著者は次の資金源を認める: 他 Kröner フレゼニウス財団 (Tienush Rassaf);ハンス ・ ウント Gertie フィッシャー財団 (Tienush Rassaf)、医学部、デュースブルク-エッセン ドイツ大学 (Tienush Rassaf、ラース ・ ミシェル) から付与します。エルンスト ・ ウント ベルタ Grimmke ・財団 (クリストス Rammos)。

に従って、すべての関連する規制へのコンプライアンスにすべての実験が完成 (' 実験と他の科学的な目的の (ディレクティブ 2010年/63/EU) や動物のケアのため使用される脊椎動物の保護に関する欧州条約は、制度のガイドラインに従って。すべての実験は、6 ヶ月の年齢で男性の C57BL/6JRj マウスで行われています。
1. 準備
<ol><li>手術顕微鏡加熱パッドと体の温度を監視する直腸プローブを準備します。きれいにし、すべての手術器具を滅菌します。</li>
	<li>血管結紮、5 cm 6-0 ポリプロピレン糸と LCA の結紮用 2 mm シリコン チューブを 10 cm の 2 個セット 5-0 絹糸を準備します。</li>
	<li>前 37 ° C で加熱する太陽光発電カテーテル校正キュベットを準備し、H2O 生理食塩水のキャリブレーションのための 15% 塩化ナトリウム (NaCl) 満ちているハミルトン シリンジ 100 μ L を準備します。</li>
	<li>場所 PV カテーテル (3 cm、1.4 F) 37 ° C に予熱 0.9% NaCl H2O (生理食塩水) 測定する前に、少なくとも 30 分。カテーテルをデータ集録デバイスに接続し、デバイスをアナログ/デジタル変換器に接続します。両方のデバイスをコンピューターに接続します。</li>
	<li>ソフトウェアを設定します。8ソフトウェア ガイド付きワークフローの要求に従い、ソフトウェア ガイド付き圧力調整とコンダクタンスの調整を実行します。</li>
</ol>2. 麻酔と鎮痛
<ol><li>ケタミン 100 mg/kg 体重とキシラジン塩酸塩 10 mg/kg を腹腔内投与によるマウスを麻酔します。私の先頭に/R 外科 0.05 mg/kg 本体重量ブプレノルフィン鎮痛効果を維持するために腹腔内を管理します。</li>
	<li>10 分後 20 G の静脈内投与 (iv) カテーテルを用いた気管内挿管を行い 40% 酸素 (O2) 2% (v) イソフルランとマウスを換気します。適切な換気パラメーター (例えば220 μ L ストローク ボリューム、150/分 25 30 g C57BL/6JRj マウス) を設定します。</li>
	<li>直腸プローブを介して体内温度を継続的に監視します。加熱平板上捜査官に向かって指して頭でマウスを固定します。マウスの正常な体温は 36.5-38 ° C です。加熱温度の調整による体温 1 度以内を維持します。</li>
</ol>3. 左心室カテーテル
<ol><li>胸や betadine と 70% アルコールの 3 つの交互になるスクラブと首を消毒します。 皮膚消毒乾燥するを待ちます。胸の毛を削除するには、小さな動物シェービング システムを使用します。</li>
	<li>10 mm 縦正中切開手術用のハサミを使用して胸骨に向かって下唇の下に 5 mm を実行します。</li>
	<li>左と右、鉗子を用いた鈍準備を介して顎下腺部を解剖します。右のコミューンの頚動脈を公開する右傍部の筋肉や脂肪組織形態を区切ります。動員、曲がった鉗子で容器と一緒に入念な鈍準備を介して結合組織から 5-10 mm の長さの合計のために船を区切ります。 注: は、重度の低血圧、徐脈の原因にすることができますすべての時に迷走神経や内頸動脈体の機械操作を避けます。</li>
