Name: a novel murine model of arteriovenous fistula failure: the surgical procedure in detail
Uploaded: 2016-02-03T13:00:00
Description: Watch this Scientific Journal Video about A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail at JoVE.com

This study was supported by a grant from the Dutch Kidney Foundation (KJPB 08.0003). 
Carolien Rothuizen is acknowledged for her contribution to the study. Hoang Pham is acknowledged for his assistance with the pathology work-up.

Alle forsøg blev godkendt af udvalget om dyrevelfærd i Leiden University Medical Center. 1. Animalske Forberedelse og Anæstesi <ol><li> Bedøver musen (1-3 måneder gamle) i en kontinuerlig anæstesi induktion kammer fyldt med 3-4% isofluran. </li><li> Barbere den ventrale side af halsen og den indvendige del af den venstre øvre ben under anvendelse af en elektrisk barbermaskine og bruge et stykke tape til at fjerne hår. </li><li> Påfør okulær salve på begge øjne. </li><li> Place...

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Den AVF anses for at være akilleshælen i hæmodialysebehandling. Desværre AV.F stadig lider et stort antal fejl 8-10. Trods omfattende forskning på de underliggende mekanismer, den nøjagtige patofysiologi forbliver ukendt. Talrige murine modeller for AVF svigt er allerede blevet beskrevet i litteraturen 2,3,11,12. Men ingen af ​​disse modeller indarbejde en venøs ende til arteriel anastomose-konfiguration, som er mest anvendt i den kliniske situation. Dette er meget relevant, da den resul...

En funktionel vaskulær adgang kanal er af afgørende betydning for patienter med nyresvigt, der er afhængige af kronisk hæmodialyse at holde sig i live. Opførelsen af ​​en arteriovenøs fistel (AVF) er i øjeblikket det foretrukne valg for vaskulær adgang. Imidlertid AVF relaterede komplikationer udgør en væsentlig årsag til morbiditet for patienter i kronisk hæmodialyse. Trods omfattende videnskabelig indsats, ingen af ​​romanen nærmer at reducere AVF adgang komplikationer førte til en væsentlig forbedring af AVF holdbarhed. En del af denne skuffende fremskridt angår ufuldstændig forståelse af den underliggende patofysiologi hæmodialyse adgang svigt. For at opklare patofysiologi AV adgang fiasko, dyremodeller, der nøje efterligner menneskets patologi er af allerstørste betydning. I denne henseende, ikke kun de dyrearter, men også det anastomotiske sted, den nødvendige anti-coagulatory terapi og varigheden af ​​opfølgning efter bølgebør tages ry i betragtning 1. Mens store dyr er de mest egnede til interventionsstudier rettet til at udvikle nye terapeutiske strategier, murine modeller har det største potentiale for at få mere indsigt i de molekylære mekanismer bag AV adgang fiasko på grund af tilgængeligheden af ​​transgene mus. Derudover kan der anvendes et stort antal mus til dette formål ved lavere omkostninger i forhold til større anvendelse dyr. Den første murin model for AVF svigt blev beskrevet i 2004 af Kwei og et al. 2 I denne model blev AVFs konstrueret under anvendelse halspulsåren og halsvenen i en ende-til-ende måde under anvendelse et intravaskulært kateter. Denne model kunne være nyttigt at studere tidlig venøs tilpasning i AVFs selvom end-to-end konfiguration og tilstedeværelsen af ​​et intravaskulært kateter begrænse gyldigheden af ​​denne model for humane AVFs. En forbedret AVF modellen blev introduceret af Castier og et al. 3, i hvilken enden afcarotidarterien er forbundet til den side af halsvenen. Imidlertid er AVFs i hæmodialysepatienter sædvanligvis konstrueret ved anatomizing udgangen af ​​en vene på siden af ​​en arterie. Den nøjagtige konfiguration af AVF er en afgørende egenskab ved en AV adgang model, da det bestemmer hæmodynamisk profil inden ledningen 4. Sidstnævnte er en vigtig bidragyder til endotel dysfunktion og efterfølgende udvikling af intimahyperplasi (IH) 5. Et hidtil ukendt murin model blev for nylig udviklet med en identisk anatomisk konfiguration som anvendes i mennesker 6. I denne model er AV.F skabt i C57BL / 6 mus ved anastomosering enden af ​​en gren af ​​den eksterne halsvene til den side af den fælles carotidarterie med afbrudte suturer. I det foreliggende papir, vi fokuserer på mikrokirurgisk procedure af denne model for at lette den udbredte brug af denne murine model, havde til formål at opklare komplekse patofysiologiaf hæmodialyse Fejl i adgang.

