The study was supported by research grants from the Roche Organ Transplant Research Foundation (ROTRF) and Astellas. Markus Selzner was supported by an ASTS Career Development Award. Matthias Knaak was supported by the Astellas Research Scholarship. We thank Uwe Mummenhoff and the Birmingham family for their generous support.

<ol>
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The authors have nothing to disclose.

実験ブタOLTxは、臨床シナリオの集中治療資源のない研究の設定のための挑戦的な手順です。可能性のある合併症は、血行動態不安定、出血、臓器虚血、低体温、および代謝、ならびに呼吸器、代償があります。いずれの研究グループでは、外科的手法5と同様に豚麻酔14,15の十分な手続き訓練が代表と再現性のある結果を得るために必須です。 多くの技術的な機微は、特に、血管再建段階5について 、文献に記載されています。上記のOLTxプロトコルは人間OLTx似静脈-交換モデルに必要な情報を提供します。得られた結果は、両方のHBDとDCDモデルで信頼性の高い動物の生存および移植片の回復を示しています。プロトコルは、グラフト再灌流EXPEで使用短期生存のシナリオに適用可能ですriments、例えば、ならびに耐性の研究と長期生存モデルにおいて。 ブタOLTxの一つの大きな障害は、静脈と門脈クロスクランプの比較的低い許容範囲です。肝外性の段階の間に内臓渋滞があっても、臓器再灌流7後に不可逆的なショックの点に主要な腸管虚血や血行動態不安定になる可能性があり、静脈高血圧および毛細管損傷を引き起こします。大静脈を完全に肝実質内に埋め込まれているので、静脈温存ピギーバック手順は実行可能ではありません。静脈再建段階中の大静脈の完全閉塞は、豚の血行動態の安定性を損ないます。いくつかの報告は、ブタOLTx未満25分16,17の合計静脈と門脈閉塞の間に達成することができることを示しているが、血管再建の時間ポルト静脈-頸静バイパス技術は、より安全で実用的な選択肢7- 9,18。目でEの著者の経験は、受動ポルト頚バイパスは肝外性の相の間に安定した豚の血行動態を維持する最適ではありません。肝臓下の静脈と門脈の両方の活性伸長を含むバイパスモデルは、予期せぬ合併症に延長しても、クランプ時間は肝上大静脈と門脈吻合の穏やかな再構築フェーズを可能にします。ポータルバイパスカテーテルが除去されると以前の報告7に反して、脾臓摘出は必須ではありません。脾動脈と静脈の両方が十分に灌流近位半分を残して約途中脾臓の長さに沿って閉じられています。によるバイパス断線に出血や空気塞栓症などの合併症は、バイパスを慎重に配置され、適切に固定されていることを確実にすることによって回避されています。 長期生存OLTx実験では、胆管吻合は、その高い合併症率19に弱点を考えられています。胆管組織は非常に壊れやすいとネブラスカ処理されている場合は、特に注意をEDS。多くの異なる吻合技術が5,19に記載されています。エンドツーエンドの吻合は、技術的に容易で、最小限の合併症19と関連しています。 peribiliary結合組織の大きなセクションを含む非切断針と連続縫合糸が結節縫合よりも優れていることが表示されます。中断された縫合糸の単一の縫い目が結ばれるとき胆管が不要張力下に置かれます。これは、組織の涙と連続した胆汁漏れになることがあります。縫合材料 - 吸収性または非吸収性の - ブタが終了するまでの限られた寿命を与え、通常は重要ではありません。数ヶ月にわたって長期生存モデルでは、吸収性縫合糸 - 人間OLTxのようには - が好ましいです。 特定のケアは、術後のフォローアップで撮影する必要があります。十分な栄養と流体供給、信頼性のある鎮痛プロトコル、および適切な免疫抑制政権は義務です。長期的な実験のために、免疫抑制は特に重要であると思われます。他の哺乳動物に比べて、豚はOLTx 20,21の後に驚くほど低い免疫拒絶率を示しています。円形細胞浸潤は、移植後の第2週の間に最大であり、さらには免疫抑制せずに自然に減少します。拒絶反応はほとんどブタOLTx 22後の死亡原因ではありません。しかし、ここで述べたステロイドIVおよびカルシニューリン阻害剤の経口投与することを含む、免疫抑制プロトコルで、移植片拒絶はOLTx後約4日で開始トランスアミナーゼの軽度の増加によって示され、見かけ上のポータルフィールド円形細胞浸潤を確認しました。カルシニューリン阻害剤は経口23,24又は静脈25,26のいずれかを挙げることができます。両方の方法には欠点があります。でも経口適用助剤と、胃腸管に到達する実際の量は、とらえどころのないままになります。一方、連続的な静脈内注入でアクティブな動物と豚のペンは困難です。したがって、静脈内アプリケーションは、潜在的な毒性効果とともに高い薬物濃度ピークになり、ボーラスとして実行する必要があります。それにもかかわらず、アプリケーションの両方の方法は、長期生存を可能にするように思われます。 臨床設定と同様に、術後ストレス潰瘍の予防が推奨されます。消化性潰瘍の術後の出血が頻繁な問題であり、障害肝機能27に関連し得ます。両方OLTx群で消化管出血のいくつかのケースの後、著者は、パントプラゾールとの定期的な予防を始めて以来、任意の消化管出血を経験しませんでした。 臨床手術室内の条件に匹敵する手術滅菌条件の厳格な保守、およびその結果としての抗生物質の予防は、感染性合併症のリスクを減少させます。 結論として、この記事のProvides研究設定でブタOLTxプログラムを確立するための実用的な情報。十分な献身、練習、およびチームワークは、学習期間を減少させる信頼性のある結果を生成するために、コストおよび研究動物の数を減少させるために重要です。