	<li>船の下で 2 つの準備された絹の糸を渡します。タイトな結び目と遠位血管を結紮し、まだカテーテルの通過を可能にする近位の露出部の緩い結び目を配置します。</li>
	<li>これはカテーテルの導入を促進する船に軽い緊張を適用するマウスの頭の横にある頭蓋 (タイト) 結び目のスレッドを修正します。元に戻せる状態の血流をブロックする緩い結び目の近位近位血管の止血血管クランプを配置します。</li>
	<li>くさび状切開 1 mm マイクロのハサミで容器を開くに頭蓋の結び目に近位を実行します。 注: 小さい血のしたたりはこのステップの適切な実行を示します。</li>
	<li>10 mm。 カテーテル データの記録の開始のために慎重にカテーテルを挿入します。 注: 切開部を鉗子でストレッチ、このプロセス容易になります。</li>
	<li>血管クランプを抽出します。カテーテルの動きを容易にするために切開部に生理食塩水 1 〜 2 滴を追加します。別に 10 mm 程度のカテーテルを導入することを続行します。結び目を慎重にちょうど固定センサー先端部と近位部の結び目を通過した後カテーテルの動きを損なうことがなくカテーテルの薄い部分と一緒に逆流の血を防ぐために十分な。 注: 血管クランプを抽出するとき、カテーテルの先端にセンサーのサイズは血液の逆流を防ぎます。</li>
	<li>優しく圧力解析 (図 3 a) 大動脈にカテーテルが置かれることを示す血圧プロファイルが表示されるまで、カテーテルの挿入を続行します。 注: カテーテル大動脈弁を達するは、耐光性とカテーテルのパルスに同期した動きで示されます。</li>
	<li>いつ大動脈弁を進めるに抵抗を発生して、プル カテーテル再び 5 mm と事前 LV カテーテル、拡張期血圧が 0 件に達するので PV 解析の変化に示されますまで 20 mmHg (図 3 b)。さらにセンサー チップ (図 3) の左の心室の配置を確認するための監視量の変化に注意してください。カテーテルの動きを防ぐために近位の結び目をよりしっかりと固定します。</li>
</ol>4. 虚血/再灌流外科
<ol><li>肋骨を視覚化することができますまで、全長の 15 ミリメートル。 進む 2 つの筋層の鈍的準備のため左腋窩に向かって尾側の胸骨から皮膚切開を実行します。</li>
	<li>3 番目と 4 番目の左肋骨間切開を介して胸郭を開きます。心膜へのアクセスを得るために手術のフックを使用します。心臓より心膜を切除します。LCA 結紮、有効な解析の太陽光発電データを記録する動物に触れることがなく待機 30 秒を続ける前に。</li>
	<li>左耳介の下で新興と降順の決戦に向けて心の左側で LCA をローカライズします。左耳介の下に 2 mm のループで動脈を取り囲むように 6-0 ポリプロピレン縫合糸を使用します。ループの下の小さなシリコン チューブを置き、上記のタイトな結び目を配置します。 注: 回っている灰色の遠位心筋は LCA オクルー ジョン6のポジティブ コントロールとして機能します。私/営業調査から独立して 5 分以内 R 手術を行う必要があります。</li>
	<li>1 mm の長さで縫合糸をカットします。手術のフックを解除し、上記の切開部の筋層を手動で閉じる。太陽光発電データを継続的に記録しながら 45 分を待ちます。</li>
	<li>45 分後に再度切開を開くし、再灌流を誘導するためにシリコン チューブを削除します。別の 20 分のデータを記録します。 注: 虚血前に見られる赤い色への変更は再灌流成功を示します。</li>
</ol>5. 校正
