1。はじめに植込み型除細動器（ICD）生き残ったSCDの後、または障害左心室機能に起因するSCDのリスクがある患者では心臓突然死（SCD）を防ぐことができます。しかし、不適切な治療の危険性が特にシングルチャンバーデバイスで、高いです。これらの余分な電気放電が有害であると患者の生活の質を損なう可能性があります。心房検出は、デバイスのパフォーマンスを向上させ、不適切なショックのリスクを減らす可能性があります。1,2しかしながら、心房検出はそれ自体に大きなリスクを運ぶ心房電極を必要とします。3つのメーカー、BIOTRONIK社は、心房センシング機能を備えた心室シングルチャンバ電極を開発しました。第1電極は、しかし、それは一般的に電極の剛性と、大径（3.5ミリメートル、10.5 F）のために使用されていなかった優れた検知能力を明らかにした+、Kainoxされました。4。このelectrodのさらなる発展eは小さい直径（2.6ミリメートル、7.8 F）を有し、かつ優れた注入機能とセンシング機能を示していますLinox スマート S DXリードの創出につながる5本論文では、この電極の配置を示し、データを強調するためにマスターの研究から、移植の容易さと、この電極の優れた検出機能の両方を実証する。 2。症例提示<ol><li>患者は、再発性前壁心筋梗塞（AMI）のステータスポスト、経皮的冠動脈インターベンション（PCI）、障害者の左心室機能（LVEF = 25％）、高コレステロール血症、冠動脈疾患（CAD）の歴史を持つ40歳の女性の喫煙者であったと発作性心房細動（PAF）。 </li><li> 4ヶ月前、心不全の薬物療法が開始されました。彼女のレジメンは、β遮断薬、ACE阻害薬と利尿薬が含まれていますが、左心室機能の改善はありませんでした。 </li><li>彼女の大きく損なわ左心室機能のために、患者が心臓突然死（SCD）のかなりのリスクであった。 </li><li>プレゼンテーションでは、患者は胸部誘導でR波の損失と洞調律であった。 24時間ホルター心電計は、心房細動の32分のエピソードを明らかにした。 </li><li>決定は、心房細動のさらなるエピソードを監視し、そうでなければ非常に活発な患者の不適切な治療を避けるために、心房検出機能を備えたシングルチャンバーICDを移植しました。 </li></ol> 3。診断、評価、およびプラン<ol><li>治療計画は、電気生理学的実験室で局所麻酔下BIOTRONIK Linox スマート S DXリードでLumax VR-T DX除細動器を移植することでした。 </li><li>経胸壁エコーは左心室駆出率を再評価し、禁止するかもしれない心室血栓を除外するために注入する前に行われた注入時の除細動器のテスト。 </li></ol> 4。移植手順<ol><li>周囲の手続きの準備には、予防的抗生物質と皮下ヘパリンの単回静脈内投与が含まれています。冠動脈イベントのリスクは手順の間に出血のリスクを上回るため、抗血栓療法が維持されていた</li><li>患者は適切に滅菌方法で調製と覆われました。 </li><li>患者は連続的な電気心臓モニタリング、連続的なパルスオキシメトリー、および非観血式血圧監視を含む適切なモニタリングと、適度な鎮静下に置かれた。 </li><li>鎮静投与は、局所麻酔の賢明なアプリケーションとともに、ミダゾラム、フェンタニルとプロポフォールIVから成っていた。 </li><li>注入は、無傷の皮膚と下大静脈（IVC）のワイヤの配置を介して左鎖骨下静脈の穿刺で始まった。位置は、Xが確認された線。ほとんどの介入electrophysiologistsではなくポケットから静脈を穿刺より外側アプローチよりも、この経皮的アプローチでは、より経験豊富なので、この珍しいアプローチが使用されていました。 </li><li>皮膚が鎖骨の下と平行に約2cmメスで切断した。デバイス用のポケットが左鎖骨の下に調製した後、静脈内の線はポケットとSeldinger法で導入された8フランスの鞘に描かれた。 </li><li>電極は、右心房にシースを介してSVCを導入した。湾曲したスタイレット（S 65-K、BIOTRONIK社）は、電極に導入された後、電極を右心室流出路に三尖弁かかわらず、押された。 </li><li>ストレートスタイ（S65-C、BIOTRONIK社）は、電極に導入した。電極は劣って右心室に落ちて右室心尖部に操縦されました。電極先端の位置だけでなく、世代アトリウムの2つの電極のERAL位置はX線によりモニターした。 2心房リング電極は、SVCと右心房の接合部に配置された。 </li><li>電極は適切に配置した後、心房および心室の信号の測定を行った。 </li><li>心室ペーシング電極のしきい値は、（ビデオ= &quot;7時27分&quot;の時間）を測定した。心房信号が6.5と8mVの（ビデオ= &quot;午前7時56分&quot;の時間）の間で測定した。心房信号は装置内のフィルタの設定で三回強化されました。心室信号が8.4と9.5 mVの間で測定した。これらのセンシングとペーシング·しきい値を使用すると、電極は、鎖骨下静脈の入り口に修正されました。 </li><li>電極は、その後除細動器に接続されています。 </li><li>すべてのメジャーが再確認し、心室細動除細動器を介してT波ショックによって誘導され、デバイスによって自動的に終了しました。 （ビデオの時間= &quot;午前11時01分&quot;） </li><li>パットientは、病棟に持ってきて、次の日まで病院に残った。術後1日目に、X線は、リードの位置を確認し、気胸を除外するために取られた。しきい値を感知し、ペーシング再確認したと術中測定に類似していた。患者は回復に約4時間観察し、また移植後モニタリングした。全体的に、移植が成功したと患者は翌日退院した。フォローアップの最初の3ヶ月は平穏なだったと感知信号がこの期間にわたって安定していた。 </li></ol>

