Name: patch angioplasty in the rat aorta or inferior vena cava
Uploaded: 2017-02-27T15:00:00.000+00:00
Duration: 6 min 4 s
Description: Watch this Scientific Journal Video about Patch Angioplasty in the Rat Aorta or Inferior Vena Cava at JoVE.com

Diese Arbeit wurde zum Teil durch die National Institutes of Health Grants R56-HL095498, R01-HL-095498 (AD), R01-HL128406, die Merit Bewertung Auszeichnung I01-BX002336 aus den Vereinigten Staaten Department of Veterans Affairs biomedizinische Laborforschung unterstützt und Development Program (AD), ein Yale Abteilung für Chirurgie Ohse Auszeichnung (AD), eine Sarnoff Kardiovaskuläre Foundation Fellowship (JMS) und durch die Ressourcen und die Nutzung von Einrichtungen des Veterans Affairs Connecticut Healthcare System (West Haven, CT ). Bovine pericardial Pflaster wurden großzügig von Lemaitre Vascular Inc. (Burlington, MA) zur Verfügung gestellt.

Die Genehmigung durch die entsprechende Institutional Animal Care und Use Committee muss erhalten werden, was darauf hinweist, dass das Protokoll die Richtlinien Ihres Instituts Tierforschung Ethikkommission folgt. 1. Anästhesie und präoperative Verfahren <ol><li> Anästhesieren männlichen Wistar-Ratten mit einem Gewicht von etwa 200 g, mit verdampftem 3% Isofluran und 1 l / min Sauerstoff in eine Acrylinduktionskammer verabreicht. </li><li> Bestätigen ausreichende Anästhesie durch einen Mangel an Reaktion auf eine Zehe und Schwanz kneifen. Legen Salbe auf die Augen Trockenheit zu verhindern, während die Tiere unter Narkose sind. Positionieren Sie die jede Ratte liegt auf dem Rücken der Betätigungsplatte aus Kunststoff und positionieren, um eine Silikonmaske zu liefern verdampfte 2 - 3% Isofluran durch kontinuierliches Einatmen. Verwenden Sie kein Tier unbeaufsichtigt lassen, bis es genügend Bewusstsein zu halten Brustlage wiedergewonnen hat. </li><li> Während sterile Handschuhe tragen, entfernen Sie das ventrale Abdomen Haar einen Haarentferner verwenden. BUPRenorphine, entweder subkutan oder intraperitoneal, wird häufig an dieser Stelle gegeben. </li></ol> 2. Operative Verfahren <ol><li> Patch - venoplasty <ol><li> Vor der Operation, schneiden Sie die bovine Perikardpatch mit einem microscissor zu einem 3 mm x 1,5 mm x 0,6 mm Größe. Einweichen der Patch in 10 ml sterilisierter Kochsalzlösung für 5 min in einer Zellkulturschale. </li><li> Bereiten Sie die Inzisionsstelle mit einem Antiseptikum nach Ihren institutionellen Protokoll und tragen Sie eine Operationstuch. Verwenden Sie sterile Handschuhe und Instrumente zur aseptischen Bedingungen in der gesamten Operation erhalten. Lokalanästhesie kann in die Stelle der geplanten Inzision eingespritzt werden. </li><li> Mit einem Skalpell, machen Sie eine Mittellinie Bauchschnitt die sich von der Ebene der xiphoid oberhalb des Schambeins nur. </li><li> Legen Sie eine Aufroller und ausweiden alle Eingeweide aus der Bauchhöhle auf der rechten Seite. Wickeln Sie die Eingeweide in Gaze, getränkt mit Kochsalzlösung. </li><li> Setzen Sie die infrarenal Hohlvene (IVC). Der Ort der Patch Implantation beträgt etwa 2 mm unter dem Niveau der den Ursprung der Nierenvenen; sezieren die IVC an dieser Stelle frei. Abzubinden und teilen alle Lenden- und Nebenvenen auf dieser Ebene mit 6-0 Nylonnaht. </li><li> Platzieren zwei Mikro Clips über beide proximale und distale infarenal IVC. Durchführen eines Venenschnitt mit einer 25 G Nadel durch die Vorderwand der IVC Punktierung und dann erstrecken sie auf etwa 3 mm mit einer Schere (1A). </li><li> Schließen Sie die Venotomie mit dem Patch mit Laufen oder