フランセーズデ連盟が、シオンペドロバリーデラマーサとシオンアルフォンソマルティンエスクデロ（DFR）、循環器フェローシップのスペイン語協会が、NHLBI助成金P01 - HL039707とP01 - HL087226とLeducq財団（JJおよびOB）によって部分的にサポート心臓リズム学会フェローシップ賞でCardiologie（RPM）、、財団法人日本心臓財団/日本心電学会（MY）のフェローシップ。

1。心臓の除去とランゲンドルフ灌流 35〜40キロの重量を量る羊は4-6 mg / kgのプロポフォールとペントバルビタールナトリウムの60から100 mg / kgを使用して麻酔する。ハーツは、開胸により除去し（95％O2、5％CO2）240〜270ミリリットル/分、pHは7.4と35.5〜37.5℃の一定流量でタイロード溶液を酸素循環にランゲンドルフ灌流システムに接続されていますタイロードの組成は（mMで）です：塩化ナトリウム130、KClを4.0、MgCl2の1、塩化カルシウム1.8、NaHCO3水溶液24、リン酸二水素ナトリウム1.2、グルコース5.6、およびアルブミン0.04グラム/ L Blebbistatin 10μM（エンツォライフサイエンスインターナショナル、INC。プリマスミーティング、ペンシルバニア州、米国）は、収縮力を減少させるために使用されます。 2。ランゲンドルフ灌流羊の心臓のストレッチ誘発性心房細動隔離された、冠動脈潅流心臓は心房の両方で等化腔内圧力を有効にするには、心房トランス中隔穿刺を受ける。と、そのオープンエンド流出のカニューレに、すべての静脈の開口部は、その後、カニューレを挿入し、デジタルセンサー（モンテシステム、（株）、ゴレタ、カリフォルニア州、米国モンテシステムトランスデューサ- TSD104A）に接続されて下大静脈、を除いて、密封されています心房からの高さは、心房内圧を制御します。圧力は、その後6センチメートルH 2 Oの量に心房容積の相対的なの〜30％の増加につながる12センチメートルH 2 O、に増加しています圧力は、実験全体を通して安定して維持されます。事前の静脈を密閉するtetrapolar電極カテーテルは（Torqでは、メドトロニック社/ミネアポリス/ミネソタ州/アメリカ）モンテシステムアンプを使用して、2つの遠位電極（サンプリングレート、1.0 kHzの）からバイポーラ信号を記録するために肺静脈のそれぞれに配置されます（DA100C、モンテシステム、（株）、ゴレタ、カリフォルニア州、米国）。つの追加custum製双極電極は左心耳（LAA）と右心耳の上部の屋根上に配置されています。 3。光学マッピングで設定する<ol><li>左心耳の心外膜マッピング。 5〜10ミリリットルジ- 4 - ANEPPS（10 mg / mLの）（Sigma - Aldrich社、セントルイス、MO、米国）と10分のローディング期間は、レーザー励起時に得られる電位感受性蛍光ために必要なのボーラス注射（532nm）を心外膜面の。放出された蛍光は、（模式図を参照して長いフィルター通過の600 nmを透過してLittleJoe CCDビデオカメラ（80 × 80ピクセルは、アナリティカルシステムズ、（株）ディケーター、ジョージア州、米国をSciMeasure）に投影し、毎秒800フレームの速度で取得され図1A上）。 5秒間のムービーは、AF中に2分間隔で取得されます。マップされた心外膜面の面積は〜14 cm 2である。 </li><li>そのまま心のPLAの心内膜光学マッピング。第二LittleJoe CCDカメラ（80 × 80ピクセル）心外膜カメラと同期しています。ビューの90度のフィールドを持つ直径10mmのデュアルチャネルリジッドボアスコープ（エベレストVIT（株）フランドル、NJ、米国）は、僧帽弁を越え、左心室の前壁を介して導入し、心内膜表面に焦点を当てているPLAの。 PLAで光学的にマップされた領域は、4つの肺静脈と心房septo -肺バンドルを可視化することができます（図1A、B）〜4 cm 2と 、なります。ボアスコープは、カスタムメイドの接眼アダプタを介してCCDカメラにC -マウントされています。レーザー波長532 nmの光は、液体、光ガイド（コアでは0.2）を介してボアスコープの励起チャネルに配信されます。 </li></ol> 4。心房細動のプロトコル連続的な心房の伸展下でAFがLAAの上部に位置するペーシング電極によってバーストペーシング（12 Hzの、5ミリ秒のパルスを、2倍の拡張しきい値）を介して誘導される。 AFは、光学ムービーが2つ分の間隔で取得された50分、5秒のために継続して許可されます。バイポーラ記録は継続的に収集されます。光学映画の買収は、バイポーラの録音の5秒間のセグメントの同時取得をトリガします。 5。周波数分析周波数解析には、左と右心房の間の周波数勾配とともに、AF時の高い活性化率を持つ領域の同定を可能にします。支配的な周波数（DF）のマップは、各ピクセルで記録された時系列の蛍光信号に高速フーリエ変換アルゴリズム（FFT）を適用した後、各光学ムービーから得られる7 FFTはまた5秒間のバイポーラ信号（ハイパスフィルタ処理に適用される3 Hzと低域の光ムービーと同期）は、35 Hzでフィルタリング。における 6。心房細動のダイナミクス<ol><li>相マップの生成。 AFダイナミクスの解析は、ヒルベルト変換によって生成された位相のムービーを利用しています。14簡単に言うと、各ピクセルで記録された活動電位の瞬時位相毎のスペクトル成分を、対応する四半期サイクルでシフトされるように、元の時系列信号を変換することによって決定される戦後の15DS、信号の瞬時位相は元の信号に変換された信号の比の逆正接から取得されます。とπラジアン-πの間の値で位相角は、連続的な空間的な相変化が励起、再分極と回復のプロセスを反映した位相マップを、構築するために連続的なカラースキームとして表されます。14 </li><li>活性化パターンのキャラクタリゼーション。活性化パターンの様々なクラスは次のような位相の映画を（図2）、使用して識別することができます。 <ul><li>ローターが1回転を超える（図2A）を持続する特異点に収束するすべての相の存在によって識別されます。 </li><li>画期的な、パターンのようなターゲットにビューのフィールドに表示されていると（図2B）外側に伝播する波面として定義されています。 </li><li>時空間に組織化周期的な波は、同様の方向と間波の間隔（図2C）と、視野の同じ場所から出てきた4つの連続周期的な波の最小値として定義されています。 </li></ul></li></ol>さらに、定量化は、その特定の地域から得られた活性化の最も一般的なパターンで最も高い周波数領域の空間相関することができます。それは一般的に最も高い周波数ドメインは急性AF中に配置されている領域を表すので、後者は、PLAの心内膜表面をマッピングするのに重要な役割を強調。 7。代表的な結果： PLAからLAAとRAAへの支配的な周波数（DF）勾配は、急性ストレッチ誘発性心房細動中に存在している。最高のDFの領域は肺静脈またはどこかPLAでの一つで、または近辺にローカライズされている。11が代表的なAFのエピソードは、最高のDFは、PLA（右下肺静脈）に局在している、図3に示されています。結果は、左と発作性のヒト心房細動のアブレーション手順中に観察された右DFの勾配への一貫したPLA運転AFにおける高周波源の存在をサポートしています。16 位相マップのムービーを使用してアクティベーションのパターンの定量化は、ローターの最高数はPLAとPLAとLAAの間の接合部で発見されることを示しています。8は時折その回転の中心（特異点）長期的なローターを識別することが可能です。最高周波数領域で局在する。10は心房組織は、三次元構造を表しているため、PLAのマップされた心内膜表面にローターを識別すると、それらのローターの回転の中心（フィラメント）が最終的に垂直マッピング領域の表面にあることを示唆している。図4はまた、PLAとLAA（それぞれ9および6.4 Hz）の間の周波数の勾配と相関LAA、に向かって同時fibrillatory伝導によるPLAの心内膜から記録されたそのようなローターを示しています。ローターの数は、このモデルでは不整脈を維持するためにPLAで再入国の重要な役割を示唆するLAA、よりPLAで一貫して高くなっています。 全体的に、結果は左心房の安定と高速ローターが急性ストレッチ誘発性心房細動と発せられる波がfib​​rillatory伝導として発現すると徐々に支配的な減少、右心房に向かって、彼らの頭のような複雑な、空間的に分散伝導ブロックのパターンを受ける駆動可能という理論を支持周波数。 <img src="/files/ftp_upload/3103/3103fig1.jpg" alt="図1" /> 図1実験の模式図は、設定する。 ：硬質ボアスコープは、左心室の前壁および僧帽弁口を介して導入し、後部左心房（PLA）の心内膜表面に焦点を当てています。 CCDカメラは、ボアスコープに結合され、レーザー照射は、ボアスコープの下部に接続されているレーザーの液体のガイドを介して提供されます。心外膜マッピングはLAAに実行されます。バイポーラ電極を右心房と左心房の屋根の上に配置されます。追加のバイポーラ信号は肺静脈から取得されます。 B：説明のために横方向の壁を開いて左心房の以下の側面図。ボアスコープの先端には、PLAの心内膜表面を照らします。バイポーラ電極を左心房の屋根の上に位置しています。 LAA：左心耳。 LV：左心室。 RA：右心房。 RV：右心室。 <img src="/files/ftp_upload/3103/3103fig2.jpg" alt="図2" /> 図2相のムービーの生成後に特定されたアクティベーションのさまざまなパターン。 ：左心耳（LAA）のシーケンシャルスナップショットは、回転の中心（特異点）の周りローターの旋回を示す。左から右へ、一周は完了です。 B：LAA上のサンプルの画期的な活性化パターン。波は最大に表示されますビューと外側に伝播するの欄の右上隅あたり。 C：LAAに向かってPLAの地域から来る四時空主催定期的な波（それぞれ0、182、352、512ミリ秒、で）。等時は10ミリ秒の間隔でプロットされます。底、活動電位のさまざまなフェーズのためのキーは色分けされています。 <img src="/files/ftp_upload/3103/3103fig3.jpg" alt="図3" /> 図3。ランゲンドルフ灌流絶縁羊の心臓の急性ストレッチ誘発性心房細動時の最高周波数の活性を持つ領域の同定。 ：左心耳（LAA）、右心耳（RAA）と後部左心房（PLA）の解剖学的ビュー。 PLA画像は、4つの肺静脈（PV）とでマップされた領域の内視鏡ビューです。 B：LAAとPLAの光学マッピングによって得られたDFマップ。 RAAの周波数の値は、バイポーラelectrogramsから入手した。最高の周波数領域はPLAに位置しています。 C：最大のDFは右のPVのPLAの地域は12.4 Hzに対応している代表的なパワースペクトル、。 LSPV：左上肺静脈。 LIPV：左下肺静脈。 RSPV：右上肺静脈。 RIPV：右下肺静脈。再現リファレンス11（デイヴィッドFilgueirasラマ＆ホセJalife。心房細動のメカニズム。 基礎科学における臨床Electrophysiologistために 、第3巻（編チャールズAntzelevitchは）141から156（サンダース、2011）から。 <img src="/files/ftp_upload/3103/3103fig4.jpg" alt="図4" /> 図4。Simultaneousphaseマップ（A、B）と後部左心房（PLA）と左心耳（LAA）から支配的な周波数マップ（C）。 ：ローターとその特異点のドリフトを示すPLAからのシーケンシャルスナップショット。 B：LAAから同時相のスナップショット。活性化のパターンがfibrillatory伝導と互換性の伝播波を示しています。特異点でもfibrillatory伝導地域のwavebreaksと相関関係に存在する。 PLAとLAAの同時支配的な周波数のマップ：C（ビデオ4を参照してください）​​。最速領域は、位相マップの分析でローターの存在と相関するPLA（9 Hz）を、に位置しています。 LAAでの最高周波数はfibrillatory伝導と相関6 Hzの、です。パネルCの右側に、PLAとLAAから単一ピクセルの光アクティベーションが表示されます。

