This work was supported in part by the National Institutes of Health Grants R56-HL095498,&#160;R01-HL-095498 (to AD),&#160;R01-HL128406, the Merit Review Award I01-BX002336 from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Program (to AD), a Yale Department of Surgery Ohse award (to AD), a Sarnoff Cardiovascular Foundation Fellowship (to JMS), and through the resources and the use of facilities at the Veterans Affairs Connecticut Healthcare System (West Haven, CT). Bovine pericardial patches were generously provided by LeMaitre Vascular Inc. (Burlington, MA).

Approval by the appropriate Institutional Animal Care and Use Committee must be obtained, indicating that your protocol follows the guidelines of your institution&#39;s animal research ethics committee.
1. Anesthesia and Pre-operative Procedures
<ol>
	<li>Anesthetize male Wistar rats, weighing around 200 g, with vaporized 3% isoflurane and 1 L/min oxygen administered into an acrylic induction chamber.</li>
	<li>Confirm adequate anesthesia through a lack of reaction to a toe and tail pinch. Place ointment on the eyes to prevent dryness while the animals are under anesthesia. Position the each rat supine on the plastic operation plate and position a silicone mask to deliver vaporized 2 - 3% isoflurane by continuous inhalation. Do not leave an animal unattended until it has regained sufficient consciousness to maintain sternal recumbency.</li>
	<li>While wearing sterile gloves, remove the ventral abdomen hair using a hair remover. Buprenorphine, either subcutaneously or intraperitoneally, is frequently given at this point.</li>
</ol>
2. Operative Procedures
<ol>
	<li>Patch venoplasty
	<ol>
		<li>Before the surgery, trim the bovine pericardial patch using a microscissor to a 3 mm x 1.5 mm x 0.6 mm size. Soak the patch in 10 mL of sterilized saline for 5 min in a cell culture dish.</li>
		<li>Prepare the incision site with a topical antiseptic according to your institutional protocol and apply a surgical drape. Use sterile gloves and instruments to maintain aseptic technique throughout the surgery. &#160;Local anesthesia can be injected into the site of the planned skin incision.</li>
		<li>Using a scalpel, make a midline abdominal incision extending from the level of the xiphoid to just above the pubis.</li>
		<li>Insert a retractor and eviscerate all bowels from the abdominal cavity towards the right side. Wrap the bowels in gauze soaked with saline.</li>
		<li>Expose the infrarenal vena cava (IVC). The site of patch implantation is approximately 2 mm below the level of the origin of the renal veins; dissect the IVC free at this site. Ligate and divide all lumbar and tributary veins at this level using 6-0 nylon sutures.</li>
		<li>Place two microsurgery clips across both the proximal and distal infarenal IVC. Perform a venotomy with a 25 G needle by puncturing the anterior wall of the IVC, and then extend it to around 3 mm using scissors (Figure 1A).</li>
		<li>Close the venotomy with the patch using running or interrupted 10-0 nylon sutures (Figure 1B).</li>
		<li>Complete the venoplasty closure. Remove the distal clamp first to vent the patch and then remove the proximal clamp to restore blood flow to the IVC.</li>
		<li>Confirm hemostasis by observing for 30 s without compression. Return the bowels to their natural position. Close the abdomen with a running suture according to approved animal protocols.</li>
	</ol>
	</li>
	<li>Patch arterioplasty
	<ol>
		<li>Before the surgery, trim the bovine pericardial patch using a microscissor to a 3 mm x 1.5 mm x 0.6 mm size. Soak it in sterilized saline.</li>
		<li>Prepare the incision site with a topical antiseptic and apply a surgical drape. Use sterile gloves and instruments to maintain aseptic technique throughout the surgery.</li>
		<li>Using a scalpel, make a midline abdominal incision extending from the level of the xiphoid to just above the pubis.</li>
		<li>Insert a retractor and eviscerate all bowels from the abdominal cavity towards the right side. Wrap the bowels in gauze soaked with saline.</li>
		<li>Expose the aorta. The site of patch implantation is approximately 2 mm below the level of the origin of the renal arteries; dissect the aorta free at this site. Ligate and divide all lumbar arteries at this level using 6-0 nylon sutures.</li>
