Diese Studie wurde von der &quot;Deutschen Forschungsgemeinschaft&quot; (DFG) gefördert. K. Schleimer wurde von der Lise-Meitner-Stipendium des Ministeriums für Wissenschaft und Forschung des Landes NRW unterstützt. Wir möchten Frau Mary-Joan Blümich für ihre ausgezeichnete Bearbeitung Unterstützung danken. Dr. Maria Kokozidou wurde von der Fresenius 2011_A61 finanziert.

1. Versuchstiere <ol><li> Besorgen Sie sich eine Ethikkommission die Genehmigung für alle Experimente, die durchgeführt werden, in Übereinstimmung mit den Tierschutz FELASA Richtlinien (K 40, 17/99). </li><li> Verwenden männlichen Lewis-Ratten zur Verfügung, um von jeder kommerziellen Züchter (zB Charles River Wiga GmbH, Sulzfeld, Deutschland) erwerben. Hier, 224 Tiere (112 Spendern, 112 Empfänger) wurden verwendet, um 112 Transplantationen durchzuführen. Die Empfänger wurden bei 6 Wochen nach der Operation getötet. Zum Zeitpunkt der Operation sollten die Tiere 250-350 g wiegen. </li><li> Halten Sie die Tiere in klimatisierten Räumen mit freiem Zugang zu Nahrung und Wasser. </li></ol> 2. Anästhesie und Operative Vorbereitung <ol><li> Platzieren Sie die Ratte in einem Plexiglaskasten zu der Anästhesiemaschine mit einer Sauerstoffdurchflussrate von 1 l / min und einer Isofluran Verdampfer mit 5% Narkosegas Anästhesie herbei verbunden. Aufrechterhaltung einer Narkose bei 1,5% Isofluran. </li><li> Legen Sie die Ratten inRückenlage auf einer Warmhalteplatte. </li><li> Entfernen Sie das Fell des Bauches mit einer Enthaarungscreme. </li><li> Bereiten Sie einen sterilen OP-Bereich wie folgt: Verwenden Sie ein Desinfektionsmittel, um den Tisch reinigen. Zur Desinfektion von der Inzisionsstelle Verwendung Chlorhexidin ersten, zweiten Alkohol und schließlich einer Waschlösung (zB Chlorhexidin und 70% Isopropylalkohol). Tragen Sie einen Einweg-OP-Kittel und OP-Handschuhen. </li><li> Sterile Mikroinstrumenten. </li><li> Verwenden Sie ein Operationsmikroskop in 12-20-fache Vergrößerung. </li></ol> 3. Chirurgische Verfahren <ol><li> Spender Betrieb Vorbereitung <ol><li> Führen Sie eine mediane Laparotomie und Resektion der linken Seitenlappen und der Mittellappen des Transplantats durch Higgins beschrieben. 14 </li><li> Dann bereiten die Ligamentum hepatoduodenale. Ersten ligieren den Gallengang, um Staus und Dilatation der kleinen Gallengang zu induzieren. Dann ligieren und durchtrennen die gastroduodenal Vene und Arterie. Anschließend isolieren Zöliakie Stamm und die gemeinsame Leberarterie und durchschneiden die linke Magenarterie und die Milzarterie. Inzision der Gallengang verstopft, und die Einführung einer 20-G-Stent hinein. Die Positionierung des Stents muss die Entwässerung der gesamten hilar Gallengangsystems zu gewährleisten. Schneiden den Gallengang distal des Stents. </li><li> Isolieren Sie die infrahepatische Segment der Hohlvene rechts über der rechten Nierenvene. Perfusion </li><li> Nach der Ligation der Aorta oberhalb des Truncus, klemmen die Pfortader und einzuschneiden es. Einführung der Perfusion Katheter (14 G) in die Pfortader, und führen Sie die Perfusion mit 30 ml Histidin-Tryptophan-Ketoglutarat (HTK) -Lösung (12 cm H2O, 4 ° C). </li><li> Schneiden Sie die Membran und das suprahepatischen Hohlvene, damit das Perfusat zu fließen. </li><li> Verbrauchsteuern Das Zöliakie-Stamm zusammen mit einem Aorten-Patch und spülen Sie es mit Histidin-Tryptophan-Ketoglutarat-Lösung. Explantation </li><li> Durchschneiden die infrahepatische Hohlvene rechts über der rechten Nierenvene. </li><li> Legen Sie dann einen Stent mit einem Durchmesser von 0,3 mm in der Pfortader und fixieren Sie es mit einer Ligatur. Beim folgenden Vorgang wird die Pfortader über die rechte Nierenarterie arterialisiert. Durchschneiden die