学内資金このプロジェクトのことは、学内研究部門、国立心臓、肺、血液研究所、国立衛生研究所によって提供されました。博士ジェームス ・ ホーキンス、博士ロバート ・ ホイト、獣医のリソースの NIH の部門および NIH における胸部外科研究プログラムのスタッフを確認したいと思います。

ここで説明している手順国立心臓、肺、血液研究所動物愛護および国立衛生研究所利用委員会によって承認され、の公衆衛生サービス ポリシーに記載されているポリシーに準拠思いやりのあるケアと実験動物の動物福祉法とケアのためのガイドの使用および実験動物の使用。
 注: この手術の目的は、重篤な冠動脈疾患患者に臨床的に関連する治療法の開発に使用することができます慢性の心筋虚血の動物モデルを生成します。これは 生体外 モデルを使用して実行できない。
 1 です動物 <ol><li>男性ヨークシャー豚重さ 12 〜 15 キロの間を使用して、</li></ol>。
 2. pre-surgical プロシージャ <ol><li>アモキシシリンとクラブラン酸カリウム 15 mg/kg を手術前に 24 h を始めて、1 日 2 回経口使用予防的抗生物質のため 。
	注: この経口抗生物質が手術豚はそれを飲み込むことを確認し、また、薬へのアレルギー反応に対して手術後がないことを確認する前に開始します</li>。
	<li>食品と手術前に 12 h 豚から水を差し控える</li>。
	<li>手術の日、麻酔のケタミン (33 mg/kg)、ミダゾラム (0.5 - 0.75 mg/kg)、およびアトロピン (0.01 mg/kg) の筋肉 (IM) を与えられたのカクテルが豚</li>。
	<li>は耳静脈内 20 G の静脈内投与 (IV) カテーテルを置き 7.0 Fr 気管内チューブと動物を挿管します 。
	注: IV カテーテルとブタのサイズに応じて気管内チューブのサイズを調整します</li>。
	<li>臍に肩と脊柱に腹部正中線から豚の左側の毛 (ひげ) を削除します</li>。
	<li>予防的抗生物質を投与する (ピペラシリンとタゾバクタム: 100 mg/kg IV) 薬を痛みと (ブプレノルフィン持続リリース: 0.2 mg/kg 皮下 (SC) やフェンタニル経皮パッチ 25 50 μ g/h). 
	注: IV 抗生物質を投与動物手術前 12 時間絶食し、今回の間に前述のように経口抗生物質が届かないので</li>。
	<li>は手術室に豚を輸送、気管内チューブを気道ガスを監視する副流センサーを搭載した麻酔器に接続します。機械的に換気開始点として 10 mL/kg の一回換気量を使用して豚と 30 cm H 2 o. セット分 (bpm) あたり 10-20 呼吸間呼吸の気道圧を超える、呼気終末 CO 2 (を保つために必要に応じて調整28 と 35 mm hg 維持イソフルラン (1-3%) と (2-5%) セボフルラン麻酔の間 PetCO 2) レベル</li>。
	<li>は、オペレーティング テーブルの上に豚の右側を配置します。体温 (BT)、心電図 (ECG)、パルス酸素濃度計 (スポ 2) 等 を監視するためすべての必要なプローブを添付</li> <li>2% クロルヘキシジン、70% アルコールで交互ボディス クラブ 3 経由で手術部位を準備 (において、外側に移動してセンターで始まる円運動).</li>
	<li>無菌 21 を使用して手術部位をドレープします</li>。
</ol> 3。手術 <ol><li>左開胸により心を公開します。
	<ol><li>皮膚切開を 4 番目 に平行になるよう、5 番目 の肋間スペース約 8-9 cm 長さ号 10 メス刃を使用しています</li>。
		<li>はリブロース筋肉デカールバサミ Metzenbaum、ブラウン アドソン鑷子のペアを使用して広背筋と前鋸をカットします。必要に応じて止血を維持するために電気焼灼器を使用します</li>。
		<li>は、4 番目 と 4 番目 の肋骨の前方の面に沿って Metzenbaum はさみ切断と 5 番目 のリブの間の胸腔内肋間筋を入力します。誤って肺の損傷のチャンスを減らすためには、胸腔内に入る直前に息を吐くのこのベンチレーターを切る。胸腔内が破られて、一度オンに戻すベンチレーター</li>。
		<li>心を公開する離れて、肋骨を広げるため小さな Finochietto リトラクターを使用します</li>。
	</ol></li> <li>使用 Debakey 鉗子をつかみ、心膜を持ち上げます。ポッツはさみを使って、心膜、心膜のスペースを入力する空気の小さい穴を作る。LAD と LCX の動脈の接合点ポッツ ハサミで切開を続ける</li>。
	<li>使用バブコック鉗子左心耳を撤回します。LCX 動脈の前にまたは近位端の周囲の組織から 1 st の鈍縁枝を解剖 Debakey と小さな直角鉗子を使用します</li>。
	<li>は、切り裂かれた LCX 動脈、各端に 1 つ下 2 つの容器のループを配置します。サイズ 3.0 mm アメロイド収縮を持つ小さな直角鉗子、収縮の開口部を通して LCX 動脈をゆっくりとガイド船ループを持ち上げます。開口部を向いているので、ゆっくり括約筋を回転させます。容器ループを削除します。 図 1 を参照してください 。
	注: 適切な動脈解離は、よじれを防ぐために不可欠です。個々 の動物に適切なサイズの収縮を選択します。適切なサイズの収縮が密接にせず最初船船を取り囲みます。アメロイド constrictors サイズ 2.5-3.5 ミリメートル 12 〜 15 キロの重量を量る国内の豚が必要です。船舶のアメロイド収縮の場所は虚血領域のサイズに依存します</li>。
	<li>心膜を再近似し、4-0 ポリプロピレン縫合糸で閉じる</li>。
	<li>12 Fr の胸腔チューブまたはそれと同等を閉鎖、一般に 2 つの肋間開胸術サイトに後方の層の間を終了終了と胸膜腔に挿入することで呼吸器の負圧を再確立します 。
	注: は、肋骨を閉じる前に無気肺を観察します。30 mmhg の圧力まで手動で肺を膨らませる過少膨張の兆候が認められた場合</li>。
	<li>は、肋間神経の層、皮下層の 2-0 ポリプロピレン縫合糸と真皮層の 3-0 ポリプロピレン縫合糸鋸と筋膜層のポリプロピレン縫合糸 0 1 ポリプロピレン縫合糸を使用して、胸を閉じます。ホチキス止めや皮膚を縫合します</li>。
	<li>胸管の端に 3 ウェイ ストップ コックを接続および否定的なシールを達成するまで、40-60 cc 注射器で胸に空気を避難させます。すべてのエアコンの取り外しを容易にするその胸骨または反対側に動物をロールバックします。胸は、負圧を維持して、一度胸管を外し、出口部を縫合します。切開することができます数日間包帯をされる動物は単独で手術後建物される場合</li>。
</ol> 4。術後 <ol><li>閉鎖、0.25% ブピバカインで開胸術サイトの両側に沿って切開に潜入します</li>。
	<li>人工呼吸器を動物を引き離すし、麻酔をオフに。動物は独自に呼吸したら気管内チューブを削除し、嚥下します</li>。
	(目を覚まし、胸骨)、それは完全に回復するまで、<li>は動物を監視します。異常はないはず、不整脈心電図、BT は 38.7-39.8 ° C をする必要がありますまたは SpO 2 は 95-100% にする必要があります、呼吸数は 32 58 bpm をする必要があります</li>。
	<li>管理アミオダロン (100 mg、1 日 2 回経口投与)、血栓症や不整脈を防ぐためにクロピドグレル硫酸水素 (75 mg、1 日 1 回経口投与)。アモキシシリンとクラブラン酸カリウム 15 mg/kg 1 日 2 回経口投与を続行します。10 日後の操作。術後の痛みは、ブプレノルフィン SR (持続的なリリース) で制御 0.2 mg/kg。SQ 3 日おき。ブプレノルフィンの SR は一度カルプロフェン 4.4 mg/kg で補うことができ、(2.2 mg/kg) PO または IM 入札します</li>。
	<li>動物の寝具と採材をすべてを保つ &#39; 住宅地切開は完全に治癒するまで s</li>。
</ol>

