Name: vein interposition model: a suitable model to study bypass graft patency
Uploaded: 2017-01-15T13:00:00
Description: Watch this Scientific Journal Video about Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency at JoVE.com

The authors thank Christiane Pahrmann for her technical assistance. This study was funded by the Deutsche Stiftung fuer Herzforschung (F/28/14). D.W. was supported by the travel award from the International Society for Heart and Lung Transplantation. T.D. received the Else Kro&#776;ner Excellence Stipend from the Else-Kro&#776;ner-Fresenius-Stiftung (2012_EKES.04). S.S. received research grants from the Deutsche Forschungsgemeinschaft (DFG; DE2133/2-1, T.D.&#160; and SCHR992/3- 1, SCHR992/4-1, S.S.).

Animals received humane care in compliance with the Guide for the Principles of Laboratory Animals, prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health. All animal protocols were approved by the responsible local authority (&#34;Amt f&#252;r Gesundheit und Verbraucherschutz, Hansestadt (Office for Health and Consumer Protection) Hamburg&#34;).
1. Animal Care
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This video demonstrates a rat vein interposition model to investigate vein graft loss and to allow for the exploration of the underlying pathological processes and the testing of new drugs or therapeutic options.
Anesthesia is a crucial aspect of surgical procedures. A continuous inhalative anesthesia system is recommended, as this is a safe and easy method, especially during prolonged operations. This can be of great importance during the training phase, when the operation takes more than 1 h...

Coronary artery diseases and their complications are among the leading causes of death worldwide. Current therapeutic strategies focus on re-establishing the blood flow, either by dilating the narrowed vessel or by creating a bypass. Coronary artery bypass grafting (CABG) using vein autografts was first described in 1968 and has been refined over the years. Apart from the revascularization of the left anterior descending coronary artery, saphenous vein conduits are most commonly used1. However, graft patency remains the Achilles heel of saphenous vein grafts (SVG). One year after surgery, graft patency is 85%, dropping to 61% after ten years2,3. Unveiling the pathophysiological mechanisms and causes of SVG patency loss is therefore an important task.
This video demonstrates a rat vein interposition model to investigate vein graft loss. The overall goals of this method are to explore the underlying pathobiological and -physiological processes during disease progression and to develop a suitable model for drug or therapeutic option testing. By transplanting the superficial epigastric vein into the arterial system, this model closely mimics the clinical setting of coronary artery bypass grafting. Surgical trauma, ischemia, and wall stress are important triggers of pathological vascular changes and are imitated in the model described.
Different models and species are available to investigate vein graft patency loss. Large animal models, such as pigs4, sheep5, dogs6, and monkeys7, resemble human vessel and anatomical structures and thus enable complex therapeutic strategies, such as bypass stenting or new surgical techniques, to be tested8. However, special housing, equipment, and staff are required. In addition, high costs and the need for an additional anesthetist during surgery impede their broader application. Small animals, including rats, are easy to handle, do not require special housing, and have manageable costs. Compared to mouse models9,10, rat models have the advantage of better operability and therefore less variability in the outcome. Rats are physiologically and genetically more similar to humans than mice11,12. In addition, most wild-type mice only develop limited myointima13, which make mouse models prone to type II errors. The histology of the main mouse veins, such as the inferior vena cava, only consists of a few cell layers and renders early evaluation difficult13. A further disadvantage is the small amount of tissue available for subsequent analysis after graft recovery.
The model described in this video is reproducible, inexpensive, and easy to perform, and it can be established quickly and reliably. It is especially suitable for evaluating expensive experimental therapeutic agents, such as viral vectors for gene therapy, in an economical fashion.

