Name: implantation of human-sized coronary stents into rat abdominal aorta using a trans-femoral access
Uploaded: 2020-11-19T13:00:00
Description: Watch this Scientific Journal Video about Implantation of Human-Sized Coronary Stents into Rat Abdominal Aorta Using a Trans-Femoral Access at JoVE.com

We would like to thank Mrs. Angela Freund for her invaluable technical assistance with embedding and slides production. We would also like to thank Mr. Tadeusz Stopinski at the Institute for Laboratory Animal Science &#38; Experimental Surgery for his insightful help with the veterinary work.

The experiments were performed in accordance with the German animal welfare law (TSchG) and Directive 2010/63/EU pertaining to the protection of animals used for scientific purposes. The official approval for this study was granted by the Governmental Animal Care and Use Committee (Protocol No.: AZ 87-51.04.2010.A065; Landesamt f&#252;r Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen, Recklinghausen, Germany). The study protocol complied with the Guide for the Care and Use of Laboratory Animals. Postoperative pai...

<ol>
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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=ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS+2017+Appropriate+Use+Criteria+for+Coronary+Revascularization+in+Patients+With+Stable+Ischemic+Heart+Disease:+A+Report+of+the+American+College+of+Cardiology+Appropriate+Use+Criteria+Task+Force,+American+Association+for+Thoracic+Surgery,+American+Heart+Association,+American+Society+of+Echocardiography,+American+Society+of+Nuclear+Cardiology,+Society+for+Cardiovasular+Angiography+and+Interventions,+Society+of+Cardiovascular+Computed+Tomography,+and+Society+of+Thoracic+Surgeons.">ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria for Coronary Revascularization in Patients With Stable Ischemic Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovasular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons.</a> Journal of the American College of Cardiology. 69 (17), 2212-2241 (2017).</li><li>Virmani, R., Farb, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathology+of+in-stent+restenosis.">Pathology of in-stent restenosis.</a> Current Opinion in Lipidology. 10 (6), 499-506 (1999).</li><li>Buccheri, D., Piraino, D., Andolina, G., Cortese, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+and+managing+in-stent+restenosis:+a+review+of+clinical+data,+from+pathogenesis+to+treatment.">Understanding and managing in-stent restenosis: a review of clinical data, from pathogenesis to treatment.</a> Journal of Thoracic Disease. 8 (10), 1150-1162 (2016).</li><li>Perkins, L. 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Deviation of man from the usual pattern.</a> Circulation Research. 25 (6), 677-686 (1969).</li><li>Lowe, H. C., James, B., Khachigian, L. M. <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+model+of+in-stent+restenosis:+rat+aortic+stenting.">A novel model of in-stent restenosis: rat aortic stenting.</a> Heart. 91 (3), 393-395 (2005).</li><li>Unthank, J. L., Nixon, J. C., Lash, J. 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This protocol describes the implantation of human-sized coronary stents into the abdominal aorta of apoE-/- rats. Several technical points are worth emphasizing. First, a mismatch between the stent size and the size of the aorta should be avoided. Placing too small a stent can lead to stent malapposition, whereas implantation of a stent that is too large for the aorta can cause overstretch, tearing, and injury of the vessel. Therefore, we recommend using stents between 2.0 and 2.5 mm in diameter, and to keep i...

