Name: improvement of a closed chest porcine myocardial infarction model by standardization of tissue and blood sampling procedures
Uploaded: 2018-03-12T14:30:00
Description: Watch this Scientific Journal Video about Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures at JoVE.com

著者は、FXIIa 阻害剤と、対応するコントロールを提供する教授クリスチャン Heinis を認識したいです。また感謝するラミナー Beslac、博士ダニエル メトラー、実験的手術ユニット、生物医学研究、テクニカル サポートのためのベルンの大学のための部門からケイ Nettelbeck。セリーヌ Guillod と診断、Interventional ベルン大学病院小児放射線科からマティアス ラウシュ Inselspital は x 線装置と技術サポートを提供しました。このプロジェクトは、スイスの全米科学財団のプロジェクト号 320030_156193 によって賄われていた。我々 はまたコミュニケーションとマーケティング、ベルン大学病院映像記録実験用 Inselspital から氏 Reto Haenni に感謝したいと思います。

1. 動物:
すべての動物は、スイスの国内法のガイドラインに従って扱われました。研究は、ベルンのカントンのローカル動物実験委員会によって承認された (アクセス許可なし。25/16 である)。
男女の大きな白豚を使う (~ 30 ± 5 kg)。2 つのグループに動物を盲目的に分割受信 FXIIa の環 (80 kDa プロテアーゼ) 阻害剤または治療の選択やその他のアクティブ?...

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Position Paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology.</a> Cardiovasc Res. 87, 406-423 (2010).</li><li>Neri, M., Riezzo, I., Pascale, N., Pomara, C., Turillazzi, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ischemia/Reperfusion+Injury+following+Acute+Myocardial+Infarction:+A+Critical+Issue+for+Clinicians+and+Forensic+Pathologists.">Ischemia/Reperfusion Injury following Acute Myocardial Infarction: A Critical Issue for Clinicians and Forensic Pathologists.</a> Mediators Inflamm. 2017, 1-14 (2017).</li><li>Yang, Q., He, G. -. W., Underwood, M. J., Yu, C. -. 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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=Myocardial+infarction+and+intramyocardial+injection+models+in+swine.">Myocardial infarction and intramyocardial injection models in swine.</a> Nat Protoc. 7, 1479-1496 (2012).</li><li>Koudstaal, 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=Myocardial+infarction+and+functional+outcome+assessment+in+pigs.">Myocardial infarction and functional outcome assessment in pigs.</a> J Vis Exp. , e51269 (2014).</li><li>Kamat, P., 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=Dexrazoxane+Shows+No+Protective+Effect+in+the+Acute+Phase+of+Reperfusion+during+Myocardial+Infarction+in+Pigs.">Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs.</a> PLoS One. 11, e0168541 (2016).</li><li>Carden, D. 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Clinical value of its stimulation.</a> Circulation. 23, 766-789 (1961).</li><li>Regueiro-Purri&#241;os, M., 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=Ventricular+Arrhythmias+and+Mortality+Associated+with+Isoflurane+and+Sevoflurane+in+a+Porcine+Model+of+Myocardial+Infarction.">Ventricular Arrhythmias and Mortality Associated with Isoflurane and Sevoflurane in a Porcine Model of Myocardial Infarction.</a> J Am Assoc Lab Anim Sci. , (2011).</li><li>Roberts, L. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evans+blue+toxicity.">Evans blue toxicity.</a> Can Med Assoc J. 71, 489-491 (1954).</li><li>Ellenbroek, G. H. J. 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心筋私/R 負傷後急性心筋梗塞3患者の予後に直接変換は最終梗塞サイズに大きな影響があります。心筋の病態生理を理解私/R 傷害は減らすか、それを防ぐために最初のステップです。心筋私/R の損傷、閉塞血管の再灌流直後後に発生する急性の状態。私/R 負傷は自然免疫応答の活性化につながるし、再灌流と周囲組織20のサイトで細胞の損傷が発生しました?...