注: PV カテーテル システムのキャリブレーションは、測定後に実行する必要がある 2 つの 4 つの必須ステップで構成されています。校正は、有効な結果を確保するためのすべての実験の後で繰り返す必要があります。
<ol><li>圧力校正とコンダクタンス ステップ 1.5 で説明されているように実験の前にキャリブレーションを実行します。</li>
	<li>実験自体は終了後カテーテルは左心室に置かれた生理食塩水の調整を実行します。準備された領域で頚動脈の外側を右頸静脈をローカライズします。注入 10 μ 25% データを記録しながら注射器 H2Oでハミルトンの塩化ナトリウム。</li>
	<li>ボリューム曲線 (図 5) で上昇相を強調することによって取得ソフトウェアを使用して校正を計算します。3 回の合計のためのこのプロセスを繰り返します。注射器抽出後血液の損失を回避するには、急速に圧縮、穿刺する血管クランプを使用します。</li>
	<li>標準化されたボリュームの解析によるボリューム データ集録を調整するボリューム調整を実行します。心臓穿刺から若干ヘパリン 1 mL 注射器 (例えば、200 の IE ヘパリンあたり 5 μ L) で約 500 μ L マウス血を取得します。太陽光発電のカテーテルを引き戻す、カテーテルの損傷を避けるために 10-15 mm。</li>
	<li>37 ° C 予熱校正キュベット (図 5 a) に得られた血液を入力します。泡を避けるため、それが結果を妨げる可能性があります。各レコードとデータにカテーテル先端を追加します。ソフトウェア ガイド分析 (図 5 b) によって標準曲線を得します。3 回の合計のためのプロセスを繰り返します。</li>
	<li>十分なイソフルラン麻酔はすべての時間を維持したまま、急激または頚部転位によるマウスを安楽死させます。</li>
</ol>6. データの分析
<ol><li>校正の手順を完了すると、ソフトウェア ガイド データ解析を実行します。したがって、 PV ワークフローの分析セクション内で適切なセクション (少なくとも 10 サイクル) を強調表示し、ベースライン分析を実行します。必要に応じて換気または操作のための偏差とサイクルを除外する (図 3 D)。</li>
	<li>直前に、LCA 閉塞後大動脈弁 (動脈圧のみ) の通路の前に PV ベースライン解析を実行します。太陽光発電ベースライン解析を実施して、虚血と再灌流後 5 分の間隔で進んでください。実験の終わりに、左心室 (血圧) からカテーテルの撤回後圧力データの分析を実行します。</li>
	<li>サンプリング エラーを避けるために、少なくとも 10 の連続したサイクルを分析します。換気、5 の最大の換気の一時的な中断と値を得た場合の強い干渉が発生して s を考えることができます。</li>
	<li>ベースライン分析(図 3 D) 左心室機能を特徴付けるための計算は、次のパラメーターを使用します。<ol>
<li>ストローク量 (μ L)</li>
		<li>駆出分画: ストローク ボリューム/末期量 (%)</li>
		<li>心拍出量: ストローク ボリューム * 心拍数 (μ L/分)</li>
		<li>心係数: 心拍出量/体表面積 (µL/(min*cm²) のボディ</li>
		<li>打撃の仕事: 太陽光発電のカーブの内側領域 (mmHg * μ L)</li>
		<li>最高圧力 (Pmax);平均圧 (Pmean)</li>
		<li>左室収縮機能のパラメーターとして最大 dP/dt (mmHg/秒)</li>
		<li>左心室コンプライアンスのパラメーターとして分 dP/dt (mmHg/秒)</li>
		<li>等容弛緩の時定数: タウ (ms)</li>
	</ol>
</li>
</ol>