		<li>Clamp the infrarenal aorta. Use a 25 G needle to perform an arteriotomy by puncturing the anterior wall of the aorta, and then extend it to around 3 mm using scissors (Figure 1C).</li>
		<li>Close the arteriotomy with the patch using running 10-0 nylon sutures (Figure 1D). Complete the arterioplasty closure. Remove the distal clamp first to vent the patch and then remove the proximal clamp to restore blood flow to the aorta.</li>
		<li>Confirm hemostasis by observing for 30 s without compression. Return the bowels to their natural position. Close the abdomen with a running suture according to approved animal protocols.</li>
	</ol>
	</li>
</ol>
3. Post-operative Procedures
<ol>
	<li>After the closure of the abdomen, discontinue the anesthesia. Apply post-operative care, including analgesia and wound care, in accordance with instructions recommended by the Institutional Animal Care and Use Committee.</li>
	<li>For analgesia, use buprenorphine at 0.1 mg/kg intramuscularly no less than every 12 h for 24 h following the surgical procedures. Check the status of the animal every day in the animal room, ensuring proper recovery from the peri-operative period as well as adequate treatment of post-surgical pain. Do not return an animal that has undergone surgery to the company of other animals until it has fully recovered.</li>
</ol>
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<ol>
	<li>Muto, A., Nishibe, T., Dardik, H., Dardik, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patches+for+carotid+artery+endarterectomy:+current+materials+and+prospects.">Patches for carotid artery endarterectomy: current materials and prospects.</a> J Vasc Surg. 50 (1), 206-213 (2009).</li><li>Li, X., 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=Current+usage+and+future+directions+for+the+bovine+pericardial+patch.">Current usage and future directions for the bovine pericardial patch.</a> Ann Vasc Surg. 25 (4), 561-568 (2011).</li><li>Biasi, G. M., Sternjakob, S., Mingazzini, P. M., Ferrari, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nine-year+experience+of+bovine+pericardium+patch+angioplasty+during+carotid+endarterectomy.">Nine-year experience of bovine pericardium patch angioplasty during carotid endarterectomy.</a> J Vasc Surg. 36 (2), 271-277 (2002).</li><li>Papakostas, J. 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=Use+of+the+vascu-guard+bovine+pericardium+patch+for+arteriotomy+closure+in+carotid+endarterectomy.+Early+and+long-term+results.">Use of the vascu-guard bovine pericardium patch for arteriotomy closure in carotid endarterectomy. Early and long-term results.</a> Ann Vasc Surg. 28 (5), 1213-1218 (2014).</li><li>Ohwada, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glutaraldehyde-fixed+heterologous+pericardium+for+vena+cava+grafting+following+hepatectomy.">Glutaraldehyde-fixed heterologous pericardium for vena cava grafting following hepatectomy.</a> Hepatogastroenterology. 46 (26), 855-858 (1999).</li><li>Mori, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standard+hepatic+vein+reconstruction+with+patch+plasty+using+the+native+portal+vein+in+adult+living+donor+liver+transplantation.">Standard hepatic vein reconstruction with patch plasty using the native portal vein in adult living donor liver transplantation.</a> Liver Transpl. 18 (5), 602-607 (2012).</li><li>Bai, 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=Pericardial+patch+venoplasty+heals+via+attraction+of+venous+progenitor+cells.">Pericardial patch venoplasty heals via attraction of venous progenitor cells.</a> Physiological Reports. 4 (12), (2016).</li><li>Li, X., 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=Pericardial+patch+angioplasty+heals+via+an+Ephrin-B2+and+CD34+positive+cell+mediated+mechanism.">Pericardial patch angioplasty heals via an Ephrin-B2 and CD34 positive cell mediated mechanism.</a> PLoS One. 7 (6), 38844 (2012).</li><li>Bai, 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=Pretreatment+of+pericardial+patches+with+antibiotics+does+not+alter+patch+healing+in+vivo.">Pretreatment of pericardial patches with antibiotics does not alter patch healing in vivo.</a> J Vasc Surg. 63 (4), 1063-1073 (2016).</li><li>Muto, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Eph-B4+prevents+venous+adaptive+remodeling+in+the+adult+arterial+environment.">Eph-B4 prevents venous adaptive remodeling in the adult arterial environment.</a> J Exp Med. 208 (3), 561-575 (2011).</li></ol>

