Name: human internal mammary artery (ima) transplantation and stenting: a human model to study the development of in-stent restenosis
Uploaded: 2012-05-09T12:00:00
Description: Watch this Scientific Journal Video about Human Internal Mammary Artery IMA Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis at JoVE.com

The authors thank Christiane Pahrmann for her contribution. Special thanks to Ethicon, Norderstedt, Hamburg (Germany) for providing the suture material.
Funding
Sonja Schrepfer has received a research grant from the Deutsche Forschungsgemeinschaft (DFG) (SCHR992/3 1 and SCHR992/4-1).] The work was supported by the ISHLT Shumway Career Development Grant 2010 and the Falk Research Funding (Stanford University).

1. Internal Mammary Artery (IMA) Preparation
<ol>
	<li>The arterial endothelium is denuded by the passage of a 2-french Fogarty arterial embolectomy catheter (Baxter Healthcare, Deerfield, IL, USA). The catheter is pulled through the whole vessel length twice to ensure endothelial damage.</li>
	<li>Use any human stent of 8mm length and 2.5 mm-3 mm in diameter (e.g. Translumina, Yukon stent). CAUTION: The diameter of the stent should not exceed the vessel diameter by more than 10% to avoid pre- and post-stent stenosis. ...

<ol>
	<li>Deuse, T., Ikeno, F., Robbins, R. C., Schrepfer, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Imaging+In-Stent+Restenosis:+An+Inexpensive,+Reliable,+and+Rapid+Preclinical+Model.">Imaging In-Stent Restenosis: An Inexpensive, Reliable, and Rapid Preclinical Model.</a> J. Vis. Exp. (31), e1346 (2009).</li><li>Oyamada, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trans-iliac+rat+aorta+stenting:+a+novel+high+throughput+preclinical+stent+model+for+restenosis+and+thrombosis.">Trans-iliac rat aorta stenting: a novel high throughput preclinical stent model for restenosis and thrombosis.</a> J. Surg. Res. 166, e91-e95 (2011).</li><li>Chamberlain, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+mouse+model+of+in+situ+stenting.">A novel mouse model of in situ stenting.</a> Cardiovascular research. 85, 38-44 (2010).</li><li>Deuse, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Introducing+the+first+polymer-free+leflunomide+eluting+stent.">Introducing the first polymer-free leflunomide eluting stent.</a> Atherosclerosis. 200, 126-134 (2008).</li><li>Finn, A. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+healing+after+sirolimus,+paclitaxel,+and+bare+metal+stent+placement+in+combination+with+peroxisome+proliferator-activator+receptor+gamma+agonists:+requirement+for+mTOR/Akt2+in+PPARgamma+activation.">Differential healing after sirolimus, paclitaxel, and bare metal stent placement in combination with peroxisome proliferator-activator receptor gamma agonists: requirement for mTOR/Akt2 in PPARgamma activation.</a> Circulation research. 105, 1003-1012 (2009).</li><li>Tellez, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+bare+metal+stent+implantation+in+homozygous+LDL+receptor+deficient+swine+induces+a+neointimal+formation+pattern+similar+to+humans.">Coronary bare metal stent implantation in homozygous LDL receptor deficient swine induces a neointimal formation pattern similar to humans.</a> Atherosclerosis. 213, 518-524 (2010).</li><li>Suzuki, Y., Yeung, A. C., Ikeno, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+pre-clinical+animal+model+in+the+translational+research+of+interventional+cardiology.">The pre-clinical animal model in the translational research of interventional cardiology.</a> JACC Cardiovasc. Interv. 2, 373-383 (2009).</li><li>Holt, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intimal+proliferation+in+an+organ+culture+of+human+internal+mammary+artery.">Intimal proliferation in an organ culture of human internal mammary artery.</a> Cardiovascular research. 26, 1189-1194 (1992).</li><li>Swanson, N., Javed, Q., Hogrefe, K., Gershlick, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+internal+mammary+artery+organ+culture+model+of+coronary+stenting:+a+novel+investigation+of+smooth+muscle+cell+response+to+drug-eluting+stents.">Human internal mammary artery organ culture model of coronary stenting: a novel investigation of smooth muscle cell response to drug-eluting stents.</a> Clin. Sci. (Lond). 103, 347-353 (2002).</li></ol>

Although different in vivo research models are existing to investigate the development of intimal hyperplasia after stent placement, these models still facing translational hurdles to overcome. Furthermore, large animal models are expensive and special housing conditions as well as surgical equipment is not available for all laboratories.
Using a human IMA to study the development of human intimal proliferation and in-stent restenosis was studied before ex situ in organ ...