<ol>
	<li>B&#228;nsch, D., Steffgen, F., Gronefeld, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+1+1+trial+-+A+prospective+trial+of+a+dual-+versus+a+single-chamber+implantable+defibrillator+in+patients+with+slow+ventricular+tachycardias.">The 1+1 trial - A prospective trial of a dual- versus a single-chamber implantable defibrillator in patients with slow ventricular tachycardias.</a> Circulation. 110, 1022-1029 (2004).</li><li>Gilliam, F. R., Hayes, D. L., Boehmer, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real+World+Evaluation+of+Dual-Zone+ICD+and+CRT-D+Programming+Compared+to+Single-Zone+Programming.">Real World Evaluation of Dual-Zone ICD and CRT-D Programming Compared to Single-Zone Programming.</a> The ALTITUDE REDUCES Study. Journal of Cardiovascular Electrophysiology. 22, 1023-1029 (2011).</li><li>Dewland, T. A., Pellegrini, C. N., Wang, Y. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual-Chamber+Implantable+Cardioverter-Defibrillator+Selection+Is+Associated+With+Increased+Complication+Rates+and+Mortality+Among+Patients+Enrolled+in+the+NCDR+Implantable+Cardioverter-Defibrillator+Registry.">Dual-Chamber Implantable Cardioverter-Defibrillator Selection Is Associated With Increased Complication Rates and Mortality Among Patients Enrolled in the NCDR Implantable Cardioverter-Defibrillator Registry.</a> Journal of the American College of Cardiology. 58, 1007-1013 (2011).</li><li>Sticherling, C., Zabel, M., Spencker, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+a+Novel,+Single-Lead+Atrial+Sensing+System+With+a+Dual-Chamber+Implantable+Cardioverter-Defibrillator+System+in+Patients+Without+Antibradycardia+Pacing+Indications+Results+of+a+Randomized+Study.">Comparison of a Novel, Single-Lead Atrial Sensing System With a Dual-Chamber Implantable Cardioverter-Defibrillator System in Patients Without Antibradycardia Pacing Indications Results of a Randomized Study.</a> Circulation-Arrhythmia and Electrophysiology. 4, 56-63 (2011).</li><li>Safak, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+atrial+sensing+quality+in+ICD+patients+with+a+floating+atrial+dipole+ICD+lead+(interim+results).">Assessment of atrial sensing quality in ICD patients with a floating atrial dipole ICD lead (interim results).</a> Europace. , 1027-1027 (2011).</li><li>Deisenhofer, I., Kolb, C., Ndrepepa, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Do+current+dual+chamber+cardioverter+defibrillators+have+advantages+over+conventional+single+chamber+cardioverter+defibrillators+in+reducing+inappropriate+therapies?+A+randomized,+prospective+study.">Do current dual chamber cardioverter defibrillators have advantages over conventional single chamber cardioverter defibrillators in reducing inappropriate therapies? A randomized, prospective study.</a> J. Cardiovasc. Electrophysiol. 12, 134-142 (2001).</li><li>Dewland, T. A., Pellegrini, C. N., Wang, Y. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual-Chamber+Implantable+Cardioverter-Defibrillator+Selection+Is+Associated+With+Increased+Complication+Rates+and+Mortality+Among+Patients+Enrolled+in+the+NCDR+Implantable+Cardioverter-Defibrillator+Registry.">Dual-Chamber Implantable Cardioverter-Defibrillator Selection Is Associated With Increased Complication Rates and Mortality Among Patients Enrolled in the NCDR Implantable Cardioverter-Defibrillator Registry.</a> Journal of the American College of Cardiology. 58, 1007-1013 (2011).</li><li>Poole, J. E., Gleva, M. J., Mela, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Complication+Rates+Associated+With+Pacemaker+or+Implantable+Cardioverter-Defibrillator+Generator+Replacements+and+Upgrade+Procedures+Results+From+the+REPLACE+Registry.">Complication Rates Associated With Pacemaker or Implantable Cardioverter-Defibrillator Generator Replacements and Upgrade Procedures Results From the REPLACE Registry.</a> Circulation. 122, 1553-1U43 (2010).</li><li>Niehaus, M., Schuchert, A., Thamasett, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multicenter+experiences+with+a+single+lead+electrode+for+dual+chamber+ICD+systems.">Multicenter experiences with a single lead electrode for dual chamber ICD systems.</a> Pacing Clin. Electrophysiol. 24, 1489-1493 (2001).</li><li>Gradaus, R., Block, M., Dorszewski, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Implantation+of+a+dual+chamber+pacing+and+sensing+single+pass+defibrillation+lead.">Implantation of a dual chamber pacing and sensing single pass defibrillation lead.</a> Pacing Clin. Electrophysiol. 24, 416-423 (2001).</li></ol>

