Name: hemodynamic characterization of rodent models of pulmonary arterial hypertension
Uploaded: 2016-04-11T14:00:00
Description: Watch this Scientific Journal Video about Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension at JoVE.com

SR is supported by NIH K08HL114643, Gilead Research Scholars in Pulmonary Arterial Hypertension and a Burroughs Wellcome Fund Career Award for Medical Scientists.

記載されているすべての手順は、医学のデューク大学の動物のケアのガイドラインに従ってください。 1.前に手順を開始します注：任意の動物の手続きの前に、適切な機関の許可が得られていることを確認してください。すべての手順と同じように、何の動物の苦痛がないことを保証するために、適切な鎮痛薬を使用します。 <ol><li>開通性を確保?...

<ol>
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The protocols outlined here describe a comprehensive characterization of hemodynamics and right ventricular function in rodent models of pulmonary hypertension. While right heart catheterization as described here is a terminal procedure, the mortality associated with echocardiography is minimal, which allows for screening and follow-up of disease progression. However, similar to patients with PH having markedly increased mortality with anesthesia17, in our experience, rats with severe PH do not tolerate anesth...

肺動脈高血圧症（PAH）の炎症性細胞浸潤、平滑筋の増殖および内皮細胞のアポトーシスに関連した肺血管系の疾患です。これらの変更は、その後、右心室（RV）機能不全と心不全につながる、肺動脈の閉塞につながります。 PAHにおけるPAHおよびRV障害の根底にある病態生理を理解するために、この病気を研究するための遺伝的および薬理学的モデルを含む異なるモデルの数は、（他の場所で1,2件）が開発されています。 これらのモデルのうち、最も人気のあるラットにおける低酸素誘導マウスにおける（Hxの）PAHおよびモノクロタリン（MCT）およびSU5416-低酸素症（SuHx）モデルがあります。マウスHxのモデルでは、マウスは内側増殖の結果として開発して、（0.10のFIO2と18000フィートの高度に対応し、normobaricや低気圧のいずれか）、低酸素の4週間にさらされている、RVシステムオフラインを増加オリッチ圧力とRV肥大3の開発。その後、PAH 4の開発につながる不明な機構を介して肺の血管内皮細胞への傷害で60ミリグラム/キログラム結果の単回投与でMCT。 SU5416は、類似の病理学的変化と永続的な肺高血圧症における3週間の結果を得るために、慢性低酸素症への暴露に続いて60 10mg / kgの単回皮下注射で、血管内皮増殖因子受容体（VEGFR）1および2ブロッカーの阻害剤、および治療でありますそれに閉塞性血管病変5の形成と、ヒトの疾患で見られます。過去数年間では、肺高血圧のためのいくつかのトランスジェニックマウスモデルが開発されてきました。 BMPR2遺伝子変異がPAHの両方家族性および特発性の形態、ヘムオキシゲナーゼ-1ノックアウト及び（他1,2レビュー）IL-6の過剰発現に見られるように、これらは、ノックアウトおよび骨形成タンパク質受容体2（BMPR2）の突然変異を含みます。 PHのこれらの異なるげっ歯類モデルは、肺高血圧症、右心室肥大および右室不全の異なるレベルを有します。低酸素症および様々なトランスジェニックマウスモデルは、ラットモデル1のいずれよりもはるかに、より穏やかなPAHになるが、それは別の遺伝子変異の試験およびそれに関連する分子のシグナル伝達経路を可能にします。 MCTは、複数の組織4に内皮細胞に毒性があることが表示されますが、MCTのモデルは、重度のPAHにつながるん。 SuHxモデルは、血管によって特徴付けられる薬理学的操作と低酸素暴露の両方を必要とするが、ヒトでの特発性PAHで見られるものと類似変更されます。また、これらのモデルの全てにおいて、PAHの開発に関連した組織病理学的変化、肺動脈圧およびRV機能との間に断線があるかもしれません。これは、組織病理学的変化の間の比例関係が通常存在するヒト疾患、とは対照的にpulmonの重症度であり​​ます進高血圧とRVの障害の程度。このように、PHのこれらの齧歯類モデルの総合的な特性評価が必要であり、（心臓カテーテルによって）（典型的には、心エコー検査によって）RV機能の評価、血行動態および心臓の組織病理学および（組織採取）から肺を伴います。 このプロトコルでは、我々はラットとマウスにおけるPAHモデルの血行動態の特徴付けのために使用される基本的なテクニックについて説明します。これらの一般的な技術は、右心室と肺血管系のいずれの研究にも適用することができ、PAHのモデルに限定されるものではありません。心エコー検査によってRVの可視化ラットでは比較的簡単であるが、それらの大きさとRVの複雑な形状にマウスではより困難です。また、このようなTAPSE、肺動脈（PA）加速時間とPAドプラ波形のノッチとしてRV機能を定量化するために使用されるいくつかのサロゲートは、ヒトにおいて十分に検証されていないとPUの評価を弱くしか相関します侵襲的血行動態によるlmonary高血圧およびRV機能。インピーダンスカテーテルと開胸カテーテル法は、圧力 - 容積（PV）の決意を可能にするループし、より詳細な血行動態の特徴付けが、RVの血行動態の決意は最高のインスピレーションと負の胸腔内圧の効果を維持するために、クローズド胸で行われています。任意の手順と同様に、手続きの経験を開発することが実験的な成功に不可欠です。

