Die Autoren haben keine Bestätigungen.

alle Tierversuche wurden durchgeführt in Übereinstimmung mit dem deutschen Gesetz über Tier (TierSchG) und wurden von der lokalen Tierschutz-Ausschuss (unteren sächsischen Landesamt für Verbraucherschutz und Lebensmittelsicherheit, Protokoll genehmigt TSA 14/1556). Das minimale Gewicht der Maus für dieses Modell geeignet ist 25 g.
 1. präoperativen Vorbereitungen Hinweis: alle Eingriffe werden sauber, unsterilen Bedingungen mit autoklaviert Instrumenten durchgeführt.
<ol><li>50-60 Platz 8 cm lange Propylen hohlen Fasern in ein Rohr parallel und verbinden Sie mit einem T-Adapter auf beiden Seiten. Füllen den Raum zwischen den Hohlfasern und der externe Teil der T-Adapter mit Leim.
	<ol><li>Erlauben mindestens 24 Stunden Aushärten des Klebers. Die hohlen Fasern aus der T-Adapter mit einem standard Mikrotom schneiden und ziehen Sie den Silikonschlauch über die Verbindungspunkte.</li>
	</ol></li> <li>2 Fr Polyurethan Kanüle eine Metallnadel 27 G (von einem 26G Branule) einfügen. Verwenden Sie eine chirurgische Klinge und Mikro-Schere unter dem Mikroskop (8-12 X Vergrößerung) zu drei bis vier Fenestrationen von je ca. 0,15 cm im distalen Drittel der Kanüle zu gewährleisten optimale venösen Rückfluss.
	<ol><li>Entfernen des Drahtes nach Abschluss. Verwenden Sie Wattestäbchen für stumpfe Dissektion und Retraktion der Strukturen. Gaze-Tupfer (5 x 5 cm 2) verwenden, um tanken überschüssige Flüssigkeit zu Gewebe Austrocknung zu verhindern.</li>
	</ol></li> <li>Bereiten das Priming-Volumen. Fügen Sie für die Fertigstellung 30 IU Heparin pro mL Lösung und 2,5 % V/V einer 8.4 % Lösung von Nahco3 3 für die Pufferung zu grundieren hinzu. Speichern Sie diese Lösung bei 4 ° C bis verwendet.</li>
	<li>Füllen die CPB-Schaltung (d. h., Pumpe, Luft Trapper, Tubing und beide Kanülen) mit 850 µL-Priming-Lösung über die venöse Kanüle. Sobald gefüllt, halten die CPB im Umlauf, bis das Tier zur Kanülierung bereitsteht.</li>
</ol> 2. Tierische Narkose <ol><li>Anästhesie zu verwalten, legen Sie das Tier in eine Induktion Kammer unter 2,5 % V/V Isofluran/Sauerstoff-Gemisch. Bestätigen Sie ordnungsgemäße Betäubung durch Beurteilung von Pedal Rückzug Reflex, Tail Prise Reflex und Auge blinzeln Reflex. Tierärztliche Auge Salbe zur Vermeidung von Augentrockenheit.</li>
	<li>Legen Sie das Tier auf eine Erwärmung mit klimaregulierende Funktion. Messen der Körpertemperatur mit einer Sonde rektal eingeführt und angeschlossen an das Datenerfassungssystem.</li>
	<li>Nach Vollnarkose erreicht ist, Intubation der tierischen Orotracheally mit einer 20G Kunststoff Braunule, mündlich einlegen und schob es in die Luftröhre unter Sichtkontrolle. Mechanische Lüftung, die Verwendung einer Isofluran Vaporizer, verbunden mit einem Maus-Ventilator zu starten. Je nach Tier die Lüftung so einstellen, dass ein Tidalvolumen von 250-350 µL erreicht wird.</li>
	<li>Komplette Analgesie versichern Spritzen subkutan 5 mg/kg Körpergewicht tierischen Carprofen. Es wird empfohlen, dass Isofluran Konzentration zwischen 1,3-2,5 % Sauerstoff gehalten werden. Isofluran Konzentration kann manuell eingestellt werden, je nach Stadium des Verfahrens.</li>
</ol> 3. Chirurgische Eingriffe <ol><li>nach Vollnarkose und Intubation ist erreicht, führen Sie einen Mittellinie Hautschnitt am Hals mit einer scharfen Schere feinen Muskeln in einem stumpfen Mode zu trennen und Aussetzen der rechten Halsschlagader und linken Halsschlagader. Während der Zubereitung gerinnen kleine Schiffe mit einer tierärztlichen Coagulator verbunden, bipolare Pinzetten, um minimaler Blutverlust zu gewährleisten.</li>
	<li>Nach der Präparation der Vena Schiffe, cranially verbinden das distale Segment der linke gemeinsame Halsschlagader zu seiner Gabelung mit seidenen Fäden 8-0.</li>
	<li>Verbinden das distale Ende der Kanüle 27 G auf den arteriellen Zustrom Schlauch mit einem Silikon-Stecker (0,5 mm ID, 1 mm OD), Platz 8-0 Seide Naht Rutsch am proximalen Segment der Arterie, und legen Sie die Spitze der Kanüle in die Halsschlagader Knoten.</li>