Pfortader distal des Stents. </li><li> Nach der Ligation der suprahepatischen Hohlvene, Transekt es zusammen mit einer Manschette des Zwerchfells. </li><li> Explantation der Prothese und speichern sie in Histidin-Tryptophan-Ketoglutarat (HTK) -Lösung bei 4 ° Celsius in einer Plastiktüte auf Eis. Platz Ecke Nähte (8-0 Ethilon) in der infrahepatische Hohlvene. </li></ol></li><li> Empfänger Betrieb <ol><li> Führen Sie eine mediane Laparotomie und bereiten die infrahepatische Hohlvene. Dann isolieren die rechte Nierenarterie und der Harnleiter, ligieren den Harnleiter und durchschneiden sie. Klemmen Sie die rechte Nierenarterie an seinem Ursprung, dann ligieren das Recht Nierenvenen. Dann, nach Durchtrennung der beiden neunal Gefäße, führen Sie die Nephrektomie. Anschließend verkürzen die rechte Nierenarterie, spülen Sie es mit Heparin Kochsalzlösung (40 UI Heparin / ml Kochsalzlösung). </li><li> Durchschneiden das Recht Nierenvenen proximal der Ligatur nach proximal und distal Klemmung des infrahepatische Hohlvene zu einer ovalen Lumen im infrahepatische Hohlvene erstellen. Spülen Sie die Hohlvene mit Heparin Kochsalzlösung. Implantieren das Transplantat in der rechten Nierengegend des Bauches des Empfängers. </li><li> Anastomosieren infrahepatische Hohlvene Ende-zu-Seite des Spenders auf die recipient`s Hohlvene mit einem 8-0 Ethilon laufende Naht. </li><li> Nach dem Spülen mit Heparin / Kochsalzlösung einzuführen, den Stent in der Pfortader in der rechten Nierenarterie (3). Schließen Sie die Pfortader und Nierenarterie mit 2 Maschen (8-0 Ethilon). Befestigen Sie die Verknüpfung Stent in der Nierenarterie mit einer Ligatur (geflochtene Seide schwarz 7-0). </li><li> Der Reperfusion zu ermöglichen, zunächst die Arterienklemme zu entfernen, dann beidevenösen Klemmen (4). </li><li> Bereiten Sie die infrarenalen Aorta, dann einen proximalen und distalen microCLAMP und einschneiden die Aorta rechts zwischen den beiden Klemmen. Führen Sie eine Ende-zu-Seit-Anastomose zwischen der Aorta und Truncus des Spenders, mit einem Aorten-Patch, mit einem 10-0 Ethilon laufende Naht. </li><li> Legen Sie die Gallengang in den Zwölffingerdarm: Tragen Sie eine Tabaksbeutelnaht im Zwölffingerdarmwand, machen Sie einen kleinen Schnitt in der Zwölffingerdarmwand in der Mitte der Tabaksbeutel. Einführung der Stent Gallengang in den Zwölffingerdarm, und ziehen Sie die Tabaksbeutelnaht. Schließlich halten den Zwölffingerdarm und der Gallengang fest zusammen mit zwei Maschen (Ethilon 8-0) (Abbildung 5). </li><li> Führen Sie dann eine Zwischensumme Resektion des nativen Leber, zuerst von Emond et al. um akute Leberversagen zu imitieren. 7 </li><li> Fixieren die suprahepatischen Hohlvene des Transplantats mit einer Manschette Membran, an der seitlichen Bauchwand von der Wiederfänger mit 4-0 Vicryl Naht. Spülung der Bauch mit Kochsalzlösung (Abbildung 6). </li><li> Für die Muskelschicht mit einem 4-0 Vicryl genäht und die für die Haut ein 3-0 Vicryl fortlaufende Naht. </li></ol></li></ol> 4. Wiederherstellung und Postoperative Behandlung <ol><li> Lassen Sie die Tiere aus der Narkose zu erholen unter einer Infrarotwärmelampe. </li><li> Injizieren Buprenorphin in einer Dosierung von 0,03-0,05 mg / kg KG sc alle 8-12 Stunden für 2 Tage. </li><li> Untersucht die Tiere über den Allgemeinzustand und Anzeichen von Krankheit oder Infektionen. </li></ol> 5. Berechnung des Anfangsmutterlebergewicht Berechnen Sie die ersten nativen Lebergewicht in der folgenden Weise: subtrahieren das Gewicht der resezierten Leberlappen aus der vollständigen Lebergewicht (2,66% des Körpergewichts (dieser Wert mit einer Standardabweichung von 0,49% +/- wurde in früheren Experimenten mit n bestimmt = 80 Tiere des gleichen Stamms undge)). 15

