Name: murine model of femoral artery wire injury with implantation of a perivascular drug delivery patch
Uploaded: 2015-02-10T14:00:00
Description: Watch this Scientific Journal Video about Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch at JoVE.com

The authors would like to acknowledge support through the American Heart Association (10SDG2630139), the Welch Foundation and through the NIH Director&#8217;s New Innovator Grant (1DP2 OD008716-01). The authors would like to thank the services provided by the ICMB (Institute of Cellular and Molecular Biology) core facility and TherapeUTex at University of Texas at Austin.

NOTE: All methods shown in this protocol have been approved by the Institutional Animal Care and Use Committee.
1. Preparation of Surgical Table
<ol>
	<li>Set up the heating pad with recirculating warm water on the surgical table, under the dissection microscope. Place the stainless steel base plate onto the heating pad. Place a sterile absorbent pad on the base plate and heating pad.</li>
	<li>Arrange sterile surgical tools on an adjacent sterile absorbent pad. Gather two pairs of angled fi...

<ol>
	<li>Hoffmann, R., Mintz, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+in-stent+restenosis+-+predictors,+treatment+and+prevention.">Coronary in-stent restenosis - predictors, treatment and prevention.</a> Eur Heart J. 21 (21), 1739-1749 (2000).</li><li>Erbel, R., 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=Coronary-artery+stenting+compared+with+balloon+angioplasty+for+restenosis+after+initial+balloon+angioplasty.+Restenosis+Stent+Study+Group.">Coronary-artery stenting compared with balloon angioplasty for restenosis after initial balloon angioplasty. Restenosis Stent Study Group.</a> N Engl J Med. 339 (23), 1672-1678 (1998).</li><li>Farooq, V., Gogas, B. D., Serruys, P. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Restenosis:+delineating+the+numerous+causes+of+drug-eluting+stent+restenosis.">Restenosis: delineating the numerous causes of drug-eluting stent restenosis.</a> Circ Cardiovasc Interv. 4 (2), 195-205 (2011).</li><li>Iqbal, J., Gunn, J., Serruys, P. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+stents:+historical+development,+current+status+and+future+directions.">Coronary stents: historical development, current status and future directions.</a> Br Med Bull. 106, 193-211 (2013).</li><li>Garg, S., Serruys, P. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+stents:+current+status.">Coronary stents: current status.</a> J Am Coll Cardiol. 56 (10 Suppl), S1-S42 (2010).</li><li>Park, S. J., Kim, Y. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+status+of+percutaneous+coronary+intervention+with+drug-eluting+stents+in+Asia.">Current status of percutaneous coronary intervention with drug-eluting stents in Asia.</a> Circulation. 118 (25), 2730-2737 (2008).</li><li>Alfonso, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+drug-eluting+stent+restenosis+the+new+pilgrimage:+quo+vadis.">Treatment of drug-eluting stent restenosis the new pilgrimage: quo vadis.</a> J Am Coll Cardiol. 55 (24), 2717-2720 (2010).</li><li>Dake, M. 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=Paclitaxel-eluting+stents+show+superiority+to+balloon+angioplasty+and+bare+metal+stents+in+femoropopliteal+disease:+twelve-month+Zilver+PTX+randomized+study+results.">Paclitaxel-eluting stents show superiority to balloon angioplasty and bare metal stents in femoropopliteal disease: twelve-month Zilver PTX randomized study results.</a> Circ Cardiovasc Interv. 4 (5), 495-504 (2011).</li><li>Bosiers, 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=Results+of+the+Protege+EverFlex+200-mm-long+nitinol+stent+(ev3)+in+TASC+C+and+D+femoropopliteal+lesions.">Results of the Protege EverFlex 200-mm-long nitinol stent (ev3) in TASC C and D femoropopliteal lesions.</a> J Vasc Surg. 54 (4), 1042-1050 (2011).</li><li>Duda, S. H., 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=Drug-eluting+and+bare+nitinol+stents+for+the+treatment+of+atherosclerotic+lesions+in+the+superficial+femoral+artery:+long-term+results+from+the+SIROCCO+trial.">Drug-eluting and bare nitinol stents for the treatment of atherosclerotic lesions in the superficial femoral artery: long-term results from the SIROCCO trial.</a> J Endovasc Ther. 13 (6), 701-710 (2006).</li><li>Kumar, A., Lindner, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remodeling+with+neointima+formation+in+the+mouse+carotid+artery+after+cessation+of+blood+flow.">Remodeling with neointima formation in the mouse carotid artery after cessation of blood flow.</a> Arterioscler Thromb Vasc Biol. 17 (10), 2238-2244 (1997).