Name: murine model of central venous stenosis using aortocaval fistula with an outflow stenosis
Uploaded: 2019-07-11T13:00:00
Description: Watch this Scientific Journal Video about Murine Model of Central Venous Stenosis using Aortocaval Fistula with an Outflow Stenosis at JoVE.com

This work was supported by US National Institute of Health (NIH) Grant R01-HL128406; the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Program Merit Review Award I01-BX002336; as well as with the resources and the use of facilities at the VA Connecticut Healthcare System, West Haven, CT.

All experiments were performed with approval from the Yale University Institutional Animal Care and Use Committee (IACUC).
1. Anesthesia and pre-operative procedures
<ol>
	<li>Sterilize all surgical instruments and materials by autoclaving. Turn on the thermal support device to be certain it is warm (40&#8211;42 &#176;C).</li>
	<li>Place a 9&#8211;11-week old C57BL/6 mouse into an acrylic induction chamber and anesthetize it with vaporized 2.5% isoflurane and 0.8 L/min oxygen. Anesthesia ind...

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	<li>Dember, L. M., 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=Effect+of+clopidogrel+on+early+failure+of+arteriovenous+fistulas+for+hemodialysis:+a+randomized+controlled+trial.">Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial.</a> JAMA. 299 (18), 2164-2171 (2008).</li><li>Dixon, B. 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(130), (2017).</li><li>Nam, D., 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=Partial+carotid+ligation+is+a+model+of+acutely+induced+disturbed+flow,+leading+to+rapid+endothelial+dysfunction+and+atherosclerosis.">Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis.</a> American Journal of Physiology: Heart and Circulatory Physiology. 297 (4), H1535-H1543 (2009).</li><li>Ene-Iordache, B., Remuzzi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Disturbed+flow+in+radial-cephalic+arteriovenous+fistulae+for+haemodialysis:+low+and+oscillating+shear+stress+locates+the+sites+of+stenosis.">Disturbed flow in radial-cephalic arteriovenous fistulae for haemodialysis: low and oscillating shear stress locates the sites of stenosis.</a> Nephrology, Dialysis, Transplantation. 27 (1), 358-368 (2012).</li><li>Yamamoto, 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=Disturbed+shear+stress+reduces+Klf2+expression+in+arterial-venous+fistulae+in+vivo.">Disturbed shear stress reduces Klf2 expression in arterial-venous fistulae in vivo.</a> Physiological reports. 3, (2015).</li><li>Remuzzi, A., Ene-Iordache, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+paradigms+for+dialysis+vascular+access:+upstream+hemodynamics+and+vascular+remodeling+in+dialysis+access+stenosis.">Novel paradigms for dialysis vascular access: upstream hemodynamics and vascular remodeling in dialysis access stenosis.</a> Clinical Journal of the American Society of Nephrology. 8 (12), 2186-2193 (2013).</li></ol>

The murine AVF model has been used to study the basic mechanisms and molecular events leading to AVF maturation13,14. In this study, we modified an established murine AVF model to create a novel murine aortocaval fistula model with an IVC stenosis in the outflow tract of the fistula. Our ligation model is similar to several previously described murine models that use vascular ligation. A murine model of deep vein thrombosis was created using partial IVC ligation ...

Arteriovenous fistulae (AVF) are the most common accesses for hemodialysis, with superior patency and reduced infection compared to other accesses such as grafts or central venous catheters. However, up to 60% of AVF fail to mature1,2,3; a recent systematic review reported that primary patency rates at 1 year were only 60%4. Stenosis along the venous outflow predominantly causes failure of AVF maturation5,6. There are certain characteristic locations prone to stenosis proximal to the fistula: the juxtaanastomotic swing segment for the radiocephalic fistula, the cephalic arch region for the brachiocephalic fistula and the central vein for the fistula with previously placed ipsilateral subclavian or internal jugular vein catheters7,8.
Central venous stenosis is often asymptomatic in patients without an AVF, but can cause ipsilateral extremity edema by venous hypertension as well as failure of fistula maturation when challenged by fistula flow9. The pathophysiology of central venous stenosis is most likely related to inflammation and the activated coagulation cascade after device placement. Furthermore, constant movement of the catheter tip as well as increased flow from the fistula can alter shear stress, resulting in platelet deposition and venous wall thickening10. To understand the basic mechanisms underlying AVF failure caused by central venous stenosis, an animal model mimicking central venous stenosis with an AVF is required.
We have established a murine aortocaval fistula model that is easy to perform and master and recapitulates the clinical course of human AVF.11 We applied the concepts and technique of several previously established murine models to create a novel murine AVF model with venous stenosis. We introduce a murine aortocaval fistula model with an IVC stenosis in the outflow fistula that can be used for the study of central venous stenosis.