<ol>
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利害の衝突は宣言されません。

孤立した羊の心臓の急性ストレッチ誘発性心房細動の特徴は、人間の発作性心房細動のプロパティの一部に似ています。羊の心臓の心房内圧の急性増加は、心房細動のリスクが高い心房拡張症患者で観察と同様の長時間、のためのAFのメンテナンスを行うことができます。1の左から右DFの勾配の存在羊心房にも人間の電気生理学的研究に登録されているものと似ています。従って1...

<table border="1"><tbody><tr><td> 材料名 </td><td> 会社 </td><td> カタログ番号 </td></tr><tr><td> 安楽死 </td><td></td><td></td></tr><tr><td>ヘパリン</td><td>シグマ</td><td> H3393 </td></tr><tr><td>プロポフォール</td><td>アボット</td><td> 5206-04-03 </td></tr><tr><td>ペントバルビタール</td><td>ルンドベック社</td><td> NDC 67386-501-55 </td></tr><tr><td>イントロデューサ18ゲージ</td><td>テルモ</td><td> SS * FF1832 </td></tr><tr><td>カフ付き気管内チューブ（9ミリメートル） </td><td> DRE獣医</td><td> ＃9440 </td></tr><tr><td>光ファイバー喉頭鏡のケース</td><td> DRE獣医</td><td> ＃991 </td></tr><tr><td>光ファイバーブレード</td><td> DRE獣医</td><td>第984位</td></tr><tr><td>営業はさみ</td><td> DRE獣医</td><td> ＃9702＃1944 </td></tr><tr><td>スカルペルハンドル＃3ソリッド4&quot; </td><td> Roboz手術器械株式会社</td><td> RS - 9843 </td></tr><tr><td>滅菌メスブレード</td><td> Roboz手術器械株式会社</td><td> RS - 9801〜10 </td></tr><tr><td>換気のバッグ</td><td> Westmed </td><td> 562013 </td></tr><tr><td>ブラント/シャープカーブシムズはさみ</td><td> Roboz手術器械株式会社</td><td> RS - 7035 </td></tr><tr><td>組織鉗子（× 2） </td><td> DRE獣医</td><td> ＃1895 </td></tr><tr><td>カントロウィッツ胸部鉗子、11&quot; </td><td>生物医学研究インスツルメンツ株式会社</td><td> 34から1980 </td></tr><tr><td> Finochietto大型チェストスプレッダー</td><td>カップ手術器具（株） </td><td> KS - 7301 </td></tr><tr><td>開胸さみ</td><td> Rostfreiゾーリンゲン</td><td></td></tr><tr><td>プラスチックトレイ</td><td> Nalgene </td><td>フィッシャー</td></tr><tr><td> 光学マッピング </td><td></td><td></td></tr><tr><td>ボンハサミ（× 2） </td><td> Roboz手術器械（株）、株式会社</td><td> RS - 5840SC </td></tr><tr><td>外科絹</td><td>フィッシャー</td><td> 50-900-04214 </td></tr><tr><td>ミクロ解剖鉗子</td><td> Roboz手術器械（株）、株式会社</td><td> RS - 5130 </td></tr><tr><td> Tetrapolar電極カテーテル（Torqを）（× 4） </td><td>メドトロニック株式会社</td><td> 05580SP </td></tr><tr><td>デジタルセンサー。モンテシステムトランスデューサ</td><td>モンテシステム、（株） </td><td> RX104A </td></tr><tr><td>モンテシステムアンプ</td><td>モンテシステム、（株） </td><td> DA - 100C </td></tr><tr><td>ジ-4 ANEPPS </td><td>シグマアルドリッチ、セントルイス</td><td> D8604 - 5mgの</td></tr><tr><td> Blebbistatin </td><td>エンツォ生命科学インターナショナル、INC。 </td><td> BML - E1315 - 0025 </td></tr><tr><td> LittleJoe CCDビデオカメラ（× 2） </td><td>アナリティカルシステムズ、（株）をSciMeasure </td><td></td></tr><tr><td>デュアルチャネルリジッドボアスコープ</td><td>エベレストVIT（株） </td><td> R10 - 25 - 0から90まで</td></tr><tr><td>血流ポンプ（× 2） </td><td>コー​​ルパーマー</td><td> GK - 77920〜30 </td></tr><tr><td>温度プローブ</td><td>コー​​ルパーマー</td><td> R - 08491〜02 </td></tr><tr><td> pHメータ</td><td>フィッシャー</td><td> 01-913-806 </td></tr><tr><td>デジタル温度計</td><td>コー​​ルパーマー</td><td> GK89000 - 10 </td></tr><tr><td>人工肺のフィルター</td><td>ソリン</td><td> 05318 </td></tr><tr><td>シリコン灌流チューブ（L / S 15） </td><td> MasterFlex </td><td> 96410〜15 </td></tr><tr><td>レーザー光ガイド（× 6） </td><td>オリエ株式会社</td><td> 77536 </td></tr><tr><td>液体ライトガイド（コアでは0.2） </td><td>ニューポートコーポレーション</td><td> 77556 </td></tr><tr><td>レーザー発生器（1ワット）（× 1） </td><td>上海ドリームLsaer Tecchnology </td><td> SDL - 532 - 1000T </td></tr><tr><td>レーザー発生器（5ワット）（× 1） </td><td>スペクトラフィジックスレーザー</td><td> MILL 5​​sJ </td></tr></tbody></table>

high-resolution endocardial and epicardial optical mapping in a sheep model of stretch-induced atrial fibrillation

心房細動（AF）は、高い罹患率と死亡率との複雑な不整脈です。1,2は、それが臨床の現場で見られるし、その有病率は今後数年間で増加すると予想される最も一般的な持続的な心臓のリズム障害です。3は心房内圧を増加と拡張が長いAF、動物モデルを使用しての妥当性を強調し、AFのダイナミクスを研究するためにストレッチ1,4につながることが認識されている。 AFのメカニズムを理解することは、高い空間分解能と時間分解能を持つ心臓の電気的な波の可視化が必要です。高時間分解能は伝統的に人間の電気生理学的研究で使用されている従来の電気マッピングすることによって達成することができますが、同時に使用することができます心房内電極の数が少ない空間分解能を制限し、不整脈の中に電波のいずれかを詳細に追跡を排除する。動物モデル5,6のサブミリメートルの空間分解能と一緒にfibrillatory活動の90年代初頭対応広視野特性の光学的マッピングの導入と急速にfibrillatoryの源として電気波のパターン（ローター）の回転が同定された心室または心房で発生する可能性のある活動。7-9組み合わせた時間と光学マッピングの周波数領域解析を使用すると、それは左と右心房の間の周波数勾配とともに、AF時の高周波周期的な活動の離散的な部位を実証することが可能です。 。最速ローターと地域が最も高い周波数で有効化され、全体的な不整脈を駆動する。このようなロータから発せられる10,11波がfibrillatory伝導の現象で、その結果、彼らのパスで機能的または解剖学的のどちらかの障害物との対話12のマッピングの心内膜面後方左心房（PLA）は、最高回転周波数と地域のAF波ダイナミクスの追跡を可能にします。重要なのは、PLAは、腔内カテーテルベースのアブレーティブ手順は左心房の内側からAFのダイナミクスを研究の妥当性を強調患者、13の終端AF最も成功している。領域ですここでは、人間の発作性心房細動の特性のいくつかのような急性ストレッチ誘発性心房細動、の羊のモデルを説明します。左心房での心外膜マッピングは、硬質ボアスコープは、AFのメンテナンスのために最も関連性の高い領域では活性化のパターンを視覚化する最も直接的なアプローチを表すCCDカメラにCマウントのデュアルチャネルを使用してPLAの心内膜マッピングによって補完されます。