同所性肝移植（OLTx）は、末期肝疾患や進行肝細胞癌患者のための唯一の治療選択肢です。過去25年の間、待機リストの候補の数は徐々に増加し、現在までのところ利用可能な移植片の数を超えています。ほとんどの移植領域では、肝移植の待機リストに患者〜20の30％が臓器移植を受けることなく死ぬかによる疾患の進行に上場を廃止しています。戦略は、このように、利用可能な移植片の数は、必死に必要とされる、ドナーのプールを増加させました。拡張基準臓器配分、長期の移植片の保存、および免疫寛容の誘導は、依然として主要な臨床課題1-3を表します。したがって、実験的OLTx調査は、臨床OLTxの練習を最適化するために極めて重要です。 ブタOLTxがlを含む多くの方法で人間OLTxに似ている十分に確立された実験モデルでありますアイバーサイズ、解剖学、生理学4-6。したがって、このような外科技術、生理学、免疫学、保存、および虚血 - 再灌流傷害などの研究分野における標準的な実験方法となりました。グラフト調達、レシピエント肝切除、及び、特に、血管再構築の多くの技術が文献5に記載されています。適切な技術の選択は、研究者の好みや技術的能力に応じて変化します。 人間のシナリオとは対照的に、肝外性の段階の間に内臓の混雑は、ブタOLTxにおける重要な問題です。その後の腸管虚血およびうっ血性血管損傷は、このように、実験7-9の成功を豚の生存を危険にさらすと、重度の血行動態不安定性を引き起こす可能性があります。そのため、十分な腸解凍が特に少ない技術的に洗練された実験的な設定では、必須です。 米国る肝外性の相の期間中、アクティブポルト大静脈 - 頚シャントは、腸の混雑を避けるために信頼性の高いオプションです。システムは、初期の再灌流実験ならびに長期生存のシナリオのために使用することができます。以下のプロトコルは、肝切除とエンドツーエンドの血管再構成技術、および術後ケアを含むドナー肝臓調達、受信者動作を含むブタの安定かつ再現性の肝移植モデル、に関するすべての情報が含まれています。