<ol>
	<li>Boudjema, K., 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=Auxiliary+liver+transplantation+for+fulminant+and+subfulminant+hepatic+failure.">Auxiliary liver transplantation for fulminant and subfulminant hepatic failure.</a> Transplantation. 59, 218-223 (1995).</li><li>Boudjema, K., Jaeck, D., Sim&#233;oni, U., Bientz, J., Chenard, M. P., Brunot, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Temporary+auxiliary+liver+transplantation+for+subacute+liver+failure+in+a+child.">Temporary auxiliary liver transplantation for subacute liver failure in a child.</a> The Lancet. 342, 778-779 (1993).</li><li>Chenard-Neu, M. 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=Auxiliary+liver+transplantation:+Regeneration+of+the+native+liver+and+outcome+in+30+patients+with+fulminant+hepatic+failure+-+a+multicenter+European+study.">Auxiliary liver transplantation: Regeneration of the native liver and outcome in 30 patients with fulminant hepatic failure - a multicenter European study.</a> Hepatology. 23, 1119-1127 (1996).</li><li>Gubernatis, G., Pichlmayr, R., Kemnitz, J., Gratz, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auxiliary+partial+orthotopic+liver&#8211;transplantation+(APOLT)+for+fulminant+hepatic+failure:+first+successful+case+report.">Auxiliary partial orthotopic liver&#8211;transplantation (APOLT) for fulminant hepatic failure: first successful case report.</a> World J Surg. 15, 660-666 (1991).</li><li>Erhard, J., Lange, R., Giebler, R., Rauen, U., de Groot, H., Eigler, F. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arterialization+of+the+portal+vein+in+orthotopic+and+auxiliary+liver+transplantation.">Arterialization of the portal vein in orthotopic and auxiliary liver transplantation.</a> Transplantation. 60, 877-879 (1995).</li><li>Erhard, 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=Auxiliary+liver+transplantation+with+arterialization+of+the+portal+vein+for+acute+hepatic+failure.">Auxiliary liver transplantation with arterialization of the portal vein for acute hepatic failure.</a> Transpl Int. 11, 266-271 (1998).</li><li>Emond, J., Capron-Laudereau, M., Meriggi, F., Bernuau, J., Reynes, M., Houssin, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extent+of+Hepatectomy+in+the+rat.">Extent of Hepatectomy in the rat.</a> Eur Surg Res. 21, 251-259 (1989).</li><li>Mas, A., Rode`s, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fulminant+hepatic+failure.">Fulminant hepatic failure.</a> Lancet. 349, 1081-1085 (1997).</li><li>Terpstra, O. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auxiliary+liver+grafting:+a+new+concept+in+liver+transplantation.">Auxiliary liver grafting: a new concept in liver transplantation.</a> The Lancet. 342, 758 (1993).</li><li>Terpstra, O. T., Reuvers, C. B., Schalm, S. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auxiliary+heterotopic+liver+transplantation.">Auxiliary heterotopic liver transplantation.</a> Transplantation. 45, 1003-1007 (1988).</li><li>Schleimer, K., Lange, R., Rauen, U., Erhard, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auxiliary+liver+transplantation+in+acute+liver+failure+in+the+rat+-+an+illustrated+description+of+a+new+surgical+approach.">Auxiliary liver transplantation in acute liver failure in the rat - an illustrated description of a new surgical approach.</a> Langenbecks Arch Surg. 384 (2), 204-208 (1999).</li><li>Schleimer, K., 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=Physiologic+microcirculation+of+the+heterotopically+transplanted+rat+liver+with+portal+vein+arterialization+depending+on+optimal+stent+diameter.">Physiologic microcirculation of the heterotopically transplanted rat liver with portal vein arterialization depending on optimal stent diameter.</a> Med Sci Monit. 28 (BR140-145), (2006).</li><li>Hong, H. Q., 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=Study+of+portal+arterialization+with+auxiliary+liver+in+rats.">Study of portal arterialization with auxiliary liver in rats.</a> Hiroshima J. Med. Sci. 40, 29-33 (1991).</li><li>Higgins, G. M., Anderson, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+pathology+of+the+liver.+I--Restoration+of+the+liver+of+the+white+rat+following+partial+surgical+removal.">Experimental pathology of the liver. I--Restoration of the liver of the white rat following partial surgical removal.</a> Arch. Path. 12, 186-202 (1931).</li><li>Schleimer, K., 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=Auxiliary+liver+transplantation+with+flow-regulated+portal+vein+arterialization+offers+a+successful+therapeutic+option+in+acute+hepatic+failure--investigations+in+heterotopic+auxiliary+rat+liver+transplantation.">Auxiliary liver transplantation with flow-regulated portal vein arterialization offers a successful therapeutic option in acute hepatic failure--investigations in heterotopic auxiliary rat liver transplantation.</a> Transpl Int. 19 (7), 581-588 (2006).</li><li>Lee, S., Edgington, T. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liver+transplantation+in+the+rat.">Liver transplantation in the rat.</a> Surg. Forum. 17, 220-222 (1966).</li><li>Hess, F., Willemen, A., Jerusalem, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auxiliary+liver+transplantation+in+the+rat,+influence+of+the+condition+of+the+recipient's+liver+on+the+fate+of+the+graft.">Auxiliary liver transplantation in the rat, influence of the condition of the recipient's liver on the fate of the graft.</a> Eur. Surg. Res. 9, 270-279 (1977).</li><li>Aguirrezabalaga, J., Arnal, F., Marini, M., Centeno, A., Fernandez-Selles, C., Rey, I., Gomez, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auxiliary+liver+transplantation+with+portal+arterialization+in+the+rat:+description+of+a+new+model.">Auxiliary liver transplantation with portal arterialization in the rat: description of a new model.</a> Microsurgery. 22, 21-26 (2002).</li><li>Palmes, D., Dietl, K. H., Drews, G., Holzen, J. P., Spiegel, H. U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auxiliary+partial+orthotopic+liver+transplantation:+treatment+of+acute+liver+failure+in+a+new+rat+model.">Auxiliary partial orthotopic liver transplantation: treatment of acute liver failure in a new rat model.</a> Langenbecks Arch Surg. (386), 534-541 (2002).</li><li>Schleimer, K., 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+microcirculation+of+a+liver+graft+by+controlled+portal+vein+arterialization.">Improved microcirculation of a liver graft by controlled portal vein arterialization.</a> J Surg Res. 116 (2), 202-210 (2004).</li><li>Schleimer, K., 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=Portal+hyperperfusion+causes+disturbance+of+microcirculation+and+increased+rate+of+hepatocellular+apoptosis:+investigations+in+heterotopic+rat+liver+transplantation+with+portal+vein+arterialization.">Portal hyperperfusion causes disturbance of microcirculation and increased rate of hepatocellular apoptosis: investigations in heterotopic rat liver transplantation with portal vein arterialization.</a> Transplant Proc. 38 (3), 725-729 (2006).</li></ol>