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		<tr height="21">
			<td height="21" style="height:21px;width:443px;">Vevo 2100 Imaging System (120V)&#160;</td>
			<td style="width:183px;">VisualSonics, inc.&#160;</td>
			<td style="width:191px;">VS-11945</td>
			<td style="width:167px;"></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:443px;">Vevo 2100 Imaging Station&#160;</td>
			<td style="width:183px;">VisualSonics, inc.&#160;</td>
			<td style="width:191px;"></td>
			<td></td>
		</tr>
		<tr height="27">
			<td height="27" style="height:27px;width:443px;">High-frequency Mechanical Transducers</td>
			<td style="width:183px;">VisualSonics, inc.&#160;</td>
			<td style="width:191px;">MS250, MS550D, MS400</td>
			<td></td>
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		<tr height="25">
			<td height="25" style="height:25px;width:443px;">Ultrasound Gel Parker&#160;</td>
			<td style="width:183px;">Laboratories Inc.&#160;</td>
			<td style="width:191px;">01-08</td>
			<td></td>
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			<td height="21" style="height:21px;">PowerLab 4/35</td>
			<td>ADInstruments</td>
			<td>ML765</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Labchart 8</td>
			<td>ADInstruments</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">BP transducer with stopcock and cable</td>
			<td>ADInstruments</td>
			<td>MLT1199</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">BP transducer calibration kit</td>
			<td style="width:183px;">ADInstruments</td>
			<td style="width:191px;">MLA1052</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Mikro-Tip Pressure Catheter for mouse</td>
			<td>Millar</td>
			<td>SPR-1000</td>
			<td>Alternative catheter available from Scisense FT111B (mouse) and FT211B (rat)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">Mikro-Tip Pressure Catheter for rat</td>
			<td style="width:183px;">Millar</td>
			<td style="width:191px;">SPR-513</td>
			<td>Alternative catheter available from Scisense FT111B (mouse) and FT211B (rat)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Millar Mikro-Tip&#160;ultra-miniature PV loop catheter for mice</td>
			<td>Millar</td>
			<td>PVR-1035</td>
			<td>Alternative catheter available from Scisense FT112 (mouse)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">Millar Mikro-Tip ultra miniature PV loop catheter for rats</td>
			<td style="width:183px;">Millar</td>
			<td style="width:191px;">SPR-869</td>
			<td>Alternative catheter available from Scisense FT112 (mouse)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Millar PV system MPVS-300&#160;</td>
			<td>Millar</td>
			<td>MPVS-300</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;">4-0 Silk Black Braid 100 Yard Spool</td>
			<td>Roboz Surgical</td>
			<td>SUT-15-2</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">6-0 Silk Black Braid 100 Yard Spool</td>
			<td>Roboz Surgical</td>
			<td>SUT-14-1</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Iris Scissors, Delicate, Integra Miltex</td>
			<td>VWR</td>
			<td>21909-248</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">VWR Dissecting Scissors, Sharp/Blunt Tip</td>
			<td style="width:183px;">VWR</td>
			<td style="width:191px;">82027-588</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">VWR Delicate Scissors, 4 1/2&#34;</td>
			<td style="width:183px;">VWR</td>
			<td style="width:191px;">82027-582</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">Two star Hemostats, Excelta</td>
			<td style="width:183px;">VWR</td>
			<td style="width:191px;">63042-090</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">Neutral-buffered formalin</td>
			<td style="width:183px;">VWR</td>
			<td style="width:191px;">89370-094</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">Crotaline</td>
			<td style="width:183px;">Sigma</td>
			<td style="width:191px;">C2401</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">SU5416</td>
			<td style="width:183px;">Tocris Biosciences</td>
			<td align="right" style="width:191px;">3037</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">3.5X-45X Boom Stand Trinocular Zoom Stereo Microscope&#160;</td>
			<td>AmScope</td>
			<td>SM-3BX</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">PE (Polyethylene Tubing)-10</td>
			<td>Braintree Scientific Inc</td>
			<td style="width:191px;">PE10 36 FT</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">PE (Polyethylene Tubing)-50</td>
			<td>Braintree Scientific Inc</td>
			<td style="width:191px;">PE50 36 FT</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">PE (Polyethylene Tubing)-60</td>
			<td style="width:183px;">Braintree Scientific Inc</td>
			<td style="width:191px;">PE60 36 FT</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Tabletop Isoflurane Anesthesia Unit</td>
			<td>Kent Scientific</td>
			<td style="width:191px;">ACV-1205S</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Surgisuite multi-functional surgical platform</td>
			<td>Kent Scientific</td>
			<td style="width:191px;">Surgisuite</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Retractor set</td>
			<td>Kent Scientific</td>
			<td>SURGI-5002</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Anesthesia induction chamber</td>
			<td>VetEquip</td>
			<td align="right" style="width:191px;">941443</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">Anesthesia Gas filter canister</td>
			<td style="width:183px;">Kent Scientific</td>
			<td style="width:191px;">ACV-2001</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:443px;">Rodent nose cone</td>
			<td style="width:183px;">VetEquip</td>
			<td align="right" style="width:191px;">921431</td>
			<td></td>
		</tr>
	</tbody>
</table>