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著者はある利益相反を開示します。

アメロイド constrictors は慢性心筋虚血、慢性の心筋梗塞や心不全5,6,7,9,10の動物モデルを作成する広く使用されています。,11,12,13,15,16,17,18,19,22. 科学文献のアメロイド使用の有病率により研究者と自分の仕事の結果をより正確に比較するため、これらのモデルは、ステント、油圧改善や固定狭窄改善を使用して作成できますが、以前研究5,6,7,9,10、11,12,13,を公開15,16,17,18,19,22. アメロイド収縮を使用してのもう一つの利点は、プロシージャは比較的簡単です、合理的な手術技能を持つユーザーが正常に実行できる専用計測器は必要ありません。その他の上記の方法は大きい技術的なスキルを必要として、油圧の遮蔽の場合外部デバイス6,13による強烈な術後監視が必要です。
アメロイド収縮を使用しての主な制限は、オクルー ジョン9,13の率の変動です。一般に、アメロイド収縮を使用してほとんどの研究は、完全閉塞が発生する23,24まで最初の 2 週間で最高とし、徐々 に先細りする狭窄率を発見しました。アメロイド内腔の閉鎖率を直接測定前のヴィヴォ研究は、内腔の直径の最大の減少が最初の 2 週間で発生し、25,26がその後低下を確認しました。ただし、これらの同じ研究はグルコースとタンパク質濃度を取り巻く率およびアメロイド閉鎖、それにより生体内での条件のほとんどの場合、変動の示唆の完全性影響を与えることを示しているもアメロイドの閉塞率25,26です。他の研究者は、機械的外傷、炎症、線維化、および血栓形成アメロイド配置プロシージャ自体によって引き起こされるこの変動5,6,25 に貢献するかもしれないことを示唆しています。.後者のシナリオはほとんど早死にと本研究では, 心の障害の理由です。それは容器のよじれを防ぐためにアメロイドの両側に繊細、かつ十分なの動脈解離を行うための重要性を十分に強調することはできません。
アメロイド収縮の適切な配置は心の治療に十分な大きさの虚血領域を開発する重要なほど大規模な死になります。ヨークシャー豚で最適に動作する最初の鈍縁枝が表示される前に、LCX のアメロイド収縮筋を配置すること。他の報告、これは左心室の6の 25-30% 程度の虚血領域になりました。本研究で調査されていた特定の治療には不十分だった虚血性の地区結果、アメロイドの配置も低い。
手術中に発生する不整脈はまれです。研究の終わりまで経口アミオダロン術後の管理と、アメロイドは遮断し、2 〜 3 週間後操作中に不整脈を防ぐことができます。また、ばんと医療スタッフは肺浮腫/心不全の初期兆候になることができるこの期間中任意の咳の注意で特に警戒する必要があります。
長年にわたってアメロイド収縮のデザインに改善されました。Ameroids は、現在外科医はオクルード容器の直径に一致するアメロイドを選択するを許可する多くのサイズで利用可能。アメロイドの外側のリングはステンレス鋼、チタン、またはプラスチックで利用できます。MRI を使用して影響を受ける心を評価するとき、これは特に重要です。すべての金属は、MRI 画像でアイテムになります。チタン ameroids は、一方プラスチック葉なしすべてのステンレス鋼よりも加工品が少なくなります。チタン アメロイドとプラスチック アメロイドの違いを示す MRI 画像はそれぞれ図 2と図 3のとおりです。図2 心臓の右側にあるアーティファクトは被覆、アメロイド チタン リングによって引き起こされます。最近まで、プラスチック アメロイドに封じ込めリングだったあまりにもかさばる容器を屈曲することがなく冠動脈の周囲に配置します。本研究で用いたアメロイド収縮 (材料の表を参照) は金属の ameroids と同じ外径より合理化されたバージョン。