Percutaneous coronary intervention (PCI), combined with the deployment of a coronary stent, represents the gold standard in interventional treatment of coronary artery disease1. The long-term success of stents, however, can be limited by the occurrence of in-stent restenosis (ISR) that is determined by an excessive proliferation of neointimal tissue within the stent2,3. ISR may require a re-intervention either with coronary artery bypass or re-PCI. A variety of animal models have been suggested for the study of ISR, each of them featuring advantages and shortcomings. The major drawbacks of the most commonly used porcine coronary and rabbit iliac artery models, albeit developing lesions markedly similar to humans after stent implantation4,5, are large animal and housing costs which brings up logistical difficulties especially in long-term studies, as well as limitations in handling and equipment. Furthermore, availability of antibodies to cellular proteins of swine and rabbits is limited. On the other hand, murine models provide the major advantages of high throughput and reproducibility, as well as ease of handling, housing, and therefore cost-effectiveness. Furthermore, a higher number of antibodies are available. However, while apolipoprotein E-deficient (apoE-/-) mice have been broadly used for the study of atherosclerosis6,7,8, they are unsuitable for the study of ISR as stents have to be miniaturized to be implanted into mice, potentially changing the stents&#8217; mechanical properties. Moreover, the aortic wall of mice measures between 50 &#181;m in young mice and 85 &#181;m in old mice9, and stents have to be deployed using pressure levels as low as 2 atm, which might lead to malapposition of the stent10. Rats, however, allow for the implantation of commercially available human coronary stents, and demonstrate a vascular healing course similar to larger animals after aortic stent implantation, first reported by Langeveld et al.11. This technique originally required a trans-abdominal access, which necessitated a physical constriction of the aorta to achieve a temporary interruption of blood flow. To avoid the potentially associated vessel injury and inflammatory reactions, the technique was later refined by the introduction of a trans-iliac access, which additionally resulted in a higher survival rate of the animals12.
Because wildtype rats do not develop atherosclerotic lesions13, apoE-/- rats have been generated using nuclease techniques such as Transcription Activator-Like Effector Nuclease (TALEN)14, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9)15, and Zinc Finger (ZF)16. ApoE-/- rats have been commercially available since 2011. Providing an atherogenic background, apoE-/- rats allow for a more realistic evaluation of human-sized coronary stents, especially with regards to ISR.
Herein, we describe the method via the transfemoral access route and using a commercially available thin-strut cobalt-chromium drug-eluting stent (DES), however, it can also be applied for the study of other stent types, such as bare metal stents (BMS) or biodegradable stents.

