認知と行動の脳開発を犬の磁気共鳴イメージングを実行する彼らの財務および科学サポートのオハイオ州立大学で中心を感謝したいと思います。

<ol>
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F., Eitzman, D. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+Models+of+Thrombosis.">Animal Models of Thrombosis.</a> Current Opinion In Hematology. 16 (5), 342-346 (2009).</li><li>Sachs, U. J. H., Nieswandt, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+thrombus+formation+in+murine+models.">In vivo thrombus formation in murine models.</a> Circulation Research. 100 (7), 979-991 (2007).</li><li>Bonnard, T., Hagemeyer, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ferric+Chloride-induced+Thrombosis+Mouse+Model+on+Carotid+Artery+and+Mesentery+Vessel.">Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel.</a> Journal of Visualized Experiments. (100), e52838 (2015).</li><li>Kurz, K. D., Main, B. W., Sandusky, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rat+model+of+arterial+thrombosis+induced+by+ferric+chloride.">Rat model of arterial thrombosis induced by ferric chloride.</a> Thrombosis Research. 60 (4), 269-280 (1990).</li><li>Karatas, H., Erdener, S. E., 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=Thrombotic+distal+middle+cerebral+artery+occlusion+produced+by+topical+FeCl(3)+application:+a+novel+model+suitable+for+intravital+microscopy+and+thrombolysis+studies.">Thrombotic distal middle cerebral artery occlusion produced by topical FeCl(3) application: a novel model suitable for intravital microscopy and thrombolysis studies.</a> Journal of Cerebral Blood Flow and Metabolism. 31 (6), 1452-1460 (2011).</li><li>Li, W., McIntyre, T. M., Silverstein, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ferric+chloride-induced+murine+carotid+arterial+injury:+A+model+of+redox+pathology.">Ferric chloride-induced murine carotid arterial injury: A model of redox pathology.</a> Redox Biology. 1 (1), 50-55 (2013).</li><li>Vilahur, G., Padro, T., Badimon, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atherosclerosis+and+Thrombosis:+Insights+from+Large+Animal+Models.">Atherosclerosis and Thrombosis: Insights from Large Animal Models.</a> Journal of Biomedicine and Biotechnology. 2011, 1-12 (2011).</li><li>Coller, B. S., Folts, J. D., Smith, S. R., Scudder, L. E., Jordan, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Abolition+of+in+vivo+Platelet+Thrombus+Formation+in+Primates+with+Monoclonal+Antibodies+to+the+Platelet+GPIIb/IIIa+Receptor.+Correlation+with+Bleeding+Time,+Platelet+Aggregation,+and+Blockade+of+GPIIb/IIIa+Receptors.">Abolition of in vivo Platelet Thrombus Formation in Primates with Monoclonal Antibodies to the Platelet GPIIb/IIIa Receptor. Correlation with Bleeding Time, Platelet Aggregation, and Blockade of GPIIb/IIIa Receptors.</a> Circulation. 80 (6), 1766-1774 (1989).</li><li>Folts, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+in+vivo+Model+of+Experimental+Arterial+Stenosis,+Intimal+Damage,+and+Periodic+Thrombosis.">An in vivo Model of Experimental Arterial Stenosis, Intimal Damage, and Periodic Thrombosis.</a> Circulation. 83 (6 Suppl), (1991).</li><li>Yasuda, T., 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=A+canine+model+of+coronary+artery+thrombosis+with+superimposed+high+grade+stenosis+for+the+investigation+of+rethrombosis+after+thrombolysis.">A canine model of coronary artery thrombosis with superimposed high grade stenosis for the investigation of rethrombosis after thrombolysis.</a> Journal of the American College of Cardiology. 13 (6), 1409-1414 (1989).</li><li>Schob, 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=Correlation+Between+Aquaporin+4+Expression+and+Different+DWI+Parameters+in+Grade+I+Meningioma.">Correlation Between Aquaporin 4 Expression and Different DWI Parameters in Grade I Meningioma.</a> Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging. 19 (1), 138-142 (2017).</li><li>Schob, 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=Diffusion-Weighted+Imaging+Using+a+Readout-Segmented,+Multishot+EPI+Sequence+at+3+T+Distinguishes+between+Morphologically+Differentiated+and+Undifferentiated+Subtypes+of+Thyroid+Carcinoma-A+Preliminary+Study.">Diffusion-Weighted Imaging Using a Readout-Segmented, Multishot EPI Sequence at 3 T Distinguishes between Morphologically Differentiated and Undifferentiated Subtypes of Thyroid Carcinoma-A Preliminary Study.</a> Translational Oncology. 9 (5), 403-410 (2016).</li><li>Schob, 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=Diffusion-Weighted+MRI+Reflects+Proliferative+Activity+in+Primary+CNS+Lymphoma.">Diffusion-Weighted MRI Reflects Proliferative Activity in Primary CNS Lymphoma.</a> Public Library of Science One. 11 (8), e0161386 (2016).</li></ol>