生産とこのビデオの記事のフリーアクセスがBIOTRONIK社が主催しています。

Lumax DX ICD、BIOTRONIK社と一緒に、新しいLinox SMART S DX電極の注入は、任意の単一チャンバーICDの配置と同じくらい簡単でした。この経験は、未発表のマスターDX-試験からのデータによってサポートされています。5 Linox SMART S DX電極が心房リードの欠点はなく、心房センシングの利点を提供しています。心房信号は、DX-試験で実証されているとして、我々の患者に時間をかけて安定していた5。 デュアルチャンバーデバイスは、1つだけの前向き無作為化試験では単室の検出上の優位性を実証した1 +1トライアルと呼ばれる。1この試験では、ゆっくりとVTの患者は、次のいずれかで、デュアルプログラムされたデュアルチャンバーICDを移植したまたはシングルチャンバー検出。複合エンドポイントは、検出率以下SVTsとVTSに応答して不適切な治療法の数であった。このエンドポイントは、1 +1裁判は、sを実証従来のプログラミングシングルチャンバー（SCH）の検出と比較して長い頻拍の検出間隔（TDI）を搭載したデュアルチャンバー（DCH）の検出ignificant優位。この発見は、Deisenhoferらによって、再訪されました。、ランダムDCH-SCHまたはICDの移植に患者を割り当てられた人。しかし、彼らの裁判は、特に平均頻拍の検出間隔は368ミリ秒だったので遅いのVTの患者に対処し、シングルおよびデュアルチャンバー装置は生命を脅かす心室性頻脈性不整脈の治療のために等しく有効であると結論づけていませんでした。 DCHデバイスは、頻拍の診断と分化のためのデュアルチャンバーICDのために、単にそれを注入するという概念の利点にもかかわらず優れたリズムの分類を持っている例を示しますが、SVTs中に不適切な治療を最小限に抑えるという点でSCHデバイスよりも異なっていません。6た改良された検出リードcomplicのリスクの増加により、カウンターバランスであるため、検出は、一般的に受け入れられませんゴム手袋だけでなく、増加した死亡率および罹患率。したがって、2,7,8、デュアルチャンバー検出のための注入法、またはVDD-システムの改善が必要である。9,10。 Lumax DX ICD組み合わせるLinox SMART S DX電極は、この利点を提供しています。センシング機能は、デュアルチャンバー装置と類似しており、合併症の発生率は、従来の単室除細動器の場合ほど低くなっています。5 結論 Lumax VR-T DXを確実に心房信号を感知し、心房性不整脈の早期発見を可能にするために貴重な情報を収集することが実証されています。さらに、デバイスが安全なショック低減のためのSMARTのAV差別を提供しています。利用可能な心房IEGMチャネルの診断ICD検出と治療の妥当性を、それによって不適切なショックを低減し、デバイスのプログラミングを最適化するための情報を得る。