<ol>
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著者が明らかに何もありません。

リアルタイム体内心原性ショックと私の左心室機能障害の評価法として PV が急性心筋梗塞における左室血行動態のモニタリング/R 負傷。太陽光発電カテーテルは、左室収縮および拡張機能に関するパラメーターの広いスペクトルを提供できます。心エコー検査や MRI (商工会議所ボリューム、EF、拍出量と心拍出量) によって得られる通常 LV 体積パラメーターに加えて太陽光発電分析は?...

心血管疾患は、西洋文明1の死の最も一般的な原因です。急性心筋梗塞は、急性および慢性の高死亡率2に関連付けられている重要なイベントです。血行再建術は、達成を介して緊急経皮的冠動脈インターベンション (PCI) は、たとえ死亡まま高、特に急性心筋梗塞の3症例では症状の発症後最初の 48 時間以内です。左心室 (LV) 関数で急性の減少に伴う心原性ショックは、これらの患者の3で院内死亡率の主要な原因です。この早期左室機能の低下、心筋障害による虚血と再灌流。このいわゆる虚血/再灌流 (私/R) 傷害活性酸素種4、5の誇張された生成など細胞メタボロームの変化によって媒介されます。
臨床設定で心筋の損傷の減少につながる可能性の保護メカニズムを調べるには、信頼性の高いマウス モデルがポスト R LV 関数6の評価方法を含むが不可欠です。この設定の経胸壁心エコー法7磁気共鳴画像 (MRI)6広く機能的なフェノタイピング8,9に使用されます。ただし、これらのメソッドは、重症左室不全および進行中の急性心筋梗塞における心原性ショックの評価には適していませんし、直接左心室圧データを表示できません。Ex vivoアッセイの心臓を用いた蛍光装置は初期段階の基礎となる病因についての情報を提供します私/R 負傷10。このメソッドは、生体内で自律神経系やホルモン調節、酸塩基の恒常性の調節などの適応メカニズムを再現できないのため制限されます。心原性ショック、心筋を中に現在進行中の左心室不全の完全な機能表現の現在いるメソッドがない私/R 負傷。
カテーテル検査圧力ボリューム (PV) と非定常手術左冠動脈 (LCA) 咬合の組み合わせで同期のアプローチは有益であるが、技術的に困難な可能性があります。私の中に心外血行動態安定/不安定な麻酔または血損失が大きく結果に影響するので、R の傷害が有効な結果のために不可欠。小説は私の血行力学的表現型解析のアプローチ/R 傷害を介してLV PV カテーテルと一時的な LCA 咬合が心原性ショックと急性心筋梗塞における左心室機能不全に関する新たな洞察をもたらすとの将来の分析の方法として耐性獲得。

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			<td height="26" style="height:27px;width:237px;">Contura professional hair trimmer</td>
			<td style="width:164px;">Wella</td>
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			<td style="width:243px;">Surgical forceps</td>
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			<td height="26" style="height:27px;width:237px;">Foris FS2434</td>
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			<td height="26" style="height:27px;width:237px;">Hamilton Syringe 100 &#181;l needle</td>
			<td style="width:164px;">Hamilton</td>
			<td style="width:119px;">80621</td>
			<td>100&#181;l syringe with needle</td>
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		<tr height="26">
			<td height="26" style="height:27px;width:237px;">Heated Small animal OP table</td>
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			<td>Heated OP table</td>
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		<tr height="26">
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		<tr height="26">
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			<td height="26" style="height:27px;width:237px;">Micro-tip catheter transducer</td>
			<td style="width:164px;">Millar instruments</td>
			<td style="width:119px;">SPR-839</td>
			<td>PV catheter</td>
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		<tr height="26">
			<td height="26" style="height:27px;width:237px;">MiniVent</td>
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			<td>ventilation</td>
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		<tr height="26">
			<td height="26" style="height:27px;width:237px;">MPVS Ultra</td>
			<td style="width:164px;">Millar instruments</td>
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			<td>PV catheter data acquisition device</td>
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		<tr height="26">
			<td height="26" style="height:27px;width:237px;">Octenisept</td>
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			<td style="width:119px;">REF 303172</td>
			<td>1ml syringe</td>
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		<tr height="26">
			<td height="26" style="height:27px;width:237px;">PowerLab 8/35</td>
			<td style="width:164px;">AD Instruments</td>
			<td style="width:119px;">PL3508</td>
			<td>analog/digital converter</td>
		</tr>
		<tr height="26">
			<td height="26" style="height:27px;width:237px;">Prolene 6-0</td>
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			<td style="width:119px;">XNEH7814.P31</td>
			<td>Polypropylene suture</td>
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		<tr height="26">
			<td height="26" style="height:27px;width:237px;">Retraction Kit</td>
			<td style="width:164px;">FST</td>
			<td>18200-20</td>
			<td>retraction of surgical situs</td>
		</tr>
		<tr height="26">
			<td height="26" style="height:27px;width:237px;">Seraflex 5-0</td>
			<td style="width:164px;">Naila</td>
			<td style="width:119px;">IC108000</td>
			<td>silk suture</td>
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		<tr height="26">
			<td height="26" style="height:27px;width:237px;">Small and micro-scissors</td>
			<td style="width:164px;">FST Essen</td>
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			<td height="26" style="height:27px;width:237px;">Small silicon tube</td>
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			<td>tube for LCA occlusion</td>
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			<td height="26" style="height:27px;width:237px;">Sodium Chloride</td>
			<td style="width:164px;">Sigma-Aldrich</td>
			<td style="width:119px;">S7653</td>
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			<td height="26" style="height:27px;width:237px;">testo 108</td>
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			<td height="26" style="height:27px;width:237px;">Vasofix Safety 20G</td>
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			<td>intubation catheter</td>
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			<td height="26" style="height:27px;width:237px;">Windows 10</td>
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			<td style="width:164px;">Ceva</td>
			<td style="width:119px;">6324464.00.00</td>
			<td>Xylazine hydrochloride</td>
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	</tbody>
</table>