虚血性心疾患、特に急性心筋梗塞 (MI) は、先進国1の死の主な原因です。今日、MI の標準治療は、経皮的冠動脈インターベンション (PCI)、バルーン カテーテル治療です。急性 MI の PCI 治療を受けた患者の予後と生活の質に影響を与える重要な要因の 1 つは、梗塞サイズです。サイズの削減は、患者の生存率と予後2大きな影響を持つことができます。心筋虚血・再灌流 (私/R) 傷害は、心血管の研究の主要な目的の 1 つは、回避または低減心筋梗塞巣の大きさに大きな影響私/R 負傷3。私の正確なメカニズム R 負傷がまだ調査4/。プラズマ カスケードと内皮細胞の活性化は、私の特徴/R 負傷5。凝固系の活性化は明らかに関与する6,7です。最近では、血液凝固カスケードの接触相活性化に伴う初期上流ペプチドとして FXII の役割は、FXII で示されている脳のモデルラットをノックアウト私/R 負傷8。ブタのモデルにこれらの結果の検証は、臨床の翻訳に重要なステップです。したがって、我々 は心筋のコンテキストで、新規環 (80 kDa) FXIIa プロテアーゼインヒビターをテスト私/パイロット研究で R 負傷。
急性 MI と PCI 治療の臨床状況を模倣、動物モデルが私たち理解心筋の病態を改善するために不可欠である/R 負傷、新規治療法の選択肢をテストします。豚の良い動物モデルを表す臨床心筋私/R 負傷。これは、彼らの心は解剖学と冠循環に関する人間の心に非常に似ていますが、それらはまた心筋の虚血と再灌流9,10と同様の病態生理学的応答を示すためだけではありません。ラットやマウスなどの他のモデルいないこれらの基準を満たすし、犬などが多くのより多くの担保の冠血管人間と比較して人間の心11,12と比較されたときかなりの相違を表示13。
ブタ心筋梗塞モデルは調べる心筋虚血性心疾患を含む循環器病研究で広く使用されています私/R 負傷14,15,16,17。後者は胸骨に関連する炎症性反応を最小化するため、炎症性疾患や開開胸手術使用が不可欠であります。C アーム血管造影の臨床を用いた閉胸のモデルは、この問題を克服します。さらに、最も重要なポイントの一つは梗塞サイズ (虚血性壊死、NIT) ができるように、我々 のプロトコルが虚血性 (リスク、AAR の領域) と非虚血性左心室 (ANR 危険でない領域) 部の正確な区別を提供することは正確に決定されます。今回の私たちの目的は心筋、ブタの再現方法を明確に定義する私/R 傷害モデル、特に私の分子メカニズムのより正確な分析を可能にする心筋組織サンプリングに関して/R 傷害と薬剤治療の効果の鮮明な画像。