unterbrochen 10-0 Nylonnähten (1B). </li><li> Füllen Sie das venoplasty Schließung. Entfernen Sie die distale Klammer zuerst den Patch zu entlüften und dann die proximale Klemme entfernen Blutfluss in den IVC wiederherzustellen. </li><li> Bestätigen Sie die Hämostase von 30 s ohne Komprimierung zu beobachten. Bringen Sie die Eingeweide in ihre natürliche Position. Schließen Sie den Bauch mit einem fortlaufenden Naht nach anerkannten Tier Protokolle. </li></ol></li><li> Patch - arterioplasty <ol><li> Vor der Operation, schneiden Sie die bovine Perikardpatch mit einem microscissor zu einem 3 mm x 1,5 mm x 0,6 mm Größe. Genießen Sie es in sterilisierte Kochsalzlösung. </li><li> Bereiten Sie die Inzisionsstelle mit einem Antiseptikum und ein Operationstuch anwenden. Verwenden Sie sterile Handschuhe und Instrumente zur aseptischen Bedingungen in der gesamten Operation erhalten. </li><li> Mit einem Skalpell, machen Sie eine Mittellinie Bauchschnitt die sich von der Ebene der xiphoid oberhalb des Schambeins nur. </li><li> Legen Sie eine Aufroller und ausweiden alle Eingeweide aus der Bauchhöhle auf der rechten Seite. Wickeln Sie die Eingeweide in Gaze, getränkt mit Kochsalzlösung. </li><li> Setzen Sie die Aorta. Der Ort der Patch Implantation beträgt etwa 2 mm unter dem Niveau des Ursprungs der Nierenarterien; die Aorta frei an dieser Stelle sezieren. Abzubinden und teilen alle Lumbalarterien auf dieser Ebene mit 6-0 Nylonnaht. </li><li> Klemmen Sie die infra Aorta. Verwenden Sie eine 25 G-Nadel eine Arteriotomiestelle von puncturi auszuführenng der vorderen Wand der Aorta, und erstrecken sich dann auf etwa 3 mm mit einer Schere (Abbildung 1C). </li><li> Schließen Sie die Arteriotomiestelle mit dem Patch unter fließendem 10-0 Nylonnähten (1D). Füllen Sie das arterioplasty Schließung. Entfernen Sie die distale Klammer zuerst den Patch zu entlüften und dann die proximale Klemme entfernen den Blutfluss in der Aorta wieder herzustellen. </li><li> Bestätigen Sie die Hämostase von 30 s ohne Komprimierung zu beobachten. Bringen Sie die Eingeweide in ihre natürliche Position. Schließen Sie den Bauch mit einem fortlaufenden Naht nach anerkannten Tier Protokolle. </li></ol></li></ol> 3. Post-operative Verfahren <ol><li> Nach der Schließung des Bauches, unterbrechen die Anästhesie. Bewerben postoperative Pflege, einschließlich Analgesie und Wundversorgung, in Übereinstimmung mit den Anweisungen von der Institutional Animal Care und Use Committee empfohlen. </li><li> Für Analgesie, verwenden Buprenorphin bei 0,1 mg / kg intramuskulär nicht weniger als alle 12 h für 24 Stunden folgening die chirurgischen Verfahren. Überprüfen Sie den Status des Tieres jeden Tag im Tierraum, richtige Erholung von der perioperativen Periode sowie eine adäquate Behandlung von postoperativen Schmerzen zu gewährleisten. Nicht ein Tier zurück, die Operation an die Firma von anderen Tieren unterzogen wurde, bis sie vollständig erholt hat. </li></ol><style type="text/css">p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px Helvetica}
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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.

Wir beschreiben eine Patch-Angioplastie-Modell in der Ratte, die entweder in Venen oder Arterien verwendet werden können, einen Patch oder ein Patch venoplasty arterioplasty Erstellen, respectively. Unter Verwendung dieses Perikardpatch Modell haben wir gezeigt , aggressive und stabile neointimale Hyperplasie in Ratten - IVC venoplasty Vergleich zu der Aorta arterioplasty (Abbildung 2) 7, 8. Mehrere technische Aspek...