Alle Autoren erklärten keine Interessenkonflikte.

Der erste Hilfs heterotopen Rattenlebertransplantation wurde von Lee et al., 16 1966, gefolgt von Hess. 17 Pfortader des Transplantats wurde mit der Pfortader des Empfängers anastomosiert. Während dieser Prozedur wird die Pfortader Blutversorgung des nativen Leber beeinträchtigt. Im Jahr 1991 durchgeführt Hong HALT mit PVA über die Beckenarterie des Empfängers. Ohne 13 Blutfluss Regulierung massiven Portal und Sinus Staus aufgetreten. <p cl...

Akute Leberversagen stellt ein schwerwiegendes Problem in der klinischen Medizin, die zu einer Mortalitätsrate von 60-80%. 8 In akuten Leberversagen ist die Hilfslebertransplantation eine vielversprechende alternative Therapie, um die akute Phase überbrücken. Die native Leber ist links zu regenerieren und nach dem Regenerations die Immunsuppression Medikamente können abgesetzt werden. Als Folge das Transplantat werden atrophisch. Allerdings ist die Operationstechnik für Hilfslebertransplantation ist immer noch diskutiert. 1-3 In diesem Zusammenhang berichtet Terpstra den Mangel an Platz für das Transplantat, das Portal Blut stehlen Phänomen und das Problem der venösen Stauung und Entwässerung. 9-10 Pfortader des Spenders wurde Pfortader des Empfängers anastomosiert Ende-zu-Seite. Dies führte zu Portal-Flow Wettbewerb zwischen dem Transplantat und der nativen Leber und in Portalvenenthrombose. Die meisten dieser technischen Probleme können bei der Verwendung des APOLT-Methode (orthotop vermiedenic Implantation von Hilfssegmente). 4 Allerdings erfordert diese Methode umfangreichen Resektionen sowohl der nativen Leber und des Transplantats. 4 1998 Erhard und sein Team entwickelten die heterotope Hilfslebertransplantation (HALT) unter Verwendung Pfortader Arterialisation (PVA) (Abbildung 1 ). Hilus und die Pfortader der nativen Leber mit der Verwendung dieses Verfahrens eingehalten. Das schont die Empfänger von unerwünschten Nebenwirkungen wie Thrombose der Pfortader und Portalblut stehlen Phänomen, das Mutter Leber Erholung stören könnten. Darüber hinaus werden keine umfangreichen Leber Resektionen der nativen Leber und Transplantat für diese Methode zur Überbrückung (Graft) und Regeneration (native Leber) erforderlich, damit mit weniger Blutungen und verbleibende Gesamt Leberparenchymzellen Masse. Diese Technik zeigte vielversprechende erste klinische Ergebnisse. 5-6 Das Ziel dieser experimentellen Arbeit war die Entwicklung eines HALT-Technik mit Pfortader in Arterialisationdie Ratte für Forschungszwecke (Abbildung 2). In den Vorversuchen haben wir nicht berücksichtigen, das den Blutfluss Regulierung der arterialisierte Pfortader 11 Seitdem der Blutfluss in der Pfortader arterialisierte nehmen, die in Staus des transplantierten Transplantat nach Reperfusion und massive Blutungen aus der Leberkapsel geführt. wurde mit einem Stent, der mit einem Innendurchmesser von 0,3 mm und einer Länge von 8 mm geregelt. Modellversuche habe gezeigt, dass ein Stent Durchmesser von 0,3 mm ergibt sich eine mittlere Durchblutung im arterialisierten Pfortader, die innerhalb des oberen physiologischen Bereich liegt (1,7 +/- 0,4 ml / min / g Lebergewicht). 12 Unsere Ergebnisse ohne Blutflussregel korrelieren mit den Ergebnissen der Hong, der HALT mit PVA über die Beckenarterie des Empfängers 13 In seinen Experimenten. ohne Blutfluss Regulierung massiven Portal durchgeführt und Sinus Staus aufgetreten. Das Ziel unserer Video ist auf demonstrate schrittweise dies ne.w Versuchsoperationstechnik bei der Ratte. Auf lange Sicht kann die vorgeschlagene Technik in Studien zur Leberregeneration und inter Leber Wettbewerb und Pfortader Arterialisation, Pfortader Hyperperfusion und Portalblutflussregelung verwendet werden.