The authors have nothing to disclose.

We describe a patch angioplasty model in the rat that can be used in either veins or arteries, creating a patch venoplasty or patch arterioplasty, respectively. Using this pericardial patch model, we showed aggressive and stable neointimal hyperplasia in the rat IVC venoplasty compared to the aortic arterioplasty (Figure 2)7,8.
Several technical aspects are notable. In the aortic arterioplasty, it is important that the...

Vascular surgeons commonly close blood vessels with pericardial patches, either bovine or porcine, to reduce the risk of restenosis1,2. In arterial surgery, pericardial patch angioplasty reduces the rate of restenosis compared to a primary closure3,4. Patch venoplasty is also similarly performed to close veins, although less frequently when compared to arterial procedures5,6. Patches typically develop neointimal hyperplasia on their luminal surfaces; however, the mechanism of neointimal formation remains unclear, especially in the comparison of differences in neointimal formation between the arterial and venous environments. We previously showed that pericardial patches attract progenitor cells in both the arterial and the venous environments and that venous patch angioplasty shows more aggressive neointimal formation as compared to the arterial patches7,8.
In this study, we describe the rat model of pericardial patch angioplasty that is common to closing both veins and arteries and that may be used to study neointimal formation; this method is a small-animal model of an operative technique commonly used in human patients. The rat model has a larger diameter than the mouse model, facilitating technical aspects of the surgery and improving the learning curve for the model.

<table border="0" cellpadding="0" cellspacing="0" width="523">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Bovine pericardial patch</td>
			<td colspan="2" style="width:307px;">LeMaitre Vascular</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Vascular clamp</td>
			<td>Roboz Surgical Instrument Co.</td>
			<td>RS-5424</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Clamp applying forceps</td>
			<td>Roboz Surgical Instrument Co</td>
			<td>RS-5410</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">10-0 Prolene suture</td>
			<td>Arosurgical Co.</td>
			<td>T05A10N10-13</td>
		</tr>
	</tbody>
</table>

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.

After the patch angioplasty, there was no thrombosis in either the venous (n = 42) or arterial (n = 24) patch groups. Survival at day 7 was 100% in both groups with either a venous or arterial patch.
The patches were harvested on day 7 and stained with hematoxylin and eosin, and the neointimal thickness was compared as previously described7. Because of the distinct morphological difference between the patch and the ne...

Watch this Scientific Journal Video about Patch Angioplasty in the Rat Aorta or Inferior Vena Cava at JoVE.com

Patch Angioplasty in the Rat Aorta or Inferior Vena Cava

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, ...

patch-angioplasty-in-the-rat-aorta-or-inferior-vena-cava

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

10.5K Views.  Yale University. 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.

