This work was supported in part by the National Institute of Health grant R01-HL095498, as well as with the resources and the use of facilities at the VA Connecticut Healthcare System, West Haven, CT.

1. Anesthesia and Pre-operative Procedures
<ol>
 <li>Induction of general anesthesia 
 Approval by the appropriate Institutional Animal Care and Use Committee is obtained. Male C57/black mice, aged 10 weeks, are anesthetized. Deliver 4% isoflurane with 0.8 L/min oxygen to a Plexiglas box via an isoflurane vaporizer and place the mouse inside. Alternatively, if preferred by the surgeon, intraperitoneal anesthesia can be used.</li>
 <li>Preserving anesthesia 
 After confirmation of anesthesia by lack of reactio...

<ol>
	<li>Allon, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+management+of+vascular+access.">Current management of vascular access.</a> Clinical Journal of the American Society of Nephrology. 2 (4), 786-800 (2007).</li><li>Dixon, B. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Why+don't+fistulas+mature?.">Why don't fistulas mature?.</a> Kidney International. 70 (8), 1413-1422 (2006).</li><li>Roy-Chaudhury, P., Spergel, L. M., Besarab, A., Asif, A., Ravani, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Biology+of+arteriovenous+fistula+failure.">Biology of arteriovenous fistula failure.</a> Journal of Nephrology. 20 (2), 150-163 (2007).</li><li>Kudo, F. A., Muto, A., 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=Venous+identity+is+lost+but+arterial+identity+is+not+gained+during+vein+graft+adaptation.">Venous identity is lost but arterial identity is not gained during vein graft adaptation.</a> Arteriosclerosis, Thrombosis, and Vascular Biology. 27 (7), 1562-1571 (2007).</li><li>Muto, A., Yi, 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=Eph-B4+prevents+venous+adaptive+remodeling+in+the+adult+arterial+environment.">Eph-B4 prevents venous adaptive remodeling in the adult arterial environment.</a> The Journal of Experimental Medicine. 208 (3), 561-575 (2011).</li><li>Croatt, A. J., Grande, J. 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=Characterization+of+a+model+of+an+arteriovenous+fistula+in+the+rat:+the+effect+of+L-NAME.">Characterization of a model of an arteriovenous fistula in the rat: the effect of L-NAME.</a> The American Journal of Pathology. 176 (5), 2530-2541 (2010).</li><li>Misra, S., Fu, A. A., 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=The+rat+femoral+arteriovenous+fistula+model:+increased+expression+of+matrix+metalloproteinase-2+and+-9+at+the+venous+stenosis.">The rat femoral arteriovenous fistula model: increased expression of matrix metalloproteinase-2 and -9 at the venous stenosis.</a> Journal of Vascular and Interventional Radiology. 19 (4), 587-594 (2008).</li><li>Kojima, T., Miyachi, 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=The+relationship+between+venous+hypertension+and+expression+of+vascular+endothelial+growth+factor:+hemodynamic+and+immunohistochemical+examinations+in+a+rat+venous+hypertension+model.">The relationship between venous hypertension and expression of vascular endothelial growth factor: hemodynamic and immunohistochemical examinations in a rat venous hypertension model.</a> Surgical Neurology. 68 (3), 277-284 (2007).</li><li>Caplice, N. M., Wang, 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=Neoangiogenesis+and+the+presence+of+progenitor+cells+in+the+venous+limb+of+an+arteriovenous+fistula+in+the+rat.">Neoangiogenesis and the presence of progenitor cells in the venous limb of an arteriovenous fistula in the rat.</a> American Journal of Physiology Renal Physiology. 293 (2), F470-F475 (2007).</li><li>Nath, K. A., Kanakiriya, S. K., Grande, J. P., Croatt, A. J., Katusic, Z. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+venous+proinflammatory+gene+expression+and+intimal+hyperplasia+in+an+aorto-caval+fistula+model+in+the+rat.">Increased venous proinflammatory gene expression and intimal hyperplasia in an aorto-caval fistula model in the rat.</a> The American Journal of Pathology. 162 (6), 2079-2090 (2003).</li><li>Karram, T., Hoffman, A., 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=Induction+of+cardiac+hypertrophy+by+a+controlled+reproducible+sutureless+aortocaval+shunt+in+the+mouse.">Induction of cardiac hypertrophy by a controlled reproducible sutureless aortocaval shunt in the mouse.</a> Journal of Investigative Surgery. 18 (6), 325-334 (2005).</li><li>Perry, G. J., Mori, 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=Genetic+variation+in+angiotensin-converting+enzyme+does+not+prevent+development+of+cardiac+hypertrophy+or+upregulation+of+angiotensin+II+in+response+to+aortocaval+fistula.">Genetic variation in angiotensin-converting enzyme does not prevent development of cardiac hypertrophy or upregulation of angiotensin II in response to aortocaval fistula.</a> Circulation. 103 (7), 1012-1016 (2001).</li><li>Guzman, R. J., Krystkowiak, A., Zarins, C. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+and+sustained+medial+cell+activation+after+aortocaval+fistula+creation+in+mice.">Early and sustained medial cell activation after aortocaval fistula creation in mice.</a> The Journal of Surgical Research. 108 (1), 112-121 (2002).</li><li>Castier, Y., Lehoux, 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=Characterization+of+neointima+lesions+associated+with+arteriovenous+fistulas+in+a+mouse+model.">Characterization of neointima lesions associated with arteriovenous fistulas in a mouse model.</a> Kidney International. 70 (2), 315-320 (2006).</li></ol>