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			<td height="19" style="height:19px;width:276px;">Atropine Sulphate 15mg/30mL</td>
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			<td height="20" style="height:20px;width:276px;">Buprenorphine 0.3mg/mL</td>
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			<td height="19" style="height:19px;width:276px;">Cefazolin 1g</td>
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			<td style="width:257px;">Pharmaceutical Partners of Canada Inc.</td>
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			<td height="20" style="height:20px;width:276px;">Ketamine Hydrochloride&#160; 5000mg/50mL</td>
			<td style="width:257px;">Bimeda-MTC Animal Health Inc.</td>
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			<td height="20" style="height:20px;width:276px;">Lactated Ringer&#8217;s + 5% Dextrose, 0.5L</td>
			<td style="width:257px;">Baxter Corporation</td>
			<td align="right" style="width:201px;">61131</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Lacteted Ringer&#8217;s, 1L</td>
			<td style="width:257px;">Baxter Corporation</td>
			<td align="right" style="width:201px;">61085</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Metronidazole 500mg/100mL</td>
			<td style="width:257px;">Baxter Corporation</td>
			<td align="right" style="width:201px;">870420</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Midazolame 50mg/10mL</td>
			<td style="width:257px;">Pharmaceutical Partners of Canada Inc.</td>
			<td align="right" style="width:201px;">2242905</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Pantoprazole 40mg</td>
			<td style="width:257px;">Sandoz Canada Inc.</td>
			<td align="right" style="width:201px;">2306727</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Potassium Chloride 40mEq/20mL</td>
			<td style="width:257px;">Hospira Healthcare Corporation</td>
			<td align="right" style="width:201px;">37869</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Propofol 1000mg/100mL</td>
			<td style="width:257px;">Pharmascience Inc.</td>
			<td align="right" style="width:201px;">2244379</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Protamine Sulfate 50mg/5mL</td>
			<td style="width:257px;">Pharmaceutical Partners of Canada Inc.</td>
			<td align="right" style="width:201px;">2139537</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Saline 0.9%, 1L</td>
			<td style="width:257px;">Baxter Corporation</td>
			<td align="right" style="width:201px;">60208</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Sodium Bicarbonate 50 mEq/50mL</td>
			<td style="width:257px;">Hospira Healthcare Corporation</td>
			<td align="right" style="width:201px;">261998</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Solu-Medrol 500mg</td>
			<td style="width:257px;">Pfizer Canada Inc.</td>
			<td align="right" style="width:201px;">2367963</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Tranexamic Acid 1000mg/10mL</td>
			<td style="width:257px;">Pfizer Canada Inc.</td>
			<td align="right" style="width:201px;">2064413</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">University of Wisconsin Solution, SPS-1</td>
			<td style="width:257px;">Organ Recovery Systms</td>
			<td style="width:201px;">SPS-1</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Xylocaine Endotracheal 10mg/50mL</td>
			<td style="width:257px;">AstraZeneca</td>
			<td align="right" style="width:201px;">2003767</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Appose ULC 35W skin stapler</td>
			<td style="width:257px;">Covidien Canada</td>
			<td align="right" style="width:201px;">803712</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Maxon, 1</td>
			<td style="width:257px;">Covidien Canada</td>
			<td align="right" style="width:201px;">606173</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Sofsilk, 0</td>
			<td style="width:257px;">Covidien Canada</td>
			<td style="width:201px;">S606</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Sofsilk, 2-0</td>
			<td style="width:257px;">Covidien Canada</td>
			<td style="width:201px;">S405</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Sofsilk, 3-0</td>
			<td style="width:257px;">Covidien Canada</td>
			<td style="width:201px;">S404</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Surgipro II, 4-0</td>
			<td style="width:257px;">Covidien Canada</td>
			<td style="width:201px;">VP581X</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Surgipro II, 5-0</td>
			<td style="width:257px;">Covidien Canada</td>
			<td style="width:201px;">VP725X</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Surgipro II, 6-0</td>
			<td style="width:257px;">Covidien Canada</td>
			<td style="width:201px;">VP733X</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;"></td>
			<td style="width:257px;"></td>
			<td style="width:201px;"></td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Catheter i.v, 18 G</td>
			<td style="width:257px;">BD Canada</td>
			<td align="right" style="width:201px;">381147</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Cook TPN catheter, 9.5Fr</td>
			<td style="width:257px;">Cook Medical Company</td>
			<td style="width:201px;">C-TPNS-9.5-90</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">PSI Kit for sheath catheter, 8.5Fr</td>
			<td style="width:257px;">Arrow International</td>
			<td style="width:201px;">ASK-09803-UHN</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Infusion Pump Line</td>
			<td style="width:257px;">Smith Medical ASD Inc.</td>
			<td style="width:201px;">21-0442-25</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Liver Admin Set (flush line)</td>
			<td style="width:257px;">CardioMed Supplies Inc</td>
			<td align="right" style="width:201px;">17175</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Mallinckrodt, Tracheal Tube, 6.5mm</td>
			<td style="width:257px;">Covidien Canada</td>
			<td align="right" style="width:201px;">86449</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Med-Rx Suction Connecting Tube</td>
