビジョンの下で測定された近位大動脈径と比較して、大動脈の50％の増加によって定義された。我々の経験に基づいて、成功率は大動脈バーストに主に起因する早期死亡、（未発表データ）を含め、90％で</li><li>大動脈分岐部にも近首に大動脈を解剖。動脈瘤は左腎静脈下数ミリを生じた場合、これは遠首とカテーテルを挿入するために遠位クランプの間に十分な長さを可能にし、大動脈を縫合。 Stentgraft長は動脈瘤の大きさに依存します。両方の近位端および遠位ネックは、少なくとも2ミリメートルによってカバーされるべきである。 </li><li>近首ダブルループシルクをラップします。動脈瘤と、b上記近位大動脈クランプ左腎動脈をelow、および遠位大動脈分岐上。 </li><li> stentgraftを導入する際に大動脈壁を引き裂く回避するために、直前の大動脈切開の上に大きな大動脈切開を行います。血栓の整合性を維持するために大動脈を洗浄しないでください。近クランプ向かっstentgraftを押してください。クランプでを削除し、移植の進行を可能にするために絹の張力を制御します。 stentgraftの近位端、近位首に達しただけでなく、これは、近位クランプを除去した後に大量出血を防ぐことができますまで、stentgraft進行を可能にするために提供するカテーテルの周りに緊張を適応させる。バルーン送達カテーテルの近位端部は、腎動脈、腎動脈ではなく下方に配備しなければならないstentgraftを覆うことができる。 </li><li> 8気圧でインフレータ注射器を用いて直接視覚的な制御下stentgraftを展開します。絹を締めながら、バルーンを収縮し、バルーンシャフトを取り外します。 </li><li> Sを洗う生理食塩水でtentgraft。ただ動脈瘤の遠位部以下クランプ、および中断10-0 PROLENE縫合と密接大動脈を置きます。 </li><li>傷口を閉じ、皮下カルプロフェンを注入し、動物が自分のケージに戻るまで放置します。標準的な実験餌と水を広告libidumを与える。 </li></ol> 3。ステップ3：Stentgraft開存のコントロール（30日目） stentgraft挿入後15日間は、移植片開存性を制御するために、動脈造影を行う<ol><li>麻酔後、肘の切開を横断肘を実行します。左総頸動脈は、顎と舌下腺の下と胸骨乳筋肉の下に位置しています。長さ2cmの露出することをお勧めします。 </li><li> 4-0シルクと遠位動脈を連結。クランプ近後、逆行18Gカテーテルを挿入し、頸動脈の周囲二回渡され、縛ら4-0絹糸で固定します。十分な長さは、挿入を可能にし、カテーテルが確保される前面近クランプは削除されます。それは動脈2cmの公開するのは難しい場合は、チューブは、生理食塩水で満たされた後にクランプは、近位クランプを取り外しながら、近位にプッシュすることができます。 </li><li>直接X線透視下でカテーテルを介してコントラストを注入。両方stentgraftの不適切な展開の可能性がありますエンドリークがないことを確認し、stentgraft開通性を確認するために、血管造影stentgraft制御を行う。担保血管の高い数字でも血栓stentgraftで十分な脚灌流を可能にするため、この手順は重要です。私たちは二重超音波検査を実行しようとしませんでした：私たちはstentgraft鉄骨構造はstentgraft開通やエンドリークの正しい評価を妨げることを仮定。 </li><li>勧告18に従って瀉血によってラットを犠牲にし、動脈瘤は、stentgraft、血栓と大動脈壁は組織学的または生化学的研究のために収穫されます。 </li></ol>

<ol>
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私は、開示することは何もありません。

AAAの二つのモデルは、すでに私たちの研究室に記載されている：異種移植片19およびエラスターゼ誘発モデル1エラスターゼモデルが人間の大動脈瘤に最も類似しています。大円周管腔内血栓は、その後、血管内動脈瘤の修復によって除外されています。 エンドリークはEVAR 14,15の通常の合併症である。 AAA破裂ローエンドリークと、時には動脈瘤?...