Gefäßchirurgen häufig enge Blutgefäße mit pericardial Patches, entweder Rind oder Schwein, das Risiko einer Restenose 1, 2 zu reduzieren. Bei der arteriellen Chirurgie reduziert Perikardpatch Angioplastie die Rate der Restenose im Vergleich zu einem primären Wundverschluss 3, 4. Patch - venoplasty auch in ähnlicher Weise zu schließen Venen durchgeführt, wenn auch weniger häufig im Vergleich zu den arteriellen Verfahren 5, 6. Patches typischerweise Neointimalhyperplasie auf ihre Lumenoberflächen zu entwickeln; Jedoch bleibt der Mechanismus der neointimalen Bildung unklar, insbesondere im Vergleich der Unterschiede in Neointima-Bildung zwischen den arteriellen und venösen Umfeld. Wir haben bereits gezeigt, dass pericardial Patches Vorläuferzellen sowohl im arteriellen und venösen den Umgebungen und dass venösen Patch Angioplastie ziehen mehr A zeigtggressive Neointima - Bildung im Vergleich zu den arteriellen patches 7, 8. In dieser Studie beschreiben wir die Rattenmodell der Perikardpatch Angioplastie, die Bildung zu studieren neointimalen verwendet werden, um beide Venen und Arterien zu schließen und das kann ist üblich; Diese Methode ist ein Kleintiermodell einer Operationstechnik häufig bei menschlichen Patienten verwendet. Das Rattenmodell hat einen größeren Durchmesser als das Mausmodell, technische Aspekte der Operation zu erleichtern und die Lernkurve für das Modell zu verbessern.

<table><tbody><tr><td>Bovine pericardial patch</td><td>LeMaitre Vascular</td><td></td><td></td></tr><tr><td>Vascular clamp</td><td>Roboz Surgical Instrument Co.</td><td>RS-5424</td><td></td></tr><tr><td>Clamp applying forceps</td><td>Roboz Surgical Instrument Co</td><td>RS-5410</td><td></td></tr><tr><td>10-0 Prolene suture</td><td>Arosurgical Co.</td><td>T05A10N10-13</td><td></td></tr></tbody></table>

patch angioplasty in the rat aorta or inferior vena cava

Pericardial Patches werden in der Gefäßchirurgie zu schließen Gefäße verwendet. Studien der neointimalen Hyperplasie erleichtern, die auf dem Patch bildet, entwickelten wir ein Rattenmodell der Patch-Angioplastie, die entweder in einer Vene oder einer Arterie verwendet werden können, einen Patch oder ein Patch venoplasty arterioplasty zu schaffen, respectively. Technische Aspekte dieses Modells diskutiert. Die Infrarot-Nieren-IVC oder Aorta seziert und dann geklemmt proximal und distal. A 3 mm Venotomie oder Arteriotomie wird in der infrarenalen Vena cava inferior oder Aorta von 6 bis 8 Wochen alte Wistar-Ratten durchgeführt. Ein Rinder Perikardpatch (3 mm x 1,5 mm x 0,6 mm) wird dann verwendet, um die Seite mit einem 10-0-Nylonnaht zu schließen. Im Vergleich zum arteriellen Patches zeigen venöse Patches neointimale Dicke am ersten postoperativen Tag erhöht 7. Dieses neue Modell von Perikardpatch Angioplastie verwendet werden Neointimalhyperplasie auf vaskuläre Biomaterialien zu untersuchen, sowie die Unterschiede zwischen dem arteriellen und venösen vergleichenUmgebungen.

Nach dem Patch-Angioplastie, gab es keine in Thrombose entweder das venöse (n = 42) oder arterieller (n = 24) Patch-Gruppen. Überleben am Tag 7 war zu 100% in beiden Gruppen entweder mit einer venösen oder arteriellen Patch. Die Pflaster wurden an Tag 7 geerntet und gefärbt mit Hämatoxylin und Eosin und die Neointima - Dicke verglichen wurde , wie zuvor beschrieben 7. Aufgrund der ausgeprägten morphologischen ...

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.

Patch-Angioplastie in der Ratte Aorta oder 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, ...

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

Research

JoVE Journal

Medicine

10.5K Aufrufe.  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.

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

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant vasculopathy (TVP).
The commonly used animal model for cardiovascular chronic rejection studies is the heterotopic heart transplant model performed in laboratory rodents. This model is used widely in experiments since Ono and Lindsey (3) published their technique. To analyze the findings in the blood vessels, the heart has to be sectioned and all vessels have to be measured.
Another method to investigate chronic rejection in cardiovascular questionings is the aortic transplant model (1, 2). In the orthotopic aortic transplant model, the aorta can easily be histologically evaluated (2). The PVG-to-ACI model is especially useful for CAV studies, since acute vascular rejection is not a major confounding factor and Cyclosporin A (CsA) treatment does not prevent the development of CAV, similar to what we find in the clinical setting (4). A7-day period of CsA is required in this model to prevent acute rejection and to achieve long-term survival with the development of TVP.
This model can also be used to investigate acute cellular rejection and media necrosis in xenogeneic models (5).