<table border="0" cellpadding="0" cellspacing="0" width="573">
	<tbody>
		<tr height="41">
			<td height="41" style="height:41px;width:216px;">Braided Silk black 7-0&#160;</td>
			<td style="width:71px;">Ethicon Products</td>
			<td style="width:119px;">892100</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="41">
			<td height="41" style="height:41px;width:216px;">Vicryl 3-0</td>
			<td style="width:71px;">Ethicon Products</td>
			<td style="width:119px;">J285G</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="41">
			<td height="41" style="height:41px;width:216px;">Vicryl 4-0</td>
			<td style="width:71px;">Ethicon Products</td>
			<td style="width:119px;">J284G</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="41">
			<td height="41" style="height:41px;width:216px;">Ethilon 8-0</td>
			<td style="width:71px;">Ethicon Products</td>
			<td style="width:119px;">1714G</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="41">
			<td height="41" style="height:41px;width:216px;">Ethilon 10-0</td>
			<td style="width:71px;">Ethicon Products</td>
			<td style="width:119px;">7770G</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Vasofix safety 14G</td>
			<td style="width:71px;">B Braun</td>
			<td style="width:119px;">2758853</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Vasofix safety 20G</td>
			<td style="width:71px;">B Braun</td>
			<td style="width:119px;">2758818</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="201">
			<td height="201" style="height:201px;width:216px;">2 French (.012&#8221;/0.3mm ID x .025&#8221;/0.6mm OD) x 24&#8221;/60cm polyurethane catheter</td>
			<td style="width:71px;">Access technologies a division of Norfolk Medical, Inc., Illinois, USA</td>
			<td style="width:119px;">CNC-2P</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="119">
			<td height="119" style="height:119px;width:216px;">HTK solution,</td>
			<td rowspan="2" style="width:71px;">Dr. Franz K&#246;hler Chemie GmbH, Alsbach-H&#228;hnlein, Germany</td>
			<td rowspan="2" style="width:119px;"></td>
			<td rowspan="2" style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Custodiol</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Isofluorane 5 %</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Any genericon</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Heparin</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Any genericon</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">0.9% saline</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Any genericon</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Buprenorphine</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Any genericon</td>
		</tr>
	</tbody>
</table>

heterotopic auxiliary rat liver transplantation with flow-regulated portal vein arterialization in acute hepatic failure

In akuten Leberversagen Hilfslebertransplantation ist eine interessante Alternative Ansatz. Ziel ist es, eine vorübergehende Unterstützung bieten, bis die ausgefallene nativen Leber regeneriert hat. 1-3 Die APOLT-Methode, die orthotope Implantation von Hilfs segments- wendet die meisten technischen Probleme. Allerdings erfordert diese Methode umfangreichen Resektionen sowohl der nativen Leber und des Transplantats. 4 Im Jahr 1998 entwickelte Erhard heterotopen Hilfslebertransplantation (HALT) unter Verwendung Pfortader Arterialisation (PVA) (Abbildung 1). Diese Technik zeigte vielversprechende erste klinische Ergebnisse. 5-6 Wir entwickelten eine HALT-Technik mit stromgeregelten PVA bei der Ratte um den Einfluss der Strömungs geregelt PVA auf die Transplantat Morphologie und Funktion (Abbildung 2) zu untersuchen. Eine Lebertransplantat auf 30% seiner ursprünglichen Größe verringert wurde heterotop in der rechten Nierengegend des Empfängers nach der Explantation der rechten Niere implantiert.60; Die Infrarot-Leber Hohlvene des Transplantats wurde mit dem infrahepatische Hohlvene des Empfängers anastomosiert. Die Arterialisierung Pfortader des Spenders wurde über rechte Nierenarterie des Empfängers mit dem Stent-Technik durchgeführt. Der Blutdurchflussregulierung des arterialisierten Pfortader wurde mit der Verwendung eines Stents mit einem Innendurchmesser von 0,3 mm erreicht. Die Zöliakie-Stamm des Transplantats war Ende-zu-Seite mit der Aorta des Empfängers und des Gallengangs anastomosiert wurde in den Zwölffingerdarm implantiert. Eine Zwischensumme Resektion des nativen Leber wurde durchgeführt, um akutes Leberversagen auslösen. 7 Auf diese Weise wurden 112 Transplantationen durchgeführt. Die perioperative Überlebensrate betrug 90% und der 6-Wochen-Überlebensrate betrug 80%. Sechs Wochen nach der Operation, die native Leber regeneriert, zeigt eine Gewichtszunahme von 2,3 ± 0,8 g auf 9,8 ± 1 g. Zu dieser Zeit, Gewichtsabnahme des Transplantats von 3,3 ± 0,8 g auf 2,3 ± 0,8 g. </p&gt; Wir waren in der Lage, vielversprechende langfristige Ergebnisse in Bezug auf die Transplantat-Morphologie und Funktion zu erhalten. HALT mit stromgeregelten PVA zuverlässig überbrückt akutes Leberversagen, bis die einheimischen Leber regeneriert.