<table border="1">
<tbody>
 <tr>
 <td>Name of the reagent</td>
 <td>Company</td>
 <td>Catalog number</td>
 <td>Comments </td>
 </tr>
 <tr>
 <td>2 French Fogarty catheter</td>
 <td>Baxter Healthcare, Deerfield, IL, USA</td>
 <td>120602F</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Yukon Stent</td>
 <td>Translumina GmbH, Hechingen, Germany</td>
 <td>&nbsp;</td>
 <td>Use the stent of your choice according to your study protocol</td>
 </tr>
 <tr>
 <td>RPMI media</td>
 <td>Biochrom </td>
 <td>Nr.F1275 </td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>heparin</td>
 <td>Baxter</td>
 <td>2B0953 </td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>isoflurane</td>
 <td>Abbot</td>
 <td>B506 </td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Provo-Iodine</td>
 <td>Betadine Puredue Pharma</td>
 <td>EAN:5995327165830 </td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>80% ethanol</td>
 <td>Geyer</td>
 <td>ETV 80/0500</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Micro clamp</td>
 <td>Harvard Apparatus</td>
 <td>PY2-61-0186</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Sutures 8-0</td>
 <td>Johnson&amp; Johnson,</td>
 <td>2808G</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Sutures 6-0</td>
 <td>Johnson&amp; Johnson,</td>
 <td>1698 H </td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Carprofen</td>
 <td>Feizer Vet</td>
 <td>PZN:0110208</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Metamizol</td>
 <td>Ratiopharm</td>
 <td>&nbsp;</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Target retrieval solution, pH9</td>
 <td>Dako</td>
 <td>S2368 </td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Image-iT FX signal enhancer </td>
 <td>Invitrogen</td>
 <td>I36933 </td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>mouse monoclonal anti-GFP antibody </td>
 <td>BD living colors</td>
 <td>632381 </td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>primary antibody diluent </td>
 <td>Dako</td>
 <td>S3022</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>goat-anti-mouse IgG, Alexa Fluor 488 </td>
 <td>Invitrogen</td>
 <td>A11017</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>secondary antibody diluent </td>
 <td>Dako</td>
 <td>S0809</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>rabbit polycolonal anti-smooth muscle &alpha;-actin </td>
 <td>Abcam,</td>
 <td>ab5694</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>goat-anti-rabbit IgG, Alexa Fluor 555 </td>
 <td>Invitrogen</td>
 <td>A21430</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Prolong Gold antifade reagent</td>
 <td>Invitrogen</td>
 <td>P36930</td>
 <td>&nbsp;</td>
 </tr>
 </tbody>
</table>

human internal mammary artery (ima) transplantation and stenting: a human model to study the development of in-stent restenosis

Preclinical in vivo research models to investigate pathobiological and pathophysiological processes in the development of intimal hyperplasia after vessel stenting are crucial for translational approaches1,2.
The commonly used animal models include mice, rats, rabbits, and pigs3-5. However, the translation of these models into clinical settings remains difficult, since those biological processes are already studied in animal vessels but never performed before in human research models6,7. In this video we demonstrate a new humanized model to overcome this translational gap. The shown procedure is reproducible, easy, and fast to perform and is suitable to study the development of intimal hyperplasia and the applicability of diverse stents.
This video shows how to perform the stent technique in human vessels followed by transplantation into immunodeficient rats, and identifies the origin of proliferating cells as human.

Watch this Scientific Journal Video about Human Internal Mammary Artery IMA Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis at JoVE.com

Human Internal Mammary Artery IMA Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis

This video shows a model to study the development of intimal hyperplasia after stent deployment using a human vessel (IMA) in an immunodeficient rat model.

Human Internal Mammary Artery (IMA) Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis

Preclinical in vivo research models to investigate pathobiological and pathophysiological processes in the development of intimal hyperplasia after vessel ...

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