<table>
	<tbody>
		<tr>
			<td>Diet</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>SNIFF High Fat diet + Clopidogrel (15 mg/kg)</td>
			<td>SNIFF Spezialdi&#228;ten GmbH, Soest</td>
			<td>custom prepared</td>
			<td>Western Diet</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Drugs and Anesthetics</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Buprenorphine</td>
			<td>Essex Pharma</td>
			<td>997.00.00</td>
			<td></td>
		</tr>
		<tr>
			<td>ISOFLO (Isoflurane Vapor) vaporiser</td>
			<td>Eickemeyer</td>
			<td>4802885</td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Forene Abbott</td>
			<td>B 506</td>
			<td></td>
		</tr>
		<tr>
			<td>Isotonic (0.9%) NaCl solution</td>
			<td>DeltaSelect GmbH</td>
			<td>PZN 00765145</td>
			<td></td>
		</tr>
		<tr>
			<td>Ringer&#39;s lactate solution</td>
			<td>Baxter Deutschland GmbH</td>
			<td>3775380</td>
			<td></td>
		</tr>
		<tr>
			<td>(S)-ketamine</td>
			<td>CEVA Germany</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Xylazine</td>
			<td>Medistar Germany</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Consumable supplies</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>10 mL syringes</td>
			<td>BD Plastipak</td>
			<td>4606108V</td>
			<td></td>
		</tr>
		<tr>
			<td>2 mL syringes</td>
			<td>BD Plastipak</td>
			<td>4606027V</td>
			<td></td>
		</tr>
		<tr>
			<td>6-0 prolene suture</td>
			<td>ETHICON</td>
			<td>N-2719K</td>
			<td></td>
		</tr>
		<tr>
			<td>4-0 silk suture</td>
			<td>Seraflex</td>
			<td>IC 158000</td>
			<td></td>
		</tr>
		<tr>
			<td>Bepanthen Eye and Nose Ointment</td>
			<td>Bayer Vital GmbH</td>
			<td>6029009.00.00</td>
			<td></td>
		</tr>
		<tr>
			<td>Cotton Gauze swabs</td>
			<td>Fuhrmann GmbH</td>
			<td>32014</td>
			<td></td>
		</tr>
		<tr>
			<td>Durapore silk tape</td>
			<td>3M</td>
			<td>1538-1</td>
			<td></td>
		</tr>
		<tr>
			<td>Poly-Alcohol Skin Desinfection Solution</td>
			<td>Antiseptica GmbH</td>
			<td>72PAH200</td>
			<td></td>
		</tr>
		<tr>
			<td>Sterican needle 18 G</td>
			<td>B. Braun</td>
			<td>304622</td>
			<td></td>
		</tr>
		<tr>
			<td>Sterican needle 27 3/4 G</td>
			<td>B.Braun</td>
			<td>4657705</td>
			<td></td>
		</tr>
		<tr>
			<td>Tissue Paper</td>
			<td>commercially available</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Surgical instruments</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Graefe forceps curved x1</td>
			<td>Fine Science Tools Inc.</td>
			<td>11151-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Graefe forceps straight</td>
			<td>Fine Science Tools Inc.</td>
			<td>11050-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Needle holder Mathieu</td>
			<td>Fine Science Tools Inc.</td>
			<td>12010-14</td>
			<td></td>
		</tr>
		<tr>
			<td>Scissors</td>
			<td>Fine Science Tools Inc.</td>
			<td>14074-11</td>
			<td></td>
		</tr>
		<tr>
			<td>Semken forceps</td>
			<td>Fine Science Tools Inc.</td>
			<td>11008-13</td>
			<td></td>
		</tr>
		<tr>
			<td>Small surgical scissors curved</td>
			<td>Fine Science Tools Inc.</td>
			<td>14029-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Small surgical scissors straight</td>
			<td>Fine Science Tools Inc.</td>
			<td>14028-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Standard pattern forceps</td>
			<td>Fine Science Tools Inc.</td>
			<td>11000-12</td>
			<td></td>
		</tr>
		<tr>
			<td>Vannas spring scissors</td>
			<td>Fine Science Tools Inc.</td>
			<td>15000-08</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Equipment</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dissecting microscope</td>
			<td>Leica MZ9</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Temperature controlled heating pad</td>
			<td>Sygonix</td>
			<td>26857617</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Equipment for stent implantation</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Drug-eluting stent Xience 2,25mm x 8mm</td>
			<td>Abbott Vascular USA</td>
			<td>1009544-18</td>
			<td></td>
		</tr>
		<tr>
			<td>Guide wire Fielder XT PTCA guide wire: 0.014&#34; x 300cm</td>
			<td>ASAHI INTECC CO., LTD Japan</td>
			<td>AGP140302</td>
			<td></td>
		</tr>
		<tr>
			<td>Inflation syringe system</td>
			<td>Abbott 20/30 Priority Pack</td>
			<td>1000186</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Tissue processing and analysis</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>30% H2O2</td>
			<td>Roth</td>
			<td>9681</td>
			<td>Histology</td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>Roth</td>
			<td>K928.1</td>
			<td>Histology</td>
		</tr>
		<tr>
			<td>Giemsas Azur-Eosin-Methylenblau</td>
			<td>Merck</td>
			<td>109204</td>
			<td>Histology</td>
		</tr>
		<tr>
			<td>Graphic Drawing Tablet</td>
			<td>WACOM Europe GmbH</td>
			<td>CTL-6100WLK-S</td>
			<td></td>
		</tr>
		<tr>
			<td>Roti Histofix, Formaldehyd 4% buffered</td>
			<td>Roth</td>
			<td>P087</td>
			<td>Histology</td>
		</tr>
		<tr>
			<td>Technovit 9100</td>
			<td>Morphisto</td>
			<td>12225.K1000</td>
			<td>Histology</td>
		</tr>
	</tbody>
</table>

implantation of human-sized coronary stents into rat abdominal aorta using a trans-femoral access

Percutaneous coronary intervention (PCI), combined with the deployment of a coronary stent, represents the gold standard in interventional treatment of coronary artery disease. In-stent restenosis (ISR) is determined by an excessive proliferation of neointimal tissue within the stent and limits the long-term success of stents. A variety of animal models have been used to elucidate pathophysiological processes underlying in-stent restenosis (ISR), with the porcine coronary and the rabbit iliac artery models being the most frequently used. Murine models provide the advantages of high throughput, ease of handling and housing, reproducibility, and a broad availability of molecular markers. The apolipoprotein E deficient (apoE-/- ) mouse model has been widely used to study cardiovascular diseases. However, stents must be miniaturized to be implanted into mice, involving important changes of their mechanical and (potentially) biological properties. The use of apoE-/- rats can overcome these shortcomings as apoE-/- rats allow for the evaluation of human-sized coronary stents while at the same time providing an atherogenic phenotype. This makes them an excellent and reliable model to investigate ISR after stent implantation. Here, we describe, in detail, the implantation of commercially available human coronary stents into the abdominal aorta of rats with an apoE-/- background using a trans-femoral access.