Watch this Scientific Journal Video about High-Resolution Endocardial and Epicardial Optical Mapping in a Sheep Model of Stretch-Induced Atrial Fibrillation at JoVE.com

High-Resolution Endocardial and Epicardial Optical Mapping in a Sheep Model of Stretch-Induced Atrial Fibrillation

このレポートは、ストレッチ誘発性心房細動時のランゲンドルフ灌流羊の心臓の無傷の左心房の電気的興奮を同時に心内膜と心外膜の光学的マッピングの方法論と結果の詳細な説明を提供します。

ストレッチ誘発性心房細動の羊のモデルで高解像度の心内膜と心外膜光学マッピング

 Atrial fibrillation (AF) is a complex cardiac arrhythmia with high morbidity and mortality.1,2 It is the most common sustained cardiac rhythm disturbance ...

high-resolution-endocardial-epicardial-optical-mapping-sheep-model

Research

JoVE Journal

Medicine

14.7K ビュー.  University of Michigan. このレポートは、ストレッチ誘発性心房細動時のランゲンドルフ灌流羊の心臓の無傷の左心房の電気的興奮を同時に心内膜と心外膜の光学的マッピングの方法論と結果の詳細な説明を提供します。

ビデオ: High-Resolution Endocardial and Epicardial Optical Mapping in a Sheep Model of Stretch-Induced Atrial Fibrillation

The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States 1. Since AF affects primarily elderly people, its prevalence increases parallel with age. As such, it is expected that 15.9 million Americans will be affected by the year 2050 2. Ischemic stroke occurs in 5% of non-anticoagulated AF patients each year. Current treatments for AF include rate control, rhythm control and prevention of stroke 3.
The American College of Cardiology, American Heart Association, and European Society of Cardiology currently recommended rate control as the first course of therapy for AF 3. Rate control is achieved by administration of pharmacological agents, such as &beta;-blockers, that lower the heart rate until it reaches a less symptomatic state 3. Rhythm control aims to return the heart to its normal sinus rhythm and is typically achieved through administration of antiarrhythmic drugs such as amiodarone, electrical cardioversion or ablation therapy. Rhythm control methods, however, have not been demonstrated to be superior to rate-control methods 4-6. In fact, certain antiarrhythmic drugs have been shown to be associated with higher hospitalization rates, serious adverse effects 3, or even increases in mortality in patients with structural heart defects 7. Thus, treatment with antiarrhythmics is more often used when rate-control drugs are ineffective or contraindicated. Rate-control and antiarrhythmic agents relieve the symptoms of AF, including palpitations, shortness of breath, and fatigue 8, but don't reliably prevent thromboembolic events 6.
Treatment with the anticoagulant drug warfarin significantly reduces the rate of stroke or embolism 9,10. However, because of problems associated with its use, fewer than 50% of patients are treated with it. The therapeutic dose is affected by drug, dietary, and metabolic interactions, and thus requires detailed monitoring. In addition, warfarin has the potential to cause severe, sometimes lethal, bleeding 2. As an alternative, aspirin is commonly prescribed. While aspirin is typically well tolerated, it is far less effective at preventing stroke 10. Other alternatives to warfarin, such as dabigatran 11 or rivaroxaban 12 demonstrate non-inferiority to warfarin with respect to thromboembolic events (in fact, dabigatran given as a high dose of 150 mg twice a day has shown superiority). While these drugs have the advantage of eliminating dietary concerns and eliminating the need for regular blood monitoring, major bleeding and associated complications, while somewhat less so than with warfarin, remain an issue 13-15.
Since 90% of AF-associated strokes result from emboli that arise from the left atrial appendage (LAA) 2, one alternative approach to warfarin therapy has been to exclude the LAA using an implanted device to trap blood clots before they exit. Here, we demonstrate a procedure for implanting the WATCHMAN Left Atrial Appendage Closure Device. A transseptal cannula is inserted through the femoral vein, and under fluoroscopic guidance, inter-atrial septum is crossed. Once access to the left atrium has been achieved, a guidewire is placed in the upper pulmonary vein and the WATCHMAN Access Sheath and dilator are advanced over the wire into the left atrium. The guidewire is removed, and the access sheath is carefully advanced into the distal portion of the LAA over a pigtail catheter. The WATCHMAN Delivery System is prepped, inserted into the access sheath, and slowly advanced. The WATCHMAN device is then deployed into the LAA. The device release criteria are confirmed via fluoroscopy and transesophageal echocardiography (TEE) and the device is released.