<table>
	<tbody>
		<tr>
			<td>ABL 90 Flex, blood gas analyser</td>
			<td>Radiometer</td>
			<td>-</td>
			<td>Blood gas analysis (BGA)</td>
		</tr>
		<tr>
			<td>ACT Plus</td>
			<td>Medtronic</td>
			<td>-</td>
			<td>Activated clotting time</td>
		</tr>
		<tr>
			<td>Atropin</td>
			<td>Sintetica</td>
			<td>-</td>
			<td>Atropinum Sulfas, 0,5mg/ml</td>
		</tr>
		<tr>
			<td>Balance (20-500 Kg)</td>
			<td>NAGATA Scale, Tiwan</td>
			<td>HTB/HTR</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Balance (21-4200 g)</td>
			<td>Mettler toledo, Switzerland</td>
			<td>MS4002SDR</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Blood collection tubes: EDTA, citrate and serum</td>
			<td>S-Monovette, Nuembrecht, Germany</td>
			<td>05.1167.001, 
			05.1071.001 
			and 
			05.1557.001 respectively</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>BV Pulsera mobile C-arm</td>
			<td>Philips</td>
			<td>-</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Centrifuge</td>
			<td>Labcare, UK</td>
			<td>ALC PK120R</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Defibrillator Lifepak 12</td>
			<td>Medtronic</td>
			<td>-</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Dextran from Leuconostoc mesenteroides</td>
			<td>Sigma-Aldrich, Germany</td>
			<td>D3759</td>
			<td>Average M.wt 48000-90000</td>
		</tr>
		<tr>
			<td>Digital single lens reflex camera</td>
			<td>Sony, Thailand</td>
			<td>DSLR-A500/A550</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Dissecting forceps</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>EMPIRA RX PCI dilatation catheter</td>
			<td>Cordis, Johnson&#38;Johnson, USA</td>
			<td>85R15300S</td>
			<td>Diameter 3 mm, length 15 mm, Alternative products can be used</td>
		</tr>
		<tr>
			<td>EMPIRA RX PCI dilatation catheter</td>
			<td>Cordis, Johnson&#38;Johnson, USA</td>
			<td>85R15350S</td>
			<td>Diameter 3.5 mm, length 15 mm, Alternative products can be used</td>
		</tr>
		<tr>
			<td>Evans Blue</td>
			<td>Sigma-Aldrich, Germany</td>
			<td>E2129</td>
			<td>Toxic</td>
		</tr>
		<tr>
			<td>Fabius GS premium respirator</td>
			<td>Dr&#228;ger, L&#252;beck, Germany</td>
			<td>-</td>
			<td>Anesthesia work station, Alternative products can be used</td>
		</tr>
		<tr>
			<td>Fentanyl</td>
			<td>Inselspital ISPI</td>
			<td>-</td>
			<td>Fentanyl 2500mcg/50ml</td>
		</tr>
		<tr>
			<td>Formaldehyde</td>
			<td>Pathology Institute, Bern University</td>
			<td>SI148701</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>FXIIa inhibitor</td>
			<td>Provided by Prof. Christian Heinis&#39; laboratory in EPFL</td>
			<td></td>
			<td>Novel bicyclic peptide</td>
		</tr>
		<tr>
			<td>Galeo, coronary guidewire</td>
			<td>Biotronik, Germany</td>
			<td>125497</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Guidance catheter</td>
			<td>Boston Scientific, Florida, USA</td>
			<td>34356-06</td>
			<td>6F (100 cm, EB3.75). Alternative products can be used</td>
		</tr>
		<tr>
			<td>Heparin Sodium</td>
			<td>Drossapharm, Basel, Switzerland</td>
			<td>-</td>
			<td>Liquemin, 25000 U.I./5 ml</td>
		</tr>
		<tr>
			<td>High end electrosurgery</td>
			<td>BOWA, Germany</td>
			<td>ARC 400</td>
			<td>Electrical source for blood suction. Alternative products can be used</td>
		</tr>
		<tr>
			<td>Hydro-Guardmini breathing filter</td>
			<td>Intersurgical, Lithuania</td>
			<td>1745000</td>
			<td>Filters</td>
		</tr>
		<tr>
			<td>Image J</td>
			<td>National Institute of Health, USA</td>
			<td>1.47v</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Inflation device, Atrion QL2530</td>
			<td>Atrion medical product, Alabama, USA</td>
			<td>96402</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>IntelliVue MP 70</td>
			<td>Philips, Boeblingen, Germany</td>