This protocol describes stent implantation in the abdominal aorta of rats using a trans-femoral access route (Figure 1). The first central point of this animal model is that it allows for the deployment of human-sized coronary stents. A commercially available crimped and balloon-mounted coronary stent can be placed into the abdominal aorta of rats. Thus, in addition, the same principle of stent deployment as in humans can be applied. Another advantage of the use of rats is the availability o...

Watch this Scientific Journal Video about Implantation of Human-Sized Coronary Stents into Rat Abdominal Aorta Using a Trans-Femoral Access at JoVE.com

Implantation of Human-Sized Coronary Stents into Rat Abdominal Aorta Using a Trans-Femoral Access

This protocol describes the implantation of human coronary stents into the abdominal aorta of rats with an apoE-/- background using a trans-femoral access. Compared with other animal models, murine models carry the advantages of high throughput, reproducibility, ease of handling and housing, and a broad availability of molecular markers.

Percutaneous coronary intervention (PCI), combined with the deployment of a coronary stent, represents the gold standard in interventional treatment of ...

This protocol uses an animal model to establish an accessible method for characterizing the effects of human coronary stents on vascular pathology. The main advantages of our model are that is minimally invasive, highly reproducible, and easily performed even by researchers with little operative experience. Demonstrating the the procedure will be Roberta Florescu, a physician from our laboratory.Following this procedure, other clinical and pathology diagnostic tools can be used, such as optical coherence tomography or histological analysis. After confirming a lack of response to pedal reflex in an anesthetized adult rat, place the rat on a heating pad in the supine position with the right hind limb fully extended and in line with the spine, and fix the upper and lower limbs with medical tape. Apply ointment to the animal's eyes and shave the fur from the groin and lower abdomen.Then sterilize the exposed skin with a povidone iodine solution. For implantation of the stent, make a 0.5 to one centimeter medial incision in the right groin to open the skin and underlying fascia, and bluntly dissect and probe the tissue until the pulsating left femoral artery is located. Using very fine forceps, gently remove the connective tissue surrounding the artery and carefully insert the top of the forceps under the vessel.Thread pieces of 4-0 silk suture under the distal and proximal parts of the artery to form slings and clamp the ends of each of the two threads slings between the branches of a surgical clamp. Use the surgical clamps to control the artery and gently stretch and lift the artery to temporarily interrupt the blood flow. Using sharp micro-scissors, quickly perform in arteriotomy in the middle of the femoral artery and introduce a guide wire into the arteriotomy.When the proximal thread sling is reached, move the surgical clamp to release the tension of the thread and advance the guide wire toward the abdominal aorta. Introduce a 2.25 by eight millimeter crimped and balloon-mounted coronary stent over the guide wire into the femoral artery. Advance the stent to the abdominal aorta until it is just above the aortic bifurcation, but below the renal arteries.When the stent is in place, use an inflation syringe system to inflate the balloon catheter to its nominal pressure. After 15 seconds, deflate the balloon catheter and maintain negative pressure according to the manufacturer's recommendations for the stent in use. Next, slowly withdraw the deflated catheter while leaving the stent in place.Just before removing the guide wire, use the surgical clamp to create tension on the threaded loop above the incision to interrupt the blood flow and remove the guide wire. Directly ligate the vessel proximally and tie the proximal and distal thread loops to ligate the femoral artery. Then confirm adequate hemostasis of the arteriotomy and use 6-O non-resorbable sutures to close the muscle overlying the artery and the skin incision.In this representative analysis, human-sized coronary stents were successfully deployed with no sign of malapposition or vessel injury. Homozygous apolipoprotein E knockout rats developed markedly elevated neointimal hyperplasia and in-stent restenosis compared to wild type rats. Although the apolipoprotein E knockout background renders animals more susceptible to atherosclerosis, no antecedent atherosclerotic plaques were observed in these rats.Selecting the proper stent size for each animal and using rats weighing over 500 grams for the human coronary stent implantation are critical to the success of the procedure.