real-time pressure-volume analysis of acute myocardial infarction in mice

急性心筋梗塞は、急性心不全、心原性ショックにつながることができます。血行動態の評価は、急性左心室 (LV) に対して指示される任意の潜在的な治療アプローチの評価にとって重要です。現在の画像診断 (e.g。、心エコー検査や磁気共鳴画像) 左心室圧のデータは直接測定できないのでいくつかの制限があります。LV カテーテル冠動脈閉塞を受けているマウスでは、左心室機能のリアルタイム評価手法として勤めるかもしれません。
プロシージャの先頭にマウスは続いて気管内挿管麻酔をかけられました。LV のカテーテル法、右頚動脈だった中間首切開を介して公開されています。カテーテルは導入され、LV キャビティに置かれます。左開胸を行い左主冠動脈 (LCA) を結紮します。再灌流を誘導して、すべての回で 45 分圧ボリューム データが記録された後の縫合がリリースされました。
LCA の結紮は行程容積、左室駆出率 (EF) と心拍出量の 30% の減少によって証明されるよう左心室収縮機能の低下を発生します。左心室の収縮性のパラメーターとして最大 dP/dt も有意に減少したし、拡張機能は重度に障害 (最低 dP/dt-40%)。20 分の期間にわたって再灌流は左心室機能の完全な回復には至らなかった。
リアルタイム圧容積解析は、マウスにおける急性心筋梗塞における心機能をモニタリングのための有効な処置として提供しています。安定した麻酔と標準化された外科的アプローチを維持することは、有効な結果を確保するために重大だった。急性心筋梗塞の初期段階は罹患率と死亡率の重要な線引きの方法は耐性獲得の新しい戦略の前臨床評価のために有益かもしれない。

LV カテーテル検査後再灌流の 10 分に続いて 45 分リバーシブル LCA 結紮を行った。太陽光発電データは、(図 1) 回で記録されました。
PV カテーテルの正しい配置特性 LV PV グラフ (図 2 a) を取得することによって確認されました。LV カテーテル留置が 0 - 最小限の典型的な心室圧力...

Watch this Scientific Journal Video about Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice at JoVE.com

Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice

マウスにおける急性心筋梗塞は、急性が不完全に特徴付けられる左心室 (LV) の機能変化を誘導します。LV カテーテル冠動脈閉塞を受けているマウスでは、左心室機能のリアルタイム評価手法として提供しています。

マウスにおける急性心筋梗塞のリアルタイム圧解析

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any ...

real-time-pressure-volume-analysis-acute-myocardial-infarction

Research

JoVE Journal

Medicine

9.0K ビュー.  University Hospital Essen. マウスにおける急性心筋梗塞は、急性が不完全に特徴付けられる左心室 (LV) の機能変化を誘導します。LV カテーテル冠動脈閉塞を受けているマウスでは、左心室機能のリアルタイム評価手法として提供しています。

ビデオ: Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice

Acute Myocardial Infarction in Rats

With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial infarction (AMI). This model is also referred to as an acute ischemic cardiomyopathy or ischemia followed by reperfusion (IR); which is induced by an acute 30-minute period of ischemia by ligation of the left anterior descending artery (LAD) followed by reperfusion of the tissue by releasing the LAD ligation (Vasilyev and McConnell). This protocol will focus on assessment of the infarct size and the area-at-risk (AAR) by Evan's blue dye and triphenyl tetrazolium chloride (TTC) following 4-hours of reperfusion; additional comments toward the evaluation of cardiac function and remodeling by modifying the duration of reperfusion, is also presented. Overall, this AMI rat animal model is useful for studying the consequence of a myocardial infarction on cardiac pathophysiological and physiological function.

