作者は彼らの技術支援のためにパスカルPaschendaとMareikeシュルツに感謝します。

<ol>
	<li>Puhl, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low+viscosity+histidine-tryptophan-ketoglutarate+graft+flush+improves+subsequent+extended+cold+storage+in+University+of+Wisconsin+solution+in+an+extracorporeal+rat+liver+perfusion+and+rat+liver+transplantation+model.">Low viscosity histidine-tryptophan-ketoglutarate graft flush improves subsequent extended cold storage in University of Wisconsin solution in an extracorporeal rat liver perfusion and rat liver transplantation model.</a> Liver Transpl. 12, 1841-1849 (2006).</li><li>Yagi, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+Preservation+and+Microcirculation+with+POLYSOL+After+Partial+Liver+Transplantation+in+Rats.">Improved Preservation and Microcirculation with POLYSOL After Partial Liver Transplantation in Rats.</a> J Surg Res. 167, e375-e383 (2011).</li><li>Engemann, R., Ulrichs, K., Thiede, A., Muller-Ruchholtz, W., Hamelmann, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Value+of+a+physiological+liver+transplant+model+in+rats.+Induction+of+specific+graft+tolerance+in+a+fully+allogeneic+strain+combination.">Value of a physiological liver transplant model in rats. Induction of specific graft tolerance in a fully allogeneic strain combination.</a> Transplantation. 33, 566-568 (1982).</li><li>Sumimoto, R., Shinomiya, T., Yamaguchi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+hepatic+arterial+blood+flow+in+rats+with+liver+transplants.+Examination+of+donor+liver-derived+serum+class+I+MHC+antigen+in+rats+with+liver+transplants+with+or+without+hepatic+arterial+reconstruction.">Influence of hepatic arterial blood flow in rats with liver transplants. Examination of donor liver-derived serum class I MHC antigen in rats with liver transplants with or without hepatic arterial reconstruction.</a> Transplantation. 51, 1138-1139 (1991).</li><li>Chaland, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Orthotopic+liver+transplantation+with+hepatic+artery+anastomoses.+Hemodynamics+and+response+to+hemorrhage+in+conscious+rats.">Orthotopic liver transplantation with hepatic artery anastomoses. Hemodynamics and response to hemorrhage in conscious rats.</a> Transplantation. 49, 675-678 (1990).</li><li>Imamura, H., Rocheleau, B., Cote, J., Huet, P. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+consequence+of+rat+orthotopic+liver+transplantation+with+and+without+hepatic+arterial+reconstruction:+a+clinical,+pathological,+and+hemodynamic+study.">Long-term consequence of rat orthotopic liver transplantation with and without hepatic arterial reconstruction: a clinical, pathological, and hemodynamic study.</a> Hepatology. 26, 198-205 (1997).</li><li>Zhong, Z., Theruvath, T. P., Currin, R. T., Waldmeier, P. C., Lemasters, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=NIM811,+a+mitochondrial+permeability+transition+inhibitor,+prevents+mitochondrial+depolarization+in+small-for-size+rat+liver+grafts.">NIM811, a mitochondrial permeability transition inhibitor, prevents mitochondrial depolarization in small-for-size rat liver grafts.</a> Am. J. Transplant. 7, 1103-1111 (2007).</li><li>Spiegel, H. U., Palmes, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+techniques+of+orthotopic+rat+liver+transplantation.">Surgical techniques of orthotopic rat liver transplantation.</a> J. Invest. Surg. 11, 83-96 (1998).</li><li>Lee, S., Charters, A. C., Chandler, J. G., Orloff, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+technique+for+orthotopic+liver+transplantation+in+the+rat.">A technique for orthotopic liver transplantation in the rat.</a> Transplantation. 16, 664-669 (1973).</li><li>Lee, S., Charters, A. C., Orloff, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simplified+technic+for+orthotopic+liver+transplantation+in+the+rat.">Simplified technic for orthotopic liver transplantation in the rat.</a> Am. J. Surg. 130, 38-40 (1975).</li><li>Kamada, N., Calne, R. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Orthotopic+liver+transplantation+in+the+rat.+Technique+using+cuff+for+portal+vein+anastomosis+and+biliary+drainage.">Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage.</a> Transplantation. 28, 47-50 (1979).</li><li>Howden, B., Jablonski, P., Grossman, H., Marshall, V. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+importance+of+the+hepatic+artery+in+rat+liver+transplantation.">The importance of the hepatic artery in rat liver transplantation.</a> Transplantation. 47, 428-431 (1989).</li><li>Gao, W., Lemasters, J. J., Thurman, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+new+method+for+hepatic+rearterialization+in+rat+orthotopic+liver+transplantation.+Reduction+of+liver+injury+and+improvement+of+surgical+outcome+by+arterialization.">Development of a new method for hepatic rearterialization in rat orthotopic liver transplantation. Reduction of liver injury and improvement of surgical outcome by arterialization.</a> Transplantation. 56, 19-24 (1993).</li><li>Zhao, D., Zimmermann, A., Wheatley, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Morphometry+of+the+liver+after+liver+transplantation+in+the+rat:+significance+of+an+intact+arterial+supply.">Morphometry of the liver after liver transplantation in the rat: significance of an intact arterial supply.</a> Hepatology. 17, 310-317 (1993).</li><li>Omura, T., Ascher, N. L., Emond, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fifty-percent+partial+liver+transplantation+in+the+rat.">Fifty-percent partial liver transplantation in the rat.</a> Transplantation. 62, 292-293 (1996).</li><li>Lehmann, T. G., Bunzendahl, H., Langrehr, J. M., Neuhaus, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arterial+reconstruction+in+rat+liver+transplantation--development+of+a+new+tubing+technique+of+the+common+hepatic+artery.">Arterial reconstruction in rat liver transplantation--development of a new tubing technique of the common hepatic artery.</a> Transpl. Int. 18, 56-64 (2005).</li><li>Reck, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+arterialization+on+hepatic+oxygen+supply,+tissue+energy+phosphates,+and+outcome+after+liver+transplantation+in+the+rat.">Impact of arterialization on hepatic oxygen supply, tissue energy phosphates, and outcome after liver transplantation in the rat.</a> Transplantation. 62, 582-587 (1996).</li><li>Hasuike, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+simple+method+for+orthotopic+liver+transplantation+with+arterial+reconstruction+in+rats.">A simple method for orthotopic liver transplantation with arterial reconstruction in rats.</a> Transplantation. 45, 830-832 (1988).</li><li>Steffen, R., Ferguson, D. M., Krom, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+method+for+orthotopic+rat+liver+transplantation+with+arterial+cuff+anastomosis+to+the+recipient+common+hepatic+artery.">A new method for orthotopic rat liver transplantation with arterial cuff anastomosis to the recipient common hepatic artery.</a> Transplantation. 48, 166-168 (1989).</li><li>Knoop, M., Bachmann, S., Keck, H., Steffen, R., Neuhaus, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experience+with+cuff+rearterialization+in+600+orthotopic+liver+grafts+in+the+rat.">Experience with cuff rearterialization in 600 orthotopic liver grafts in the rat.</a> Am. J. Surg. 167, 360-363 (1994).</li><li>Hickman, R., Engelbrecht, G. H., Duminy, F. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+technique+for+liver+transplantation+in+the+rat.">A technique for liver transplantation in the rat.</a> Transplantation. 48, 1080 (1989).</li><li>Liu, T., Freise, C. E., Ferrell, L., Ascher, N. L., Roberts, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+modified+vascular+"sleeve"+anastomosis+for+rearterialization+in+orthotopic+liver+transplantation+in+rats.">A modified vascular "sleeve" anastomosis for rearterialization in orthotopic liver transplantation in rats.</a> Transplantation. 54, 179-180 (1992).</li><li>Li, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modified+sleeve+anastomosis+for+reconstruction+of+the+hepatic+artery+in+rat+liver+transplantation.">Modified sleeve anastomosis for reconstruction of the hepatic artery in rat liver transplantation.</a> Microsurgery. 22, 62-68 (2002).</li><li>Martins, P. N., Theruvath, T. P., Neuhaus, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rodent+models+of+partial+hepatectomies.">Rodent models of partial hepatectomies.</a> Liver Int. 28, 3-11 (2008).</li><li>Russell, W. M. S., Burch, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The Principles of Humane Experimental Technique. , (1992).</li></ol>