a new single chamber implantable defibrillator with atrial sensing: a practical demonstration of sensing and  ease of implantation

植込み型除細動器（ICD）は、高い有効性と心室頻拍（VT）や心室細動（VF）を終了し、心臓突然死（SCD）から患者を保護することができます。頻拍が誤診される場合は、不適切なショックが発生する可能性があります。不適切なショックは害があり、患者の生活の質を損なう。不適切な治療のリスクは、ICDでプログラミング低い検出率で増加します。追加の心房情報の利点を持っているデュアルチャンバー装置と比較した場合、シングルチャンバーの検出は、誤診のために大きなリスクをもたらす。第二の電極に関連するリスクが検出の利点を上回るかもしれないので、しかし、単に検出のためのデュアルチャンバー装置を使用しては、一般的に受け入れられません。したがって、BIOTRONIK社は番目の心房部に位置する2つの電極から心房信号の検出を可能にするLinox SMART S DXと呼ばれる心室リードを開発し、eの心室電極。このデバイスは、2つのリング電極を含んでいます。1その連絡先は、心房細上大静脈（SVC）の接合部で壁やアトリウムにおける電極の浮遊部に位置1。優れた信号品質は、ICDの特殊なフィルタ設定（Lumax 540と740 VR-T DX、BIOTRONIK社）によって達成することができます。ここでは、システムの移植のしやすさが実証されます。

Watch this Scientific Journal Video about A New Single Chamber Implantable Defibrillator with Atrial Sensing: A Practical Demonstration of Sensing and  Ease of Implantation at JoVE.com

A New Single Chamber Implantable Defibrillator with Atrial Sensing: A Practical Demonstration of Sensing and  Ease of Implantation

デュアルチャンバ植込み型除細動器（ICD）は、心房細動の検出だけでなく、頻拍の分化を改善することができます。しかし、この利点は、従来のデュアルチャンバーデバイスで必要とされる第2の電極と、関連付けられた合併症によって損なわれています。したがって、BIOTRONIK社はLinoxと呼ばれる新しい電極を開発しました。<sup&gt; SMART</supLumax DX ICDと組み合わせて使用​​するときに、&gt; S DXは、第二電極に関連するリスクなしに、デュアルチャンバー検出を提供しています。

心房センシングによる新しいシングルチャンバー植込み型除細動器：センシングと注入の容易さの実用的なデモンストレーション

Implantable cardioverter-defibrillators (ICDs) terminate ventricular tachycardia (VT) and ventricular fibrillation (VF) with high efficacy and can protect ...

a-new-single-chamber-implantable-defibrillator-with-atrial-sensing

Research

JoVE Journal

Medicine

25.9K ビュー.  University Hospital of Rostock, Germany. デュアルチャンバ植込み型除細動器（ICD）は、心房細動の検出だけでなく、頻拍の分化を改善することができます。しかし、この利点は、従来のデュアルチャンバーデバイスで必要とされる第2の電極と、関連付けられた合併症によって損なわれています。したがって、BIOTRONIK社はLinoxと呼ばれる新しい電極を開発しました。 SMART

ビデオ: A New Single Chamber Implantable Defibrillator with Atrial Sensing: A Practical Demonstration of Sensing and  Ease of Implantation

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 ...