This video demonstrates the orthotopic aortic transplant model as a simple model to study the development of transplant vasculopathy (TVP) in rats.

Orthotopen Aorten-Transplantation: Ein Rattenmodell die Entwicklung von chronischen Vaskulopathie Study

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

Forschung

Medizin

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.

Angiogenese im ischämischen 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 ...

A New Murine Model of Endovascular Aortic Aneurysm Repair

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of Abdominal aortic aneurysm (AAA) pathophysiology. There is no abdominal aortic aneurysm endograft exclusion model cheap and reproducible, which would allow deep investigations of AAA before and after treatment. We hereby describe how to induce, and then to exclude with a covered coronary stentgraft an abdominal aortic aneurysm in a rat. The well known elastase induced AAA model was first reported in 19901 in a rat, then described in mice2. Elastin degradation leads to dilation of the aorta with inflammatory infiltration of the abdominal wall and intra luminal thrombus, matching with human AAA. Endovascular exclusion with small covered stentgraft is then performed, excluding any interactions between circulating blood and the aneurysm thrombus. Appropriate exclusion and stentgraft patency is confirmed before euthanasia by an angiography thought the left carotid artery. Partial control of elastase diffusion makes aneurysm shape different for each animal. It is difficult to create an aneurysm, which will allow an appropriate length of aorta below the aneurysm for an easy stentgraft introduction, and with adequate proximal and distal neck to prevent endoleaks. Lots of failure can result to stentgraft introduction which sometimes lead to aorta tear with pain and troubles to stitch it, and endothelial damage with post op aorta thrombosis. Giving aspirin to rats before stentgraft implantation decreases failure rate without major hemorrhage. Clamping time activates neutrophils, endothelium and platelets, and may interfere with biological analysis.

Histological and biochemical modifications after aneurysm endograft exclusion are still unclear. We describe a new model of endograft implantation on a murine aneurysm. Through thrombus analysis with and without persistant circulating blood stream interface, and new endovascular biomaterials evaluation, this model will help to better understand endovascular aneurysm exclusion pathobiology.

Ein neues Mausmodell der endovaskuläre Aortenaneurysma Repair

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of ...

Imaging In-Stent Restenosis: An Inexpensive, Reliable, and Rapid Preclinical Model

Preclinical models of restenosis are essential to unravel the pathophysiological processes that lead to in-stent restenosis and to optimize existing and future drug-eluting stents.
A variety of antibodies and transgenic and knockout strains are available in rats. Consequently, a model for in-stent restenosis in the rat would be convenient for pathobiological and pathophysiological studies. 
In this video, we present the full procedure and pit-falls of a rat stent model suitable for high throughput stent research. We will show the surgical procedure of stent deployment, and the assessment of in-stent restenosis using the most elegant technique of OCT (Optical Coherence Tomography). This technique provides high accuracy in assessing plaque CSAs (cross section areas) and correlates well with histological sections, which require special and time consuming embedding and sectioning techniques. OCT imaging further allows longitudinal monitoring of the development of in-stent restenosis within the same animal compared to one-time snapshots using histology.

This video demonstrates how to use a preclinical inexpensive and reliable model to study pathobiological and pathophysiological processes of in-stent restenosis development. Longitudinal in vivo monitoring using OCT (Optical Coherence Tomography) and analysis of OCT images are also demonstrated.

Imaging In-Stent-Restenose: eine kostengünstige, zuverlässige und schnelle Präklinische Modell

Preclinical models of restenosis are essential to unravel the pathophysiological processes that lead to in-stent restenosis and to optimize existing and ...