我々は、開示することは、競合する利害関係はありません。ラットは実験動物学協会（FELASA）の連盟のガイドラインによると、特定の病原体フリーの条件下で飼育されています。すべての実験は、動物の保護及び &quot;実験動物の管理と使用に関する指針&quot;（厚生公開番号86から23の国立研究所、1985年改訂）に関するドイツの連邦法に準拠して実施された。

ラットOLTの最初のモデルはLee らによって報告されました。1973年9において、肝動脈を含む、すべての船舶は手縫いの方法により再構築され、体外脈大循環シャントが使用されたインチこのモデルは、技術的に複雑であり、実行することが困難でした。次のモデルは、1975年に10同じ著者らによって開発された肝動脈再建と体外シャントなしの1だった。その後1979年に、鎌田らは肝rearterialization 11無しのモデルカフ吻合技術を導入しました。これらの変更により、ラットにおけるOLTは、受信者の操作で短縮肝外性の時間に簡略化され、広く受け入れられた実験モデルとして使用されてきた。 動脈化は厳しい作業だったが、しかし、ラットの肝動脈化OLT 8の意義の上、それ以来かなりの論争があったディ移植後の生存率に影響を及ぼさないと思います。様々な再構成技術を用いた肝動脈化に関する多くの研究は、このような大動脈セグメントツー大動脈吻合3,9,17、カフ吻合技術18,19,20、伸縮テクニック5、ステント技術13として、8が報告されている16、スリーブ吻合技術12,21-23。ラットOLT用技術は今日でも標準化されていないものの、arterializedモデルはますますその生理的優位8,12,13,14の点で好まれています。上記の技術の中で、実行するために簡単かつ迅速であったステント技術はレーマンらによって報告された2005年の16。研究では、優れた結果を示した：全く閉塞率は、再灌流後8時間、24時間、6ヶ月目に再構築された肝動脈では観察されなかった。そこで我々は、肝動脈化のためにこの技術を採用した。 我性能SHVCとIHVCの復興のためのミリアンペア手縫い吻合。この方法では、血栓症発生率の減少8に導く最適な生理条件と吻合部位を提供し、最高の顕微手術シミュレーションおよび外科医のためのトレーニングです。また、吻合は短い容器の切り株があっても可能であることができます。 IHVCの吻合に関しては、この方法は、カフ吻合技術と比較して移植側の長いIHVCを必要としません。したがって、ドナー腎静脈が長い移植IHVCを作るために解剖されている場合、このメソッドは、このような短い肝と右横と尾ローブで構成され、30％のグラフトとして、長いIHVCを必要とする小さな移植片の移植にも適用可能であるSHVC 2なし下大静脈。 いくつかの方法をこれまでに、ラットでは肝切除の手法について報告されている、2つの主要な技術は、古典的なマス結紮技術であると血管指向技術24。我々は50％の肝切除15の古典的な結紮法を実行しますが、手術用顕微鏡下に手順を細かくし、残りのローブと構造への損傷を避けるために。 我々は、我々のモデルでレシピエントラットからの代表的な結果を説明し、ラットは明らかな合併症はなく、7日間の観察期間中に生き残った。モデルは、長期冷蔵、心臓死の後に寄付を含む長時間の温虚血、および肝障害又は疾患の実験モデルから小さい肝臓移植片または移植片の使用など、さまざまな設定を選択することにより、実験の異なる目的のために修正することができます。 ;動作時間は、e失血量：我々の経験では、移植、ラットのOLTの転帰改善のための最も信頼性の高いパラメータの後に生存に影響を及ぼす可能性のあるプロシージャ全体で3つの主要な要因がありますおよび狭窄、血栓症、または出血につながる各容器の再建の妥当性、特に門脈とIHVCの時間をクランプする。このモデルの研修期間では、障害のほとんどは、おそらくこれらの要因に関連している可能性があります。このビデオの記事では、我々は肝動脈再建を持つ部分OLTの私たちのラットモデルのための外科的処置のためのステップバイステップの手順を紹介します。 OLTのラットモデルが複​​雑かつ高度な顕微スキルを必要とされていますが、この記事では、このモデルの訓練と学習のための良いガイドとなるべき実用的なたくさんの情報を提供しています。効率的に、このモデルを学習することで、学習期間を短縮する練習のために必要な動物やコストの数を減らすこと、およびそれ以降の実験で信頼性の高い結果を再現するために特に重要である。これはでRussellとBurchによって仮定された動物実験の3Rのコンセプト（交換·還元·改良）、に沿ったものである1959年25。