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			<td height="17" style="height:17px;width:247px;">Dissecting microsocpe</td>
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			<td height="17" style="height:17px;">Forceps</td>
			<td>Medicon</td>
			<td>07.61.25</td>
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			<td>S&#38;T</td>
			<td>JFL-3D.2</td>
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			<td height="17" style="height:17px;">Micro scissor 5 mm blade</td>
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			<td>15000-08</td>
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			<td height="17" style="height:17px;">Micro scissor 2 mm blade</td>
			<td>Fine science tools</td>
			<td>15000-03</td>
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			<td>Medicon</td>
			<td>05.12.21</td>
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			<td height="17" style="height:17px;">Clip applier 1</td>
			<td>S&#38;T</td>
			<td>CAF-4</td>
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			<td height="17" style="height:17px;">Vascular clamp 1</td>
			<td>S&#38;T</td>
			<td>B-1V</td>
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			<td height="17" style="height:17px;">Clip applier 2</td>
			<td>BBraun</td>
			<td>FE572K</td>
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			<td>BBraun</td>
			<td>FE740K</td>
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			<td height="17" style="height:17px;">Hemostatic forceps</td>
			<td>BBraun</td>
			<td>BH110</td>
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			<td height="17" style="height:17px;">10.0 sutures</td>
			<td>BBraun</td>
			<td>G1117041</td>
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			<td height="17" style="height:17px;">6.0 sutures</td>
			<td>BBraun</td>
			<td>768464</td>
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			<td height="17" style="height:17px;">Cauterizer</td>
			<td>Fine science tools</td>
			<td>18010-00</td>
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			<td height="17" style="height:17px;">Needle holder</td>
			<td>Medicon</td>
			<td>11.82.18</td>
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			<td height="17" style="height:17px;">Ocular ointment</td>
			<td>Pharmachemie</td>
			<td>41821101</td>
			<td></td>
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		<tr height="17">
			<td height="17" style="height:17px;">Chlorhexidine tincture 0,5%</td>
			<td>Leiden University Medical Center</td>
			<td>NA</td>
			<td></td>
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		<tr height="17">
			<td height="17" style="height:17px;">Heparin</td>
			<td>Leo Pharma</td>
			<td>012866-08</td>
			<td></td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;">Buprenorphin</td>
			<td>RB Pharmaceuticals&#160;</td>
			<td>283732</td>
			<td></td>
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			<td height="17" style="height:17px;">Isoflurane</td>
			<td>Pharmachemie</td>
			<td>45,112,110</td>
			<td></td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;">Anesthesia mask</td>
			<td>Maastricht university</td>
			<td>custom made</td>
			<td></td>
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		<tr height="17">
			<td height="17" style="height:17px;">Midazolam</td>
			<td>Actavis</td>
			<td>AAAC6877</td>
			<td></td>
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			<td height="17" style="height:17px;">Dexmedetomidine</td>
			<td>Orion</td>
			<td>141-267</td>
			<td></td>
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			<td height="17" style="height:17px;">Fentanyl</td>
			<td>Bipharma</td>
			<td>15923002</td>
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			<td height="17" style="height:17px;">Continuous anaesthetic induction chamber</td>
			<td>Vet-tech solutions</td>
			<td>AN010R</td>
			<td></td>
		</tr>
	</tbody>
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a novel murine model of arteriovenous fistula failure: the surgical procedure in detail

The arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient remodeling and intimal hyperplasia from which the exact pathophysiology remains unknown. In order to unravel the pathophysiology a murine model of AVF-failure was developed in which the configuration of the anastomosis resembles the preferred situation in the clinical setting. A model was described in which an AVF is created by connecting the venous end of the branch of the external jugular vein to the side of the common carotid artery using interrupted sutures. At a histological level, we observed progressive stenotic intimal lesions in the venous outflow tract that is also seen in failed human AVFs. Although this procedure can be technically challenging due to the small dimensions of the animal, we were able to achieve a surgical success rate of 97% after sufficient training. The key advantage of a murine model is the availability of transgenic animals. In view of the different proposed mechanisms that are responsible for AVF failure, disabling genes that might play a role in vascular remodeling can help us to unravel the complex pathophysiology of AVF failure.

Efter oprettelsen af anastomose (figur 1), bør åbenheden vurderes af kort tid okkluderende den venøse udstrømning tarmkanalen med en vaskulær pincet. Når anastomose er patentet, bør det vaskulære tarmkanalen proximalt til okklusion klart ekspandere på pulserende vis. Desuden er åbenheden bekræftet ved hjælp nær infrarød gennemlysning (NIRF), der effektivt fungerer som en angiografi (figur 2). En fejl i den kirurgiske procedure kan føre til en okklusion af anastomosen som ...

Watch this Scientific Journal Video about A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail at JoVE.com

A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail

Here we present a murine model of arteriovenous fistula (AVF) failure in which a clinically relevant anastomotic configuration is incorporated. This model can be used to study the pathophysiology and to test possible therapeutic interventions.

A Novel murin model af arteriovenøs fistel Fejl: den kirurgiske procedure i Detail

The arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient remodeling and intimal hyperplasia from which the ...

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