冠動脈疾患 (CAD)、心筋虚血につながる世界4前後約 1 米1,2で死亡して起因する医療費、死、障害の主要な原因は、します。,3,4,5,6CAD から苦しんでいる患者の 3 分の 1 ほどが時代、貧しい人々 の健康、または最適ではない解剖学4,のためのこれらの治療法の対象外である経皮的と外科的治療には多くの進歩をされているが、。5,6,7. 画像診断や治療の新しい方法を評価するために適切な動物モデルの開発が重要です。
ときに病気の動物モデルの開発、誘導障害は人間8,9の障害の解剖学的・生理学的特性を精密にエミュレートする必要があります。豚は心血管の研究の最も広く使われて大規模な動物の一つであります。豚の心臓は、サイズ、解剖学と生理学の3,6面で人間の心に最も密接に似ています。人間の心と同様に、ブタの心臓の心筋には豊富な側副血行6は持っていません。このため、豚の心臓も、急性冠閉塞は容認しないが、それは漸進的な冠動脈閉塞を耐えることができます。慢性心筋虚血、慢性心筋梗塞と心不全5,6,9,10,モデルとして使用ことができる場合は冠動脈が閉塞ゆっくり11,12,13。 慢性心筋虚血は、ステント留置や油圧オクルーダ、固定狭窄オクルーダ アメロイド収縮の配置を誘起すること。様々 な出版物6,9,13で詳細に記載されているこれらのすべてのメソッドの長所と短所がありますが、最も一般的に使用されるメソッドはアメロイド配置5、 6,10,11。
アメロイド収縮は、カゼインの材料ステンレス鋼、プラスチック、またはチタン リング内鉄骨で構成されます。徐々 に絞り込む内部ルーメンを引き起こす周囲の流体をカゼイン素材が吸収し、遅い狭窄を模倣 (通常、動脈左前下行枝冠 (LAD) または、左冠動脈回旋枝 (LCX)) 動脈の周囲に配置、一度、動脈を行い最後ににおけるはオクルー ジョン9,13,14に。この手順を単独で慢性心筋虚血や梗塞を開発し、新しいイメージング技術8を評価するために有用されている心臓の左心室の領域の他のメソッドの結果と組み合わせて使用 10、15治療7,16,17,18手術19,20。