Die mittlere Dauer der Transplantation war etwa 150 min. Die kalte Ischämie Zeit betrug 64 min +/- 7, die warme Ischämie Zeit weniger als 25 min. Die perioperative Überlebensrate betrug 90% und der 6-Wochen-Überlebensrate betrug 80%. Der Verlust von 20% ist auf Peritonitis, da der Stent-Dislokation und Gallen Leckage (vier Tiere) während der ersten postoperativen Woche und wegen Lungenentzündung, intra-abdominalen Abszess und Ileus (sieben Tiere) in den folgenden fünf Wochen. Die übe...

Watch this Scientific Journal Video about Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure at JoVE.com

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

Hilfslebertransplantation bietet eine temporäre Unterstützung in akuten Leberversagen, bis die Regeneration der Leberversagen. Die heterotope Hilfslebertransplantation (HALT) mit Pfortader Arterialisation (PVA) macht ausreichende Leberfunktion. Wir entwickelten eine analoge Technik in der Ratte, um den Einfluss der Pfortader Arterialisation auf die Morphologie und Funktion des Transplantats zu untersuchen.

Heterotope Hilfs Ratte Leber-Transplantation mit strömungs geregelt Pfortader Arterialisation in akutes Leberversagen

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

heterotopic-auxiliary-rat-liver-transplantation-with-flow-regulated

Research

JoVE Journal

Medicine

12.6K Aufrufe.  University Hospital RWTH Aachen.  Hilfslebertransplantation bietet eine temporäre Unterstützung in akuten Leberversagen, bis die Regeneration der Leberversagen. Die heterotope Hilfslebertransplantation (HALT) mit Pfortader Arterialisation (PVA) macht ausreichende Leberfunktion. Wir entwickelten eine analoge Technik in der Ratte, um den Einfluss der Pfortader Arterialisation auf die Morphologie und Funktion des Transplantats zu untersuchen. 

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

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.

Chirurgische Verfahren für eine Ratte Modell Teilweise Lebertransplantation mit arteriellen Rekonstruktion

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

Forschung

Medizin

Rat Heterotopic Abdominal Heart/Single-lung Transplantation in a Volume-loaded Configuration

Herein, we describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The configuration of the transplant graft involves anastomosis of donor inferior vena cava (IVC) to recipient IVC, and donor ascending aorta (Ao) to recipient abdominal Ao. The right upper and middle lung lobes are preserved and function as conduits for blood flow from right heart to left heart.
There are several advantages to using this technique, and it lends itself to a broad range of applications. Because the graft is transplanted in a configuration that allows for dyamic volume-loading, cardiac function may be directly assessed in vivo. The use of pressure-volume conductance catheters permits characterization of load-dependent and load-independent hemodynamic parameters. The graft may be converted to a loaded configuration by applying a clamp to the recipient&#8217;s infra-hepatic IVC. We describe modified surgical techniques for both donor and recipient operations, and an ideal myocardial protection strategy. Depending on the experimental aim, this model may be adapted for use in both acute and chronic studies of graft function, immunologic status, and variable ventricular loading conditions. The conducting airways to the transplanted lung are preserved, and allow for acute lung re-ventilation. This facilitates analysis of the effects of the mixed venous and arterial blood providing coronary perfusion to the graft.
A limitation of this model is its technical complexity. There is a significant learning curve for new operators, who should ideally be mentored in the technique. A surgical training background is advantageous for those wishing to apply this model. Despite its complexity, we aim to present the model in a clear and easily applicable format. Because of the physiologic similarity of this model to orthotopic transplantation, and its broad range of study applications, the effort invested in learning the technique is likely to be worthwhile.

We describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The transplant configuration results in a partially loaded graft circulation, allowing direct functional assessment. This model may be employed for acute or chronic studies of function and immunologic status of the transplanted graft.

Rat Heterotope Abdominal Herz / Einzel-Lungen-Transplantation in einer Volume-Konfiguration geladen

Herein, we describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The configuration of the transplant graft ...