血管内のスキルは、1991年3パロディによる最初の血管内大動脈瘤修復（EVAR）以降に進んでいる、すべての腹部動脈瘤のほぼ半分になりましEVAR 4で扱われます。手術とは異なり、EVARは、全身血流から、それを除いて、血栓を残します。動脈瘤は、ヘモグロビンリッチ多層血栓、薄い媒体、およびfibrosedと外膜炎症によって特徴づけられる。動脈瘤の進行におけるタンパク質分解5の重要な役割は、30年前に実証されている6、7：動脈瘤嚢血栓が薄い大動脈壁、エラスチンの溶解、メディアにおける平滑筋細胞の低密度、および免疫の高いレベルに関連付けられています炎症外膜反応8,9。これらの変化は、タンパク質分解酵素活性は血栓ではなく、直接、大動脈壁における内で発生することを示唆している。 また、血栓の管層が凝集赤血球CEが豊富であるヘモグロビンを放出しLLS。それらは主に、フィブリン形成、血小板活性化およびトロンビ​​ン形成を誘発に関与している。最後に、血栓もフィブリン溶解と募集白血球、主に好中球に関与しているのt-PAとプラスミノゲン保持を、誘導する。これらは血流10に比べて血栓で12倍以上に重要です。彼らの存在は、マトリックスメタロタイプ8（MMP-8）、MMP-9およびエラスターゼ率が高いに関連付けられている：彼らは繊維状マトリックスの劣化につながる粒状セリンプロテアーゼとプロ酸化エージェントを解放し、最終的に大動脈壁破裂9,11 -13。 選択科目動脈瘤の介入は破裂を防ぐことを目指しています。 EVARは、動脈瘤壁と血栓の両方をそのまま残します。したがって、大動脈担保（腰動脈、下腸間膜動脈...）によって動脈瘤の血流は、エンドリーク名前が付けられ、血管内治療14,15の具体的な合併症である、時には破裂前夜につながっている低圧内部漏れのn。さらに、特定の患者では、動脈瘤の直径が16の増加がない。循環血液と動脈瘤壁の間の相互作用は、前述の内腔の血栓生物活性を維持しています。したがって、識別エンドリークせずに動脈瘤嚢の拡張として定義タイプVエンドリークは、動脈瘤の血栓内部酵素活性によって説明できる。 どちらも放射線イメージング（18FDG-PETスキャン、血小板活性化シンチグラフィー、鉄oxydeコントラストMRI17）も直接ヒトの大動脈瘤に対する血管内への影響を調査するために使用される末梢血サンプリング（MMP-9、血小板由来マイクロパーティクル、プラスミン/抗プラスミン複合体）生化学的経路を評価する。 我々の知識では、任意の再現性と安価な実験的動脈瘤除外動物モデルは存在しません。こちらは、前後の動脈瘤の除外生物学的および組織学的改変を探検することができます。