した FeCl3誘導血管損傷モデル小動物における血栓症の研究に用い、利点の多数の大きい動物、臨床前モデルに変換するは簡単です。プロトコルを犬に合わせて若干の変更により薬理学的介入とする前に、容器の衛生を評価するために血管造影後の脳卒中と出血のボリュームを評価するために両方の磁気共鳴イメージングの利用中に、後の治療。他の血栓の大動物モデル損傷部位で安?...

主な理由は心血管系疾患での介入は薬物療法と血管内治療介入1によく反応が主、脳卒中治療は冠動脈疾患治療後モデル化します。これらの治療法は、しかしが適切に変換できなかった脳梗塞に。現在の脳卒中治療の難しさは、遺伝子組換え組織プラスミノーゲン活性化因子 (当社) が逆ことはできませんと出血性変換2,3,の重大な 6.4% リスクを管理に運ぶ4. 結果罹患率と死亡率はしばしば実現不可能の小さいウィンドウ5の使用を制限します。また、閉塞と再狭窄発生初期の神経学的改善を逆転させる初期の血栓溶解療法後しばしば。要約すると、虚血性脳血管障害の侮辱に苦しむ患者の大多数 (~ 90%) を除く当社を管理する狭い時間窓があります。
静脈内投与の抗血小板療法の役割は、改良された血管再開通、生存の結果2と虚血性脳卒中の治療に約束を示しています。残念ながら、これらの薬内頭蓋と余分な頭蓋内出血の予測可能な副作用を持って、主な理由は十分にする方法はありませんが逆にまたは彼らの活動2を制御します。血小板凝集を防止に効果的な中の出血とその活動を逆にすることができないリスクが脳卒中患者ケア ルーチンでの使用を排除します。必要がある、したがって、単独または組み合わせを防止し、血栓を溶解する作用はまだ出血が容認されて悪い、脳など閉鎖、低ボリュームの領域で使用できるようになります安全性プロファイルを持っている強力な抗血栓薬の存在します。
動脈血栓症と再狭窄のメカニズムを理解し、血栓溶解剤との再狭窄を防ぐ薬の評価は、前臨床試験の医薬品開発の一部として両方の小規模および大規模な動物モデルを必要があります。塩化第二鉄による血管障害は迅速かつ正確には、マウス、ラット、モルモット、露出血管の血栓の形成を誘導するために広く利用技術、ウサギ6,7,8,9,10,11,12. これらの小さい種が遺伝的操作、安価な動物購入および低日当住宅費の使いやすさを含むいくつかの利点を提供します。残念ながら、小動物実験は、術中アクセス血小板反応性、血液ガス分析、および炎症性応答に複数の血の描画を否定します。もっと重要なは、大型の動物は大いにもっと密接にひと血小板生理6,13を模倣します。血栓症の病態生理の研究、新規抗血小板剤や抗凝固薬の検証および潜在的な血栓溶解剤6の発見した FeCl3頚動脈損傷モデルは支配的な役割を果たしています。,7,8,9,10,11,12です前モデルのマウス、ラット、モルモット、ウサギは、使いやすさと遺伝的操作の柔軟性を提供している、翻訳可能な前臨床モデル、潜在的な治療6 の患者の投与と毒性の研究に重要な。 ,13。血栓性疾患のいくつかのモデルは、マウス、血栓症の末梢血管疾患に適用される大型の動物モデルで開発されている心筋梗塞や脳卒中はいくつかと遠い。猿、犬、豚で最初の血栓症モデルは狭窄、船舶、一般流の周期性削減14,15,16の結果に止血剤と後シリンダーを適用することに焦点を当てた。塩化第二鉄のモデルのように血管内皮細胞障害のサイトにて閉塞性血栓、代わりにこれらのモデル内の血栓は繰返し血栓症、遠位部塞栓に起因した、通常の血流に戻る。比較では、塩化第二鉄モデル大型動物は、損傷部位の閉塞血栓の結果でここで変更安定化及び血栓溶解治療前に血管造影を行いです。Diem、イヌ科動物および十分な外科的専門知識の購入あたり私たちの詳細ここで血栓症を手術、イメージングおよび組織学的利用を研究する研究所を許可するように血管損傷の大きい犬モデルの調査官が潤沢な資金供給を持ってテクニック。