hemodynamic characterization of rodent models of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. 
Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed.

げっ歯類で右心カテーテル法は、典型的には、縦のフォローアップには適用されませんターミナル手続きであるように、心エコー検査は、スクリーニングのための優れた非侵襲的な代替手段であり、フォローアップ12。心エコー検査でヒトPAHにおける肺動脈収縮期圧は、通常、頂端図で得ることが通常簡単である三尖弁逆流から誘導されるが、このようなビューを確実ドップラーによ...

Watch this Scientific Journal Video about Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension at JoVE.com

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a disease of pulmonary arterioles that leads to their obliteration and the development of right ventricular failure. Rodent models of PAH are critical in understanding the pathophysiology of PAH. Here we demonstrate hemodynamic characterization, with right heart catheterization and echocardiography, in the mouse and rat.

肺動脈性肺高血圧症の齧歯類モデルの血行動態特性評価

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle ...

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Medicine

Magnetic Resonance Imaging Quantification of Pulmonary Perfusion using Calibrated Arterial Spin Labeling

キャリブレーション動脈スピンラベリングを用いた肺血流の磁気共鳴イメージングの定量化

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, ...

Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets

増加肺動脈の拍動流が豚における低酸素性肺高血圧を改善しました

Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular ...

Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet

慢性血栓塞栓性肺高血圧症とピグレットにおける右室機能の評価

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. ...

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

流れ誘導性の肺動脈性肺高血圧症のためのラットモデルにおけるシャント手術、右心カテーテル、および血管形態計測

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 ...

Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats

肝硬変ラットにおけるポータル高血圧症侵襲血行動態評価

This is a detailed protocol describing invasive hemodynamic measurements in cirrhotic rats for the characterization of portal hypertensive syndrome. ...

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

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 ...

Induction and Phenotyping of Acute Right Heart Failure in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension

慢性血栓塞栓性肺高血圧症の大型動物モデルにおける急性右心不全の誘導とフェノタイピング

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The ...

Left Atrial Stenosis Induced Pulmonary Venous Arterialization and Group 2 Pulmonary Hypertension in Rat

左心房狭窄による肺静脈動脈化術とグループ 2 肺高血圧症ラット

The mechanism of mitral stenosis-induced pulmonary venous arterialization and group 2 pulmonary hypertension (PH) is unclear. There is no rodent model of ...

The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats

組み合わせてモノクロまたは Sugen 肺高血圧ラットのモデルとして左肺全摘

In this protocol, we detail the correct procedural steps and necessary precautions to successfully perform a left pneumonectomy and induce PAH in rats ...

Induction and Characterization of Pulmonary Hypertension in Mice using the Hypoxia/SU5416 Model

低酸素/SU5416モデルを用いたマウスにおける肺高血圧の誘導と特徴づけ

Pulmonary Hypertension (PH) is a pathophysiological condition, defined by a mean pulmonary arterial pressure exceeding 25 mm Hg at rest, as assessed by ...