Heterotopic Cervical Heart Transplantation in Mice

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies this model by avoiding challenging suture anastomoses of small vessels thereby reducing warm ischemia time. In comparison to abdominal graft implantation the cervical model is less invasive and the implanted graft is easily accessible for further follow-up examinations. Anastomoses are performed by pulling the ascending aorta of the graft over the cuff with the recipient&#8217;s common carotid artery and by pulling the main pulmonary artery over the cuff with the external jugular vein. Selection of appropriate cuff size and complete mobilization of the vessels are important for successful revascularization. Ischemia-reperfusion (I/R) injury can be minimized by perfusing the graft with a cardioplegic solution and by hypothermia. In this article, we provide technical details for a simplified and improved cuff technique, which should allow surgeons with basic microsurgical skills to perform the procedure with a high success rate.

The cuff technique shortens and facilitates the model of heterotopic cervical heart transplantation in mice by avoiding technically challenging suture anastomoses of small vessels. The technical details shown in this video paper should allow researches to establish this model in their laboratories.

Heterotope Cervical Herztransplantation bei Mäusen

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies ...

Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver metastases, the amount of liver tissue left behind after liver resection has become the main limiting factor of resectability of large or multiple liver tumors. A minimal amount of functional tissue is required to avoid the severe complication of post-hepatectomy liver failure, which has high morbidity and mortality. Inducing liver growth of the prospective remnant prior to resection has become more established in liver surgery, either in the form of portal vein embolization by interventional radiologists or in the form of portal vein ligation several weeks prior to resection. Recently, it was shown that liver regeneration is more extensive and rapid, when the parenchymal transection is added to portal vein ligation in a first stage and then, after only one week of waiting, resection performed in a second stage (Associating Liver Partition and Portal vein ligation for Staged hepatectomy = ALPPS). ALPPS has rapidly become popular across the world, but has been criticized for its high perioperative mortality. The mechanism of accelerated and extensive growth induced by this procedure has not been well understood. Animal models have been developed to explore both the physiological and molecular mechanisms of accelerated liver regeneration in ALPPS. This protocol presents a rat model that allows mechanistic exploration of accelerated regeneration.

Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy ALPPS Procedure

Inducing rapid liver hypertrophy using Associating Liver Partition and Portal vein ligation for a Staged hepatectomy (ALPPS) has been proposed for resection of borderline resectable liver tumors. This model may elucidate mechanisms involved in rapid hypertrophy and allows testing of drugs that promote or block the acceleration of regeneration.

Rattenmodell der Leber Partition zuordnen und Pfortader Ligation inszenierten Hepatektomie (ALPPS) Verfahren

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver ...

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.

Re Arterialized Ratte teilweise Leber Transplantation mit einem in Vivo Schiff-orientierte 70 % Hepatektomie

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

Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats

This is a detailed protocol describing invasive hemodynamic measurements in cirrhotic rats for the characterization of portal hypertensive syndrome. Portal hypertension (PHT) due to cirrhosis is responsible for the most severe complications in patients with liver disease. The full picture of the portal hypertensive syndrome is characterized by increased portal pressure (PP) due to the increased intrahepatic vascular resistance (IHVR), hyperdynamic circulation, and increased splanchnic blood flow. Progressive splanchnic arterial vasodilation and increased cardiac output with elevated heart rate (HR) but low arterial pressure characterizes the portal hypertensive syndrome.
Novel therapies are currently being developed that aim to decrease PP by either targeting IHVR or increased splanchnic blood flow &#8212; but side effects on systemic hemodynamics may occur. Thus, a detailed characterization of portal venous, splanchnic, and systemic hemodynamic parameters, including measurement of PP, portal venous blood flow (PVBF), mesenteric arterial blood flow, mean arterial pressure (MAP), and HR is needed for preclinical evaluation of the efficacy of novel treatments for PHT. Our video article provides the reader with a structured protocol for performing invasive hemodynamic measurements in cirrhotic rats. In particular, we describe the catheterization of the femoral artery and the portal vein via an ileocolic vein and the measurement of portal venous and splanchnic blood flow via perivascular Doppler-ultrasound flow probes. Representative results of different rat models of PHT are shown.

Here we describe a detailed protocol for invasive measurements of hemodynamic parameters including portal pressure, splanchnic blood flow, and systemic hemodynamics in order to characterize the portal hypertensive syndrome in rats.

Invasive hämodynamische Charakterisierung des Portal-hypertensiven Syndroms in zirrhotischen Ratten

This is a detailed protocol describing invasive hemodynamic measurements in cirrhotic rats for the characterization of portal hypertensive syndrome. ...

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.

Generierung eines Rattenmodells für akutes Leberversagen durch Kombination von 70% partieller Hepatektomie und Acetaminophen

Acute liver failure (ALF) is a clinical condition caused by various etiologies resulting in the loss of metabolic, biochemical, synthesizing, and ...