			<td style="width:257px;">Benlan Inc.</td>
			<td style="width:201px;">70-8120</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Organ Bag</td>
			<td style="width:257px;">CardioMed Supplies Inc</td>
			<td align="right" style="width:201px;">2990</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Suction Tip</td>
			<td style="width:257px;">Tyco Healthcare Group LP</td>
			<td align="right" style="width:201px;">8888501023</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Valleylab, Cautery Pencil</td>
			<td style="width:257px;">Covidien Canada</td>
			<td style="width:201px;">E2515H</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Valleylab, Patient Return Electrode</td>
			<td style="width:257px;">Covidien Canada</td>
			<td style="width:201px;">E7507</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;"></td>
			<td style="width:257px;"></td>
			<td style="width:201px;"></td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Bypass Connector 3/8&#8221; x 1/4&#8220;</td>
			<td style="width:257px;">Raumedic AG</td>
			<td style="width:201px;">955083-001</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Bypass Connector 3/8&#8221; x 3/8&#8221; Luer Lock</td>
			<td style="width:257px;">Raumedic AG</td>
			<td style="width:201px;">955163-001</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Bypass Connector Y 3/8&#8221; x 3/8&#8221; x 1/4&#8221;</td>
			<td style="width:257px;">Raumedic AG</td>
			<td style="width:201px;">961360-002</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Bypass Tubing 1/4&#8221; x 1/16&#8221;</td>
			<td style="width:257px;">Raumedic AG</td>
			<td style="width:201px;">039505-010</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Bypass Tubing 3/8&#8221; x 3/32&#8221;</td>
			<td style="width:257px;">Raumedic AG</td>
			<td style="width:201px;">039535-005</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Rotaflow Cenrtifugal Pump</td>
			<td style="width:257px;">Maquet-Dynamed</td>
			<td style="width:201px;">HC 2821</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Stainless Steel Hose Clamp Ring, 5mm</td>
			<td style="width:257px;">Oetiker</td>
			<td align="right" style="width:201px;">16700007</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Abdominal Retractor</td>
			<td style="width:257px;">Medite GmbH</td>
			<td style="width:201px;">N/A</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">De Bakey &#8211; Beck, Infrahepatic Cava Clamp</td>
			<td style="width:257px;">Aesculap Inc.</td>
			<td style="width:201px;">FB519R</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Diethrich, Atraumaitc Clamp (Portal Vein)</td>
			<td style="width:257px;">Aesculap Inc.</td>
			<td style="width:201px;">FB525R</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Gregory Bull Dog Clamp, curved</td>
			<td style="width:257px;">Aesculap Inc.</td>
			<td style="width:201px;">FB382R</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Gregory Bull Dog Clamp, straight</td>
			<td style="width:257px;">Aesculap Inc.</td>
			<td style="width:201px;">FB381R</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Potts &#8211; De Martel, Scissors</td>
			<td style="width:257px;">Aesculap Inc.</td>
			<td style="width:201px;">BC648R</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Satinsky, Suprahepatic Cava Clamp</td>
			<td style="width:257px;">Aesculap Inc.</td>
			<td style="width:201px;">FB605R</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:276px;">Symetrical Tubing Clamp</td>
			<td style="width:257px;">Codman Instruments</td>
			<td align="right" style="width:201px;">198010</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Anesthesia Machine, Optimax</td>
			<td style="width:257px;">Moduflex Anesthesia Equipment</td>
			<td style="width:201px;">SN5180</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Bypass Flow meter, HT 110</td>
			<td style="width:257px;">Transonic Systems Inc.</td>
			<td style="width:201px;">HT110B11106</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Flow meter probe, H6XL</td>
			<td style="width:257px;">Transonic Systems Inc.</td>
			<td style="width:201px;">H6Xl689</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Heat Therapy Pump, T/Pump</td>
			<td style="width:257px;">Gaymar Industries Inc</td>
			<td style="width:201px;">TP500-G89D19</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Infusion Pump 3000</td>
			<td style="width:257px;">SIMS Graseby LTD.</td>
			<td style="width:201px;">SN300050447</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Isoflurane Vapor 19.1</td>
			<td style="width:257px;">Draeger Medical Canada Inc.</td>
			<td style="width:201px;">N/A</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Monitor, Datex AS 3</td>
			<td style="width:257px;">Instrumentarium Corp./ Hitachi</td>
			<td style="width:201px;">D-VHC14-23-02</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Rotaflow Centrifugal Drive Unit</td>
			<td style="width:257px;">Marquet-Dynamed</td>
			<td align="right" style="width:201px;">952301</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Rotaflow Console</td>
			<td style="width:257px;">Marquet-Dynamed</td>
			<td align="right" style="width:201px;">706035</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Temperature Therapy Pad</td>
			<td style="width:257px;">Gaymar Industries Inc</td>
			<td style="width:201px;">TP26E</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Valleylab Force Tx</td>
			<td style="width:257px;">Valleylab Inc.</td>
			<td align="right" style="width:201px;">216151480</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Ventilator, AV 800</td>
			<td style="width:257px;">DRE Medical Equipment</td>
			<td style="width:201px;">40800AVV</td>
			<td style="width:240px;"></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:276px;">Warm Touch, Patient Warming System</td>
			<td style="width:257px;">Nellcor/ Covidien Canada</td>
			<td style="width:201px;">5015300A</td>
			<td style="width:240px;"></td>
		</tr>
	</tbody>
</table>