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	<tbody>
		<tr height="40">
			<td height="40" style="height:40px;width:397px;">1/8&#8221; umbilical tape&#160;</td>
			<td style="width:195px;">Jorgensen Laboratories Inc.,&#160;</td>
			<td style="width:344px;">#J0025UA&#160;</td>
			<td style="width:201px;">for ferric chloride application</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">4% paraformaldehyde in PBS</td>
			<td>Alfa Aesar</td>
			<td>AAJ61899AP</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">10% neutral buffered formalin&#160;</td>
			<td>Richard-Allan Scientific</td>
			<td>5701</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">&#160;2% 2,3,5-triphenyltetrazolium chloride (TTC in PBS, pH 7.4)&#160;</td>
			<td>Sigma Aldrich</td>
			<td>T8877</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">ADP/Collagen cartridges</td>
			<td>Siemens Diagnostics</td>
			<td>B417021A</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">4.5 ml 3.2% sodium citrate blood vacutainer&#160;</td>
			<td>Becton Dickinson</td>
			<td>BD 369714</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">4.5 ml lithium heparin vacutainer&#160;</td>
			<td>Becton Dickinson</td>
			<td>BD 368056</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">EDTA K3 vacutainers&#160;</td>
			<td>Becton Dickinson</td>
			<td>BD455036</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Doppler flow probe</td>
			<td>Transonic Systems Inc</td>
			<td>MA2.5PSL</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Hematoxylin 560&#160;</td>
			<td>Surgipath</td>
			<td>3801570</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Eosin</td>
			<td>Surgipath</td>
			<td>3801602</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">LabChart Software</td>
			<td>ADInstruments Inc.</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Prisma Fit 3 tesla (3T) magnet</td>
			<td>Siemen&#39;s Diagnostics</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Sodium heparin for injection (to coat blood gas syringe)</td>
			<td>NovaPlus</td>
			<td>402525D</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">HUG-U-VAC positioning system &#160;</td>
			<td>DRE Veterinary</td>
			<td>1320</td>
			<td></td>
		</tr>
	</tbody>
</table>

ferric chloride-induced canine carotid artery thrombosis: a large animal model of vascular injury

世界的に、毎年、虚血性脳卒中や心筋梗塞につながる閉塞性動脈血栓症が 1300 万の死に貢献します。ここでは、我々 は大規模な動物 (犬) に予防や血栓溶解剤の前臨床スクリーニングのため使用することができますわずかな修正と小動物から血管損傷モデルを翻訳しています。手術方法に加えては、修正されたプロトコルは、脳と頚動脈を確認する組織学的解析のための頚動脈の両方を処理するための詳細な手順について、血管造影による頸動脈運河を評価するためにステップバイ ステップ方法をについて説明します。運河と、脳出血や磁気共鳴画像 (MRI) を用いて下流の血栓塞栓イベントの評価を完了するための特定のパラメーター。さらに、大規模な動物 (犬) の血管損傷に翻訳する必要以前老舗の小さな動物モデルから特定の手順の変更を説明します。

本明細書の詳細な手順は、閉塞動脈の介入の予防や血栓の評価のために使用できるモデルの開発になります。図 1 aは、商業ソフトウェアによって記録された治療中、前後の基準流速と結果の血流速度を示しています。この録音からのデータは、この犬の治療と頚動脈損傷を再灌流の割合を判断する使用できます。図 1 bは?...