医学

Rapid Point-of-Care Assay of Enoxaparin Anticoagulant Efficacy in Whole Blood

There is the need for a clinical assay to determine the extent to which a patient's blood is effectively anticoagulated by the low-molecular-weight-heparin (LMWH), enoxaparin. There are also urgent clinical situations where it would be important if this could be determined rapidly. The present assay is designed to accomplish this. We only assayed human blood samples that were spiked with known concentrations of enoxaparin. The essential feature of the present assay is the quantification of the efficacy of enoxaparin in a patient's blood sample by degrading it to complete inactivity with heparinase. Two blood samples were drawn into Vacutainer tubes (Becton-Dickenson; Franklin Lakes, NJ) that were spiked with enoxaparin; one sample was digested with heparinase for 5 min at 37 &deg;C, the other sample represented the patient's baseline anticoagulated status. The percent shortening of clotting time in the heparinase-treated sample, as compared to the baseline state, yielded the anticoagulant contribution of enoxaparin. We used the portable, battery operated Hemochron 801 apparatus for measurements of clotting times (International Technidyne Corp., Edison, NJ). The apparatus has 2 thermostatically controlled (37 &deg;C) assay tube wells. We conducted the assays in two types of assay cartridges that are available from the manufacturer of the instrument. One cartridge was modified to increase its sensitivity. We removed the kaolin from the FTK-ACT cartridge by extensive rinsing with distilled water, leaving only the glass surface of the tube, and perhaps the detection magnet, as activators. We called this our minimally activated assay (MAA). The use of a minimally activated assay has been studied by us and others. 2-4 The second cartridge that was studied was an activated partial thromboplastin time (aPTT) assay (A104). This was used as supplied from the manufacturer. The thermostated wells of the instrument were used for both the heparinase digestion and coagulation assays. The assay can be completed within 10 min. The MAA assay showed robust changes in clotting time after heparinase digestion of enoxaparin over a typical clinical concentration range. At 0.2 anti-Xa I.U. of enoxaparin per ml of blood sample, heparinase digestion caused an average decrease of 9.8% (20.4 sec) in clotting time; at 1.0 I.U. per ml of enoxaparin there was a 41.4% decrease (148.8 sec). This report only presents the experimental application of the assay; its value in a clinical setting must still be established.

Demonstration of a rapid quantitative assay of the inhibition of blood coagulation by the low-molecular-weight-heparin, enoxaparin. The contribution of enoxaparin is assessed by removing its influence through digestion with heparinase. A fuller description of the assay is detailed in our published paper.1 The assay still requires clinical confirmation.

全血におけるエノキサパリン抗凝固効果の迅速なポイントオブケアアッセイ

There is the need for a clinical assay to determine the extent to which a patient's blood is effectively anticoagulated by the ...

Surgical Technique for Spinal Cord Delivery of Therapies: Demonstration of Procedure in Gottingen Minipigs

This is a compact visual description of a combination of surgical technique and device for the delivery of (gene and cell) therapies into the spinal cord. While the technique is demonstrated in the animal, the procedure is FDA-approved and currently being used for stem cell transplantation into the spinal cords of patients with ALS. While the FDA has recognized proof-of-principle data on therapeutic efficacy in highly characterized rodent models, the use of large animals is considered critical for validating the combination of a surgical procedure, a device, and the safety of a final therapy for human use. The size, anatomy, and general vulnerability of the spine and spinal cord of the swine are recognized to better model the human. Moreover, the surgical process of exposing and manipulating the spinal cord as well as closing the wound in the pig is virtually indistinguishable from the human. We believe that the healthy pig model represents a critical first step in the study of procedural safety.

Short visual description of the surgical technique and device used for the delivery of (gene and cell) therapies into the spinal cord. The technique is demonstrated in the animal but is entirely translatable and currently being used for human application.

セラピーの脊髄配達のための外科テクニック：ゲッティンゲンミニブタの手順のデモンストレーション

This is a  compact visual description of a combination of surgical technique and device  for the  delivery of (gene and cell) therapies into the spinal ...