technique of porcine liver procurement and orthotopic transplantation using an active porto-caval shunt

The success of liver transplantation has resulted in a dramatic organ shortage. Each year, a considerable number of patients on the liver transplantation waiting list die without receiving an organ transplant or are delisted due to disease progression. Even after a successful transplantation, rejection and side effects of immunosuppression remain major concerns for graft survival and patient morbidity. 
Experimental animal research has been essential to the success of liver transplantation and still plays a pivotal role in the development of clinical transplantation practice. In particular, the porcine orthotopic liver transplantation model (OLTx) is optimal for clinically oriented research for its close resemblance to human size, anatomy, and physiology. 
Decompression of intestinal congestion during the anhepatic phase of porcine OLTx is important to guarantee reliable animal survival. The use of an active porto-caval-jugular shunt achieves excellent intestinal decompression. The system can be used for short-term as well as long-term survival experiments. The following protocol contains all technical information for a stable and reproducible liver transplantation model in pigs including post-operative animal care.

最初の移植の研究では、心臓鼓動ドナーモデルでは（HBD、n = 5）をDCDモデルと比較した（n = 10）、その場で暖かい虚血の45分に暴露しました。両方のグループでは、移植片は、調達後10時間氷上で保存しました。 HBDグループでは、受信者のブタの100％が移植後5日目のフォローアップの最後まで生存しました。 DCDグループでは、受信者の豚の50％が減少し、術後肝機能の結果として、凝固の問題や代謝代償に起因する5日間生存しました。 すべての血液サンプルは、中心静脈カテーテルから採取しました。遠心分離後、血清試料を入手し、肝細胞傷害（アスパラギン酸アミノトランスフェラーゼ、AST）、胆管の機能（総ビリルビンおよびアルカリホスファターゼ）、および肝機能（INR）を分析しました。 5 -各マーカーの時間経過を図2に示されています。 <p class="jove_content"&gt; ASTレベルは、24時間（DCDグループ内のHBDグループ内の1414±538 U / Lと2296±1313 U / L、P = 0.13）の後にピークに達し、5日後にはほぼ正常値に戻りました。 HBD群（162±54 U / L、P = 0.27）と比較した場合、同様に、アルカリホスファターゼ値が顕著に（224±111 U / L）DCDグループ内の36時間後に増加しました。総ビリルビンが（≤10マイクロモル/ Lを通じて）HBDグループで安定であったが、それは徐々に5日目までDCD群では増加した（23±31マイクロモル/ L、P = 0.43）。 DCDグループ中のビリルビン値の大きな標準偏差は、このグループの独特の不均一性胆管損傷を示しています。肝機能のマーカーとしてのINRは、AST値と同様の傾向を示しました。値は、24時間でピークに達し、5日後にはほぼ正常値に回復しました。 HBDグループはDCD群と比較して1.47±0.34でピークと低い値を示した（ピーク1.70±0.36、P = 0.32）。 ポルト大静脈-頸静シャントの図1のスキーム。バイパスが乳酸リンゲル液で満たされています。次に、大静脈部分はチューブクランプでクランプされ、頸静脈および脾臓部分があらかじめ設定されたカテーテルに接続され、バイパスが開かれ、遠心ポンプは、門脈クランプ後に開始されます。肝切除後、バイパスの大静脈部分が挿入され、腎静脈へ、肝臓下大静脈断端に頭蓋確保します。チューブクランプは、ポータル伸張に加えて、大静脈伸長を可能にするために解放されます。 <img alt="図2" src="/files/ftp_upload/52055/52055fig2.jpg" /> 図2.アスパラギン酸アミノトランスフェラーゼ（AST）（HBDはn = 5、DCDのn = 10）。ASTは、肝細胞損傷の敏感なマーカーです。ピーク後方ER 24時間より少ない肝再灌流傷害を示唆し、DCD群よりもHBDが低いです。小さい標準偏差はHBD群でより均質な結果を示しています。 <img alt="図3" src="/files/ftp_upload/52055/52055fig3.jpg" /> 図3.総ビリルビン（HBDはn = 5、DCDのn = 10）。総ビリルビンは、胆汁クリアランスと胆管の完全性のマーカーとして、HBDグループでは10マイクロモル/ L以下の値で安定して均質な傾向を示しています。 DCDグループ中のビリルビン曲線は実験群の一部のみで胆管損傷を示唆し、時間をかけて徐々に増加し、高い標準偏差を示しています。 <img alt="図4" src="/files/ftp_upload/52055/52055fig4.jpg" /> 図4アルカリホスファターゼ（HBD N = 5、DCD N = 10）。アルカリホスファターゼI胆管損傷の指標です。 HBD基の値は小さい胆管の損傷を意味するDCD群のそれよりも低いです。 <img alt="図5" src="/files/ftp_upload/52055/52055fig5.jpg" /> 図5 INR（HBD N = 5、DCD N = 10）。高INR値は、凝固因子の放出の減少に起因する肝機能の低下を示しています。 HBDとDCD両方のグループでは、INR値は、肝機能の回復を示唆し、5日目移植後正常値に戻ります。 HBDグループの値が低く表示されます。

Watch this Scientific Journal Video about Technique of Porcine Liver Procurement and Orthotopic Transplantation using an Active Porto-Caval Shunt at JoVE.com

Technique of Porcine Liver Procurement and Orthotopic Transplantation using an Active Porto-Caval Shunt

Experimental animal research plays a pivotal role in the development of clinical transplantation practice. The porcine orthotopic liver transplantation model (OLTx) closely resembles human conditions and is frequently used in clinically oriented research. The following protocol contains all information for a reliable porcine OLTx model using an active porto-caval-jugular shunt.

アクティブポルト大静脈シャントを使用して、ブタ肝臓調達と同所移植の技術

The success of liver transplantation has resulted in a dramatic organ shortage. Each year, a considerable number of patients on the liver transplantation ...

technique-porcine-liver-procurement-orthotopic-transplantation-using

Research

JoVE Journal

Medicine

16.3K ビュー.  Toronto General Hospital. Experimental animal research plays a pivotal role in the development of clinical transplantation practice. The porcine orthotopic liver transplantation model (OLTx) closely resembles human conditions and is frequently used in clinically oriented research. The following protocol contains all information for a reliable porcine OLTx model using an active porto-caval-jugular shunt.

ビデオ: Technique of Porcine Liver Procurement and Orthotopic Transplantation using an Active Porto-Caval Shunt

Orthotopic Liver Transplantation in Rats

Clinical progress in the field of liver transplantation has been largely supported by animal models1,2. Since the publication of the first orthotopic rat liver transplantation in 1979 by Kamada et al.3, this model has remained the gold standard despite various proposed alternative techniques4. Nevertheless, its broader use is limited by its steep learning curve5.
In this video paper, we show a simple and easy-to-establish revision of Kamada's two-cuff technique. The suprahepatic vena cava anastomosis is performed manually with a running suture, and the vena porta and infrahepatic vena cava anastomoses are performed utilizing a quick-linker cuff system6. Manufacturing the quick-linker kit is shown in a separate video paper.