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Research

JoVE Journal

Medicine

Rat Heterotopic Abdominal Heart/Single-lung Transplantation in a Volume-loaded Configuration

Herein, we describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The configuration of the transplant graft involves anastomosis of donor inferior vena cava (IVC) to recipient IVC, and donor ascending aorta (Ao) to recipient abdominal Ao. The right upper and middle lung lobes are preserved and function as conduits for blood flow from right heart to left heart.
There are several advantages to using this technique, and it lends itself to a broad range of applications. Because the graft is transplanted in a configuration that allows for dyamic volume-loading, cardiac function may be directly assessed in vivo. The use of pressure-volume conductance catheters permits characterization of load-dependent and load-independent hemodynamic parameters. The graft may be converted to a loaded configuration by applying a clamp to the recipient&#8217;s infra-hepatic IVC. We describe modified surgical techniques for both donor and recipient operations, and an ideal myocardial protection strategy. Depending on the experimental aim, this model may be adapted for use in both acute and chronic studies of graft function, immunologic status, and variable ventricular loading conditions. The conducting airways to the transplanted lung are preserved, and allow for acute lung re-ventilation. This facilitates analysis of the effects of the mixed venous and arterial blood providing coronary perfusion to the graft.
A limitation of this model is its technical complexity. There is a significant learning curve for new operators, who should ideally be mentored in the technique. A surgical training background is advantageous for those wishing to apply this model. Despite its complexity, we aim to present the model in a clear and easily applicable format. Because of the physiologic similarity of this model to orthotopic transplantation, and its broad range of study applications, the effort invested in learning the technique is likely to be worthwhile.

We describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The transplant configuration results in a partially loaded graft circulation, allowing direct functional assessment. This model may be employed for acute or chronic studies of function and immunologic status of the transplanted graft.

Herein, we describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The configuration of the transplant graft ...

Creation of Abdominal Adhesions in Mice

Abdominal adhesions consist of fibrotic tissue that forms in the peritoneal space in response to an inflammatory insult, typically surgery or intraabdominal infection. The precise mechanisms underlying adhesion formation are poorly understood. Many compounds and physical barriers have been tested for their ability to prevent adhesions after surgery with varying levels of success. The mouse and rat are important models for the study of abdominal adhesions. Several different techniques for the creation of adhesions in the mouse and rat exist in the literature. Here we describe a protocol utilizing abrasion of the cecum with sandpaper and sutures placed in the right abdominal sidewall. The mouse is anesthetized and the abdomen is prepped. A midline laparotomy is created and the cecum is identified. Sandpaper is used to gently abrade the surface of the cecum. Next, several figure-of-eight sutures are placed into the peritoneum of the right abdominal sidewall. The abdominal cavity is irrigated, a small amount of starch is applied, and the incision is closed. We have found that this technique produces the most consistent adhesions with the lowest mortality rate.

Abdominal adhesions that form after surgery are a major cause of pain, infertility, and hospitalization and reoperation for small bowel obstruction. Our surgical procedure for creating abdominal adhesions in mice is a reliable tool to study the mechanisms underlying the formation of adhesions.

Abdominal adhesions consist of fibrotic tissue that forms in the peritoneal space in response to an inflammatory insult, typically surgery or ...

Fabrication of Small Caliber Stent-grafts Using Electrospinning and Balloon Expandable Bare Metal Stents

Stent-grafts are widely used for the treatment of various conditions such as aortic lesions, aneurysms, emboli due to coronary intervention procedures and perforations in vasculature. Such stent-grafts are manufactured by covering a stent with a polymer membrane. An ideal stent-graft should have a biocompatible stent covered by a porous, thromboresistant, and biocompatible polymer membrane which mimics the extracellular matrix thereby promoting injury site healing. The goal of this protocol is to manufacture a small caliber stent-graft by encapsulating a balloon expandable stent within two layers of electrospun polyurethane nanofibers. Electrospinning of polyurethane has been shown to assist in healing by mimicking native extracellular matrix, thereby promoting endothelialization. Electrospinning polyurethane nanofibers on a slowly rotating mandrel enabled us to precisely control the thickness of the nanofibrous membrane, which is essential to achieve a small caliber balloon expandable stent-graft. Mechanical validation by crimping and expansion of the stent-graft has shown that the nanofibrous polyurethane membrane is sufficiently flexible to crimp and expand while staying patent without showing any signs of tearing or delamination. Furthermore, stent-grafts fabricated using the methods described here are capable of being implanted using a coronary intervention procedure using standard size guide catheters.

In the protocol, we present a method to manufacture a small caliber stent-graft by sandwiching a balloon expandable stent between two electrospun nanofibrous polyurethane layers.

Stent-grafts are widely used for the treatment of various conditions such as aortic lesions, aneurysms, emboli due to coronary intervention procedures and ...