			<td>-</td>
			<td>Monitor (ECG, heart rate, blood presure and body temperature). Alternative products can be used</td>
		</tr>
		<tr>
			<td>KCl</td>
			<td>Sintetica SA</td>
			<td>-</td>
			<td>Potassium chloride 15%</td>
		</tr>
		<tr>
			<td>Ketamine</td>
			<td>Vetoquinol</td>
			<td>-</td>
			<td>Narketan, 1ml/100mg</td>
		</tr>
		<tr>
			<td>LR-ACT</td>
			<td>Medtronic</td>
			<td>402-01</td>
			<td>ACT special syringes</td>
		</tr>
		<tr>
			<td>Midazolam</td>
			<td>Roche</td>
			<td>-</td>
			<td>Dormicum, 5mg/ml</td>
		</tr>
		<tr>
			<td>Monopolar scalpel</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Needle holder</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>High resolution camera, PathStand Macro Imaging Stand for Grossing</td>
			<td>Spotimaging, USA</td>
			<td></td>
			<td>1080 p HD resolution. Alternative products can be used</td>
		</tr>
		<tr>
			<td>PBS</td>
			<td>In-house preparation</td>
			<td>-</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Peripheral venous cannula, 18 G</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>PowerLab 4/35 data acquisition system</td>
			<td>Adinstruments, Spechbach, Germany</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>Rotamax120T</td>
			<td>Heidolph, Germany</td>
			<td>544-41200-00</td>
			<td>Shaker. Alternative can be used</td>
		</tr>
		<tr>
			<td>R&#252;schelit-Super Safety Clear Tube</td>
			<td>Teleflex, Dublin, Irland</td>
			<td>112480</td>
			<td>Air way tubing, Alternative products can be used</td>
		</tr>
		<tr>
			<td>Safe Pico Aspirator Syringes</td>
			<td>Radiometer</td>
			<td>956-622</td>
			<td>BGA special syringes</td>
		</tr>
		<tr>
			<td>Saline</td>
			<td>Sintetica Bioren</td>
			<td>-</td>
			<td>NaCl 0,9%. Alternative products can be used</td>
		</tr>
		<tr>
			<td>Sevorane 1.5%</td>
			<td>AbbVie AG</td>
			<td>-</td>
			<td>Sevorane 250ml 100%</td>
		</tr>
		<tr>
			<td>Sheath</td>
			<td>Cordis, Johnson&#38;Johnson, USA</td>
			<td>504-607 A</td>
			<td>AVANTI + / 7 F, Alternative products can be used</td>
		</tr>
		<tr>
			<td>Space infusion pump</td>
			<td>B.Braun Medical AG, Germany</td>
			<td>-</td>
			<td>For infusion of fentanyl. Alternative products can be used</td>
		</tr>
		<tr>
			<td>SPR-350 (Millar catheter)</td>
			<td>Adinstruments, Texas, USA</td>
			<td>840-8166</td>
			<td>MIKRO-TIP, 5F, 120 cm</td>
		</tr>
		<tr>
			<td>Sternotomy saw</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Sutures</td>
			<td>ETHICON, Johnson&#38;Johnson, USA</td>
			<td>Y3110H</td>
			<td>Monocryl 3-0 SH-1 Plus. Alternative products can be used</td>
		</tr>
		<tr>
			<td>Syringes (20, 10 and 5 mL)</td>
			<td>CODAN,Baar, Switzerland</td>
			<td>62.7602, 
			62.6616, 
			62.5607 
			respectively</td>
			<td>Used to inject anesthetic materials intramuscularly or directly into the central venous line. Also to inject heparin or FXIIa or the respective control. Alternative products can be used</td>
		</tr>
		<tr>
			<td>Thorax spreader</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Tissue-tek</td>
			<td>SAKURA, Netherlands</td>
			<td>4583</td>
			<td>O.C.T. compound</td>
		</tr>
		<tr>
			<td>Vascular forceps</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Xenetix 300 contrast media</td>
			<td>Guerbet, Z&#252;rich, Switzerland</td>
			<td>-</td>
			<td>Lobitridol, 300 mg iodide/ml</td>
		</tr>
		<tr>
			<td>Xylazine</td>
			<td>Vetoquinol</td>
			<td>-</td>
			<td>Xylapan, 20mg/1 mL</td>
		</tr>
		<tr>
			<td>2,3,5-Triphenyltetrazolium choride</td>
			<td>Sigma-Aldrich, Austria</td>
			<td>T8877</td>
			<td></td>
		</tr>
		<tr>
			<td>500 &#956;L tubes (eppendorf)</td>
			<td>Trefflab, Switzerland</td>
			<td>96.08185.9.03</td>
			<td>Alternative products can be used</td>
		</tr>
	</tbody>
</table>