We present an easy-to-establish revision of the classical two-cuff technique for orthotopic liver transplantation in rat.

ラット同所性肝移植

Clinical progress in the field of liver transplantation has been largely supported by animal models1,2. Since the publication of the first orthotopic rat ...

医学

Surgical Procedures for a Rat Model of Partial Orthotopic Liver Transplantation with Hepatic Arterial Reconstruction

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as studies on graft preservation and ischemia-reperfusion injury 1,2, immunological responses 3,4, hemodynamics 5,6, and small-for-size syndrome 7. The rat OLT is among the most difficult animal models in experimental surgery and demands advanced microsurgical skills that take a long time to learn. Consequently, the use of this model has been limited. Since the reliability and reproducibility of results are key components of the experiments in which such complex animal models are used, it is essential for surgeons who are involved in rat OLT to be trained in well-standardized and sophisticated procedures for this model.
While various techniques and modifications of OLT in rats have been reported 8 since the first model was described by Lee et al. 9 in 1973, the elimination of the hepatic arterial reconstruction 10 and the introduction of the cuff anastomosis technique by Kamada et al. 11 were a major advancement in this model, because they simplified the reconstruction procedures to a great degree. In the model by Kamada et al., the hepatic rearterialization was also eliminated. Since rats could survive without hepatic arterial flow after liver transplantation, there was considerable controversy over the value of hepatic arterialization. However, the physiological superiority of the arterialized model has been increasingly acknowledged, especially in terms of preserving the bile duct system 8,12 and the liver integrity 8,13,14.
In this article, we present detailed surgical procedures for a rat model of OLT with hepatic arterial reconstruction using a 50% partial graft after ex vivo liver resection. The reconstruction procedures for each vessel and the bile duct are performed by the following methods: a 7-0 polypropylene continuous suture for the supra- and infrahepatic vena cava; a cuff technique for the portal vein; and a stent technique for the hepatic artery and the bile duct.

Orthotopic liver transplantation in rats is an indispensable experimental model for biomedical research. Here we present our surgical procedures for orthotopic rat liver transplantation with hepatic arterial reconstruction using a 50% partial graft.

肝動脈再建を用いた部分同所性肝移植のラットモデルのための外科的処置

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as ...

Using the Sleeve Technique in a Mouse Model of Aortic Transplantation - An Instructional Video

Orthotopic aortic transplantation using the sleeve technique reduces injury to the aorta with failure rate of only 10-20%. The time to anastomose the aorta in mice using the sleeve method was short and easy averaging 20 min, permitting studies of iso/allo grafts. The following article describes the aortic transplantation procedure used in our laboratory. The mice were anesthetized with a mixture of 1.5% volume isoflurane and 100% oxygen through a face mask. At this point, the segment of the aorta between the renal arteries and its bifurcation was separated from the vena cava, freely prepared and clampedat the proximal and distal segments with a single silk suture. Prior to the removal of the aorta, a saline solution containing heparin was injected into the inferior vena cava. Then the aorta was cut between the clamps and a saline heparin solution was used to flush the lumen. The sleeve technique with monofilament sutures was used in order to transplant the abdominal aorta in the orthotopic position.

We present an orthotopic aortic transplantation model using the sleeve technique in mice. It is a very rapid anastomosis method, which can be employed in studies of vascular disease.

大動脈弁移植 - 教則ビデオのマウスモデルでスリーブを用いた

Orthotopic aortic transplantation using the sleeve technique reduces injury to the aorta with failure rate of only 10-20%. The time to anastomose the ...

A Rat Model of Orthotopic Liver Transplantation Using a Novel Magnetic Anastomosis Technique for Suprahepatic Vena Cava Reconstruction

The rat model of orthotopic liver transplantation (OLT) is essential for transplant research. It is a very sophisticated animal model and requires a steep learning curve. The introduction of the cuff technique for anastomosis of the portal vein (PV) and infrahepatic vena cava (IHVC) has significantly simplified the transplant procedure in rats. However, due to the short anterior wall of the recipients' suprahepatic vena cava (SHVC), the cuff technique is very difficult to use for the reconstruction of the SHVC. Most researchers in this field still use the hand-suture technique for SHVC reconstruction, which makes it the bottleneck step in rat orthotopic liver transplantation. The magnetic anastomosis technique (i.e., magnamosis) is a method of connecting two vessels using the attractive force between two magnets. Our recent study has shown that the magnetic anastomosis technique is superior to the hand-suture technique for SHVC reconstruction in rats. In this article, we show a step-by-step protocol for SHVC reconstruction in rats using the novel magnetic anastomosis technique. In this model, the reconstruction of the PV and IHVC was performed by the standard cuff technique, while the reconstruction of the bile duct (BD) was performed by a stent technique. The hepatic re-arterialization was not performed. The magnetic anastomosis technique made SHVC reconstruction much easier and significantly shortened the anphepatic phase. After a reasonable learning curve, even researchers without advanced microsurgical skills can produce reliable and reproducible results using this rat model of OLT.