A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and fluid retention. Changes in myocardial structure, electrical conduction, and energy metabolism develop with heart failure, leading to contractile dysfunction, increased risk of arrhythmias, and sudden death. Hypertensive heart disease is one of the key contributing factors of cardiac remodeling associated with heart failure. The most commonly-used animal model mimicking hypertensive heart disease is created via surgical interventions, such as by narrowing the aorta. Abdominal aortic constriction is a useful experimental technique to induce a pressure overload, which leads to heart failure. The surgery can be easily performed, without the need for chest opening or mechanical ventilation. Abdominal aortic constriction-induced cardiac pathology progresses gradually, making this model relevant to clinical hypertensive heart failure. Cardiac injury and remodeling can be observed 10 weeks after the surgery. The method described here provides a simple and effective approach to produce a hypertensive heart disease animal model that is suitable for studying disease mechanisms and for testing novel therapeutics.

A rat model of abdominal aortic constriction that induces cardiac hypertrophy and remodeling is described. An efficient, highly-reproducible, and minimally-invasive method is used to provide a simple yet useful platform for research in myocardial hypertrophy and dysfunction.

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and ...

Patch Angioplasty in the Rat Aorta or Inferior Vena Cava

Pericardial patches are commonly used in vascular surgery to close vessels. To facilitate studies of the neointimal hyperplasia that forms on the patch, we developed a rat model of patch angioplasty that can be used in either a vein or an artery, creating a patch venoplasty or a patch arterioplasty, respectively. Technical aspects of this model are discussed. The infra-renal IVC or aorta are dissected and then clamped proximally and distally. A 3 mm venotomy or arteriotomy is performed in the infrarenal inferior vena cava or aorta of 6 to 8 week-old Wistar rats. A bovine pericardial patch (3 mm x 1.5 mm x 0.6 mm) is then used to close the site using a 10-0 nylon suture. Compared to arterial patches, venous patches show increased neointimal thickness on postoperative day 7. This novel model of pericardial patch angioplasty can be used to examine neointimal hyperplasia on vascular biomaterials, as well as to compare the differences between the arterial and venous environments.

We have established a model of pericardial patch angioplasty that can be used in either small-diameter veins or arteries. This model can be used to compare venous and arterial neointimal hyperplasia formation.

Pericardial patches are commonly used in vascular surgery to close vessels. To facilitate studies of the neointimal hyperplasia that forms on the patch, ...

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ischemia and infarction in children. If left untreated, it results in a 90% mortality rate in the first year of life. In patients who survive to the adulthood, the coronary steal phenomenon and retrograde left-sided coronary flow provide a substrate for chronic subendocardial ischemia, which may lead to left ventricular dysfunction, ischemic mitral regurgitation, malignant ventricular arrhythmias, and sudden cardiac death. The average age of life-threatening presentation is 33 years and of sudden cardiac death 31 years. Therefore, surgical correction is highly recommended as soon as the diagnosis is made, regardless of age. In adult-type ALCAPA originating from the right-facing sinus of the pulmonary artery, direct re-implantation of the ALCAPA into the aorta is the more physiologically sound repair technique to re-establish the dual-coronary perfusion system and is recommended. This protocol describes the technique of direct re-implantation of adult-type ALCAPA into the aorta.

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery ALCAPA

Surgical correction of ALCAPA is highly recommended, regardless of age or the degree of intercoronary collateralization. This protocol presents a technique for the direct re-implantation of adult-type ALCAPA into the aorta to re-establish the dual-coronary perfusion. Whenever feasible, direct re-implantation is preferred to other surgical correction techniques.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ...

Balloon-based Injury to Induce Myointimal Hyperplasia in the Mouse Abdominal Aorta

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine balloon denudation model, which is comparable with established vessel injury models in large animals. The aorta denudation model with balloon catheters mimics the clinical setting and leads to comparable pathobiological and physiological changes. Briefly, after performing a horizontal incision in the aorta abdominalis, a balloon catheter will be inserted into the vessel, inflated, and introduced retrogradely. Inflation of the balloon will lead to intima injury and overdistension of the vessel. After removing the catheter, the aortic incision will be closed with single stiches. The model shown in this article is reproducible, easy to perform, and can be established quickly and reliably. It is especially suitable for evaluating expensive experimental therapeutic agents, which can be applied in an economical fashion. By using different knockout-mouse strains, the impact of different genes on MH development can be assessed.