<table border="1"><tbody><tr><td> 名前 </td><td> 会社 </td><td> カタログ番号 </td><td> 注釈 </td></tr><tr><td>外科用顕微鏡</td><td>ライカ</td><td> M651 </td><td></td></tr><tr><td>光源</td><td>ショット</td><td> KL1500LCD </td><td></td></tr><tr><td>綿棒</td><td> NOBA Verbandmittel </td><td> 974202 </td><td></td></tr><tr><td>ガーゼ綿棒（5x5のCM） </td><td>フールマン</td><td> 10002 </td><td></td></tr><tr><td>ポビドンヨード液</td><td>ムンディファーマ</td><td> 6108022.00.01 </td><td></td></tr><tr><td>油性粘土</td><td> Debika法人</td><td> 090148 </td><td></td></tr><tr><td> TachoSil </td><td>武田ファーマシューティカルズ·インターナショナル社</td><td> EU/1/04/277/001-004</td><td>切除された肝臓の表面に適用</td></tr><tr><td>メスの刃11号</td><td> PFM医療</td><td> 200130011 </td><td>カフとステントの作製</td></tr><tr><td> 14ゲージのカテーテル</td><td> B.ブラウン</td><td> 4268210S </td><td> PV用カフ</td></tr><tr><td> 18ゲージのカテーテル</td><td> B.ブラウン</td><td> 4268130S </td><td> PV経由灌流</td></tr><tr><td> 24ゲージのカテーテル</td><td> B.ブラウン</td><td> 4269071S </td><td> BDとHA用ステント</td></tr><tr><td> 4から0絹縫合</td><td> Resorba </td><td> H3F </td><td>肝臓切除術</td></tr><tr><td> 6から0絹縫合</td><td> Resorba </td><td> H1F </td><td></td></tr><tr><td> 7から0 PROLENE（ポリプロピレン）縫合</td><td>エチコン</td><td> 8701H </td><td> SHVCとIHVC </td></tr><tr><td> 4から0 VICRYL縫合</td><td>エチコン</td><td> V304H </td><td>腹部閉鎖</td></tr><tr><td> 5 mlシリンジ</td><td>テルモ</td><td> SS + T05ES1 </td><td>バック枕</td></tr><tr><td>加温パッド</td><td>サーモ</td><td> 190×260ミリメートル</td><td></td></tr><tr><td>磁気固定器退避システム</td><td>ファイン科学ツール株式会社</td><td> 18200から01 18200から02 18200から03 18200から12 </td><td></td></tr><tr><td>冷水浴</td><td>フーバー</td><td> 740.000X </td><td>移植保全</td></tr><tr><td>バイポーラ鉗子</td><td> Söring </td><td> MBC-200 </td><td></td></tr><tr><td>モスキート鉗子</td><td> BONIMED </td><td> 451-476-03 </td><td>使用される2つのペア</td></tr><tr><td>アドソンマイクロ鉗子</td><td> Dimeda </td><td> 10.176.12 </td><td></td></tr><tr><td>湾曲したマイルCRO鉗子</td><td> AESCULAP </td><td> FD281R </td><td></td></tr><tr><td>ストレートマイクロ鉗子</td><td> Bonimed </td><td> 451-476-03 </td><td></td></tr><tr><td>湾曲したマイクロ剪刀</td><td>メディコン</td><td> 05.15.83 </td><td></td></tr><tr><td>ストレートマイクロ剪刀</td><td> AESCULAP </td><td> FD12 </td><td>ファイン切開</td></tr><tr><td>はさみ</td><td> AESCULAP </td><td> BC211W </td><td></td></tr><tr><td>マイクロニードルホルダー</td><td> AESCULAP </td><td> FD241R </td><td>再建</td></tr><tr><td>市長·ヘーガーニードルホルダー</td><td>みずほIkakogyo </td><td> 06-798-00 </td><td>腹部閉鎖</td></tr><tr><td> DeBakeyブルドッグクランプ（ストレート） </td><td>ウルリッヒ</td><td> CV3054 </td><td></td></tr><tr><td> DeBakeyブルドッグクランプ（曲面） </td><td> CODMAN </td> &lt;TD&gt; 37から1062 </td><td></td></tr><tr><td> Satinskyクランプ</td><td> Mizuhoika </td><td> 09-230-24 </td><td></td></tr><tr><td>末梢血管クランプ</td><td>テレフレックスメディカル</td><td> 353494 </td><td>受信者SHVC </td></tr><tr><td>マイクロ血管クランプ（使い捨て） </td><td> AROSurgicalインスツルメンツ株式会社</td><td> TKM-1〜60グラム</td><td> PV、グラフトIHVC、および受信者のHA </td></tr><tr><td>マイクロ血管クランプ（金属製） </td><td>ファイン科学ツール株式会社</td><td> 18052から01 </td><td>受信者IHVC </td></tr><tr><td>乳酸リンゲル液</td><td>フレゼニウスカービ</td><td> 6150917.00.00 </td><td></td></tr><tr><td>生理食塩水</td><td> DeltaSelect </td><td> 1299.99.99 </td><td></td></tr><tr><td> HTKのソリューション</td><td>博士はフランツ·ケーラーケミー</td><td> 31268.00.00 </td><td>保存溶液</td></tr><tr><td>ヘパリンナトリウム</td><td> Ratiopharm </td><td> 5394.02.00 </td><td>グラフト灌流前500 IU </td></tr><tr><td> 8.4％重炭酸ナトリウム</td><td>フレゼニウスカービ</td><td> 4399.97.99 </td><td>再灌流後の0.5ミリリットル</td></tr><tr><td> 5％グルコース溶液</td><td> B.ブラウン</td><td> 6714567.06.00 </td><td>再灌流後の1.0ミリリットル</td></tr><tr><td> Cefuroximナトリウム</td><td>フレゼニウスカービ</td><td> 38985.01.00 </td><td>抗生物質、16 mg / kgの</td></tr><tr><td>ブプレノルフィン</td><td>エセックスファーマ</td><td> 997.00.00 </td><td>鎮痛剤は、0.1 mg / kgの</td></tr><tr><td>集中治療室のケージ</td><td> Brinseaプロダクツ</td><td> Vetario S10 </td><td>術後処置</td></tr></tbody></table>

surgical procedures for a rat model of partial orthotopic liver transplantation with hepatic arterial reconstruction