<table border="0" cellpadding="0" cellspacing="0" width="965">
	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;width:323px;">Anesthesia: ketamine</td>
			<td style="width:195px;">Putney, INC</td>
			<td style="width:175px;"></td>
			<td style="width:273px;">Dose: 25mg/kg, IM</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Anesthesia: midazolam</td>
			<td>App Pharmaceuticals</td>
			<td></td>
			<td>Dose: 0.75mg/kg, IM</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Anesthesia: isoflurane</td>
			<td>Baxter</td>
			<td></td>
			<td>Dose: 1-3%, INH</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Antibiotics: amoxicillin and clavulanate potassium</td>
			<td>WG Critical Care</td>
			<td></td>
			<td>Dose: 15mg/kg, IV</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Antibiotics: piperacillin and tazobactam</td>
			<td>Fresenius Kabl</td>
			<td></td>
			<td>Dose: 100mg/kg, PO</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Analgesia: buprenorphine (sustained release)</td>
			<td>Zoo Pharm</td>
			<td></td>
			<td>10mg/ml bottle, Dose: 0.2mg/kg SC</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Analgesia: fentanyl patch</td>
			<td>Mylan</td>
			<td></td>
			<td>Dose: 25-50mcg/hr, TD</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Analgesia: bupivicaine 0.25%</td>
			<td>Hospira</td>
			<td></td>
			<td>Give SC at incision site for analgesia</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Alcohol 70%</td>
			<td>Humco</td>
			<td>NDC 0395-4202-28</td>
			<td>for scrubbing surgical site</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Chlorhexidine scrub 2%</td>
			<td>Vet One</td>
			<td>510083</td>
			<td>for scrubbing surgical site</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Datex-Ohmeda Aestiva /5 anesthesia machine</td>
			<td>GE Healthcare Madison WI.</td>
			<td style="width:175px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Pediatric anesthesia circuit</td>
			<td>Westmed</td>
			<td>7-8901</td>
			<td>www.westmedinc.com</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Water blanket</td>
			<td>Cincinnati Sub Zero</td>
			<td>Blanketrol 2</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">EKG</td>
			<td>Medtronics- Physiocontrol</td>
			<td>LifePak 20</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Oxygen saturation monitor</td>
			<td>GE Healthcare Madison WI.</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Temperature probe</td>
			<td>GE Healthcare Madison WI.</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Electrical cautery unit</td>
			<td>Valley Labs</td>
			<td>Force 2</td>
			<td>Cut-30 Coag-40</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Endotracheal tube</td>
			<td>Hudson RCI</td>
			<td>HUD510312</td>
			<td>Hudson brand - appropriate size for animal</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Intravenous catheter, size 20 gauge</td>
			<td>Santa Cruz Biotechnology, Inc</td>
			<td>SC-360097</td>
			<td>Fluid and drug administration</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Lactated Ringers Solution</td>
			<td>Hospira</td>
			<td>NDC 0409-7953-03</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Macro IV drip set 15 drops/ml</td>
			<td>Hospira</td>
			<td>12672-28</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Surgical gowns</td>
			<td>Kimberly Clark</td>
			<td>90142</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Utility drapes</td>
			<td>Kimberly Clark</td>
			<td>89731</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Adult laparotomy drape</td>
			<td>Medline</td>
			<td>DYNJP3004</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Sterile surgical gloves</td>
			<td>Cardinal Health (Allegiance)</td>
			<td>22537-570</td>
			<td>Size 7 - use appropriate size for surgeon</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Needle mat - sterile</td>
			<td>Medline</td>
			<td>NC30MBR</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Cautery pencil</td>
			<td>Medline</td>
			<td>ESPB 2000</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Suction tubing</td>
			<td>Medline</td>
			<td>DYND50251</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Suction tip; Yankauer</td>
			<td>Medline</td>
			<td>DYND50130</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Suction cannister</td>
			<td>Cardinal Health (Allegiance)</td>
			<td>65651-220</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Ameroid constrictors sizes 2.5mm -3.5mm</td>
			<td>Research Instruments SW, Inc.</td>
			<td>760-764-9411</td>
			<td>Types: Stainless steel, titanium, or plastic</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">3-way stopcock</td>
			<td>Cardinal Health (Allegiance)</td>
			<td>455991</td>
			<td>For chest tube</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Stomach tube - 18 Fr</td>
			<td>Cardinal Health (Allegiance)</td>
			<td>DC4418</td>
			<td>For chest tube</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">60cc syringe</td>
			<td>Cardinal Health (Allegiance)</td>
			<td>SY35060LL</td>
			<td>For chest tube</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">3cc syringe</td>
			<td>Cardinal Health (Allegiance)</td>
			<td>SY35003LL</td>
			<td>For post-op analgesia injection</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Skin stapler - 35W</td>
			<td>Ethicon&#160; Endo-Surgery</td>
			<td>PMW 35</td>
			<td>skin closure</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Scalpel blade - size #10</td>
			<td>Cardinal Health (Allegiance)</td>
			<td>32295-010</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Mini silicone vessel loops&#160; 1 Pak</td>
			<td>Aspen Surgical</td>
			<td>011001PBX</td>
			<td>for elevating circumflex artery to apply ameroid</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">1 (polypropylene) taper</td>
			<td>Ethicon</td>
			<td>BB #8425H</td>
			<td>close ribs</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">2-0 (polypropylene) taper</td>
			<td>Ethicon</td>
			<td>SH #8523</td>
			<td>close muscle layers</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">4-0 (polypropylene) taper</td>
			<td>Ethicon</td>
			<td>BB #8581H</td>
			<td>close pericardium</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">20 gauge needle</td>
			<td>Cardinal Health (Allegiance)</td>
			<td>81-200219</td>
			<td>post-op analgesia injection</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">antimicrobial drape</td>
			<td>3M</td>
			<td>6640EZ</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Finochietto rib retractor - infant size</td>
			<td>Codman</td>
			<td>50-8057</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Potts-Smith scissors</td>
			<td>Roboz</td>
			<td>RS-6043</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Babcock forceps</td>
			<td>Roboz</td>
			<td>RS-8022</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Pean hemostatic forceps curved</td>
			<td>Codman</td>
			<td>30-4565</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">scalpel handle #7</td>
			<td>Codman</td>
			<td>11-5534</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Brown Adson forceps</td>
			<td>Roboz</td>
			<td>RS-5231</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Debakey forceps</td>
			<td>Roboz</td>
			<td>RS-7562</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Mayo scissors</td>
			<td>Roboz</td>
			<td>RS-6870SC</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Metzenbaum dissecting scissors</td>
			<td>Codman</td>
			<td>36-5011</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Metzenbaum dissecting scissors</td>
			<td>Codman</td>
			<td>36-5016</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Mayo-Hegar needle holder</td>
			<td>Codman</td>
			<td>36-2017</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Ryder needle holder</td>
			<td>Codman</td>
			<td>36-3012</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Kelly hemostatic forceps</td>
			<td>Roboz</td>
			<td>RS-7130</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Reynolds hemostatic forcep</td>
			<td>Roboz</td>
			<td>RS-7211</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Weitlander retractor</td>
			<td>Roboz</td>
			<td>RS-8612</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Yorkshire domestic pigs</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

