ワイルドタイプと突然変異のHCNチャネルを組み合わせた生物電子心臓ペースメーカーの組み合わせです
Annalisa Bucchi1, Alexei N Plotnikov, Iryna Shlapakova
1Departments of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY 10032, USA.
Circulation
|August 23, 2006
まとめ
mE324A変異遺伝子を用いたエンジニアリングされた生物ペースメーカー (BPM) は,mHCN2.2と比較して機能改善とカテキオラミン反応性を示しています. 組み合わせたBPMと電子ペースメーカー (EPM) は,信頼性の高い,共感応答性心拍のペースを保証します.
科学分野:
- バイオメディカルエンジニアリング
- 心臓病学 心臓病学
- 遺伝子療法の遺伝子治療法
背景:
- 生物学的なペースメーカー (BPM) は,電子ペースメーカー (EPM) の潜在的な代替案を提供します.
- 以前の研究では,BPMの発達のためにマウリンHCN2 (mHCN2) 遺伝子を利用しました.
- 機能の向上と既存のペースシステムとの統合のために,BPMのさらなる最適化が必要である.
研究 の 目的:
- mE324AミュータントマウリンHCN2 (mHCN2) 遺伝子で設計されたBPMの強化された機能を評価するために.
- 個々のペースメソッドと比較して,BPM/EPMタンドムの組み合わせの有効性を評価する.
- エンジニアリングされたBPMのカテキオラミン反応性を in vivoで決定する.
主な方法:
- mE324AおよびmHCN2遺伝子活性化運動を分析するために,新生ラットミオサイトとXenopusオオサイトに関するインビトロ研究.
- 完全な心房閉塞を持つ犬の体内試験では,塩水,mHCN2,またはmE324Aウイルスを左束の枝に注入することを含む.
- 電子ペースメーカー (EPM) の埋め込みと,EPMのサポートとなしの14日間の24時間ECGモニタリング,エピネフリンに対する心拍の応答の評価.
主要な成果:
- mE324Aは,細胞モデルにおけるmHCN2と比較して,よりポジティブな活性化ミドルポイントとより速いゲーティング運動を示した.
- In vivoでは,mE324AとmHCN2のBPMは,EPMの投与が中止されたとき,対照群よりも高い基礎心拍数をもたらしました.
- BPM/EPMタンドムはEPMペースの負担を著しく減らし (対照群では83%に対して26-36%),エピネフリン刺激で心拍数が増加した (mE324Aでは50%).
結論:
- mE324A変異遺伝子はペースメーカー電流の活性化を高め,安定したカテキオラミンに敏感なリズムにつながります.
- BPM/EPMのタンドームは,信頼性の高い心拍のペースを保ち,EPMへの依存を軽減し,共感応答性を導入します.
- エンジニアリングされたBPM,特にmE324Aは,心臓ペース技術における有望な進歩を表しています.
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