全体または部分的な移植を用いたラットにおける同所性肝移植（OLT）は、このような移植保全や虚血再灌流障害の1,2の研究、免疫学的応答3,4、血行動態5,6として、移植の研究に欠かせない実験的なモデルであり、小型のためにサイズの症候群7。ラットOLTは、実験的な手術の中で最も困難な動物モデルの一つであると学ぶのに長い時間がかかる高度な顕微スキルが要求されます。したがって、このモデルの使用が制限されていた。結果の信頼性と再現性は、このような複雑な動物モデルが使用されている実験の主要なコンポーネントであるため、それがこのモデルのためのよく標準化され、洗練された手順の研修を受けたことが、ラットのOLTに関与している外科医のために不可欠です。 最初のモデルはdescrib頃から様々な技術とラットにおけるOLTの修正は8報告されているが彼らは偉大な程度に再建手続きを簡略化しているため、Lee らによって編 1973年9、肝動脈再建10、鎌田らによるカフ吻合技術の導入の排除11 は 、このモデルでは大きな進歩だった。鎌田らによるモデルでは、肝rearterializationも解消されました。ラットは、肝移植後の肝動脈流せずに生き残ることができたので、肝動脈化の価値を超えるかなりの論争があった。しかし、arterializedモデルの生理学的優位性はますます特に胆管システム8,12及び肝臓の整合8,13,14の保全の観点から、認められてきた。 本稿では、ex vivoで肝resec後に50％の部分移植を用い肝動脈再建とOLTのラットモデルの詳細な外科的処置を提示る。各血管、胆管のための再建手続は、次の方法により行われています：7から0ポリプロピレン連続用縫合前掲と肝臓下の下大静脈、門脈用カフ技術、および肝動脈用ステント技術と胆管。