a chronic cardiac ischemia model in swine using an ameroid constrictor

心血管疾患には、アメリカ合衆国における死亡率の一番の原因が残っています。これらの疾患の治療に多くの方法がありますが、各治療をテストする方法、体内モデルが必要があります。豚は心血管疾患の最もよく使われる大型動物モデルの一つです。その心は人間の解剖学および機能で似ています。アメロイド配置手法では、心筋梗塞の研究に多くの有用なアプリケーションは、心臓の虚血領域を作成します。このモデルは、外科研究、医薬品の研究、イメージング技術、細胞治療に使用されています。
心臓の虚血領域を誘導するいくつかの方法があります。その長所と短所、それぞれありますが、アメロイド収縮の配置が最も広く使用されている手法です。アメロイドを使用する主な利点は、その有病率既存研究では、様々 なサイズの解剖学を収容して収縮するため容器のサイズで、その利用、手術は比較的簡単な手順および術後監視維持するために外部のデバイスがないので、ごくわずかです。このペーパーでは、アメロイド収縮の配置の適切な技術の詳細な概要を提供します。

2 年間で私たちの施設でアメロイド配置手術から得られたデータを分析した後生存率 80% であることがわかった。12-15 の kg の重量を量る 25 ヨークシャー豚の手順を行った。25 豚の 20 は、フォロー アップのプロシージャ、繊維し、直後に閉じる、2 を重症心不全や肺水腫を安楽死させ、1 いたフォロー アップ レントゲン中麻酔死死亡した 2 に生き残った。剖検では、プロシージャの 24 時間以内に死亡した動物の左心室の梗塞領域を明らかにしました。それは疑いがあるが、アメロイドの内腔からねじれて、アメロイドの存在のために動脈がまだ開いていたこと確認できませんでした。心不全のため安楽死された動物から得られる ameroids を調べた。18 日に内腔の総閉鎖があった。
存続の動物によって磁気共鳴イメージ投射 (MRI) 28 日ポスト アメロイド配置で心臓機能と虚血領域のサイズを測定するをイメージしました。図 2と図 3は、それぞれ鉄骨チタン アメロイドと豚とプラスチック包まれたアメロイドと豚から得られる MRI 画像を示します。イメージング後、細胞の注入または偽の手順, 開胸術を行った。動物は、うち 16 週間ポスト アメロイド配置限り続いていた。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56190/56190fig1.jpg"> 
図 1: アメロイド配置手順中に心臓のブタの画像。(A)の若者、LCX、鈍角縁動脈 (OM) を示す豚の心臓のイメージ。(B)アメロイド配置の前に切り裂かれた LCX 動脈の画像です。(C)上向きまたは中心部からアメロイドの開口周り、LCX アメロイドの適切な配置のイメージ。<a href="//ecsource.jove.com/files/ftp_upload/56190/56190fig1large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/56190/56190fig2.jpg"> 
図 2: チタンのブタ心臓の MRI 画像固めてアメロイド。LCX 動脈にチタン鉄骨アメロイド収縮の留置後 4 週間を取られる豚の心臓の MRI 画像です。チタンで作成された成果物への矢印。<a href="//ecsource.jove.com/files/ftp_upload/56190/56190fig2large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/56190/56190fig3.jpg"> 
図 3: プラスチック製のと豚の心臓の MRI 画像固めてアメロイド。LCX 動脈上プラスチック包まれたアメロイド収縮の留置後 4 週間を取られる豚の心臓の MRI 画像です。矢印はアメロイド収縮。アーティファクトは認められなかった。<a href="//ecsource.jove.com/files/ftp_upload/56190/56190fig3large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。

Watch this Scientific Journal Video about A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor at JoVE.com

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

アメロイド収縮を使用して豚の慢性心筋虚血モデル

このプロトコルの目的は、豚モデルで冠動脈の周り遅れて収縮デバイス (アメロイド収縮) の配置を示すことです。このデバイスは、新しい画像診断法と治療の新しい方法を学ぶです心臓の虚血領域を作成します。

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but ...

a-chronic-cardiac-ischemia-model-in-swine-using-an-ameroid-constrictor

Research

JoVE Journal

Medicine

10.5K ビュー.  National Institutes of Health. このプロトコルの目的は、豚モデルで冠動脈の周り遅れて収縮デバイス (アメロイド収縮) の配置を示すことです。このデバイスは、新しい画像診断法と治療の新しい方法を学ぶです心臓の虚血領域を作成します。

ビデオ: A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

Normothermic Cardiac Arrest and Cardiopulmonary Resuscitation: A Mouse Model of Ischemia-Reperfusion Injury