</li><li>Sata, 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=A+mouse+model+of+vascular+injury+that+induces+rapid+onset+of+medial+cell+apoptosis+followed+by+reproducible+neointimal+hyperplasia.">A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia.</a> J Mol Cell Cardiol. 32 (11), 2097-2104 (2000).</li><li>Roque, 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=Mouse+model+of+femoral+artery+denudation+injury+associated+with+the+rapid+accumulation+of+adhesion+molecules+on+the+luminal+surface+and+recruitment+of+neutrophils.">Mouse model of femoral artery denudation injury associated with the rapid accumulation of adhesion molecules on the luminal surface and recruitment of neutrophils.</a> Arterioscler Thromb Vasc Biol. 20 (2), 335-342 (2000).</li><li>Lindner, V., Fingerle, J., Reidy, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+model+of+arterial+injury.">Mouse model of arterial injury.</a> Circ Res. 73 (5), 792-796 (1993).</li><li>Edelman, E. R., Adams, D. H., Karnovsky, 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=Effect+of+controlled+adventitial+heparin+delivery+on+smooth+muscle+cell+proliferation+following+endothelial+injury.">Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury.</a> Proc Natl Acad Sci U S A. 87 (10), 3773-3777 (1990).</li><li>Stemerman, M. B., Ross, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+arteriosclerosis.+I.+Fibrous+plaque+formation+in+primates,+an+electron+microscope+study.">Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscope study.</a> J Exp Med. 136 (4), 769-789 (1972).</li><li>Brouchet, L., 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=Estradiol+accelerates+reendothelialization+in+mouse+carotid+artery+through+estrogen+receptor-alpha+but+not+estrogen+receptor-beta.">Estradiol accelerates reendothelialization in mouse carotid artery through estrogen receptor-alpha but not estrogen receptor-beta.</a> Circulation. 103 (3), 423-428 (2001).</li><li>Filipe, C., 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=Estradiol+accelerates+endothelial+healing+through+the+retrograde+commitment+of+uninjured+endothelium.">Estradiol accelerates endothelial healing through the retrograde commitment of uninjured endothelium.</a> Am J Physiol Heart Circ Physiol. 294 (6), H2822-H2830 (2008).</li><li>Feuls, R., 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=Microvascular+denudation+of+the+femoral+artery+of+the+mouse+as+a+model+for+restenosis.">Microvascular denudation of the femoral artery of the mouse as a model for restenosis.</a> Rofo. 175 (7), 952-957 (2003).</li><li>Holt, A. W., Tulis, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+Rat+and+Mouse+Carotid+Artery+Surgery:+Injury+&amp;+Remodeling+Studies.">Experimental Rat and Mouse Carotid Artery Surgery: Injury &amp; Remodeling Studies.</a> ISRN Minim Invasive Surg. 2013, (2013).</li><li>Iafrati, M. 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=Estrogen+inhibits+the+vascular+injury+response+in+estrogen+receptor+alpha-deficient+mice.">Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice.</a> Nat Med. 3 (5), 545-548 (1997).</li><li>Sullivan, T. R., 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=Estrogen+inhibits+the+response-to-injury+in+a+mouse+carotid+artery+model.">Estrogen inhibits the response-to-injury in a mouse carotid artery model.</a> J Clin Invest. 96 (5), 2482-2488 (1995).</li><li>Yin, Y., Zhao, X., Fang, Y., Huang, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Carotid+artery+wire+injury+mouse+model+with+a+nonmicrosurgical+procedure.">Carotid artery wire injury mouse model with a nonmicrosurgical procedure.</a> Vascular. 18 (4), 221-226 (2010).</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> Am J Physiol Heart Circ Physiol. 297 (4), H1535-H1543 (2009).</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=A+model+of+disturbed+flow-induced+atherosclerosis+in+mouse+carotid+artery+by+partial+ligation+and+a+simple+method+of+RNA+isolation+from+carotid+endothelium.">A model of disturbed flow-induced atherosclerosis in mouse carotid artery by partial ligation and a simple method of RNA isolation from carotid endothelium.</a> J Vis Exp. (40), (2010).</li><li>Kuhlmann, M. 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=Implantation+of+a+carotid+cuff+for+triggering+shear-stress+induced+atherosclerosis+in+mice.">Implantation of a carotid cuff for triggering shear-stress induced atherosclerosis in mice.</a> J Vis Exp. (59), (2012).</li><li>Carmeliet, 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=Vascular+wound+healing+and+neointima+formation+induced+by+perivascular+electric+injury+in+mice.">Vascular wound healing and neointima formation induced by perivascular electric injury in mice.</a> Am J Pathol. 150 (2), 761-776 (1997).</li></ol>