This article demonstrates a murine model to study the development of myointimal hyperplasia (MH) after aortic balloon injury.

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine ...

Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions

Contemporary high-resolution ultrasound instruments have sufficient resolution to facilitate the measurement of mouse aortas. These instruments have been widely used to measure aortic dimensions in mouse models of aortic aneurysms. Aortic aneurysms are defined as permanent dilations of the aorta, which occur most frequently in the ascending and abdominal regions. Sequential measurements of aortic dimensions by ultrasound are the principal approach for assessing the development and progression of aortic aneurysms in vivo. Although many reported studies used ultrasound imaging to measure aortic diameters as a primary endpoint, there are confounding factors, such as probe position and cardiac cycle, that may impact the accuracy of data acquisition, analysis, and interpretation. The purpose of this protocol is to provide a practical guide on the use of ultrasound to measure the aortic diameter in a reliable and reproducible manner. This protocol introduces the preparation of mice and instruments, the acquisition of appropriate ultrasound images, and data analysis.

Ultrasound imaging has become a common modality to determine the luminal dimensions of thoracic and abdominal aortic aneurysms in mice. This protocol describes the procedure to acquire reliable and reproducible two-dimensional ultrasound images of the ascending and abdominal aorta in mice.

Contemporary high-resolution ultrasound instruments have sufficient resolution to facilitate the measurement of mouse aortas. These instruments have been ...

A Murine Model of Hemodialysis Access-Related Hand Dysfunction

Chronic kidney disease is a major public health problem, and the prevalence of end-stage renal disease (ESRD) requiring chronic renal replacement therapies such as hemodialysis continues to increase. Autogenous arteriovenous fistula (AVF) placement remains a primary vascular access option for ESRD patients. Unfortunately, approximately half of the hemodialysis patients experience dialysis access-related hand dysfunction (ARHD), ranging from subtle paresthesia to digital gangrene. Notably, the underlying biologic drivers responsible for ARHD are poorly understood, and no adequate animal model exists to elucidate the mechanisms and/or develop novel therapeutics for the prevention/treatment of ARHD. Herein, we describe a new mouse model in which an AVF is created between the left common iliac artery and vein, thereby facilitating the assessment of limb pathophysiology. The microsurgery includes vessel isolation, longitudinal venotomy, creation of arteriovenous anastomosis, and venous reconstruction. Sham surgeries include all the critical steps except for AVF creation. Iliac AVF placement results in clinically relevant alterations in central hemodynamics, peripheral ischemia, and impairments in hindlimb neuromotor performance. This novel preclinical AVF model provides a useful platform that recapitulates common neuromotor perturbations reported by hemodialysis patients, allowing researchers to investigate the mechanisms of ARHD pathophysiology and test potential therapeutics.

This protocol details the surgical steps of murine common iliac arteriovenous fistula creation. We developed this model to study hemodialysis access-related limb pathophysiology.

Chronic kidney disease is a major public health problem, and the prevalence of end-stage renal disease (ESRD) requiring chronic renal replacement ...

Robotic Cochlear Implantation for Direct Cochlear Access

Robot-assisted systems offer great potential for gentler and more precise cochlear implantation. In this article, we provide a comprehensive overview of the clinical workflow for robotic cochlear implantation using a robotic system specifically developed for a minimally invasive, direct cochlear access. The clinical workflow involves experts from various disciplines and requires training to ensure a smooth and safe procedure. The protocol briefly summarizes the history of robotic cochlear implantation. The clinical sequence is explained in detail, beginning with the assessment of patient eligibility and covering surgical preparation, preoperative planning with the special planning software, drilling of the middle ear access, intraoperative imaging to confirm the trajectory, milling of the inner ear access, insertion of the electrode array, and implant management. The steps that require special attention are discussed. As an example, the postoperative outcome of robotic cochlear implantation in a patient with advanced otosclerosis is presented. Finally, the procedure is discussed in the context of the authors' experience.

Robotic cochlear implantation is a procedure for minimally invasive inner ear access. Compared to conventional surgery, robotic cochlear implantation involves additional steps that need to be carried out in the operating room. In this article we give a description of the procedure and highlight the important aspects of robotic cochlear implantation.

Robot-assisted systems offer great potential for gentler and more precise cochlear implantation. In this article, we provide a comprehensive overview of ...