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused by whole-body hypoperfusion.5,6 Successful reproduction of whole-body hypoperfusion in rodent models has been fraught with 
difficulty.7-9,9,10 Models which employ focal ischemia have repeatedly demonstrated results which do not translate to the clinical setting, and larger 
animal models which allow for whole body hypoperfusion lack access to the full toolset of genetic manipulation possible in the mouse.11,12 However, in recent 
years a mouse model of cardiac arrest and cardiopulmonary resuscitation has emerged which can be adapted to model AKI.13 This model reliably reproduces 
physiologic, functional, anatomic, and histologic outcomes seen in clinical AKI, is rapidly repeatable, and offers all of the significant advantages of a murine surgical 
model, including access to genetic manipulative techniques, low cost relative to large animals, and ease of use. Our group has developed extensive experience 
with use of this model to assess a number of organ-specific outcomes in AKI.14,15

A powerful model for perioperative and critical care related acute kidney injury is presented. Using whole body hypoperfusion induced by cardiac arrest it is possible to nearly replicate the histologic and functional changes of clinical AKI.

正常体温心停止と心肺蘇生法：虚血再灌流障害のマウスモデル

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused ...

医学

A Swine Model of Neonatal Asphyxia

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, perfusion deficit, hypoxic-ischemic encephalopathy, pulmonary hypertension, vasculopathic enterocolitis, renal failure and thrombo-embolic complications. Animal models are developed to help us understand the patho-physiology and pharmacology of neonatal asphyxia. In comparison to rodents and newborn lambs, the newborn piglet has been proven to be a valuable model. The newborn piglet has several advantages including similar development as that of 36-38 weeks human fetus with comparable body systems, large body size (&tilde;1.5-2 kg at birth) that allows the instrumentation and monitoring of the animal and controls the confounding variables of hypoxia and hemodynamic derangements.
We here describe an experimental protocol to simulate neonatal asphyxia and allow us to examine the systemic and regional hemodynamic changes during the asphyxiating and reoxygenation process as well as the respective effects of interventions. Further, the model has the advantage of studying multi-organ failure or dysfunction simultaneously and the interaction with various body systems. The experimental model is a non-survival procedure that involves the surgical instrumentation of newborn piglets (1-3 day-old and 1.5-2.5 kg weight, mixed breed) to allow the establishment of mechanical ventilation, vascular (arterial and central venous) access and the placement of catheters and flow probes (Transonic Inc.) for the continuously monitoring of intra-vascular pressure and blood flow across different arteries including main pulmonary, common carotid, superior mesenteric and left renal arteries. Using these surgically instrumented piglets, after stabilization for 30-60 minutes as defined by Z&lt;10% variation in hemodynamic parameters and normal blood gases, we commence an experimental protocol of severe hypoxemia which is induced via normocapnic alveolar hypoxia. The piglet is ventilated with 10-15% oxygen by increasing the inhaled concentration of nitrogen gas for 2h, aiming for arterial oxygen saturations of 30-40%. This degree of hypoxemia will produce clinical asphyxia with severe metabolic acidosis, systemic hypotension and cardiogenic shock with hypoperfusion to vital organs. The hypoxia is followed by reoxygenation with 100% oxygen for 0.5h and then 21% oxygen for 3.5h. Pharmacologic interventions can be introduced in due course and their effects investigated in a blinded, block-randomized fashion.

Large animal models have good translational values in the examination of physiology and pharmacology of neonatal asphyxia. Using newborn piglets, we develop an experimental protocol to simulate neonatal asphyxia which has advantages of studying the systemic and regional hemodynamics, oxygen transport with biochemical and pathologic pathways and correlations.

新生児仮死の新型モデル

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, ...

Using Quantitative Real-time PCR to Determine Donor Cell Engraftment in a Competitive Murine Bone Marrow Transplantation Model

Murine bone marrow transplantation models provide an important tool in measuring hematopoietic stem cell (HSC) functions and determining genes/molecules that regulate HSCs. In these transplant model systems, the function of HSCs is determined by the ability of these cells to engraft and reconstitute lethally irradiated recipient mice. Commonly, the donor cell contribution/engraftment is measured by antibodies to donor- specific cell surface proteins using flow cytometry. However, this method heavily depends on the specificity and the ability of the cell surface marker to differentiate donor-derived cells from recipient-originated cells, which may not be available for all mouse strains. Considering the various backgrounds of genetically modified mouse strains in the market, this cell surface/ flow cytometry-based method has significant limitations especially in mouse strains that lack well-defined surface markers to separate donor cells from congenic recipient cells. Here, we reported a PCR-based technique to determine donor cell engraftment/contribution in transplant recipient mice. We transplanted male donor bone marrow HSCs to lethally irradiated congenic female mice. Peripheral blood samples were collected at different time points post transplantation. Bone marrow samples were obtained at the end of the experiments. Genomic DNA was isolated and the Y chromosome specific gene, Zfy1, was amplified using quantitative Real time PCR. The engraftment of male donor-derived cells in the female recipient mice was calculated against standard curve with known percentage of male vs. female DNAs. Bcl2 was used as a reference gene to normalize the total DNA amount. Our data suggested that this approach reliably determines donor cell engraftment and provides a useful, yet simple method in measuring hematopoietic cell reconstitution in murine bone marrow transplantation models. Our method can be routinely performed in most laboratories because no costly equipment such as flow cytometry is required.