Minimizing Post-Infusion Portal Vein Bleeding during Intrahepatic Islet Transplantation in Mice

Although the liver is currently accepted as the primary transplantation site for human islets in clinical settings, islets are transplanted under the kidney capsule in most rodent preclinical islet transplantation studies. This model is commonly used because murine intrahepatic islet transplantation is technically challenging, and a high percentage of mice could die from surgical complications, especially bleeding from the injection site post-transplantation. In this study, two procedures that can minimize the incidence of post-infusion portal vein bleeding are demonstrated. The first method applies an absorbable hemostatic gelatin sponge to the injection site, and the second method involves penetrating the islet injection needle through the fat tissue first and then into the portal vein by using the fat tissue as a physical barrier to stop bleeding. Both methods could effectively prevent bleeding-induced mouse death. The whole liver section showing islet distribution and evidence of islet thrombosis post-transplantation, a typical feature for intrahepatic islet transplantation, were presented. These improved protocols refine the intrahepatic islet transplantation procedures and may help laboratories set up the procedure to study islet survival and function in pre-clinical settings.

Here we present refined surgical procedures on successfully performing intraportal islet transplantation, a clinically relevant but technically challenging surgical procedure, in mice.

Minimierung der Venenblutung nach der Infusion während der intrahepatischen Inseltransplantation bei Mäusen

Although the liver is currently accepted as the primary transplantation site for human islets in clinical settings, islets are transplanted under the ...

Rat Model of Normothermic Ex-Situ Perfused Heterotopic Heart Transplantation

Heart transplantation is the most effective therapy for end-stage heart failure. Despite the improvements in therapeutic approaches and interventions, the number of heart failure patients waiting for transplantation is still increasing. The normothermic ex situ preservation technique has been established as a comparable method to the conventional static cold storage technique. The main advantage of this technique is that donor hearts can be preserved for up to 12 h in a physiologic condition. Moreover, this technique allows resuscitation of the donor hearts after circulatory death and applies required pharmacologic interventions to improve donor function after implantation. Numerous animal models have been established to improve normothermic ex situ preservation techniques and eliminate preservation-related complications. Although large animal models are easy to handle compared to small animal models, it is costly and challenging. We present a rat model of normothermic ex situ donor heart preservation followed by heterotopic abdominal transplantation. This model is relatively cheap and can be accomplished by a single experimenter.

Here, we present an assessment protocol of a heterotopically implanted heart after normothermic ex situ preservation in the rat model.

Rattenmodell der normothermischen Ex-situ-perfundierten heterotopen Herztransplantation

Heart transplantation is the most effective therapy for end-stage heart failure. Despite the improvements in therapeutic approaches and interventions, the ...

In-vivo-Herztransplantation zur Untersuchung des Übergangs von Endothel zu Mesenchym

A Neonatal Heterotopic Rat Heart Transplantation Model for the Study of Endothelial-to-Mesenchymal Transition

Endocardial fibroelastosis (EFE), defined by subendocardial tissue accumulation, has major impacts on the development of the left ventricle (LV) and precludes patients with congenital critical aortic stenosis and hypoplastic left heart syndrome (HLHS) from curative anatomical biventricular surgical repair. Surgical resection is currently the only available therapeutic option, but EFE often recurs, sometimes with an even more infiltrative growth pattern into the adjacent myocardium.
To better understand the underlying mechanisms of EFE and to explore therapeutic strategies, an animal model suitable for preclinical testing was developed. The animal model takes into consideration that EFE is a disease of the immature heart and is associated with flow disturbances, as supported by clinical observations. Thus, the heterotopic heart transplantation of neonatal rat donor hearts is the basis for this model.
A neonatal rat heart is transplanted into an adolescent rat&#39;s abdomen and connected to the recipient&#39;s infrarenal aorta and inferior vena cava. While perfusion of the coronary arteries preserves the viability of the donor heart, flow stagnation within the LV induces EFE growth in the very immature heart. The underlying mechanism of EFE formation is the transition of endocardial endothelial cells to mesenchymal cells (EndMT), which is a well-described mechanism of early embryonic development of the valves and septa but also the leading cause of fibrosis in heart failure. EFE formation can be macroscopically observed within days after transplantation. Transabdominal echocardiography is used to monitor the graft viability, contractility, and the patency of the anastomoses. Following euthanasia, the EFE tissue is harvested, and it shows the same histopathological characteristics as human EFE tissue from HLHS patients.
This in vivo model allows for studying the mechanisms of EFE development in the heart and testing treatment options to prevent this pathological tissue formation and provides the opportunity for a more generalized examination of EndMT-induced fibrosis.

Autor im Rampenlicht: Ein neonatales heterotopes Rattenherztransplantationsmodell für die Untersuchung des Übergangs von Endothel zu Mesenchym  

This work presents an animal model of endothelial-to-mesenchymal transition-induced fibrosis, as seen in congenital cardiac defects such as critical aortic stenosis or hypoplastic left heart syndrome, which allows for detailed histological tissue evaluation, the identification of regulatory signaling pathways, and the testing of treatment options.

Ein neonatales heterotopes Rattenherztransplantationsmodell zur Untersuchung des Übergangs von Endothel zu Mesenchym

Endocardial fibroelastosis (EFE), defined by subendocardial tissue accumulation, has major impacts on the development of the left ventricle (LV) and ...