Video: Patch Angioplasty in the Rat Aorta or Inferior Vena Cava

Hyperinsulinemic-Euglycemic Clamp in the Conscious Rat

Type 2 diabetes (T2D) is rapidly rising in prevalence. Characterized by either inadequate insulin production or the inability to utilize insulin produced, T2D results in elevated blood glucose levels. The "gold-standard" in assessing insulin sensitivity is a hyperinsulinemic-euglycemic clamp or insulin clamp. In this procedure, insulin is infused at a constant rate resulting in a drop in blood glucose. To maintain blood glucose at a constant level, exogenous glucose (D50) is infused into the venous circulation. The amount of glucose infused to maintain homeostasis is indicative of insulin sensitivity. Here, we show the basic clamp procedure in the chronically catheterized, unrestrained, conscious rat. This model allows blood to be collected with minimal stress to the animal. Following the induction of anesthesia, a midline incision is made and the left common carotid artery and right jugular vein are catheterized. Inserted catheters are flushed with heparinized saline, then exteriorized and secured. Animals are allowed to recover for 4-5 days prior to experiments, with weight gain monitored daily. Only those animals who regain weight to pre-surgery levels are used for experiments. On the day of the experiment, rats are fasted and connected to pumps containing insulin and D50. Baseline glucose is assessed from the arterial line and used a benchmark throughout the experiment (euglycemia). Following this, insulin is infused at a constant rate into the venous circulation. To match the drop in blood glucose, D50 is infused. If the rate of D50 infusion is greater than the rate of uptake, a rise in glucose will occur. Similarly, if the rate is insufficient to match whole body glucose uptake, a drop will occur. Titration of glucose continues until stable glucose readings are achieved. Glucose levels and glucose infusion rates during this stable period are recorded and reported. Results provide an index of whole body insulin sensitivity. The technique can be refined to meet specific experimental requirements. It is further enhanced by the use of radioactive tracers that can determine tissue specific insulin-stimulated glucose uptake as well as whole body glucose turnover.

The hyperinsulinemic-euglycemic clamp is the "gold standard" for the assessment of insulin action. Insulin is infused at a constant rate stimulating glucose uptake. The amount of exogenous glucose infused to counter this drop is indicative of insulin sensitivity. Here the procedure is performed on a conscious, unrestrained rat.

Type 2 diabetes (T2D) is rapidly rising in prevalence. Characterized by either inadequate insulin production or the inability to utilize insulin produced, ...

Electrolytic Inferior Vena Cava Model (EIM) of Venous Thrombosis

Animal models serve a vital role in deep venous thrombosis (DVT) research in order to study thrombus formation, thrombus resolution and to test potential therapeutic compounds (1). New compounds to be utilized in the treatment and prevention of DVT are currently being developed. The delivery of potential therapeutic antagonist compounds to an affected thrombosed vein has been problematic. In the context of therapeutic applications, a model that uses partial stasis and consistently generates thrombi within a major vein has been recently established. The Electrolytic Inferior vena cava Model (EIM) is mouse model of DVT that permits thrombus formation in the presence of continuous blood flow. This model allows therapeutic agents to be in contact with the thrombus in a dynamic fashion, and is more sensitive than other models of DVT (1). In addition, this thrombosis model closely simulates clinical situations of thrombus formation and is ideal to study venous endothelial cell activation, leukocyte migration, venous thrombogenesis, and to test therapeutic applications (1). The EIM model is technically simple, easily reproducible, creates consistent thrombi sizes and allows for a large sample (i.e. thrombus and vein wall) which is required for analytical purposes.

Electrolytic Inferior Vena Cava Model EIM of Venous Thrombosis

The electrolytic induction of endothelial activation to the internal surface of the Inferior Vena Cava results in venous type thrombus formation due to endothelial activation and partial blood stasis, two components of Virchow's triad.

Animal models serve a vital role in deep venous thrombosis (DVT) research in order to study thrombus formation, thrombus resolution and to test potential ...