Biologie

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery

The carotid artery balloon injury model in rats has been well established for over two decades. It remains an important method to study the molecular and cellular mechanisms involved in vascular smooth muscle dedifferentiation, neointima formation and vascular remodeling. Male Sprague-Dawley rats are the most frequently employed animals for this model. Female rats are not preferred as female hormones are protective against vascular diseases and thus introduce a variation into this procedure. The left carotid is typically injured with the right carotid serving as a negative control. Left carotid injury is caused by the inflated balloon that denudes the endothelium and distends the vessel wall. Following injury, potential therapeutic strategies such as the use of pharmacological compounds and either gene or shRNA transfer can be evaluated. Typically for gene or shRNA transfer, the injured section of the vessel lumen is locally transduced for 30 min with viral particles encoding either a protein or shRNA for delivery and expression in the injured vessel wall. Neointimal thickening representing proliferative vascular smooth muscle cells usually peaks at 2 weeks after injury. Vessels are mostly harvested at this time point for cellular and molecular analysis of cell signaling pathways as well as gene and protein expression. Vessels can also be harvested at earlier time points to determine the onset of expression and/or activation of a specific protein or pathway, depending on the experimental aims intended. Vessels can be characterized and evaluated using histological staining, immunohistochemistry, protein/mRNA assays, and activity assays. The intact right carotid artery from the same animal is an ideal internal control. Injury-induced changes in molecular and cellular parameters can be evaluated by comparing the injured artery to the internal right control artery. Likewise, therapeutic modalities can be evaluated by comparing the injured and treated artery to the control injured only artery.

This protocol uses a balloon catheter to cause an intraluminal injury on the rat carotid artery and henceforth elicit neointimal hyperplasia. This is a well-established model for studying the mechanisms of vascular remodeling in response to injury. It is also widely used to determine the validity of potential therapeutic approaches.

Gefäßballon Verletzung und intraluminale Verwaltung in Rattenhalsschlagader

The carotid artery balloon injury model in rats has been well established for over two decades. It remains an important method to study the molecular and ...

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is also a valuable model system to test, and to evaluate therapeutics and drugs that negate maladaptive remodeling in the vessel. The injury, or barotrauma, in the vessel lumen caused by an inflated balloon via an inserted catheter induces subsequent neointimal growth, often leading to hyperplasia or thickening of the vessel wall that narrows, or obstructs the lumen. The method described here is sufficiently sensitive, and the results can be obtained in relatively short time (2 weeks after the surgery). The efficacy of the drug or therapeutic against the induced-remodeling can be evaluated either by the post-mortem pathological and histomorphological analysis, or by ultrasound sonography in live animals. In addition, this model system has also been used to determine the therapeutic window or the time course of the administered drug. These studies can leadto the development of a better administrative strategy and a better therapeutic outcome. The procedure described here provides a tool for translational studies that bring drug and therapeutic candidates from bench research to clinical applications.

The rat carotid balloon injury model described below allows researchers to evaluate drugs or therapeutics that negate injury-induced arterial hyperplasia. Detailed pre-surgical preparation, surgical procedure, and post-surgical cares of the animal are described.

Eine Ratte Karotis-Ballon-Verletzung Modell Anti-vaskuläre Remodeling Therapeutics zu Test

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt (MCT+Flow). The shunt is created by inserting an 18-G needle from the abdominal aorta into the adjacent caval vein. Increased pulmonary flow has been demonstrated as an essential trigger for a severe form of PAH with distinct phases of disease progression, characterized by early medial hypertrophy followed by neointimal lesions and the progressive occlusion of the small pulmonary vessels. To measure the right heart and pulmonary hemodynamics in this model, right heart catheterization is performed by inserting a rigid cannula containing a flexible ball-tip catheter via the right jugular vein into the right ventricle. The catheter is then advanced into the main and the more distal pulmonary arteries. The histopathology of the pulmonary vasculature is assessed qualitatively, by scoring the pre- and intra-acinar vessels on the degree of muscularization and the presence of a neointima, and quantitatively, by measuring the wall thickness, the wall-lumen ratios, and the occlusion score.

This protocol describes a surgical procedure to create a model for flow-induced pulmonary arterial hypertension (PAH) in rats and the procedures to analyze the principle hemodynamic and histological end-points in this model.

Shunt-Chirurgie, Rechtsherzkatheter und Gefäß Morphometry in einem Rattenmodell für Durchfluss-induzierte pulmonale arterielle Hypertonie

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt ...

Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique

The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable experimental animal models to test novel embolization materials such as stents and flow diverters. The aim of the present project was to design a safe, fast, and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model.
Saccular aneurysms were created from an arterial graft from the descending aorta.The aneurysms were microsurgically transplanted through end-to-side anastomosis to the infrarenal abdominal aorta of a syngenic male Wistar rat weighing &#62;500 g. Following aneurysm anastomosis, aneurysm embolization was performed using balloon expandable magnesium stents (2.5 mm x 6 mm). The stent system was retrograde introduced from the lower abdominal aorta using a modified Seldinger technique.
Following a pilot series of 6 animals, a total of 67 rats were operated according to established standard operating procedures. Mean surgery time, mean anastomosis time, and mean suturing time of the artery puncture site were 167 &#177; 22 min, 26 &#177; 6 min and 11 &#177; 5 min, respectively. The mortality rate was 6% (n=4). The morbidity rate was 7.5% (n=5), and in-stent thrombosis was found in 4 cases (n=2 early, n=2 late in stent thrombosis).
The results demonstrate the feasibility of standardized stent occlusion of saccular sidewall aneurysms in rats - with low rates of morbidity and mortality. This stent embolization procedure combines the opportunity to study novel concepts of stent or flow diverter based devices as well as the molecular aspects of healing.

Reproducable experimental animal models are needed for the testing of novel embolization materials, which have been designed to treat endovascular occlusion of intracranial aneurysms (IA). The present study aims to develop a safe and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model.

Biologisch abbaubare Magnesium Stent-Behandlung von Saccular Aneurysms in einem Rattenmodell - Einführung der Operationstechnik

The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable ...

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Creation of a Rodent Model of Abdominal Aortic Aneurysm by Blocking Adventitial Vasa Vasorum Perfusion

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic aneurysms (AAAs). This article introduces and describes a standard protocol used to induce AAAs through adventitial VV hypoperfusion created with a combination of polyurethane catheter insertion into the aortic lumen and suture ligation of the infrarenal abdominal aorta.
The protocol involves the use of male rats weighing 300-400 g, which are provided food and water ad libitum. After laparotomy with a ventral midline abdominal incision, exfoliation of the aorta is performed, which blocks blood flow from the perivascular tissue. Aortotomy involving a small incision adjacent to the renal artery branches is performed, and a polyurethane catheter is inserted using an 18-gauge indwelling needle. After repairing the incision, tight ligation of the aorta over the catheter blocks VV blood flow from the proximal direction through the aortic wall without disturbing the aortic blood flow. This technique can induce an AAA with progressive aortic dilatation.
The greatest benefit of this model is that VV hypoperfusion causes tissue hypoxia and the development of an infrarenal AAA, which has morphological and pathological characteristics similar to those of a human AAA.

Polyurethane catheter insertion into the aortic lumen and suture ligation of the aorta induce chronic hypoxia due to hypoperfusion of the adventitial vasa vasorum. This article describes a novel animal model of abdominal aortic aneurysm (AAA) with characteristics similar to those of AAA in humans.

Erstellung eines Nagetier Modells der abdominalen Aortenaneurysma Vaskulogenese Adventitial Vasa Vasorum Perfusion

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic ...

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

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the luminal surface area in arteries thereby reducing adequate blood flow to organs and distal tissues. Clinically, revascularization procedures such as balloon angioplasty with or without stent placement aim to restore blood flow. Although these procedures reestablish blood flow by reducing plaque burden, they damage the vessel wall, which initiates the arterial healing response. The prolonged healing response causes arterial restenosis, or re-narrowing, ultimately limiting the long-term success of these revascularization procedures. Therefore, preclinical animal models are integral for analyzing the pathophysiological mechanisms driving restenosis, and provide the opportunity to test novel therapeutic strategies. Murine models are cheaper and easier to operate on than large animal models. Balloon or wire injury are the two commonly accepted injury modalities used in murine models. Balloon injury models in particular mimic the clinical angioplasty procedure and cause adequate damage to the artery for the development of restenosis. Herein we describe the surgical details for performing and histologically analyzing the modified, pressure-controlled rat carotid artery balloon injury model. Additionally, this protocol highlights how local periadventitial application of therapeutics can be used to inhibit neointimal hyperplasia. Lastly, we present light sheet fluorescence microscopy as a novel approach for imaging and visualizing the arterial injury in three-dimensions.

The rat carotid artery balloon injury mimics the clinical angioplasty procedure performed to restore blood flow in atherosclerotic vessels. This model induces the arterial injury response by distending the arterial wall, and denuding the intimal layer of endothelial cells, ultimately causing remodeling and an intimal hyperplastic response.

Eine Ratte Carotis Arterie Druck-kontrollierte segmentale Ballonverletzung mit periadventitialen therapeutischen Anwendung

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