The reconstruction of the suprahepatic vena cava (SHVC) remains a difficult step in rat orthotopic liver transplantation. In this article, we show a step-by-step protocol for SHVC reconstruction in rats using a novel magnetic anastomosis technique.

同所性同種のモデルラット Suprahepatic 上大静脈再建のため新規磁気吻合法を用いた肝移植

The rat model of orthotopic liver transplantation (OLT) is essential for transplant research. It is a very sophisticated animal model and requires a steep ...

A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart failure. Multiple small-animal models of heart transplantation have been used to study the acute and long-term effects of novel therapies. However, few are tested and demonstrated success in clinical trials. It is of critical importance to evaluate new therapies in a clinically relevant large-animal model for efficient and reliable translation of basic studies&#39;&#160;findings. Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and previously used to investigate novel cardioprotective strategies. This procedure focuses on acute ischemia-reperfusion injury and is a reliable method to investigate novel interventions which have been tested and validated in smaller experimental models, such as the murine model. We demonstrate its usefulness in assessing cardiac performance during the early post-transplantation period and other potential possibilities enabled by the model.

Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and utilized to investigate novel cardioprotective strategies.

オルソトピック心臓移植の前臨床ブタモデル

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart ...

Reduced Complications after Arterial Reconnection in a Rat Model of Orthotopic Liver Transplantation

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation of human liver transplantation due to the absence of arterial reconnection. Described here is a modified transplantation procedure that includes the incorporation of hepatic artery (HA) reconnection, leading to a marked improvement in transplant outcomes. With a mean anhepatic time of 12 min and 14 s, HA reconnection results in improved perfusion of the transplanted liver and an increase in long-term recipient survival from 37.5% to 88.2%. This protocol includes the use of 3D-printed cuffs and holders to connect the portal vein and infrahepatic inferior vena cava. It can be implemented for studying multiple aspects of liver transplantation, from immune response and infection to technical aspects of the procedure. By incorporating a simple and practical method for arterial reconnection using a microvascular technique, this modified rat OLT protocol closely mimics aspects of human liver transplantation and will serve as a valuable and clinically relevant research model.

The goal of this study is to modify the rat orthotopic liver transplant model to better represent human liver transplantation and improve recipient survival. The presented method reestablishes hepatic arterial inflow by connecting the donor liver&#39;s common hepatic artery to the recipient liver&#39;s proper hepatic artery.

ラット型異形肝移植モデルにおける動脈リコネクション後の合併症の減少

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation ...

Orthotopic Kidney Auto-Transplantation in a Porcine Model Using 24 Hours Organ Preservation And Continuous Telemetry

In the present era of organ transplantation with critical organ shortage, various strategies are employed to expand the pool of available allografts for kidney transplantation (KT). Even though, the use of allografts from extended criteria donors (ECD) could partially ease the shortage of organ donors, ECD organs carry a potentially higher risk for inferior outcomes and postoperative complications. Dynamic organ preservation techniques, modulation of ischemia-reperfusion and preservation injury, and allograft therapies are in the spotlight of scientific interest in an effort to improve allograft utilization and patient outcomes in KT.
Preclinical animal experiments are playing an essential role in translational research, especially in the medical device and drug development. The major advantage of the porcine orthotopic auto-transplantation model over ex vivo or small animal studies lies within the surgical-anatomical and physiological similarities to the clinical setting. This allows the investigation of new therapeutic methods and techniques and ensures a facilitated clinical translation of the findings. This protocol provides a comprehensive and problem-oriented description of the porcine orthotopic kidney auto-transplantation model, using a preservation time of 24 hours and telemetry monitoring. The combination of sophisticated surgical techniques with highly standardized and state-of-the-art methods of anesthesia, animal housing, perioperative follow up, and monitoring ensure the reproducibility and success of this model.

Large animal models play an essential role in preclinical transplantation research. Due to its similarities to the clinical setup, the porcine model of orthotopic kidney auto-transplantation described in this article provides an excellent in vivo setting for the testing of organ preservation techniques and therapeutic interventions.

24時間臓器保存と連続テレメトリを用いた豚モデルにおける異形性腎臓自動移植

In the present era of organ transplantation with critical organ shortage, various strategies are employed to expand the pool of available allografts for ...

Left Lung Orthotopic Transplantation in a Juvenile Porcine Model for ESLP

Lung transplantation is the gold-standard treatment for end-stage lung disease, with over 4,600 lung transplantations performed worldwide annually. However, lung transplantation is limited by a shortage of available donor organs. As such, there is high waitlist mortality. Ex situ lung perfusion (ESLP) has increased donor lung utilization rates in some centers by 15%-20%. ESLP has been applied as a method to assess and recondition marginal donor lungs and has demonstrated acceptable short- and long-term outcomes following transplantation of extended criteria donor (ECD) lungs. Large animal (in vivo) transplantation models are required to validate ongoing in vitro research findings. Anatomic and physiologic differences between humans and pigs pose significant technical and anesthetic challenges. An easily reproducible transplant model would permit the&#160;in vivo&#160;validation of current ESLP strategies and the preclinical evaluation of various interventions designed to improve donor lung function. This protocol describes a porcine model of orthotopic left lung allotransplantation. This includes anesthetic and surgical techniques, a customized surgical checklist, troubleshooting, modifications, and the benefits and limitations of the approach.