The accompanying video describes a procedure for percutaneous placement of the WATCHMAN Left Atrial Appendage (LAA) Device. The WATCHMAN is a nitinol device designed to be permanently implanted at, or slightly distal to, the opening of the left atrial appendage (LAA) to trap blood clots before they exit the LAA, preventing thromboembolic stroke.

警備員は、心房細動のために心耳の閉鎖デバイスの左

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States 1. Since AF affects primarily ...

医学

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope 4, 5. Patients with AF have a five-fold higher risk of stroke 6.
Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% 7. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range 8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug 8.
The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF 12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers 4. CA is a well-established treatment for AF symptoms 14, 15, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy 16.
Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation 17, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) 18. This device received the Conformit&eacute; Europ&eacute;enne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy 19.
Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding 20 or other warfarin-associated problems.
The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1 21. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Catheter ablation is combined with placement of the WATCHMAN Left Atrial Appendage Closure Device to prevent ischemic stroke in a patient with non-valvular atrial fibrillation.

心房細動に対する左心耳閉鎖との組み合わせでカテーテルアブレーション

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and ...

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

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic components of cardiopulmonary resuscitation in humans is herein described. The model was developed in 1988 and has been used in approximately 70 peer-reviewed publications examining a myriad of resuscitation aspects including its physiology and pathophysiology, determinants of resuscitability, pharmacologic interventions, and even the effects of cell therapies. The model featured in this presentation includes: (1) vascular catheterization to measure aortic and right atrial pressures, to measure cardiac output by thermodilution, and to electrically induce ventricular fibrillation; and (2) tracheal intubation for positive pressure ventilation with oxygen enriched gas and assessment of the end-tidal CO2. A typical sequence of intervention entails: (1) electrical induction of ventricular fibrillation, (2) chest compression using a mechanical piston device concomitantly with positive pressure ventilation delivering oxygen-enriched gas, (3) electrical shocks to terminate ventricular fibrillation and reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic and metabolic function, and (5) assessment of survival and recovery of organ function. A robust inventory of measurements is available that includes &#8211; but is not limited to &#8211; hemodynamic, metabolic, and tissue measurements. The model has been highly effective in developing new resuscitation concepts and examining novel therapeutic interventions before their testing in larger and translationally more relevant animal models of cardiac arrest and resuscitation.

This article describes a rat model of electrically-induced ventricular fibrillation and resuscitation by chest compression, ventilation, and delivery of electrical shocks that simulates an episode of sudden cardiac arrest and conventional cardiopulmonary resuscitation. The model enables gathering insights on the pathophysiology of cardiac arrest and exploration of new resuscitation strategies.

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 ...

Robotic Ablation of Atrial Fibrillation

Background: Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). During PVI an electrical conduction block between pulmonary vein (PV) and left atrium (LA) is created. This conduction block prevents AF, which is triggered by irregular electric activity originating from the PV. However, transmural atrial lesions are required which can be challenging. Re-conduction and AF recurrence occur in 20 - 40% of the cases. Robotic catheter systems aim to improve catheter steerability. Here, a procedure with a new remote catheter system (RCS), is presented. Objective of this article is to show feasibility of robotic AF ablation with a novel system. Materials and Methods: After interatrial trans-septal puncture is performed using a long sheath and needle under fluoroscopic guidance. The needle is removed and a guide wire is placed in the left superior PV. Then an ablation catheter is positioned in the LA, using the sheath and wire as guide to the LA. LA angiography is performed over the sheath. A circular mapping catheter is positioned via the long sheath into the LA and a three-dimensional (3-D) anatomical reconstruction of the LA is performed. The handle of the ablation catheter is positioned in the robotic arm of the Amigo system and the ablation procedure begins. During the ablation procedure, the operator manipulates the ablation catheter via the robotic arm with the use of a remote control. The ablation is performed by creating point-by-point lesions around the left and right PV ostia. Contact force is measured at the catheter tip to provide feedback of catheter-tissue contact. Conduction block is confirmed by recording the PV potentials on the circular mapping catheter and by pacing maneuvers. The operator stays out of the radiationfield during ablation. Conclusion: The novel catheter system allows ablation with high stability on low operator fluoroscopy exposure.

Pulmonary vein isolation (PVI) with an ablation catheter is a curative treatment for atrial fibrillation (AF). Robotic catheter systems aim to improve catheter steerability. Here, a procedure with a new robotic catheter system is presented. The goal of the procedure is electrical block between pulmonary vein and left atrium.

心房細動のロボットアブレーション

Background: Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). During PVI an electrical conduction block between ...