We have presented a method for performing vascular injury in mice and delivery therapeutic compounds to the injured region through a perivascular cuff. The ligation method for femoral and carotid arteries has been described in conventional methods papers and characterized extensively11-14,19-23 and we present an alternative method for achieving the same vascular injury that is less technically demanding procedure that can often be used in younger mice. One of the chief advantages of the using a mouse wire inju...

Arterial injury and inflammation caused by angioplasty and stent implantation can induce neointimal hyperplasia that contributes to the thickening of the arterial wall, a process known as restenosis.1,2 The formation of restenosis is major mode of failure for interventions such as angioplasty and stenting with bare metal stents.3 Due to recent concerns with the inhibition of vascular healing in arteries treated with drug eluting stents, there is also a need to find compounds that can inhibit restenosis while maintaining vascular healing and re-endothelialization.4-7 In addition, while stents have had success in the coronary vasculature, percutaneous interventions of all types in the peripheral arteries continue to fail at a higher rate due to restenosis.8-10 Mouse models of surgical interventions allow the use of powerful genetic manipulations that can provide mechanistic insight into the mechanisms underlying the failure of clinical therapies and can provide an initial test bed for compounds to inhibit intimal hyperplasia. 
Here, we describe a mouse model of vascular injury that allows the testing of therapeutic compounds to inhibit neointimal hyperplasia and assess whether their effects on re-endothelialization following endothelial denudation. A key challenge in executing vascular injury in mice is the technical skill needed to obtain vascular access and to restore flow to the injured artery following the wire injury. For this reason, simple arterial ligation models have been used to study neointimal hyperplasia in mice that do not require endovascular manipulations but are easier to implement.11 However, this type of surgical model differs substantially from the mechanical and biological aspects of a percutaneous intervention, lacking key aspects including arterial wall stretch, endothelial denudation and luminal blood flow following injury. 
We present two methods for obtaining and closing vascular access for wire injury of the femoral artery in mice. The first technique is the conventional method described by several groups previously and uses vascular access through a side branch of the femoral artery.12-14 This method requires older, larger mice and more surgical skill to implement the endoluminal access through the smaller artery. It also requires the ligation of the muscular branch of the femoral artery following the procedure. The second method we describe uses an arteriotomy in the branch point of the main and side branch and thereby allows for a larger access to the artery for performing wire injury. In this method, the arteriotomy is closed using controlled local cauterization that leaves both branches with blood flow following the procedure. The conventional method is applicable to mice of at least 20 weeks of age while the alternative method can be used in mice of at least 15 weeks of age. In both methods, the wire creates arterial stretch and abrasion leading to injury and endothelial denudation. Following either procedure a perivascular drug delivery patch can be implanted that allows the delivery of compounds to alter the response to injury. The use of the drug delivery patch allows mice to be used as a test bed for new compounds to inhibit restenosis through perivascular therapies.15,16