A New Murine Model of Endovascular Aortic Aneurysm Repair

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of Abdominal aortic aneurysm (AAA) pathophysiology. There is no abdominal aortic aneurysm endograft exclusion model cheap and reproducible, which would allow deep investigations of AAA before and after treatment. We hereby describe how to induce, and then to exclude with a covered coronary stentgraft an abdominal aortic aneurysm in a rat. The well known elastase induced AAA model was first reported in 19901 in a rat, then described in mice2. Elastin degradation leads to dilation of the aorta with inflammatory infiltration of the abdominal wall and intra luminal thrombus, matching with human AAA. Endovascular exclusion with small covered stentgraft is then performed, excluding any interactions between circulating blood and the aneurysm thrombus. Appropriate exclusion and stentgraft patency is confirmed before euthanasia by an angiography thought the left carotid artery. Partial control of elastase diffusion makes aneurysm shape different for each animal. It is difficult to create an aneurysm, which will allow an appropriate length of aorta below the aneurysm for an easy stentgraft introduction, and with adequate proximal and distal neck to prevent endoleaks. Lots of failure can result to stentgraft introduction which sometimes lead to aorta tear with pain and troubles to stitch it, and endothelial damage with post op aorta thrombosis. Giving aspirin to rats before stentgraft implantation decreases failure rate without major hemorrhage. Clamping time activates neutrophils, endothelium and platelets, and may interfere with biological analysis.

Histological and biochemical modifications after aneurysm endograft exclusion are still unclear. We describe a new model of endograft implantation on a murine aneurysm. Through thrombus analysis with and without persistant circulating blood stream interface, and new endovascular biomaterials evaluation, this model will help to better understand endovascular aneurysm exclusion pathobiology.

血管内大動脈瘤の修復の新しいマウスモデル

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of ...

Construction of Vapor Chambers Used to Expose Mice to Alcohol During the Equivalent of all Three Trimesters of Human Development

Exposure to alcohol during development can result in a constellation of morphological and behavioral abnormalities that are collectively known as Fetal Alcohol Spectrum Disorders (FASDs). At the most severe end of the spectrum is Fetal Alcohol Syndrome (FAS), characterized by growth retardation, craniofacial dysmorphology, and neurobehavioral deficits. Studies with animal models, including rodents, have elucidated many molecular and cellular mechanisms involved in the pathophysiology of FASDs. Ethanol administration to pregnant rodents has been used to model human exposure during the first and second trimesters of pregnancy. Third trimester ethanol consumption in humans has been modeled using neonatal rodents. However, few rodent studies have characterized the effect of ethanol exposure during the equivalent to all three trimesters of human pregnancy, a pattern of exposure that is common in pregnant women. Here, we show how to build vapor chambers from readily obtainable materials that can each accommodate up to six standard mouse cages. We describe a vapor chamber paradigm that can be used to model exposure to ethanol, with minimal handling, during all three trimesters. Our studies demonstrate that pregnant dams developed significant metabolic tolerance to ethanol. However, neonatal mice did not develop metabolic tolerance and the number of fetuses, fetus weight, placenta weight, number of pups/litter, number of dead pups/litter, and pup weight were not significantly affected by ethanol exposure. An important advantage of this paradigm is its applicability to studies with genetically-modified mice. Additionally, this paradigm minimizes handling of animals, a major confound in fetal alcohol research.

We demonstrate the construction of alcohol vapor chambers using readily available materials that simultaneously house 6 mouse cages. We further describe their use in a mouse model of fetal alcohol exposure equivalent to all 3&#160;trimesters of human pregnancy. This paradigm exposes animals during gestation and postnatal days 1-12.

人間開発の3つのすべての学期の等価時にはアルコールにマウスを公開するために使用蒸気チェンバースの建設

Exposure to alcohol during development can result in a constellation of morphological and behavioral abnormalities that are collectively known as Fetal ...

Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. While these therapies lead to the rapid restoration of blood flow, these technologies remain limited by restenosis in the case of bare metal stents and angioplasty, or reduced healing and possibly enhanced risk of thrombosis in the case of drug eluting stents. A key pathophysiological mechanism in the formation of restenosis is intimal hyperplasia caused by the activation of vascular smooth muscle cells and inflammation due to arterial stretch and injury. Surgeries that induce arterial injury in genetically modified mice are useful for the mechanistic study of the vascular response to injury but are often technically challenging to perform in mouse models due to the their small size and lack of appropriate sized devices. We describe two approaches for a surgical technique that induces endothelial denudation and arterial stretch in the femoral artery of mice to produce robust neointimal hyperplasia. The first approach creates an arteriotomy in the muscular branch of the femoral artery to obtain vascular access. Following wire injury this arterial branch is ligated to close the arteriotomy. A second approach creates an arteriotomy in the main femoral artery that is later closed through localized cautery. This method allows for vascular access through a larger vessel and, consequently, provides a less technically demanding procedure that can be used in smaller mice. Following either method of arterial injury, a degradable drug delivery patch can be placed over or around the injured artery to deliver therapeutic agents.

We describe a surgical technique that produces wire injury in the femoral artery of mice to induce neointimal hyperplasia to serve as a model testing system for the perivascular delivery of therapeutic compounds for the inhibition of restenosis.

血管周囲ドラッグデリバリーパッチの移植に大腿動脈ワイヤ傷害のマウスモデル

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. ...

Demonstration of the Rat Ischemic Skin Wound Model

The propensity for chronic wounds in humans increases with ageing, disease conditions such as diabetes and impaired cardiovascular function, and unrelieved pressure due to immobility. Animal models have been developed that attempt to mimic these conditions for the purpose of furthering our understanding of the complexity of chronic wounds. The model described herein is a rat ischemic skin flap model that permits a prolonged reduction of blood flow resulting in wounds that become ischemic and resemble a chronic wound phenotype (reduced vascularization, increased inflammation and delayed wound closure). It consists of a bipedicled dorsal flap with 2 ischemic wounds placed centrally and 2 non-ischemic wounds lateral to the flap as controls. A novel addition to this ischemic skin flap model is the placement of a silicone sheet beneath the flap that functions as a barrier and a splint to prevent revascularization and reduce contraction as the wounds heal. Despite the debate of using rats for wound healing studies due to their quite distinct anatomic and physiologic differences compared to humans (i.e., the presence of a panniculus carnosus muscle, short life-span, increased number of hair follicles, and their ability to heal infected wounds) the modifications employed in this model make it a valuable alternative to previously developed ischemic skin flap models.

The rat, due to its size, availability, and rather docile behavior, has been utilized as a research model for many years. The goal of this protocol is to utilize the rat as an ischemic skin wound healing model to provide valuable insight into the pathophysiology of chronic wounds.

ラット虚血皮膚創傷モデルの実証

The propensity for chronic wounds in humans increases with ageing, disease conditions such as diabetes and impaired cardiovascular function, and ...

Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms. Unfortunately, difficulties determining the etiology of ARDS, as well as a wide range of pathophysiology have resulted in a lack of critical information that could be useful in developing therapeutic strategies.
Translational animal models are valuable when their pathogenesis and pathophysiology accurately reproduce a concept proven in both in vitro and clinical settings. Although large animal models (e.g., sheep) share characteristics of the anatomy of human trachea-bronchial tree, murine models provide a host of other advantages including: low cost; short reproductive cycle lending itself to greater data acquisition; a well understood immunologic system; and a well characterized genome leading to the availability of a variety of gene deletion and transgenic strains. A robust model of low pH induced ARDS requires a murine ALI that targets mainly the alveolar epithelium, secondarily the vascular endothelium, as well as the small airways leading to the alveoli. Furthermore, a reproducible injury with wide differences between different injurious and non-injurious insults is important.
The murine gastric acid aspiration model presented here using hydrochloric acid employs an open tracheostomy and recreates a pathogenic scenario that reproduces the low pH pneumonitis injury in humans. Additionally, this model can be used to examine interaction of a low pH insult with other pulmonary injurious entities (e.g., food particles, pathogenic bacteria).

This protocol induces acute lung injury in a mouse that has close fidelity to the pathogenesis of acid pneumonitis observed in humans. We generate a maximal acute nonlethal low pH lung injury and account for differences in rodent-human anatomic respiratory structure using an open tracheostomy coupled with circumferential pressure release.

最大急性非致死肺損傷における急性肺損傷の結果のオープン気管切開胃酸吸引マウスモデル

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute ...