すべてのレシピエントラット（n = 20）は（各時点でn = 5）にポータル再灌流後（7日）1、3、24、および168時間後に採血のための計画的安楽死まで明らかに合併症なく生き残った。血液サンプルは、27ゲージの針で直接穿刺によりIHVCから収集された。 10分間5340 xgで遠心分離後、血清サンプルが得られ、移植後の肝細胞障害の程度を反映アラニンアミノトランスフェラーゼ（ALT）レベルについて分析した。血清ALT値の変化の時間経過を図16に示します。 ALTレベルは24時間でピークに達した（±標準偏差平均：212.6±67.9 IU / L）をしてから168時間（33.6±6.8 IU / L）で正常範囲内に低下した。 <img alt="図1" src="/files/ftp_upload/4376/4376fig1.jpg" /> 図1：1から門脈（PV）用カフ4ゲージのカテーテル、および24ゲージのカテーテルから肝動脈（HA）と胆管（BD）用ステント。 <img alt="図2" fo:content-width="4in" fo:src="/files/ftp_upload/4376/4376fig2highres.jpg" src="/files/ftp_upload/4376/4376fig2.jpg" /> 図2。ドナーラットから肝臓の除去のスキーマ 、BD、胆管; HA、肝動脈、IHVC、肝臓下の下大静脈、PV、門脈、SHVC、肝上の大静脈。 <img alt="図3" src="/files/ftp_upload/4376/4376fig3.jpg" /> 図3。ドナー操作。 aである。ラット固定器は、磁気リトラクションシステムと加熱パッド上に配置されます。腹部は二国間の拡張子を持つ正中切開により開かれる。ステントのb。挿入は、胆管に。門脈を介して肝臓のc。灌流。略語は説明アール図2のED。 <img alt="図4" src="/files/ftp_upload/4376/4376fig4.jpg" /> 図4。門脈にカフのアタッチメント。門脈幹を握っては、b。DeBakeyブルドッグクランプは金属カップの上に配置される。カップを砕いた氷で満たさプラスチックの箱に装着されています。C。門脈、カフ通されますd。門脈の壁が7でカフ外脾静脈の切り株にカフの上に外転さ時の位置と12時の位置にカフの拡張子は。 電子。門脈はカフ上の円周6から0絹糸で固定されています。黒い矢印は、脾静脈の切り株を示す。 <img alt="図5" src="/files/ftp_upload/4376/4376fig5.jpg" /> 図5。 エクスビボ肝動脈内ステントの挿入。 。肝臓は横隔膜の両エッジをクランプして固定されており、肝動脈は、直線動脈用結紮糸を保持することによってプルアップされています。bは。肝動脈に小さな切開の前壁がまっすぐマイクロ鉗子で保持されている。C、D。ステントは肝動脈に挿入し、6から0絹糸で固定されています。 <img alt="図6" fo:content-width="3.5in" fo:src="/files/ftp_upload/4376/4376fig6highres.jpg" src="/files/ftp_upload/4376/4376fig6.jpg" /> 図6。 ex vivoで 50％肝切除のスキーマ。グレー色のローブが削除されます。 ACLは、前方の尾状葉、PCL、後部尾状葉、LLL、左側葉、LML、中葉の左部分;中葉のRML、右の部分と、SRLは、優れた右の側葉、IRL、劣って右側葉。 図7 エクスビボ 50％肝切除。中葉。cの左側部分の茎の。後部尾状葉の茎のライゲーションますb。ライゲーション、50％切除前肝ますd。を50％切除後の肝。 <img alt="図8" src="/files/ftp_upload/4376/4376fig8.jpg" /> 図8。肝上の大静脈の ex vivo形成術。 。肝臓は蚊鉗子で横隔膜の両エッジをクランプして固定されていますb。滞在縫合7から0ポリプロピレンとは、両方の角に取り付けられている。 <img alt="図9" fo:content-width="4in" fo:src="/files/ftp_upload/4376/4376fig9highres.jpg" srC = &quot;/ files/ftp_upload/4376/4376fig9.jpg&quot; /&gt; 図9。レシピエントラットにおける移植片移植のスキーマ。再建手続き7-0連続縫合、カフ法による門脈（PV）が、肝と前掲と肝臓下の下大静脈（SHVCとIHVC）に対して実行されるステント技術による動脈（HA）と胆管（BD）。 <img alt="図10" src="/files/ftp_upload/4376/4376fig10.jpg" /> 図10。ネイティブ肝臓の除去まで、受信者の操作。 。腹部正中切開で開かれますb。右副腎静脈を結紮する。cは。ネイティブ肝臓を摘出されています。略語は図2で説明されています。 <img alt="図11" src="/files/ftp_upload/4376/4376fig11.jpg" /> 図11。 supraheの吻合patic大静脈。は、b。肝上の下大静脈のための末梢血管クランプはオイルベースの粘土の塊で固定されている。両隅に滞在縫合が吻合を広げるsuperiolaterally穏やかなトラクションを維持しています。cは。進行中の後方の行の連続腔内縫合しますd。進行中の前の行の連続縫合。 <img alt="図12" src="/files/ftp_upload/4376/4376fig12.jpg" /> 図12。門脈の再建。カフのは、b。門脈をクランプモスキート止血鉗子は、オイルベースの粘土で固定し、肝門部に向かって引っ張られているcf。挿入門脈に。 <img alt="図13" src="/files/ftp_upload/4376/4376fig13.jpg" /> 図13。肝動脈の再建。は、b。 </stron<html>グラム固有肝動脈（PHA）と胃十二指腸動脈（GDA）の分岐点での受信総肝動脈（CHA）へのステントの&gt;挿入。 <img alt="図14" src="/files/ftp_upload/4376/4376fig14.jpg" /> 図14。肝臓下の下大静脈の吻合。肝臓下の下大静脈の。両隅に滞在縫合ますb。後の行の連続縫合するc。前の行の連続縫合しますd。再潅流。略語は図2で説明されています。 <img alt="図15" src="/files/ftp_upload/4376/4376fig15.jpg" /> 図15すべての再建手続きが終了している。略語は図2で説明されています。 <img alt="&lt;/ HTML">&quot;図16&quot; SRC = &quot;/ files/ftp_upload/4376/4376fig16.jpg&quot; /&gt; 図16血清アラニンアミノトランスフェラーゼ（ALT）レベルの変化の術後経時的（N = 20;各時点でn = 5）であった。。データは標準偏差を示すエラーバー付きの手段として表現さ​​れています。 ALT値は24時間（212.6±67.9 IU / L）でピークに達し、その後168時間（33.6±6.8 IU / L）で正常範囲内に低下した。

Watch this Scientific Journal Video about Surgical Procedures for a Rat Model of Partial Orthotopic Liver Transplantation with Hepatic Arterial Reconstruction at JoVE.com

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

ラットにおける同所性肝移植は、生物医学研究のための不可欠な実験モデルである。ここで我々は50％の部分移植を用い肝動脈再建同所ラット肝移植のための私達の手術を提示します。

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 ...

surgical-procedures-for-rat-model-partial-orthotopic-liver

Research

JoVE Journal

Medicine

36.1K ビュー.  RWTH-Aachen University. ラットにおける同所性肝移植は、生物医学研究のための不可欠な実験モデルである。ここで我々は50％の部分移植を用い肝動脈再建同所ラット肝移植のための私達の手術を提示します。

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

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant vasculopathy (TVP).
The commonly used animal model for cardiovascular chronic rejection studies is the heterotopic heart transplant model performed in laboratory rodents. This model is used widely in experiments since Ono and Lindsey (3) published their technique. To analyze the findings in the blood vessels, the heart has to be sectioned and all vessels have to be measured.
Another method to investigate chronic rejection in cardiovascular questionings is the aortic transplant model (1, 2). In the orthotopic aortic transplant model, the aorta can easily be histologically evaluated (2). The PVG-to-ACI model is especially useful for CAV studies, since acute vascular rejection is not a major confounding factor and Cyclosporin A (CsA) treatment does not prevent the development of CAV, similar to what we find in the clinical setting (4). A7-day period of CsA is required in this model to prevent acute rejection and to achieve long-term survival with the development of TVP.
This model can also be used to investigate acute cellular rejection and media necrosis in xenogeneic models (5).