Mouse Complete Stasis Model of Inferior Vena Cava Thrombosis

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). In the United States (U.S.), the high morbidity and mortality rates make VTE a serious health concern 1-2. After heart disease and stroke, VTE is the third most common vascular disease 3. In the U.S. alone, there is an estimated 900,000 people affected each year, with 300,000 deaths occurring annually 3. A reliable in vivo animal model to study the mechanisms of this disease is necessary.
The advantages of using the mouse complete stasis model of inferior vena cava thrombosis are several. The mouse model allows for the administration of very small volumes of limited availability test agents, reducing costs dramatically. Most promising is the potential for mice with gene knockouts that allow specific inflammatory and coagulation factor functions to be delineated. Current molecular assays allow for the quantitation of vein wall, thrombus, whole blood, and plasma for assays. However, a major concern involving this model is the operative size constraints and the friability of the vessels. Also, due to the small IVC sample weight (mean 0.005 grams) it is necessary to increase animal numbers for accurate statistical analysis for tissue, thrombus, and blood assays such as real-time polymerase chain reaction (RT-PCR), western blot, enzyme-linked immunosorbent (ELISA), zymography, vein wall and thrombus cellular analysis, and whole blood and plasma assays 4-8.
The major disadvantage with the stasis model is that the lack of blood flow inhibits the maximal effect of administered systemic therapeutic agents on the thrombus and vein wall.

The mouse complete stasis model of inferior vena cava thrombosis yields quantifiable amounts of vein wall tissue and thrombus. It has proven useful for evaluating interactions between the vein wall and the occlusive thrombus and in assessing the progression from acute to chronic inflammation.

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE).  In the United States (U.S.), the high morbidity and ...

Angiogenesis in the Ischemic Rat Lung

The adult lung is perfused by both the systemic bronchial artery and the entire venous return flowing through the pulmonary arteries. In most lung pathologies, it is the smaller systemic vasculature that responds to a need for enhanced lung perfusion and shows robust neovascularization. Pulmonary vascular ischemia induced by pulmonary artery obstruction has been shown to result in rapid systemic arterial angiogenesis in man as well as in several animal models. Although the histologic assessment of the time course of bronchial artery proliferation in rats was carefully described by Weibel 1, mechanisms responsible for this organized growth of new vessels are not clear. We provide surgical details of inducing left pulmonary artery ischemia in the rat that leads to bronchial neovascularization. Quantification of the extent of angiogenesis presents an additional challenge due to the presence of the two vascular beds within the lung. Methods to determine functional angiogenesis based on labeled microsphere injections are provided.

The lung is perfused by both the systemic bronchial artery and pulmonary arteries. In most lung pathologies, it is the smaller systemic vasculature that shows robust neovascularization. Cessation of pulmonary blood flow promotes brisk bronchial angiogenesis. We provide surgical details of inducing left pulmonary artery ischemia that promotes bronchial neovascularization.

The  adult lung is perfused by both the systemic bronchial artery and the entire  venous return flowing through the pulmonary arteries. In most lung ...

Implantation of Inferior Vena Cava Interposition Graft in Mouse Model

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are often used for reconstructive surgery to treat congenital cardiac anomalies. The long-term clinical results showed excellent patency rates, however, with significant incidence of stenosis. To investigate the cellular and molecular mechanisms of vascular neotissue formation and prevent stenosis development in tissue engineered vascular grafts (TEVGs), we developed a mouse model of the graft with approximately 1 mm internal diameter. First, the TEVGs were assembled from biodegradable tubular scaffolds fabricated from a polyglycolic acid nonwoven felt mesh coated with &#949;-caprolactone and L-lactide copolymer. The scaffolds were then placed in a lyophilizer, vacuumed for 24 hr, and stored in a desiccator until cell seeding. Second, bone marrow was collected from donor mice and mononuclear cells were isolated by density gradient centrifugation. Third, approximately one million cells were seeded on a scaffold and incubated O/N. Finally, the seeded scaffolds were then implanted as infrarenal vena cava interposition grafts in C57BL/6 mice. The implanted grafts demonstrated excellent patency (&#62;90%) without evidence of thromboembolic complications or aneurysmal formation. This murine model will aid us in understanding and quantifying the cellular and molecular mechanisms of neotissue formation in the TEVG.

To improve our knowledge of cellular and molecular neotissue formation, a murine model of the TEVG was recently developed. The grafts were implanted as infrarenal vena cava interposition grafts in C57BL/6 mice. This model achieves similar results to those achieved in our clinical investigation, but over a far shortened time-course.