<table>
	<tbody>
		<tr>
			<td>20-60 Mhz scan head</td>
			<td>VisualSonics Inc.</td>
			<td>RMV-704</td>
			<td></td>
		</tr>
		<tr>
			<td>8-0 Sterile Micro Suture, 6mm (140 &#181;), 3/8 Circle, TAP Point Needle</td>
			<td>AROSuture</td>
			<td>T06A08N14-13</td>
			<td>polyamide monofilament sutures</td>
		</tr>
		<tr>
			<td>Induction Chamber, 2 Liter 
			3.75&#34;W x 9.00&#34;D x 3.75&#34;H</td>
			<td>VetEquip</td>
			<td>941444</td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflo, Isoflurane liquid</td>
			<td>Zoetis</td>
			<td>26675-46-7</td>
			<td></td>
		</tr>
		<tr>
			<td>Mice, C57BL/6J</td>
			<td>The Jackson Laboratory</td>
			<td>664</td>
			<td></td>
		</tr>
		<tr>
			<td>Pet Bed Microwave Heating Pad</td>
			<td>Snuggle Safe</td>
			<td>6250</td>
			<td></td>
		</tr>
		<tr>
			<td>PrecisionGlide Needle 25G</td>
			<td>BD</td>
			<td>305122</td>
			<td></td>
		</tr>
		<tr>
			<td>Surflo I.V. Catheter 22G</td>
			<td>Terumo</td>
			<td>SR-OX2225CA</td>
			<td>0.85mm outer diameter</td>
		</tr>
		<tr>
			<td>Vascular clamp</td>
			<td>Roboz Surgical Instrument</td>
			<td>RS-5424</td>
			<td></td>
		</tr>
		<tr>
			<td>Vevo770 High Resolution Imaging System</td>
			<td>VisualSonics Inc.</td>
			<td>770</td>
			<td></td>
		</tr>
	</tbody>
</table>

murine model of central venous stenosis using aortocaval fistula with an outflow stenosis

Central venous stenosis is an important entity contributing to arteriovenous fistula (AVF) failure. A murine AVF model was modified to create a partial ligation of the inferior vena cava (IVC) in the outflow of the fistula, mimicking central venous stenosis. Technical aspects of this model are introduced. The aorta and IVC are exposed, following an abdominal incision. The infra-renal aorta and IVC are dissected for proximal clamping, and the distal aorta is exposed for puncture. The IVC at the midpoint between the left renal vein and the aortic bifurcation is carefully dissected to place an 8-0 suture beneath the IVC. After clamping the aorta and IVC, an AVF is created by puncturing the infra-renal aorta through both walls into the IVC with a 25 G needle, followed by ligating a 22 G intra-venous (IV) catheter and IVC together. The catheter is then removed, creating a reproducible venous stenosis without occlusion. The aorta and IVC are unclamped after confirming primary hemostasis. This novel model of central vein stenosis is easy to perform, reproducible, and will facilitate studies on AVF failure.

Male mice underwent the operation mentioned above to create both an AVF and an IVC stenosis. Control mice underwent only laparotomy and dissection of the tissues surrounding the IVC, e.g., a sham procedure, or only creation of an IVC stenosis without simultaneous creation of an AVF.
The IVC was observed with Doppler ultrasound on day 7 after the surgical procedure (Figure 2). The fistula and stenosi...

Watch this Scientific Journal Video about Murine Model of Central Venous Stenosis using Aortocaval Fistula with an Outflow Stenosis at JoVE.com

Murine Model of Central Venous Stenosis using Aortocaval Fistula with an Outflow Stenosis

An aortocaval fistula was created by puncturing the murine infra-renal aorta through both walls into the inferior vena cava and was followed by creation of a stenosis in its outflow via partial ligation of the inferior vena cava. This reproducible model can be used to study central venous stenosis.

Central venous stenosis is an important entity contributing to arteriovenous fistula (AVF) failure. A murine AVF model was modified to create a partial ...

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