There are several reports that have described AVF in rats, including femoral AVF,6, 7 carotid to jugular AVF8 and aorto-caval AVF.9, 10 The rat is several times larger than the mouse, allowing easier surgery in the rat compared to the mouse. Nevertheless, in order to take advantage of mouse genetic strains and variants the procedure must be extended to include mouse models. Several previously published reports introduced the AVF model in mice, but these reports have generally been in the ...

The most common option chosen for renal replacement therapy in patients with end stage renal disease is hemodialysis. Access for hemodialysis is performed by arteriovenous fistula (AVF), arteriovenous graft, or temporary catheter placement. Although AVF are the preferred mode of access, AVF are still far from perfect. One-year primary AVF patency rates are only 60-65%, with many failures due to neointimal hyperplasia. The molecular biology and physiology of normal AVF formation and maladaptive formation remains poorly characterized. As such, much is to be gained in improving AVF outcomes with the accompanying gain in understanding of the regulation of fistula formation.1-3
Exposure of a vein to arterial flow is commonly studied in the context of vein grafts that are direct models of surgical bypass.4, 5 Although vein grafts and AVF similarly expose a vein to an arterial environment, there are several critical differences between them. First, the resistance of the distal runoff bed is much lower in AVF, as the AVF drains to the right atrium whereas the vein graft drains to the often diseased distal small arteries, resulting in increased blood flow and shear stress in the AVF. Second, the blood in the venous limb of the AVF can be a mixture of venous and arterial blood leading to lower oxygenation compared to the purely arterial content in the vein graft. Third, the vein in the AVF is not removed from its bed, leading to preservation of its vaso venorum and nervous innervations, compared to the complete transposition of the vein graft into the arterial bed. Lastly, the number of anastomoses is usually two in vein grafts whereas an AVF typically has only one. In this study, we introduce a mouse model of aortocaval fistula that can be used for the study of AVF.

<table border="1">
	<tbody>
		<tr>
			<td>Name of equipment</td>
			<td>Company</td>
			<td>Catalog number</td>
			<td>Comments (optional)</td>
		</tr>
		<tr>
			<td>Vevo 770 ultrasound machine</td>
			<td>Visualsonics</td>
			<td>20-60 Mhz scan head; RMV-704</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>Vascular clamp</td>
			<td>Roboz Surgical Instrument Co.</td>
			<td>RS-5424</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>Clamp applying forceps</td>
			<td>Roboz Surgical Instrument Co.</td>
			<td>RS-5410</td>
			<td>&nbsp;</td>
		</tr>
		<tr>
			<td>25 Gauge Needle</td>
			<td>Becton Dickinson</td>
			<td>BD PrecisionGlide Needle 25 G x 7/8 #305124</td>
			<td>&nbsp;</td>
		</tr>
	</tbody>
</table>

technical aspects of the mouse aortocaval fistula

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta and inferior vena cava (IVC) are exposed. The proximal infrarenal aorta and the distal aorta are dissected for clamp placement and needle puncture, respectively. Special attention is paid to avoid dissection between the aorta and the IVC. After clamping the aorta, a 25 G needle is used to puncture both walls of the aorta into the IVC. The surrounding connective tissue is used for hemostatic compression. Successful creation of the AVF will show pulsatile arterial blood flow in the IVC. Further confirmation of successful AVF can be achieved by post-operative Doppler ultrasound.

After practice, survival on the first post-operative day is typically over 95%; at post-operative day 7, survival was 91.3%. Figures 1 and 2 show the ideal puncture site in coronal and cross-sectional views; placement of the puncture site is critical to obtaining good survival without excessive hemorrhage. Intra-operative deaths and early post-operative deaths are typically due to hemorrhage. This tends to occur with excessive dissection between the aorta and the IVC, or from inadequate hemostatic pressu...

Watch this Scientific Journal Video about Technical Aspects of the Mouse Aortocaval Fistula at JoVE.com

Technical Aspects of the Mouse Aortocaval Fistula

The goal is to produce an arteriovenous fistula that is simple and reproducible. This method does not use sutures or glue adhesive. Therefore the samples can be used with the least amount of foreign materials for analysis.

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta ...

technical-aspects-of-the-mouse-aortocaval-fistula

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JoVE Journal

Medicine

16.1K 次观看.  Yale University. 我们的目标是产生一个动静脉瘘，操作简便，重现。此方法不使用缝线或胶水粘合。因此，样品可以用最少的异物的量进行分析。