Electrophysiological Assessment of Murine Atria with High-Resolution Optical Mapping

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and electrophysiological phenotype in the atria. That encourages us to utilize a genetically-engineered mouse model to elucidate the mechanism of AF. However, it is difficult to evaluate the electrophysiological properties in murine atria due to their small size. This protocol describes the electrophysiological evaluation of atria using an optical mapping system with a high temporal and spatial resolution in Langendorff perfused murine hearts. The optical mapping system is assembled with dual high-speed complementary metal oxide semiconductor cameras and high magnification objective lenses, to detect the fluorescence of a voltage-sensitive dye and Ca2+ indicator. To focus on the assessment of murine atria, optical mapping is performed with an area of 2 mm &#215; 2 mm or 10 mm x 10 mm, with a 100 &#215; 100 resolution (20 &#181;m/pixel or 100 &#181;m/pixel) and sampling rate of up to 10 kHz (0.1 ms) at maximum. A 1-French size quadripolar electrode pacing catheter is placed into the right atrium through the superior vena cava avoiding any mechanical damage to the atrium, and pacing stimulation is delivered through the catheter. An electrophysiological study is performed with programmed stimulation including constant pacing, burst pacing, and up to triple extrastimuli pacing. Under a spontaneous or pacing rhythm, the optical mapping recorded the action potential duration, activation map, conduction velocity, and Ca2+ transient individually in the right and left atria. In addition, the programmed stimulation also determines the inducibility of atrial tachyarrhythmias. Precise activation mapping is performed to identify the propagation of the excitation in the atrium during an induced atrial tachyarrhythmia. Optical mapping with a specialized setting enables a thorough electrophysiological evaluation of the atrium in murine pathological models.

This protocol describes the electrophysiological evaluation of murine atria utilizing an optical mapping system with a high temporal and spatial resolution, including dual recordings of the membrane voltage and Ca2+ transient under programmed stimulation through a specialized electrode catheter.

高解像度光学マッピングとマウスの心房の電気生理学的評価

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and ...

High-Throughput Analysis of Optical Mapping Data Using ElectroMap

Optical mapping is an established technique for high spatio-temporal resolution study of cardiac electrophysiology in multi-cellular preparations. Here we present, in a step-by-step guide, the use of ElectroMap for analysis, quantification, and mapping of high-resolution voltage and calcium datasets acquired by optical mapping. ElectroMap analysis options cover a wide variety of key electrophysiological parameters, and the graphical user interface allows straightforward modification of pre-processing and parameter definitions, making ElectroMap applicable to a wide range of experimental models. We show how built-in pacing frequency detection and signal segmentation allows high-throughput analysis of entire experimental recordings, acute responses, and single beat-to-beat variability. Additionally, ElectroMap incorporates automated multi-beat averaging to improve signal quality of noisy datasets, and here we demonstrate how this feature can help elucidate electrophysiological changes that might otherwise go undetected when using single beat analysis. Custom modules are included within the software for detailed investigation of conduction, single file analysis, and alternans, as demonstrated here. This software platform can be used to enable and accelerate the processing, analysis, and mapping of complex cardiac electrophysiology.

This protocol describes the setup and use of ElectroMap, a MATLAB-based open-source software platform for analysis of cardiac optical mapping data. ElectroMap provides a versatile high-throughput tool for analysis of optical mapping voltage and calcium datasets across a wide range of cardiac experimental models.

エレクトロマップを用いた光マッピングデータのハイスループット解析

Optical mapping is an established technique for high spatio-temporal resolution study of cardiac electrophysiology in multi-cellular preparations. Here we ...

Cooling or Warming the Esophagus to Reduce Esophageal Injury During Left Atrial Ablation in the Treatment of Atrial Fibrillation

Ablation of the left atrium using either radiofrequency (RF) or cryothermal energy is an effective treatment for atrial fibrillation (AF) and is the most frequent type of cardiac ablation procedure performed. Although generally safe, collateral injury to surrounding structures, particularly the esophagus, remains a concern. Cooling or warming the esophagus to counteract the heat from RF ablation, or the cold from cryoablation, is a method that is used to reduce thermal esophageal injury, and there are increasing data to support this approach. This protocol describes the use of a commercially available esophageal temperature management device to cool or warm the esophagus to reduce esophageal injury during left atrial ablation. The temperature management device is powered by standard water-blanket heat exchangers, and is shaped like a standard orogastric tube placed for gastric suctioning and decompression. Water circulates through the device in a closed-loop circuit, transferring heat across the silicone walls of the device, through the esophageal wall. Placement of the device is analogous to the placement of a typical orogastric tube, and temperature is adjusted via the external heat-exchanger console.

The goal of this protocol is to describe the use of esophageal temperature modulation to counteract esophageal thermal injury from left atrial ablation for the treatment of atrial fibrillation.

心房細動治療における左心房切除中の食道損傷を軽減する食道の冷却または温暖化

Ablation of the left atrium using either radiofrequency (RF) or cryothermal energy is an effective treatment for atrial fibrillation (AF) and is the most ...