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			<td height="17" style="height:17px;width:236px;">Rat LEW/Crl</td>
			<td style="width:183px;">Charles River</td>
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			<td height="51" style="height:51px;width:236px;">Rat LEW-Tg(Gt(ROSA)26Sor- 1 
			luc)11Jmsk</td>
			<td style="width:183px;">Institute of laboratory animals, Kyoto University, Japan</td>
			<td style="width:145px;">NBPR rat number 0299</td>
			<td style="width:156px;">http://www.anim.med.kyoto-u.ac.jp/NBR/</td>
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			<td height="17" style="height:17px;">PFA 4%</td>
			<td>Electron Microscopy Sciences</td>
			<td>#157135S</td>
			<td align="right">20%</td>
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			<td>Micro-Serrefine - 4mm</td>
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			<td height="17" style="height:17px;">hair removal creme</td>
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			<td height="38" style="height:38px;">EVICEL</td>
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			<td>fibrin glue</td>
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			<td>B.Braun</td>
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			<td height="34" style="height:34px;width:236px;">Vevo 770 high-resolution in vivo micro-imaging system</td>
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			<td>Gibco</td>
			<td>10010023</td>
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			<td height="17" style="height:17px;">Xenogen Ivis 200</td>
			<td>Perkin Elmer</td>
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			<td>bioluminescence imaging</td>
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			<td height="17" style="height:17px;">Weigerts iron hematoxylin Kit</td>
			<td>Merck</td>
			<td>1.15973.0002</td>
			<td>Trichrome staining</td>
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			<td height="17" style="height:17px;">Resorcine-Fuchsine Weigert</td>
			<td>Waldeck</td>
			<td>2.00E-30</td>
			<td>Trichrome staining</td>
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			<td height="17" style="height:17px;">Acid Fuchsin</td>
			<td>Sigma-Aldrich</td>
			<td>F8129-25G</td>
			<td>Trichrome staining</td>
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			<td height="17" style="height:17px;">Ponceau S solution</td>
			<td>Serva Electrophoresis</td>
			<td>33427</td>
			<td>Trichrome staining</td>
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			<td height="17" style="height:17px;">Azophloxin</td>
			<td>Waldeck</td>
			<td>1B-103</td>
			<td>Trichrome staining</td>
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		<tr height="17">
			<td height="17" style="height:17px;width:236px;">Molybdatophosphoric acid hydrate</td>
			<td>Merck</td>
			<td>1.00532.0100</td>
			<td>Trichrome staining</td>
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			<td height="17" style="height:17px;">Orange G</td>
			<td>Waldeck</td>
			<td>1B-221</td>
			<td>Trichrome staining</td>
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		<tr height="17">
			<td height="17" style="height:17px;">Light Green SF</td>
			<td>Waldeck</td>
			<td>1B-211</td>
			<td>Trichrome staining</td>
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			<td height="17" style="height:17px;">Vitro-Clud</td>
			<td>Langenbrinck</td>
			<td>04-0001</td>
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			<td height="17" style="height:17px;">Glacial Acetic Acid</td>
			<td>Sigma-Aldrich</td>
			<td align="right">537020</td>
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			<td height="17" style="height:17px;">37% HCl</td>
			<td>Sigma-Aldrich</td>
			<td>H1758</td>
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			<td height="17" style="height:17px;">Xylene</td>
			<td>Th. Geyer</td>
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			<td height="17" style="height:17px;">Paraffin</td>
			<td>Leica biosystems</td>
			<td>REF 39602004</td>
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			<td height="17" style="height:17px;">Ethanol absolute</td>
			<td>Th. Geyer</td>
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			<td></td>
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		<tr height="17">
			<td height="17" style="height:17px;">Ethanol 96%</td>
			<td>Th. Geyer</td>
			<td align="right">2295</td>
			<td></td>
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		<tr height="17">
			<td height="17" style="height:17px;">Ethanol 70%</td>
			<td>Th. Geyer</td>
			<td align="right">2270</td>
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			<td height="17" style="height:17px;">Slide Rack</td>
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			<td height="17" style="height:17px;">Bepanthen Eye and Nose ointment</td>
			<td>Bayer</td>
			<td align="right">1578675</td>
			<td>Eye ointment</td>
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vein interposition model: a suitable model to study bypass graft patency

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. Research models for bypass graft failure are essential for a better understanding of pathobiological and pathophysiological processes during graft patency loss. Large animal models, such as pigs or sheep, resemble human anatomical structures but require special facilities and equipment. This video describes a rat vein interposition model to investigate vein graft patency loss. Rats are inexpensive and easy to handle. Compared to mouse models, the convenient size of rats permits better operability and enables a sufficient amount of material to be obtained for further diverse analysis. In brief, the inferior epigastric vein of a donor rat is harvested and used to replace a segment of the femoral artery. Anastomosis is conducted via single stitches and sealed with fibrin glue. Graft patency can be monitored non-invasively using duplex sonography. Myointimal hyperplasia, which is the main cause for graft patency loss, develops progressively over time and can be calculated from histological cross sections.

The rat vein interposition model is suitable to study the development of myointima hyperplasia and vein graft failure. Animals recover well from the surgery and show excellent physical condition post-operation. Figure 1 shows the key surgical steps. After the skin incision along the linea inguinalis, the epigastric superficial vein and femoral artery are identified (Figure 1A). Harvesting of the graft should be performed carefully, without damaging the graft (Figure 1B),...

Watch this Scientific Journal Video about Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency at JoVE.com

Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency

This video demonstrates a model to study the development of myointimal hyperplasia after venous interposition surgery in rats.

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. ...

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Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are often used for reconstructive surgery to treat congenital cardiac anomalies. ...

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

A Rabbit Venous Interposition Model Mimicking Revascularization Surgery using Vein Grafts to Assess Intimal Hyperplasia under Arterial Blood Pressure

Although vein grafts have been commonly used as autologous grafts in revascularization surgeries for ischemic diseases, the long-term patency remains poor ...

Establishment and Evaluation of a Porcine Vein Graft Disease Model

Venous graft disease (VGD) is the leading cause of coronary artery bypass graft (CABG) failure. Large animal models of CABG-VGD are needed for the ...

Porcine Liver Transplantation Without Veno-Venous Bypass As an Extended Criteria Donor Model

Liver transplantation is regarded as the gold standard for the treatment of a variety of fatal hepatic diseases. However, unsolved issues of chronic graft ...