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

Scleral Cross-linking Using Riboflavin and Ultraviolet-A Radiation for Prevention of Axial Myopia in a Rabbit Model

Myopic individuals, especially those with severe myopia, are at higher-than-normal risk of cataract, glaucoma, retinal detachment and chorioretinal abnormalities. In addition, pathological myopia is a common irreversible cause of visual impairment and blindness1-3. Our study demonstrates the effect of scleral crosslinking using riboflavin and ultraviolet-A radiation on the development of axial myopia in a rabbit model. The axial length of the eyeball was measured by A-scan ultrasound in New Zealand white rabbits aged 13 days (male and female). The eye then underwent 360&#176; conjunctival peritomy with scleral crosslinking, followed by tarsorrhaphy. Axial elongation was induced in 13 day-old New Zealand rabbits by suturing their right eye eyelids (tarsorrhaphy). The eyes were divided into quadrants, and every quadrant had two scleral irradiation zones, each with an area of 0.2 cm&#178; and a radius of 4 mm. Crosslinking was performed by dropping 0.1% dextran-free riboflavin-5-phosphate onto the irradiation zones 20 sec before ultraviolet-A irradiation and every 20 sec during the 200 sec irradiation time. UVA radiation (370 nm) was applied perpendicular to the sclera at 57 mW/cm&#178; (total UVA light dose, 57 J/cm&#178;). Tarsorrhaphies were removed on day 55, followed by repeated axial length measurements. This study demonstrates that scleral crosslinking with riboflavin and ultraviolet-A radiation effectively prevents occlusion-induced axial elongation in a rabbit model.

We demonstrate the effect of scleral crosslinking with riboflavin and UVA on an axial elongation rabbit eye. Axial elongation was induced in 13 day-old New Zealand rabbits (male and female) by suturing their right eye eyelids (tarsorrhaphy).

Myopic individuals, especially those with severe myopia, are at higher-than-normal risk of cataract, glaucoma, retinal detachment and chorioretinal ...

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 ...

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 ...

A Rat Model of Orthotopic Liver Transplantation Using a Novel Magnetic Anastomosis Technique for Suprahepatic Vena Cava Reconstruction

The rat model of orthotopic liver transplantation (OLT) is essential for transplant research. It is a very sophisticated animal model and requires a steep learning curve. The introduction of the cuff technique for anastomosis of the portal vein (PV) and infrahepatic vena cava (IHVC) has significantly simplified the transplant procedure in rats. However, due to the short anterior wall of the recipients' suprahepatic vena cava (SHVC), the cuff technique is very difficult to use for the reconstruction of the SHVC. Most researchers in this field still use the hand-suture technique for SHVC reconstruction, which makes it the bottleneck step in rat orthotopic liver transplantation. The magnetic anastomosis technique (i.e., magnamosis) is a method of connecting two vessels using the attractive force between two magnets. Our recent study has shown that the magnetic anastomosis technique is superior to the hand-suture technique for SHVC reconstruction in rats. In this article, we show a step-by-step protocol for SHVC reconstruction in rats using the novel magnetic anastomosis technique. In this model, the reconstruction of the PV and IHVC was performed by the standard cuff technique, while the reconstruction of the bile duct (BD) was performed by a stent technique. The hepatic re-arterialization was not performed. The magnetic anastomosis technique made SHVC reconstruction much easier and significantly shortened the anphepatic phase. After a reasonable learning curve, even researchers without advanced microsurgical skills can produce reliable and reproducible results using this rat model of OLT.

The reconstruction of the suprahepatic vena cava (SHVC) remains a difficult step in rat orthotopic liver transplantation. In this article, we show a step-by-step protocol for SHVC reconstruction in rats using a novel magnetic anastomosis technique.

The rat model of orthotopic liver transplantation (OLT) is essential for transplant research. It is a very sophisticated animal model and requires a steep ...

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 ...