Watch this Scientific Journal Video about Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury at JoVE.com

Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury

大型動物の血管損傷モデルの利用にも特徴とし、一般的に使用される小さな動物塩化第二鉄誘起 (した FeCl3) 頚動脈損傷モデルに必要な変更を紹介します。予防、血栓溶解の薬理学的・機械的介入の前臨床試験評価のため、結果として得られるモデルを利用できます。

塩化第二鉄によるイヌ総頚動脈血栓症: 血管損傷の大動物モデル

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, ...

ferric-chloride-induced-canine-carotid-artery-thrombosis-large-animal

Research

JoVE Journal

Medicine

9.0K ビュー.  Ohio State University. 大型動物の血管損傷モデルの利用にも特徴とし、一般的に使用される小さな動物塩化第二鉄誘起 (した FeCl3) 頚動脈損傷モデルに必要な変更を紹介します。予防、血栓溶解の薬理学的・機械的介入の前臨床試験評価のため、結果として得られるモデルを利用できます。

ビデオ: Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury

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.

静脈血栓症の電解下大静脈モデル（EIM）

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

医学

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.

下大静脈血栓症のマウス完全な停滞のモデル

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

Training a Sophisticated Microsurgical Technique: Interposition of External Jugular Vein Graft in the Common Carotid Artery in Rats

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in peripheral arterial bypass surgery as well as in arteriovenous fistulas.1-5 The experimental procedure of vein graft interposition in the common carotid artery by using the cuff-technique has been applied in several research projects to examine the aetiology of neointimal hyperplasia and therapeutic options to address it. 6-8 The cuff prevents vessel anastomotic remodeling and induces turbulence within the graft and thereby the development of neointimal hyperplasia.
Using the superior caval vein graft is an established small-animal model for venous arterialization experiment.9-11 This current protocol refers to an established jugular vein graft interposition technique first described by Zou et al., 9 as well as others.12-14 Nevertheless, these cited small animal protocols are complicated.
To simplify the procedure and to minimize the number of experimental animals needed, a detailed operation protocol by video training is presented. This video should help the novice surgeon to learn both the cuff-technique and the vein graft interposition. Hereby, the right external jugular vein was grafted in cuff-technique in the common carotid artery of 21 female Sprague Dawley rats categorized in three equal groups that were sacrificed on day 21, 42 and 84, respectively. Notably, no donor animals were needed, because auto-transplantations were performed. The survival rate was 100 % at the time point of sacrifice. In addition, the graft patency rate was 60 % for the first 10 operated animals and 82 % for the remaining 11 animals. The blood flow at the time of sacrifice was 8&plusmn;3 ml/min. In conclusion, this surgical protocol considerably simplifies, optimizes and standardizes this complicated procedure. It gives novice surgeons easy, step-by-step instruction, explaining possible pitfalls, thereby helping them to gain expertise fast and avoid useless sacrifice of experimental animals.

Neointimal hyperplasia is the primary cause of stenosis in arterialized veins. We propose a new protocol whereby the right external jugular vein is grafted using the cuff technique in the common carotid artery of Sprague Dawley rats. The survival rate was 100 % at the time point of sacrifice.

ラットの総頚動脈で外頚静脈グラフトの介在：洗練された顕微鏡下手術の訓練

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in ...

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.

ラット頸動脈における血管バルーン傷害と管腔内投与

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 ...

Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel

Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric chloride injury is now a well-established technique to rapidly and accurately induce the formation of thrombi in exposed veins or artery of small and large diameter. This model has played a key role in the study of the pathophysiology of thrombosis, in the discovery and validation of novel antithrombotic drugs and in the understanding of the mechanism of action of these new agents. Here, the implementation of this technique on a mesenteric vessel and carotid artery in mice is presented. The method describes how to label circulating leukocytes and platelets with a fluorescent dye and to observe, by intravital microscopy on the exposed mesentery, their accumulation at the injured vessel wall which leads to the formation of a thrombus. On the carotid artery, the occlusion caused by the clot formation is measured by monitoring the blood flow with a Doppler probe.

The FeCl3 induced thrombosis model in mice is described herein. A method to monitor thrombus growth by intravital microscopy observation on a mesenteric vessel and by blood flow measurement in the carotid artery is presented.

塩化第二鉄誘発性頚動脈および腸間膜血管に血栓症のマウスモデル

Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric ...

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.

ラット頸動脈バルーン損傷モデルは、抗血管リモデリングの治療薬をテストします

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 ...