Setting Up a Stroke Team Algorithm and Conducting Simulation-based Training in the Emergency Department - A Practical Guide

Time is of the essence when caring for an acute stroke patient. The ultimate goal is to restore blood flow to the ischemic brain. This can be&#160;achieved by either&#160;thrombolysis with recombinant tissue-plasminogen activator (rt-PA), the standard therapy for stroke patients who present within the first hours of symptom onset without contraindications, or by an endovascular approach, if a proximal brain vessel occlusion is detected. As the efficacy of both therapies declines over time, every minute saved along the way will improve the patient&#39;s outcome.
This critical situation requires thorough work and precise communication with the patient, the family and colleagues from different professions to acquire all relevant information and reach the right decision while carefully monitoring the patient. This is a high fidelity situation. In nonmedical high-fidelity environments such as aviation, Crew Resource Management (CRM) is used to enhance safety and team efficiency.
This guide shows how a Stroke Team algorithm, which is transferable to other hospital settings, was established and how regular simulation-based trainings were performed. It requires determination and endurance to maintain these time-consuming simulation trainings on a regular basis over the course of time. However, the resulting improvement of team spirit and excellent door-to-needle times will benefit both the patients and the work environment in any hospital.
A dedicated Stroke Team of 7 persons who are notified 24/7 by a collective call via speed dial and run a binding algorithm that takes approximately 20 min, was established. To train everybody involved in this algorithm, a simulation-based team training for all new Stroke Team members was conceived and conducted at monthly intervals. This led to a relevant and sustained reduction of the mean door-to-needle time to 25 min, and enhanced the feeling of stroke readiness especially in junior doctors and nurses.

Every min counts in acute stroke care. This guide shows how to establish a Stroke Team algorithm and enhance its performance with regular simulation training. The principles of Crew Resource Management (CRM) facilitate a straight workflow, reduce door-to-needle times and increase staff satisfaction.

ストロークチームアルゴリズムを設定し、救急部におけるシミュレーションベースのトレーニングを実施 - 実践ガイド

Time is of the essence when caring for an acute stroke patient. The ultimate goal is to restore blood flow to the ischemic brain. This can ...

Isolation of Atrial Cardiomyocytes from a Rat Model of Metabolic Syndrome-related Heart Failure with Preserved Ejection Fraction

In this article, we describe an optimized, Langendorff-based procedure for the isolation of single-cell atrial cardiomyocytes (ACMs) from a rat model of metabolic syndrome (MetS)-related heart failure with preserved ejection fraction (HFpEF). The prevalence of MetS-related HFpEF is rising, and atrial cardiomyopathies associated with atrial remodeling and atrial fibrillation are clinically highly relevant as atrial remodeling is an independent predictor of mortality. Studies with isolated single-cell cardiomyocytes are frequently used to corroborate and complement in vivo findings. Circulatory vessel rarefication and interstitial tissue fibrosis pose a potentially limiting factor for the successful single-cell isolation of ACMs from animal models of this disease.
We have addressed this issue by employing a device capable of manually regulating the intraluminal pressure of cardiac cavities during the isolation procedure, substantially increasing the yield of morphologically and functionally intact ACMs. The acquired cells can be used in a variety of different experiments, such as cell culture and functional Calcium imaging (i.e., excitation-contraction-coupling).
We provide the researcher with a step-by-step protocol, a list of optimized solutions, thorough instructions to prepare the necessary equipment, and a comprehensive troubleshooting guide. While the initial implementation of the procedure might be rather difficult, a successful adaptation will allow the reader to perform state-of-the-art ACM isolations in a rat model of MetS-related HFpEF for a broad spectrum of experiments.

Here, we describe an optimized, Langendorff-based procedure for the isolation of single-cell atrial cardiomyocytes from a rat model of metabolic syndrome-related heart failure with preserved ejection fraction. A manual regulation of intraluminal pressure of cardiac cavities is implemented to yield functionally intact myocytes suitable for excitation-contraction-coupling studies.

保存された駆出率とメタボリック症候群関連心不全ラットモデルから心房の心筋細胞の単離

In this article, we describe an optimized, Langendorff-based procedure for the isolation of single-cell atrial cardiomyocytes (ACMs) from a rat model of ...