improvement of a closed chest porcine myocardial infarction model by standardization of tissue and blood sampling procedures

心筋虚血再灌流 (私/R) 心筋梗塞後, 壊死の面積のほぼ半分に貢献する損傷。心筋を回避または低減する承認薬がない日付に私/R 負傷。心筋の病態生理学的メカニズムの理解と研究/R 傷害は成功した治療法の開発が不可欠です。大規模な動物実験は、並進メソッドで重要なステップです。急性心筋梗塞のブタのモデルを確立されており、自分や他人によって記述されます。今後の実験で使用するためのサンプリング手法に焦点を当てて詳細にモデルの価値をさらに向上を目指しました。さらに、我々 は最終結果の品質に影響を与えることができる小さいが重要なステップを強調します。心筋の臨床状況を模倣する私/R 負傷、経皮的冠動脈インターベンション (PCI) カテーテルは、動脈左前下行枝冠 (LAD) 麻酔下のブタの挿入されました。このモデル模倣急性心筋梗塞、PCI 治療の領域を正確に把握する可能性を持つ人間のリスクだけでなく、壊死 ° ° °- と実行可能な虚血性の組織。ここでモデルは FXIIa の二環性のペプチド阻害剤の効果を調べるために使用されました。モデルは、心筋梗塞後の効果時間が長く再灌流を許可するように変更できます。

1 つの動物は、技術的なエラー (虚血時に、被験物質の添加前に血圧の急激な低下) による FXIIa 阻害剤または制御ペプチドの投与前に途中で死亡しました。1 つの動物は、左前下行枝 (LAD) の解剖学的異常のために虚血/再灌流障害は認められなかったので FXIIa 阻害剤グループから除外されました。尖部を含む左の心室の大部分はこの動物の回旋動脈灌流。最終的な分析?...

Watch this Scientific Journal Video about Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures at JoVE.com

Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures

ここに示すの並進価値が心筋虚血/再灌流障害の病態生理の理解を高めるために急性心筋梗塞の確立されたブタモデルのサンプリング手順を標準化するためのプロトコル新規薬剤の候補者をテストします。

組織と血液サンプリング手順の標準化による閉胸ブタ心筋梗塞モデルの改善

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved ...

Research

JoVE Journal

Medicine

Acute Myocardial Infarction in Rats

ラットにおける急性心筋梗塞

With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular ...

A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion

心筋虚血再灌流障害のマウスクローズド胸モデル

Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ...

Myocardial Infarction and Functional Outcome Assessment in Pigs

豚における心筋梗塞および機能的結果の評価

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

従来のクローズド·チェスト法による心室細動と蘇生のラットモデル

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic ...

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

急性心筋梗塞の豚モデルにおける主要アウトカム評価

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are ...

Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration

新生児マウスの心筋梗塞、心臓再生のモデル

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and ...

A Closed-chest Model to Induce Transverse Aortic Constriction in Mice

マウスで横方向の大動脈狭窄を誘導するために閉じて胸モデル

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to ...

A Cryoinjury Model to Study Myocardial Infarction in the Mouse

マウスの心筋梗塞を研究する凍結傷害モデル

The use of animal models is essential for developing new therapeutic strategies for acute coronary syndrome and its complications. In this article, we ...

Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice

マウスにおける閉鎖胸腔カテーテル法による心機能および圧力容積ループの両心室評価

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) ...

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&#246;ttingen Minipigs and Landrace Pigs

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in GÃƒÆ’Ã‚Â¶ttingen Minipigs and Landrace Pigs

ヘッティンゲンミニピッグとランドレーツ豚における閉胸冠動脈閉塞/再灌流モデルにおける心筋梗塞後心不全

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an ...