This protocol describes a juvenile porcine model of orthotopic left lung allotransplantation designed for use with ESLP research. Focus is made on anesthetic and surgical techniques, as well as critical steps and troubleshooting.

ESLPのブタ幼体モデルにおける左肺同所性移植

Lung transplantation is the gold-standard treatment for end-stage lung disease, with over 4,600 lung transplantations performed worldwide annually. ...

Porcine Liver Transplantation Without Veno-Venous Bypass As an Extended Criteria Donor Model

Liver transplantation is regarded as the gold standard for the treatment of a variety of fatal hepatic diseases. However, unsolved issues of chronic graft failure, ongoing organ donor shortages, and the increased use of marginal grafts call for the improvement of current concepts, such as the implementation of organ machine perfusion. In order to evaluate new methods of graft reconditioning and modulation, translational models are required. With respect to anatomical and physiological similarities to humans and recent progress in the field of xenotransplantation, pigs have become the main large animal species used in transplantation models. After the initial introduction of a porcine orthotopic liver transplant model by Garnier et al. in 1965, several modifications have been published over the past 60 years.
Due to specifies-specific anatomical traits, a veno-venous bypass during the anhepatic phase is regarded as a necessity to reduce intestinal congestion and ischemia resulting in hemodynamic instability and perioperative mortality. However, the implementation of a bypass increases the technical and logistical complexity of the procedure. Furthermore, associated complications such as air embolism, hemorrhage, and the need for a simultaneous splenectomy have been reported previously.
In this protocol, we describe a model of porcine orthotopic liver transplantation without the use of a veno-venous bypass. The engraftment of donor livers after static cold storage of 20 h - simulating extended criteria donor conditions - demonstrates that this simplified approach can be performed without significant hemodynamic alterations or intraoperative mortality and with regular uptake of liver function (as defined by bile production and liver-specific CYP1A2 metabolism). The success of this approach is ensured by an optimized surgical technique and a sophisticated anesthesiologic volume and vasopressor management.
This model should be of special interest for workgroups focusing on the immediate postoperative course, ischemia-reperfusion injury, associated immunological mechanisms, and the reconditioning of extended criteria donor organs.

In this protocol, a model of porcine orthotopic liver transplantation after static cold storage of donor organs for 20 h without the use of a veno-venous bypass during engraftment is described. The approach uses a simplified surgical technique with minimization of the anhepatic phase and sophisticated volume and vasopressor management.

拡張基準ドナーモデルとしての静脈バイパスなしのブタ肝移植

Liver transplantation is regarded as the gold standard for the treatment of a variety of fatal hepatic diseases. However, unsolved issues of chronic graft ...

肝臓のこわばり分布の定量解析

A Three-Dimensional Digital Model for Early Diagnosis of Hepatic Fibrosis Based on Magnetic Resonance Elastography

Hepatic fibrosis is an early stage of liver cirrhosis, and there are no better non-invasive and convenient methods for the detection and evaluation of the disease. Despite the good progress made with the liver stiffness map (LSM) based on magnetic resonance elastography (MRE), there are still some limitations that need to be overcome, including manual focus determination, manual selection of regions of interest (ROIs), and discontinuous LSM data without structural information, which makes it impossible to evaluate the liver as a whole. In this study, we propose a novel three-dimensional (3D) digital model for the early diagnosis of hepatic fibrosis based on MRE.
MRE is a non-invasive imaging technique that employs magnetic resonance imaging (MRI) to measure the liver stiffness at the scanning site through human-computer interaction. Studies have indicated a significant positive correlation between the LSM obtained through MRE and the degree of hepatic fibrosis. However, for clinical purposes, a comprehensive and precise quantification of the degree of hepatic fibrosis is necessary. To address this, the concept of Liver Stiffness Distribution (LSD) was proposed in this study, which refers to the 3D stiffness volume of each liver voxel obtained by the alignment of 3D liver tissue images and MRE indicators. This provides a more effective clinical tool for the diagnosis and treatment of hepatic fibrosis.

著者スポットライト: Advancing Hepatic Fibrosis Diagnosis Using Magnetic Resonance Elastography and AI 

The objective of this study was to develop a novel three-dimensional digital model for the early diagnosis of hepatic fibrosis, which includes the stiffness of each voxel in the patient's liver and can thus, be used to calculate the distribution ratio of the patient's liver at different fibrosis stages.

磁気共鳴エラストグラフィに基づく肝線維症の早期診断のための3次元ディジタルモデル

Hepatic fibrosis is an early stage of liver cirrhosis, and there are no better non-invasive and convenient methods for the detection and evaluation of the ...