<table border="0" cellpadding="0" cellspacing="0" width="956">
	<tbody>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Name</td>
			<td style="width:239px;">Company</td>
			<td style="width:239px;">Catalog Number</td>
			<td style="width:239px;">Comments</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Straight spring wire, 0.15&#8221; diameter</td>
			<td style="width:239px;">Cook</td>
			<td style="width:239px;">G02426</td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">High Temperature cautery</td>
			<td style="width:239px;">Bovie Medical Corp.</td>
			<td style="width:239px;">HIT1</td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">High-temperature fine tip for cautery</td>
			<td style="width:239px;">Bovie Medical Corp.</td>
			<td style="width:239px;">H101</td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Micro-scissors</td>
			<td style="width:239px;">Fine Science Tools</td>
			<td style="width:239px;">15000-13</td>
			<td style="width:239px;">For performance of arteriotomy</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:239px;">Angled fine-tipped forceps</td>
			<td style="width:239px;">Fine Science Tools</td>
			<td style="width:239px;">11251-35</td>
			<td style="width:239px;">For blunt dissection of vascular bundle</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Angled forceps</td>
			<td style="width:239px;">Roboz</td>
			<td style="width:239px;">RS-5069</td>
			<td style="width:239px;">For clearing tissues</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Surgical scissors</td>
			<td style="width:239px;">Roboz</td>
			<td style="width:239px;">RS-5840</td>
			<td style="width:239px;">For cutting skin</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Retractor</td>
			<td style="width:239px;">Fine Science Tools</td>
			<td style="width:239px;">18200-10</td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Retractor wire</td>
			<td style="width:239px;">Fine Science Tools</td>
			<td style="width:239px;">18200-05</td>
			<td style="width:239px;">Attached to retractor</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Base plate</td>
			<td style="width:239px;">Fine Science Tools</td>
			<td style="width:239px;">18200-03</td>
			<td style="width:239px;">For use with retractor</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Magnetic retractor fixator</td>
			<td style="width:239px;">Fine Science Tools</td>
			<td style="width:239px;">18200-01</td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Needle Holder</td>
			<td style="width:239px;">Roboz</td>
			<td style="width:239px;">RS-7822</td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:239px;">Hemostatic forceps</td>
			<td style="width:239px;">Biomedical Research Instruments, Inc.</td>
			<td style="width:239px;">34-1000</td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Dissecting microscope</td>
			<td style="width:239px;">Meiji Techno</td>
			<td style="width:239px;">EMZ-5TR</td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Microscope light source</td>
			<td style="width:239px;">Meiji Techno</td>
			<td style="width:239px;">FT191</td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:239px;">Warm water recirculator</td>
			<td style="width:239px;">Gaymar</td>
			<td style="width:239px;">TP-500</td>
			<td style="width:239px;">For maintaining mouse body temperature</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:239px;">Reusable heating pad</td>
			<td style="width:239px;">Gaymar</td>
			<td style="width:239px;">TP-R 22G</td>
			<td style="width:239px;">For maintaining mouse body temperature</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Lidocaine</td>
			<td style="width:239px;">Various</td>
			<td style="width:239px;"></td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:239px;">4.0 Vicryl suture with half circle needle</td>
			<td style="width:239px;">Ethicon</td>
			<td style="width:239px;">J494G</td>
			<td style="width:239px;">For post-surgical wound closure</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:239px;">Sterile cotton-tipped applicators</td>
			<td style="width:239px;">Puritan</td>
			<td style="width:239px;">25-806-2WC</td>
			<td style="width:239px;">For application of depilatory cream and absorbing fluids</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Depilatory cream</td>
			<td style="width:239px;">Nair</td>
			<td style="width:239px;"></td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Isoflurane</td>
			<td style="width:239px;">Various</td>
			<td style="width:239px;"></td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Betadine</td>
			<td style="width:239px;">Various</td>
			<td style="width:239px;"></td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">70% ethanol</td>
			<td style="width:239px;">Various</td>
			<td style="width:239px;"></td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:239px;">6.0 braided silk suture</td>
			<td style="width:239px;">Teleflex Medical</td>
			<td style="width:239px;">4-S</td>
			<td style="width:239px;">For isolation of femoral artery during surgery</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">0.9% sodium chloride</td>
			<td style="width:239px;">Various</td>
			<td style="width:239px;"></td>
			<td style="width:239px;">For irrigating tissues</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Gel eye lubricant</td>
			<td style="width:239px;">Various</td>
			<td style="width:239px;"></td>
			<td style="width:239px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Glass petri dish</td>
			<td style="width:239px;">Pyrex</td>
			<td>3160-60</td>
			<td>For femoral artery harvest</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">10% buffered formalin</td>
			<td style="width:239px;">Various</td>
			<td></td>
			<td style="width:239px;">For fixation of femoral artery</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">70% ethanol</td>
			<td style="width:239px;">Various</td>
			<td></td>
			<td style="width:239px;">For fixation of femoral artery</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Bouin&#39;s fluid</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td></td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Alcian blue, 1%</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>26385-01</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Alkaline alcohol</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>26385-02</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Orcein, 0.2%</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>26385-03</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Hematoxylin alcoholic, 5%</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>26385-04</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Ferric chloride, 10%</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>26385-05</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Lugol&#39;s Iodine</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>26385-06</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:239px;">Woodstain scarlet-acid fuchsin working solution</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>26385-07</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Acetic acid, 0.5%</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>Various</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Phosphotungstic acid, 5%</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>26385-09</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:239px;">Alcoholic saffron, 6%</td>
			<td style="width:239px;">Electron Microscopy Sciences</td>
			<td>26385-10</td>
			<td style="width:239px;">For Movat&#39;s Pentachrome staining</td>
		</tr>
	</tbody>
</table>