<table border="1">
<tbody>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Animals </td>
 </tr>
 <tr>
 <td>Wistar rats</td>
 <td></td>
 <td></td>
 <td>aged from 8 to 9 weeks. Weight range from 350 to 400 g</td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Instruments</td>
 </tr>
 <tr>
 <td>Isoflurane anesthesic system</td>
 <td></td>
 <td></td>
 <td>4,5% at the beginning, then 2%</td>
 </tr>
 <tr>
 <td>Penthobarbital</td>
 <td>Ceva sante animale, Libourne, France</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Dissection stereomicroscope</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Steriles gloves</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Microsurgical Steriles instruments</td>
 <td>Moria, Antony, France</td>
 <td></td>
 <td>Needle holder,	Forceps, Scissors,Gilbert approximator
o	3 Micro clamps</td>
 </tr>
 <tr>
 <td>N&deg;40 Silk string</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Prolen 9-0 and 10-0</td>
 <td>Ethicon, Johnson &amp; Johnson, Auneau, France</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Heat-tapered polyethylene tubing</td>
 <td>PE 10</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Syringe infusion pump</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Porcine pancreatic elastase</td>
 <td>Sigma, St. Louis, Mo., USA</td>
 <td></td>
 <td>550 &mu;l of salin is mixed with 175 &mu;l of elastase</td>
 </tr>
 <tr>
 <td>Indeflator</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>9 to 16 mm length, 3 mm diameter coronary PTFE covered stentgraft</td>
 <td>Abbott, Abbott Park, Illinois, USA</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>C-Arm OEC 9800</td>
 <td>GE Medical Systems, Milwaukee, WI</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Aspegic 1000 mg</td>
 <td>Aspirin, Sanofi-Aventis, Paris, France</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Reagent</td>
 </tr>
 <tr>
 <td>Aerane isoflurane 100ML</td>
 <td>Baxter</td>
 <td>Aerane</td>
 <td></td>
 </tr>
 <tr>
 <td>Penthobarbital</td>
 <td>Centravet</td>
 <td>053pen203</td>
 <td></td>
 </tr>
 <tr>
 <td>Silk Suture 4-0</td>
 <td>Fine Science</td>
 <td>18020-40</td>
 <td></td>
 </tr>
 <tr>
 <td>Microsurgical steriles instruments</td>
 <td>Moria</td>
 <td>9980-9983-9987-204/A-204/D-8148-4877A-4878A</td>
 <td></td>
 </tr>
 <tr>
 <td>Prolen 9-0 and 10-0</td>
 <td>Ethicon</td>
 <td>W2829 &ndash; NS2850</td>
 <td></td>
 </tr>
 <tr>
 <td>Heat tapered Polyethylene tubing : PE 10</td>
 <td>Bioseb</td>
 <td>MRE-010</td>
 <td></td>
 </tr>
 <tr>
 <td>Infusion pump</td>
 <td>World precision instrument</td>
 <td>AL-1000</td>
 <td></td>
 </tr>
 <tr>
 <td>Porcine pancreatic elastase</td>
 <td>Sigma</td>
 <td>E1250-100MG</td>
 <td></td>
 </tr>
 <tr>
 <td>Indeflator</td>
 <td>Longreal</td>
 <td>KY025 25 100</td>
 <td></td>
 </tr>
 <tr>
 <td>Aspegic 1000mg (Aspirin)</td>
 <td>Sanofi-Aventis</td>
 <td>3400931898191</td>
 <td></td>
 </tr>
 <tr>
 <td>C-Arm OEC 9800</td>
 <td>General electric.</td>
 <td>OEC 9800</td>
 <td></td>
 </tr>
 <tr>
 <td>Stentgraft : Jostent</td>
 <td>Abbott</td>
 <td>210CG1230 
 210CG1630</td>
 <td></td>
 </tr>
</tbody>
</table>