Determining donor cell engraftment presents a challenge in mouse bone marrow transplant models that lack well-defined phenotypical markers. We described a methodology to quantify male donor cell engraftment in female transplant recipient mice. This method can be used in all mouse strains for the study of HSC functions.

競争力のあるマウス骨髄移植モデルにおけるドナー細胞の生着を​​決定するために、定量的リアルタイムPCRを用いて

Murine bone marrow transplantation models provide an important tool in measuring hematopoietic stem cell (HSC) functions and determining genes/molecules ...

Urinary Bladder Distention Evoked Visceromotor Responses as a Model for Bladder Pain in Mice

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized by increased urgency and frequency of urination, as well as nocturia and general pelvic pain, especially upon bladder filling or voiding. Despite years of research, the cause of IC/BPS remains elusive and treatment strategies are unable to provide complete relief to patients. In order to study nervous system contributions to the condition, many animal models have been developed to mimic the pain and symptoms associated with IC/BPS. One such murine model is urinary bladder distension (UBD). In this model, compressed air of a specific pressure is delivered to the bladder of a lightly anesthetized animal over a set period of time. Throughout the procedure, wires in the superior oblique abdominal muscles record electrical activity from the muscle. This activity is known as the visceromotor response (VMR) and is a reliable and reproducible measure of nociception. Here, we describe the steps necessary to perform this technique in mice including surgical manipulations, physiological recording, and data analysis. With the use of this model, the coordination between primary sensory neurons, spinal cord secondary afferents, and higher central nervous system areas involved in bladder pain can be unraveled. This basic science knowledge can then be clinically translated to treat patients suffering from IC/BPS.

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized in part by pelvic pain. In order to study nervous system contributions to the condition, a physiological model of urinary bladder pain is used in mice and rats.

マウスの膀胱痛に対するモデルとしての膀胱膨満誘発内臓運動応答

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition ...

Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment methods. Here, we present such a model by tachycardia-induced cardiomyopathy, which can be produced by rapid cardiac pacing in swine.
A single pacing lead is introduced transvenously into fully anaesthetized healthy swine, to the apex of the right ventricle, and fixated. Its other end is then tunneled dorsally to the paravertebral region. There, it is connected to an in-house modified heart pacemaker unit that is then implanted in a subcutaneous pocket. 
After 4 - 8 weeks of rapid ventricular pacing at rates of 200 - 240 beats/min, physical examination revealed signs of severe heart failure - tachypnea, spontaneous sinus tachycardia, and fatigue. Echocardiography and X-ray showed dilation of all heart chambers, effusions, and severe systolic dysfunction. These findings correspond well to decompensated dilated cardiomyopathy and are also preserved after the cessation of pacing.
This model of tachycardia-induced cardiomyopathy can be used for studying the pathophysiology of progressive chronic heart failure, especially hemodynamic changes caused by new treatment modalities like mechanical circulatory supports. This methodology is easy to perform and the results are robust and reproducible.

Here, we present a protocol to produce tachycardia-induced cardiomyopathy in swine. This model represents a potent way to study the hemodynamics of progressive chronic heart failure and the effects of applied treatment.

豚の慢性心不全モデルとして頻拍誘発性心筋

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment ...

Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary Artery Bypass Graft Surgery

Chronic cardiac ischemia that impairs cardiac function, but does not result in infarct, is termed hibernating myocardium (HM). A large clinical subset of coronary artery disease (CAD) patients have HM, which in addition to causing impaired function, puts them at higher risk for arrhythmia and future cardiac events. The standard treatment for this condition is revascularization, but this has been shown to be an imperfect therapy. The majority of pre-clinical cardiac research focuses on infarct models of cardiac ischemia, leaving this subset of chronic ischemia patients largely underserved. To address this gap in research, we have developed a well-characterized and highly reproducible model of hibernating myocardium in swine, as swine are ideal translational models for human heart disease. In addition to creating this unique disease model, we have optimized a clinically relevant treatment model of coronary artery bypass surgery in swine. This allows us to accurately study the effects of bypass surgery on heart disease, as well as investigate additional or alternate therapies. This model surgically induces single vessel stenosis by implanting a constrictor on the left anterior descending (LAD) artery in a young pig. As the pig grows, the constrictor creates a gradual stenosis, resulting in chronic ischemia with impaired regional function, but preserving tissue viability. Following the establishment of the hibernating myocardium phenotype, we perform off-pump coronary artery bypass graft surgery to revascularize the ischemic region, mimicking the gold-standard treatment for patients in the clinic.

This protocol presents a surgical large animal model of chronic, single vessel ischemia that results in regional abnormalities but does not create infarct, known as hibernating myocardium. Following establishment of chronic ischemia, animals are treated with off-pump LIMA-LAD coronary artery bypass graft surgery to revascularize the ischemic tissue.

冠動脈バイパス移植手術によって治療慢性心筋虚血の外科豚モデル

Chronic cardiac ischemia that impairs cardiac function, but does not result in infarct, is termed hibernating myocardium (HM). A large clinical subset of ...

Standardized Model of Ventricular Fibrillation and Advanced Cardiac Life Support in Swine

Cardiopulmonary resuscitation after cardiac arrest, independent of its origin, is a regularly encountered medical emergency in hospitals as well as preclinical settings. Prospective randomized trials in human subjects are difficult to design and ethically ambiguous, which results in a lack of evidence-based therapies. The model presented in this report represents one of the most common causes of cardiac arrests, ventricular fibrillation, in a standardized setting in a large animal model. This allows for reproducible observations and various therapeutic interventions under clinically accurate conditions, hence facilitating the generation of better evidence and eventually the potential for improved medical treatment.