This video demonstrates the orthotopic aortic transplant model as a simple model to study the development of transplant vasculopathy (TVP) in rats.

同所性大動脈移植：慢性血管障害の発生研究のラットモデル

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

医学

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 ...

Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2).
A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.&#160; The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor&#8217;s portal vein was carried out via the recipient&#8217;s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient&#8217;s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7
In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3&#177;0.8 g to 9.8&#177;1 g. At this time, the graft&#8217;s weight decreased from 3.3&#177;0.8 g to 2.3&#177;0.8 g.
We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure until the native liver regenerates.

Auxiliary liver transplantation provides a temporary support in acute hepatic failure, until regeneration of the failing liver. The heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) renders sufficient liver function. We developed an analogous technique in the rat, to examine the influence of the portal vein arterialization on the morphology and function of the graft.

急性肝障害における流れ調節性門脈動脈血と異補助ラット肝移植

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the ...

Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells

A novel animal model involving chimeric mice with humanized livers established via human hepatocyte transplantation has been developed. These mice, in which the liver has been repopulated with functional human hepatocytes, could serve as a useful tool for investigating human hepatic cell biology, drug metabolism, and other preclinical applications. One of the key factors required for successful transplantation of human hepatocytes into mice is the elimination of the endogenous hepatocytes to prevent competition with the human cells and provide a suitable space and microenvironment for promoting human donor cell expansion and differentiation. To date, two major liver injury mouse models utilizing fumarylacetoacetate hydrolase (Fah) and uroplasminogen activator (uPA) mice have been established. However, Fah mice are used mainly with mature hepatocytes and the application of the uPA model is limited by decreased breeding. To overcome these limitations, Alb-toxin receptor mediated cell knockout (TRECK)/SCID mice were used for in vivo differentiation of immature human hepatocytes and humanized liver generation. Human hepatic stem cells (HpSCs) successfully repopulated the livers of Alb-TRECK/SCID mice that had developed lethal fulminant hepatic failure following diphtheria toxin (DT) treatment. This model of a humanized liver in Alb-TRECK/SCID mice will have functional applications in studies involving drug metabolism and drug-drug interactions and will promote other in vivo and in vitro studies.

Here, we present a novel humanized mouse liver model generated in Alb-toxin receptor mediated cell knockout (TRECK)/SCID mice following the transplantation of immature and expandable human hepatic stem cells.

ヒト肝幹細胞を用いたヒト化マウス肝臓の生成

A novel animal model involving chimeric mice with humanized livers established via human hepatocyte transplantation has been developed. These mice, in ...

Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ischemia/reperfusion (I/R) injury with myriad negative consequences. Potential I/R injury in marginal organs destined for liver transplantation contributes to the current donor shortage secondary to a decreased organ utilization rate. A significant need exists to explore hepatic I/R injury in order to mediate its impact on graft function in transplantation. Rat liver hilar clamp models are used to investigate the impact of different molecules on hepatic I/R injury. Depending on the model, these molecules have been delivered using inhalation, epidural infusion, intraperitoneal injection, intravenous administration or injection into the peripheral superior mesenteric vein. A rat liver hilar clamp model has been developed for use in studying the impact of pharmacologic molecules in ameliorating I/R injury. The described model for rat liver hilar clamp includes direct cannulation of the portal supply to the ischemic hepatic segment via a side branch of the portal vein, allowing for direct segmental hepatic delivery. Our approach is to induce ischemia in the left lateral and median lobes for 60 min, during which time the substance under study is infused. In this case, pegylated-superoxide dismutase (PEG-SOD), a free radical scavenger, is infused directly into the ischemic segment. This series of experiments demonstrates that infusion of PEG-SOD is protective against hepatic I/R injury. Advantages of this approach include direct injection of the molecule into the ischemic segment with consequent decrease in volume of distribution and reduction in systemic side effects.

A unique rat liver hilar clamp model was developed for studying the impact of pharmacologic molecules in ameliorating ischemia-reperfusion injury. This model includes direct cannulation of the portal supply to the ischemic liver segment via a branch of the portal vein, allowing for direct hepatic delivery.

ラット肝臓肝門部クランプモデルを用いたダイレクトセグメント別肝臓内送達方法

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ...