a new murine model of endovascular aortic aneurysm repair

血管内動脈瘤の除外は、動脈瘤の破裂を防ぐための検証手法である。長期的な結果は、技術の制限と腹部大動脈瘤（AAA）病態の新たな側面を強調する。治療前と後のAAAの深い調査を可能にする、安価で再現性のない腹部大動脈瘤のエンドグラフト除外モデルはありません。我々はここに誘導するために、次にカバー冠動脈stentgraftとラットにおける腹部大動脈瘤を除外する方法について説明します。周知のエラスターゼ誘発されるAAAモデルは、まずマウス2に記載ラット、1990年1に報告された。エラスチン分解は、人間のAAAとのマッチング、腹壁内および内腔の血栓の炎症性浸潤を伴う大動脈の拡張につながる。小さなカバーstentgraftと血管内の除外は、その後、循環血液と動脈瘤の血栓との間に相互作用を除いて、実行されます。適切な排除とstentgraft開存です左頸動脈思っ血管造影によって安楽死の前に確認した。エラスターゼ拡散の部分的な制御は、それぞれの動物のために動脈瘤の形状が違う。それは容易stentgraft導入の動脈瘤の下方大動脈の適切な長さを可能にする動脈瘤を作成することは困難であり、十分な近位および遠位首内部漏れを防止する。故障の多くは、時にはそれがステッチに痛みや悩みで大動脈の涙につながるstentgraft導入、ポストオペアンプ大動脈血栓症内皮損傷につながることができます。 stentgraft移植前にラットにアスピリンを与えることは大出血することなく、故障率が減少します。時間をクランプすると、好中球、内皮と血小板を活性化し、生物学的解析を妨げる可能性があります。

<html>動脈瘤は、その後、樹脂ブロックで固定するまで、生理食塩水、リン酸緩衝に、24時間の間に4％パラホルムアルデヒド溶液中で固定されています。私たちは、PTFE（ 図2）の周りに癒し増殖細胞を示す、HPS（ヘマトキシリンフロキシンサフラン）（ 図1）染色を使用しています。間葉系細胞は、その後、α-アクチン染色（ 図3）によって特徴付けられる...

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

A New Murine Model of Endovascular Aortic Aneurysm Repair

動脈瘤のエンドグラフト除外後の組織学的および生化学的な修正は、まだ不明である。我々は、マウス動脈瘤でエンドグラフト移植の新たなモデルを記述する。永続的な循環血液ストリームインタフェース、新しい血管内生体材料の評価の有無にかかわらず血栓分析を通して、このモデルでは、より良い血管内動脈瘤の除外病理生物学を理解するのに役立ちます。

血管内大動脈瘤の修復の新しいマウスモデル

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

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

Research

JoVE Journal

Medicine

14.3K ビュー.  Hôpital X. Bichat, AP-HP, Paris. 動脈瘤のエンドグラフト除外後の組織学的および生化学的な修正は、まだ不明である。我々は、マウス動脈瘤でエンドグラフト移植の新たなモデルを記述する。永続的な循環血液ストリームインタフェース、新しい血管内生体材料の評価の有無にかかわらず血栓分析を通して、このモデルでは、より良い血管内動脈瘤の除外病理生物学を理解するのに役?...

ビデオ: A New Murine Model of Endovascular Aortic Aneurysm Repair

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

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

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

脊髄虚血再灌流のマウスモデルにおいて胸部大動脈閉塞によって再現可能対麻痺

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

医学

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.

最大急性非致死肺損傷における急性肺損傷の結果のオープン気管切開胃酸吸引マウスモデル

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute ...

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

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

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

マウスモデルにおける下腹部大動脈クランプすることにより、再現性動脈侵食に起因けが

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

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

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

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

外ヴァーサ栄養血管の血流をブロックすることにより腹部の大動脈瘤の齧歯動物モデルの作成

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

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

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

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

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

Aortopathy β-アミノプロピオニ トリルによる大動脈瘤と解離のマウスモデルでのマイクロ CT 定量分析

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

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

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

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

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. ...

Murine Surgical Model of Topical Elastase Induced Descending Thoracic Aortic Aneurysm

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

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

局所エラスターゼ誘発下下胸部大動脈瘤のマウス外科モデル

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

Porcine Model of Infrarenal Abdominal Aortic Aneurysm

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

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

尿毛腹部大動脈瘤の豚モデル

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

A Murine Model of Hemodialysis Access-Related Hand Dysfunction

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

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

血液透析アクセス関連手機能障害のマウスモデル

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

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

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

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

アンジオテンシンII誘発腹部大動脈瘤のマウスモデルにおける中心静脈カテーテルによる薬物治療と3D超音波によるモニタリング

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