Cardiopulmonary resuscitation and defibrillation are the only effective therapeutic options during cardiac arrest caused by ventricular fibrillation. This model presents a standardized regimen to induce, assess, and treat this physiological state in a porcine model, thus providing a clinical approach with various opportunities for data collection and analysis.

豚における心室細動と高度心臓生活支援の標準化モデル

Cardiopulmonary resuscitation after cardiac arrest, independent of its origin, is a regularly encountered medical emergency in hospitals as well as ...

An Intact Pericardium Ischemic Rodent Model

This protocol has shown that the pericardium and its contents play an essential anti-fibrotic role in the ischemic rodent model (coronary ligation to induce myocardial injury). The majority of pre-clinical myocardial infarction models require the disruption of pericardial integrity with loss of the homeostatic cellular milieu. However, recently a methodology has been developed by us to induce myocardial infarction, which minimizes pericardial damage and retains the heart&#39;s resident immune cell population. An improved cardiac functional recovery in mice with an intact pericardial space following coronary ligation has been observed. This method provides an opportunity to study inflammatory responses in the pericardial space following myocardial infarction. Further development of the labeling techniques can be combined with this model to understand the fate and function of pericardial immune cells in regulating the inflammatory mechanisms that drive remodeling in the heart, including fibrosis.

This protocol outlines the steps for inducing myocardial infarction in mice while preserving the pericardium and its contents.

無傷心膜虚血性げっ歯類モデル

This protocol has shown that the pericardium and its contents play an essential anti-fibrotic role in the ischemic rodent model (coronary ligation to ...

Translational Rabbit Model of Chronic Cardiac Pacing

Animal models of cardiac pacing are beneficial for testing novel devices, studying the pathophysiology of artificially paced heart rhythms, and studying arrhythmia-induced cardiomyopathies and subsequent heart failure. Currently, only a few such models are available, and they mostly require extensive resources. We report a new experimental cardiac pacing model in small mammals with the potential to study arrhythmia-induced heart failure.
In six New Zealand white rabbits (mean weight: 3.5 kg) under general inhalational anesthesia the jugular region was dissected and a single pacing lead was inserted via the right external jugular vein. Using fluoroscopic guidance, the lead was further advanced to the right ventricular apex, where it was stabilized using passive fixation. A cardiac pacemaker was then connected and buried in a subcutaneous pocket.
The pacemaker implantation was successful with good healing; the rabbit anatomy is favorable for the lead placement. During 6 months of follow-up with intermittent pacing, the mean sensed myocardial potential was 6.3 mV (min: 2.8 mV, max: 12 mV), and the mean lead impedance measured was 744 &#937; (min: 370 &#937;, max: 1014 &#937;). The pacing threshold was initially 0.8 V &#177; 0.2 V and stayed stable during the follow-up.
This present study is the first to present successful transvenous cardiac pacing in a small-mammal model. Despite the size and tissue fragility, human-size instrumentation with adjustments can safely be used for chronic cardiac pacing, and thus, this innovative model is suitable for studying the development of arrhythmia-induced cardiomyopathy and consequent heart failure pathophysiology.

We present a minimally invasive leporine model of long-term cardiac pacing that can be utilized for artificial pacing and heart failure development in preclinical studies.

慢性心臓ペーシングの並進ウサギモデル

Animal models of cardiac pacing are beneficial for testing novel devices, studying the pathophysiology of artificially paced heart rhythms, and studying ...

Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to suboptimal clinical results. We set out to establish a chronic ovine model of FTR and right heart failure to investigate the mechanisms of FTR. Twenty adult male sheep (6-12 months old, 62 &#177; 7 kg) underwent a left thoracotomy and baseline echocardiography. A pulmonary artery band (PAB) was placed and cinched around the main pulmonary artery (PA) to at least double the systolic pulmonary artery pressure (SPAP), inducing right ventricular (RV) pressure overload and signs of RV dilatation. PAB acutely increased the SPAP from 21 &#177; 2 mmHg to 62 &#177; 2 mmHg. The animals were followed for 8 weeks, symptoms of heart failure were treated with diuretics, and surveillance echocardiography was used to assess for pleural and abdominal fluid collection. Three animals died during the follow-up period due to stroke, hemorrhage, and acute heart failure. After 2 months, a median sternotomy and epicardial echocardiography were performed. Of the surviving 17 animals, 3 developed mild tricuspid regurgitation, 3 developed moderate tricuspid regurgitation, and 11 developed severe tricuspid regurgitation. Eight weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and significant FTR. This large animal platform can be used to further investigate the structural and molecular basis of RV failure and functional tricuspid regurgitation.

Right ventricular failure and functional tricuspid regurgitation are associated with left-sided heart disease and pulmonary hypertension, which contribute significantly to morbidity and mortality in patients. Establishing a chronic ovine model to study right ventricular failure and functional tricuspid regurgitation will help in understanding their mechanisms, progression, and possible treatments.

右室不全と機能性三尖弁逆流の慢性ヒツジモデル

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to ...