Ferric Chloride-induced Murine Thrombosis Models

Arterial thrombosis (blood clot) is a common complication of many systemic diseases associated with chronic inflammation, including atherosclerosis, diabetes, obesity, cancer and chronic autoimmune rheumatologic disorders. Thrombi are the cause of most heart attacks, strokes and extremity loss, making thrombosis an extremely important public health problem. Since these thrombi stem from inappropriate platelet activation and subsequent coagulation, targeting these systems therapeutically has important clinical significance for developing safer treatments. Due to the complexities of the hemostatic system, in vitro experiments cannot replicate the blood-to-vessel wall interactions; therefore, in vivo studies are critical to understand pathological mechanisms of thrombus formation. To this end, various thrombosis models have been developed in mice. Among them, ferric chloride (FeCl3) induced vascular injury is a widely used model of occlusive thrombosis that reports platelet activation and aggregation in the context of an aseptic closed vascular system. This model is based on redox-induced endothelial cell injury, which is simple and sensitive to both anticoagulant and anti-platelets drugs. The time required for the development of a thrombus that occludes blood flow gives a quantitative measure of vascular injury, platelet activation and aggregation that is relevant to thrombotic diseases. We have significantly refined this FeCl3-induced vascular thrombosis model, which makes the data highly reproducible with minimal variation. Here we describe the model and present representative data from several experimental set-ups that demonstrate the utility of this model in thrombosis research.

We report a refined procedure of the ferric chloride (FeCl3)-induced thrombosis models on carotid and mesenteric artery as well as vein, characterized efficiently using intravital microscopy to monitor time to occlusive thrombi formation.

塩化第二鉄誘発性マウス血栓症モデル

Arterial thrombosis (blood clot) is a common complication of many systemic diseases associated with chronic inflammation, including atherosclerosis, ...

Invasive Hemodynamic Monitoring of Aortic and Pulmonary Artery Hemodynamics in a Large Animal Model of ARDS

One of the leading causes of morbidity and mortality in patients with heart failure is right ventricular (RV) dysfunction, especially if it is due to pulmonary hypertension. For a better understanding and treatment of this disease, precise hemodynamic monitoring of left and right ventricular parameters is important. For this reason, it is essential to establish experimental pig models of cardiac hemodynamics and measurements for research purpose. 
This article shows the induction of ARDS by using oleic acid (OA) and consequent right ventricular dysfunction, as well as the instrumentation of the pigs and the data acquisition process that is needed to assess hemodynamic parameters. To achieve right ventricular dysfunction, we used oleic acid (OA) to cause ARDS and accompanied this with pulmonary artery hypertension (PAH). With this model of PAH and consecutive right ventricular dysfunction, many hemodynamic parameters can be measured, and right ventricular volume load can be detected. 
All vital parameters, including respiratory rate (RR), heart rate (HR) and body temperature were recorded throughout the whole experiment. Hemodynamic parameters including femoral artery pressure (FAP), aortic pressure (AP), right ventricular pressure (peak systolic, end systolic and end diastolic right ventricular pressure), central venous pressure (CVP), pulmonary artery pressure (PAP) and left arterial pressure (LAP) were measured as well as perfusion parameters including ascending aortic flow (AAF) and pulmonary artery flow (PAF). Hemodynamic measurements were performed using transcardiopulmonary thermodilution to provide cardiac output (CO). Furthermore, the PiCCO2 system (Pulse Contour Cardiac Output System 2) was used to receive parameters such as stroke volume variance (SVV), pulse pressure variance (PPV), as well as extravascular lung water (EVLW) and global end-diastolic volume (GEDV). Our monitoring procedure is suitable for detecting right ventricular dysfunction and monitoring hemodynamic findings before and after volume administration.

We present a protocol of creating right ventricular dysfunction in a pig model by inducing ARDS. We demonstrate invasive monitoring of left and right ventricular cardiac output using flow probes around the aorta and the pulmonary artery, as well as blood pressure measurements in the aorta and pulmonary artery.

ARDS の大動物モデルで大動脈と肺動脈の血行動態の侵襲血行動態モニタリング

One of the leading causes of morbidity and mortality in patients with heart failure is right ventricular (RV) dysfunction, especially if it is due to ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

ワイヤー図法を使用してマウスの腸間膜動脈の等尺性収縮力測定

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

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.

過期治療アプリケーションを用いてラット頸動脈圧制御区分バルーン損傷

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