The rat model of acute myocardial infarction (AMI) is useful to study the consequence of a MI on cardiac pathophysiological and physiological function.

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 ...

医学

Induction of Myocardial Infarction in Adult Zebrafish Using Cryoinjury

The mammalian heart is incapable of significant regeneration following an acute injury such as myocardial infarction1. By contrast, urodele amphibians and teleost fish retain a remarkable capacity for cardiac regeneration with little or no scarring throughout life2,3. It is not known why only some non-mammalian vertebrates can recreate a complete organ from remnant tissues4,5. To understand the molecular and cellular differences between regenerative responses in different species, we need to use similar approaches for inducing acute injuries.
In mammals, the most frequently used model to study cardiac repair has been acute ischemia after a ligation of the coronary artery or tissue destruction after cryoinjury6,7. The cardiac regeneration in newts and zebrafish has been predominantly studied after a partial resection of the ventricular apex2,3. Recently, several groups have established the cryoinjury technique in adult zebrafish8-10. This method has a great potential because it allows a comparative discussion of the results obtained from the mammalian and non-mammalian species.
Here, we present a method to induce a reproducible disc-shaped infarct of the zebrafish ventricle by cryoinjury. This injury model is based on rapid freezing-thawing tissue, which results in massive cell death of about 20% of cardiomyocytes of the ventricular wall. First, a small incision was made through the chest with iridectomy scissors to access the heart. The ventricular wall was directly frozen by applying for 23-25 seconds a stainless steel cryoprobe precooled in liquid nitrogen. To stop the freezing of the heart, fish water at room temperature was dropped on the tip of the cryoprobe. The procedure is well tolerated by animals, with a survival rate of 95%.
To characterize the regenerative process, the hearts were collected and fixed at different days after cryoinjury. Subsequently, the specimen were embedded for cryosectioning. The slides with sections were processed for histological analysis, in situ hybridization and immunofluorescence. This undertaking enhances our understanding of the factors that are required for the regenerative plasticity in the zebrafish, and provide new insights into the machinery of cardiac regeneration. A conceptual and molecular understanding of heart regeneration in zebrafish will impact both developmental biology and regenerative medicine.

Zebrafish represents a valuable model to study the mechanisms of heart regeneration in vertebrates. Here, we present a protocol for induction of a heart infarct in adult zebrafish using cryoinjury. This method results in massive cell death within 20% of the ventricular wall, similar to that observed in mammalian infarcts.

Cryoinjuryを使用した大人のゼブラフィッシュにおける心筋梗塞の誘発

The mammalian heart is incapable of significant regeneration following an acute injury such as myocardial infarction1. By contrast, urodele amphibians and ...

MRI and PET in Mouse Models of Myocardial Infarction

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ideal model for testing novel therapeutic strategies.
In vivo magnetic resonance imaging (MRI) gives excellent views of the heart noninvasively with clear anatomical detail, which can be used for accurate functional assessment. Contrast agents can provide basic measures of tissue viability but these are nonspecific. Positron emission tomography (PET) is a complementary technique that is highly specific for molecular imaging, but lacks the anatomical detail of MRI. Used together, these techniques offer a sensitive, specific and quantitative tool for the assessment of the heart in disease and recovery following treatment.
In this paper we explain how these methods are carried out in mouse models of acute myocardial infarction. The procedures described here were designed for the assessment of putative protective drug treatments. We used MRI to measure systolic function and infarct size with late gadolinium enhancement, and PET with fluorodeoxyglucose (FDG) to assess metabolic function in the infarcted region. The paper focuses on practical aspects such as slice planning, accurate gating, drug delivery, segmentation of images, and multimodal coregistration. The methods presented here achieve good repeatability and accuracy maintaining a high throughput.

We describe how to perform MRI and PET imaging of the mouse heart. The protocol is tailored to assess treatment efficacy in models of myocardial infarction and heart failure.

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ...

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

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 ...