murine model of femoral artery wire injury with implantation of a perivascular drug delivery patch

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. While these therapies lead to the rapid restoration of blood flow, these technologies remain limited by restenosis in the case of bare metal stents and angioplasty, or reduced healing and possibly enhanced risk of thrombosis in the case of drug eluting stents. A key pathophysiological mechanism in the formation of restenosis is intimal hyperplasia caused by the activation of vascular smooth muscle cells and inflammation due to arterial stretch and injury. Surgeries that induce arterial injury in genetically modified mice are useful for the mechanistic study of the vascular response to injury but are often technically challenging to perform in mouse models due to the their small size and lack of appropriate sized devices. We describe two approaches for a surgical technique that induces endothelial denudation and arterial stretch in the femoral artery of mice to produce robust neointimal hyperplasia. The first approach creates an arteriotomy in the muscular branch of the femoral artery to obtain vascular access. Following wire injury this arterial branch is ligated to close the arteriotomy. A second approach creates an arteriotomy in the main femoral artery that is later closed through localized cautery. This method allows for vascular access through a larger vessel and, consequently, provides a less technically demanding procedure that can be used in smaller mice. Following either method of arterial injury, a degradable drug delivery patch can be placed over or around the injured artery to deliver therapeutic agents.

Following wire injury, neointimal hyperplasia develops over time and is typically examined after 14 to 28 days. The techniques described in this work lead to robust generation of intimal hyperplasia in mice as shown the histological results in Figure 3. An uninjured femoral artery will demonstrate intact elastic lamellae and a normal thickness and circumference. An injured femoral artery will show intimal hyperplasia, degraded elastic lamellae and demonstrate re-endothelialization at later time points. R...

Watch this Scientific Journal Video about Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch at JoVE.com

Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch

We describe a surgical technique that produces wire injury in the femoral artery of mice to induce neointimal hyperplasia to serve as a model testing system for the perivascular delivery of therapeutic compounds for the inhibition of restenosis.

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. ...

Research

JoVE Journal

Medicine

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography

Proximal resistance vessels, such as the mesenteric arteries, contribute substantially to the peripheral resistance. These small vessels of between ...

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite  the considerable progress made in the stent development in the last decades,  cardiovascular diseases remain the main cause of death in western ...

A Murine Model of Myocardial Ischemia-reperfusion Injury through Ligation of the Left Anterior Descending Artery

Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms ...

A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to ...

Murine Model of Intestinal Ischemia-reperfusion Injury

Intestinal ischemia is a life-threatening condition associated with a broad range of clinical conditions including atherosclerosis, thrombosis, ...

Induction of Accelerated Atherosclerosis in Mice: The "Wire-Injury" Model

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. ...

The Rabbit Model of Accelerated Atherosclerosis: A Methodological Perspective of the Iliac Artery Balloon Injury

Acute coronary syndrome resulting from coronary occlusion following atherosclerotic plaque development and rupture is the leading cause of death in the ...

Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the ...