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. To better understand the mechanism behind these surgical procedures, a rat partial liver transplantation (PLTx) model was established for relevant surgical studies. Because of the complexity of the rat PLTx model, a protocol with detailed descriptions is required. An article published previously reported a protocol in which ex vivo hepatectomy was used to achieve 50% rat PLTx. In contrast to this protocol, we introduced a re-arterialized PLTx with an in vivo 70% hepatectomy. An updated vessel-oriented hepatectomy was incorporated into the rat PLTx to refine the microsurgical procedure. The portal veins and hepatic arteries of the left lateral lobe and the median lobe were individually dissected and ligated before removal of the liver parenchyma, thereby decreasing the probability of bleeding in the remnant liver stump. Furthermore, an end-to-side vessel anastomosis between the common hepatic artery and the enlarged proper hepatic artery was introduced to re-arterialize the hepatic artery. By using this end-to-side vessel anastomosis technique, the diameter of the anastomosis was enlarged, thereby decreasing the difficulty of hand suture and maintaining a high rate of anastomotic patency. Moreover, the cuff anastomosis of the infrahepatic vena cava was slightly modified. A section of circumferential liver parenchyma around the vena cava of a recipient was preserved during cuff anastomosis to maintain the three-dimensional shape of the vascular lumen. This section of liver parenchyma was removed after completing the anastomosis. With this modification, the step involving placement of stay sutures was omitted, thereby further shortening the cuff anastomosis time. By using this protocol of rat PLTx, a low liver enzyme level, an intact liver lobular architecture and a high survival rate were achieved after microsurgery.

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Here, a protocol involving re-arterialized rat partial liver transplantation is presented. Specifically, 70% liver was resected in vivo by using an updated technique of vessel-oriented hepatectomy. The hepatic artery was reconstructed in an end-to-side manner. The cuff technique was modified to shorten the anastomosis time of the infrahepatic vena cava.

再門脈部分肝移植のラット体内血管指向 70% 肝切除

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. ...

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 ...

Orthotopic Rat Kidney Transplantation: A Novel and Simplified Surgical Approach

Kidney transplantation offers increased survival rates and improved quality of life for patients with end-stage renal disease, as compared to any type of renal replacement therapy. Over the past few decades, the rat kidney transplantation model has been used to study the immunological phenomena of rejection and tolerance. This model has become an indispensable tool to test new immunomodulatory pharmaceuticals and regimens prior to proceeding with expensive preclinical large animal studies.
This protocol provides a detailed overview of how to reliably perform orthotopic kidney transplantation in rats. This protocol includes three distinctive steps that increase the probability of success: perfusion of the donor kidney by flushing through the portal vein and the use of a cuff system to anastomose the renal veins and ureters, thereby decreasing cold and warm ischemia times. Using this technique, we have achieved survival rates beyond 6 months with normal serum creatinine in animals with syngeneic or tolerant kidney transplants. Depending on the aim of the study, this model can be modified by pre- or posttransplant treatments to study the acute, chronic, cellular, or antibody-mediated rejection. It is a reproducible, reliable, and cost-effective animal model to study different aspects of kidney transplantation.

The purpose of this manuscript and protocol is to explain and demonstrate in detail the surgical procedure of orthotopic kidney transplantation in rats. This method is simplified to achieve the correct perfusion of the donor kidney and shorten the reperfusion time by using the venous and ureteral cuff anastomosis technique.

Orthotopic ラット腎移植: 新規かつ簡便な外科的アプローチ

Kidney transplantation offers increased survival rates and improved quality of life for patients with end-stage renal disease, as compared to any type of ...

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen

Acute liver failure (ALF) is a clinical condition caused by various etiologies resulting in the loss of metabolic, biochemical, synthesizing, and detoxifying functions of the liver. In most irreversible liver damage cases, orthotropic liver transplant (OLT) remains the only available treatment. To study the therapeutic potential of a treatment for ALF, its prior testing in an animal model of ALF is essential. In the current study, an ALF model in rats was developed by combining 70% partial hepatectomy (PHx) and injections of acetaminophen (APAP) that provides a therapeutic window of 48 h. The median and left lateral lobes of the liver were removed to excise 70% of the liver mass and APAP was given 24 h postsurgically for 2 days. Survival in ALF-induced animals was found to be severely decreased. The development of ALF was confirmed by altered serum levels of the enzymes alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP); changes in prothrombin time (PT); and assessment of the international normalized ratio (INR). Study of the gene expression profile by qPCR revealed an increase in expression levels of genes involved in apoptosis, inflammation, and in the progression of liver injury. Diffused degeneration of hepatocytes and infiltration of immune cells was observed by histological evaluation. The reversibility of ALF was confirmed by the restoration of survival and serum levels of ALT, AST, and ALP after intrasplenic transplantation of syngeneic healthy rat hepatocytes. This model presents a reliable alternative to the available ALF animal models to study the pathophysiology of ALF as well as to evaluate the potential of a novel therapy for ALF. The use of two different approaches also makes it possible to study the combined effect of physical and drug-induced liver injury. The reproducibility and feasibility of current procedure is an added benefit of the model.

The acute liver failure animal model developed in the current study presents a feasible alternative for the study of potential therapies. The current model employs the combined effect of physical and drug-induced hepatic injury and provides a suitable time window to study the potential of novel therapies.