Minimal Invasive Surgical Procedure of Inducing Myocardial Infarction in Mice

Myocardial infarction still remains the main cause of death in western countries, despite considerable progress in the stent development area in the last decades. For clarification of the underlying mechanisms and the development of new therapeutic strategies, the availability of valid animal models are mandatory. Since we need new insights into pathomechanisms of cardiovascular diseases under in vivo conditions to combat myocardial infarction, the validity of the animal model is a crucial aspect. However, protection of animals are highly relevant in this context. Therefore, we establish a minimally invasive and simple model of myocardial infarction in mice, which assures a high reproducibility and survival rate of animals. Thus, this models fulfils the requirements of the 3R principle (Replacement, Refinement and Reduction) for animal experiments and assure the scientific information needed for further developing of therapeutical strategies for cardiovascular diseases.

A highly reproducible model for myocardial infarction in mice with minimal invasive manipulations is described. The model can be easily performed, resulting in a high reproducibility and survival rate. Thus, the described model will reduce the number of required animals as requested by the 3R principle (Replacement, Refinement and Reduction).

マウスにおける心筋梗塞を誘発する低侵襲手術手順

Myocardial infarction still remains the main cause of death in western countries, despite considerable progress in the stent development area in the last ...

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are therefore required to confine cardiac damage, promote survival and reduce the disease burden of heart failure. Large animal experiments are an essential part in the translational process from experimental to clinical therapies. To optimize clinical translation, robust and representative outcome measures are mandatory. The present manuscript aims to address this need by describing the assessment of three clinically relevant outcome modalities in a pig acute myocardial infarction (AMI) model: infarct size in relation to area at risk (IS/AAR) staining, 3-dimensional transesophageal echocardiography (TEE) and admittance-based pressure-volume (PV) loops. Infarct size is the main determinant driving the transition from AMI to heart failure and can be quantified by IS/AAR staining. Echocardiography is a reliable and robust tool in the assessment of global and regional cardiac function in clinical cardiology. Here, a method for three-dimensional transesophageal echocardiography (3D-TEE) in pigs is provided. Extensive insight into cardiac performance can be obtained by admittance-based pressure-volume (PV) loops, including intrinsic parameters of myocardial function that are pre- and afterload independent. Combined with a clinically feasible experimental study protocol, these outcome measures provide researchers with essential information to determine whether novel therapeutic strategies could yield promising targets for future testing in clinical studies.

Reliable and accurate outcome assessment is the key for translation of preclinical therapies into clinical treatment. The current paper describes how to assess three clinically relevant primary outcome parameters of cardiac performance and damage in a pig acute myocardial infarction model.

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

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 regeneration, and to define new targets for therapeutics. For decades, models of complete heart regeneration existed in amphibians and fish, but a mammalian counterpart was not available. The recent discovery of a postnatal window during which mice possess regenerative capabilities has led to the establishment of a mammalian model of cardiac regeneration. A surgical model of mammalian cardiac regeneration in the neonatal mouse is presented herein. Briefly, postnatal day 1 (P1) mice are anesthetized by isoflurane and placed on an ice pad to induce hypothermia. After the chest is opened, and the left anterior descending coronary artery (LAD) is visualized, a suture is placed around the LAD to inflict myocardial ischemia in the left ventricle. The surgical procedure takes 10-15 min. Visualizing the coronary artery is crucial for accurate suture placement and reproducibility. Myocardial infarction and cardiac dysfunction are confirmed by triphenyl-tetrazolium chloride (TTC) staining and echocardiography, respectively. Complete regeneration 21 days post myocardial infarction is verified by histology. This protocol can be used to as a tool to elucidate mechanisms of mammalian cardiac regeneration after myocardial infarction.

This protocol describes a highly reproducible model of cardiac regeneration by surgical induction of myocardial infarction in the left ventricle of postnatal day 1 mice. The method involves induction of hypothermic anesthesia and ligation of the left anterior descending coronary artery.

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 ...

Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease

Circulating serum microRNAs (miRNAs) have shown promise as biomarkers for the cardiovascular disease and acute myocardial infarction (AMI), being released from the cardiovascular cells into the circulation. Circulating miRNAs are highly stable and can be quantified. The quantitative expression of specific miRNAs can be linked to the pathology, and some miRNAs show high tissue and disease specificity. Finding novel biomarkers for cardiovascular diseases is of importance for medical research. Quite recently, digital polymerase chain reaction (dPCR) has been invented. dPCR, combined with fluorescent hydrolysis probes, enables specific direct absolute quantification. dPCR exhibits superior technical qualities, including a low variability, high linearity, and high sensitivity compared to the quantitative polymerase chain reaction (qPCR). Thus, dPCR is a more accurate and reproducible method for directly quantifying miRNAs, particularly for the use in large multi-center cardiovascular clinical trials. In this publication, we describe how to effectively perform digital PCR in order to assess the absolute copy number in serum samples.

Circulating microRNAs have shown promise as biomarkers for cardiovascular diseases and acute myocardial infarctions. In this study, we describe a protocol for miRNA extraction, reverse transcription, and digital PCR for the absolute quantification of miRNAs in the serum of patients with cardiovascular disease.

急性心筋梗塞と心血管疾患のマイクロ Rna を循環の定量化デジタル PCR

Circulating serum microRNAs (miRNAs) have shown promise as biomarkers for the cardiovascular disease and acute myocardial infarction (AMI), being released ...

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

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) generated by recording both pressure and volume during cardiac catheterization are vital when assessing both systolic and diastolic cardiac function. Left and right heart function are closely related, reflected in ventricular interdependence. Thus, recording biventricular function in the same animal is important to get a complete assessment of cardiac function. In this protocol, a closed chest approach to cardiac catheterization consistent with the way catheterization is performed in patients is adopted in mice. While challenging, the closed chest strategy is a more physiological approach, because opening the chest results in major changes in preload and afterload that create artifacts, most notably a fall in systemic blood pressure. While high-resolution echocardiography is used to assess rodents, cardiac catheterization is invaluable, particularly when assessing diastolic pressures in both ventricles.
Described here is a procedure to perform invasive, closed chest, sequential left and right ventricular pressure-volume (PV) loops in the same animal. PV loops are acquired using&#160;admittance technology with a mouse pressure-volume catheter and pressure-volume system acquisition. The procedure is described, beginning with the neck dissection, which is required to access the right jugular vein and the right carotid artery, to the insertion and positioning of the catheter, and finally the data acquisition. Then, the criteria required to ensure the acquisition of high-quality PV loops are discussed. Finally, the analysis of the left and right ventricular PV loops and the different hemodynamic parameters available to quantify systolic and diastolic ventricular function are briefly described.

Presented here is a protocol to assess biventricular heart function in mice by generating pressure-volume (PV) loops from the right and left ventricle in the same animal using closed chest catheterization. The focus is on the technical aspect of surgery and data acquisition.

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) ...

Utilizing Percutaneous Ventricular Assist Devices in Acute Myocardial Infarction Complicated by Cardiogenic Shock

Cardiogenic shock is defined as persistent hypotension, accompanied by evidence of end organ hypo-perfusion. Percutaneous ventricular assist devices (PVADs) are used for the treatment of cardiogenic shock in an effort to improve hemodynamics. Impella is currently the most common PVAD and actively pumps blood from the left ventricle into the aorta. PVADs unload the left ventricle, increase cardiac output and improve coronary perfusion. PVADs are typically placed in the cardiac catheterization laboratory under fluoroscopic guidance via the femoral artery when feasible. In cases of severe peripheral arterial disease, PVADs can be implanted through an alternative access. In this article, we summarize the mechanism of action of PVAD and the data supporting their use in the treatment of cardiogenic shock.

Percutaneous ventricular assist devices are increasingly being utilized in patients with acute myocardial infarction and cardiogenic shock. Herein, we discuss the mechanism of action and hemodynamic effects of such devices. We also review algorithms and best practices for the implantation, management and weaning of these complex devices.

心原性ショックによる急性心筋梗塞における経皮性心室アシスト装置の利用

Cardiogenic shock is defined as persistent hypotension, accompanied by evidence of end organ hypo-perfusion. Percutaneous ventricular assist devices ...