Sterile Pericarditis in Aachener Minipigs As a Model for Atrial Myopathy and Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia caused by structural remodeling of the atria, also called atrial myopathy. Current therapies only target the electrical abnormalities and not the underlying atrial myopathy. For the development of novel therapies, a reproducible large animal model of atrial myopathy is necessary. This paper presents a model of sterile pericarditis-induced atrial myopathy in Aachener minipigs. Sterile pericarditis was induced by spraying sterile talcum and leaving a layer of sterile gauze over the atrial epicardial surface. This led to inflammation and fibrosis, two crucial components of the pathophysiology of atrial myopathy, making the atria susceptible to the induction of AF. Two pacemaker electrodes were positioned epicardially on each atrium and connected to two pacemakers from different manufacturers. This strategy allowed for repeated non-invasive atrial programmed stimulation to determine the inducibility of AF at specified time points after surgery. Different protocols to test AF inducibility were used. The advantages of this model are its clinical relevance, with AF inducibility and the rapid induction of inflammation and fibrosis-both present in atrial myopathy-and its reproducibility. The model will be useful in the development of novel therapies targeting atrial myopathy and AF.

We describe a sterile pericarditis model in minipigs to study atrial myopathy and atrial fibrillation (AF). We present surgical and anesthetic techniques, strategies for vascular access, and a protocol to study the inducibility of AF.

心房ミオパチーおよび心房細動のモデルとしてのAachenerミニブタにおける滅菌心膜炎

Atrial fibrillation (AF) is the most common arrhythmia caused by structural remodeling of the atria, also called atrial myopathy. Current therapies only ...

High-Resolution Three-Dimensional Imaging of the Footpad Vasculature in a Murine Hindlimb Gangrene Model

Peripheral arterial disease (PAD) is a significant cause of morbidity resulting from chronic exposure to atherosclerotic risk factors. Patients suffering from its most severe form, chronic limb-threatening ischemia (CLTI), face substantial impairments to daily living, including chronic pain, limited walking distance without pain, and nonhealing wounds. Preclinical models have been developed in various animals to study PAD, but mouse hindlimb ischemia remains the most widely used. There can be significant variation in response to ischemic insult in these models depending on the mouse strain used and the site, number, and means of arterial disruption. This protocol describes a unique method combining femoral artery and vein electrocoagulation with the administration of a nitric oxide synthase (NOS) inhibitor to reliably induce footpad gangrene in Friend Virus B (FVB) mice that resembles the tissue loss of CLTI. While traditional means of assessing reperfusion such as laser Doppler perfusion imaging (LDPI) are still recommended, intracardiac perfusion of the lipophilic dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) is used to label the vasculature. Subsequent whole-mount confocal laser scanning microscopy allows for high-resolution, three-dimensional (3D) reconstruction of footpad vascular networks that complements traditional means of assessing reperfusion in hindlimb ischemia models.

The present protocol describes a unique, clinically relevant model of peripheral arterial disease that combines femoral artery and vein electrocoagulation with the administration of a nitric oxide synthase inhibitor to induce hindlimb gangrene in FVB mice. Intracardiac DiI perfusion is then used for high-resolution, three-dimensional imaging of the footpad vasculature.

マウス後肢壊疽モデルにおける足蹠血管系の高解像度3次元イメージング

Peripheral arterial disease (PAD) is a significant cause of morbidity resulting from chronic exposure to atherosclerotic risk factors. Patients suffering ...

Transesophageal Atrial Burst Pacing for Atrial Fibrillation Induction in Rats

Animal studies have brought important insights into our understanding regarding atrial fibrillation (AF) pathophysiology and therapeutic management. Reentry, one of the main mechanisms involved in AF pathogenesis, requires a certain mass of myocardial tissue in order to occur. Due to the small size of the atria, rodents have long been considered 'resistant' to AF. Although spontaneous AF has been shown to occur in rats, long-term follow-up (up to 50 weeks) is required for the arrhythmia to occur in those models. The present work describes an experimental protocol of transesophageal atrial burst pacing for rapid and efficient induction of AF in rats. The protocol can be successfully used in rats with healthy or remodeled hearts, in the presence of a wide variety of risk factors, allowing the study of AF pathophysiology, identification of novel therapeutic targets, and evaluation of novel prophylactic and/or therapeutic strategies.

The present work describes an experimental protocol of transesophageal atrial burst pacing for efficient induction of atrial fibrillation (AF) in rats. The protocol can be used in rats with healthy or remodeled hearts, allowing the study of AF pathophysiology, identification of novel therapeutic targets, and evaluation of new therapeutic strategies.

ラットにおける心房細動誘導のための経食道心房バーストペーシング

Animal studies have brought important insights into our understanding regarding atrial fibrillation (AF) pathophysiology and therapeutic management. ...