	<li>Nach der korrekten Platzierung von der Kanülenspitze der Kanülenspitze voraus, so dass es 3-4 mm proximal der Aortenbogen legt. Beheben der Kanülenspitze durch die Sicherung mit Seide Knoten 8-0.</li>
	<li>Mit mikrochirurgischen Pinzetten und Scheren, stumpfe und scharfe Dissektion durchzuführen, aussetzen der rechten Halsschlagader durch stumpfe Präparation des Gewebes seitlich an den sternocleidomastoideus-Muskel in der Nähe von Schlüsselbein, und legen Sie einen 8-0 Seide Knoten am distalen Ende und ein 8-0 Schleife am proximalen Ende.</li>
	<li>Nach Unterbindung der distalen Ende der Halsschlagader, setzen Sie die Spitze der venösen Kanüle in der rechten Halsschlagader und Fortschritte in Richtung auf den rechten Vorhof und mit der Seide Knoten sichern. Für optimale venösen Rückfluss, ist es möglicherweise erforderlich, die venöse Spitze in den rechten Ventrikel gelangen.</li>
	<li>Sobald die korrekte Kanüle Position erreicht ist, führen Sie systemische Heparinisierung durch Zugabe von 2,5 IU Heparin pro Gramm der tierischen Körpergewicht über direkte intravenöse Injektion in die Halsschlagader.</li>
	<li>Für Echtzeit-invasive Drucküberwachung, cannulate die linke Femoral Arterie. Aussetzen die Leistengegend und vorsichtig trennen die gemeinsame Femoral Arterie aus der femoral Ader und femoral Nerv unter 25 X Vergrößerung.
	<ol><li>Ligate der distale Teil der Femoral Arterie. Vorübergehend verdecken den proximalen Teil mit eine Anfangsschlaufe und machen einen kleinen Schnitt an der vorderen Wand mit Mikro-Pinzetten.</li>
		<li>Danach legen Sie eine 1 Fr Polyurethan Kanüle in die Femoral Arterie und sichern Sie es mit einem Seide 10-0 Naht. Diese Kanüle wird verwendet, um Blutproben für die Gasanalyse Blut extrahieren.</li>
	</ol></li> <li>Nach der erfolgreichen Platzierung der arteriellen und venösen Kanülen, initiieren kardiopulmonalen Bypass durch Einschalten der Pumpe. Die Intubation zum Start des CPB beträgt ca. 45 min. Starten Sie mit einer Fließgeschwindigkeit von 0,5 mL/min, je nach systemischen Druckmessungen und Erhöhung der Durchblutung innerhalb von 2 min auf vollen Durchfluss (4-6 mL/min) durch die Erhöhung der Pumpendrehzahl.</li>
	<li>Unter voller Kontrolle durchführen einer oberen Sternotomie mit scharfen Schere ab das Manubrium und 5 mm in der kaudalen Richtung gehen. Gerinnen der sternalen Kanten sofort um Blutungen zu vermeiden. Aussetzen der Aortenbogen durch Ziehen der rechten Halsschlagader in kranialer Richtung.</li>
	<li>Für optimale Kontrolle, umlaufend frei Aortenbogen aus dem Thymus und umliegendes Gewebe spannen zu erleichtern. Legen Sie eine 8: 0 Seide Schleife um die Aorta ascendens. Um die Kreuzklemme für Kardioplegie platzieren, Schlaufe die Seide in kranialer Richtung besser aussetzen der Aorta ascendens.</li>
</ol> 4. Herz-Lungen-Bypass und Blut-Gas-Analyse <ol><li>für Gas Blutanalyse (BGA), verwenden Sie Glas-Kapillarröhrchen, um 60-90 µL arterielles Blut über die Femoral Arterie Katheter zu sammeln.
	<ol><li>Eine kleine Klemme auf der Silikonschlauch und lösen Sie den Schlauch vom Katheter. Druck langsam auf die Klemme ermöglicht kontrollierte Füllung des Kapillarröhrchens.</li>
		<li>Befestigen Sie den Silikonschlauch des Katheters. Blut-Gas-Analysator für Messungen zu den folgenden Zeitpunkten Kapillarröhrchen einfügen: 10 min nach der Einleitung der CPB mit Belüftung (BGA1) nach 25 min von CPB und 15 min von Atemstillstand (BGA2) nach 40 min von CPB und 30 min von Atemstillstand (BGA3) nach 55 min von CPB, 45 min der Atemwege und 20 min an Herzstillstand (BGA4)</li></ol></li> <li>durch stabile CPB fließen, Initiative Te Atemstillstand durch Anhalten Lüftung.</li>
	<li>Nach Beendigung der Belüftung, stellen die Erwärmung Pad 28 º c und starten Sie topisch Kühlung das Tier auf 28 ° c Körpertemperatur innerhalb der ersten 20 Minuten Atemstillstand mit Gaze in kalten Kochsalzlösung getränkt.</li>
	<li>Einmal eine Temperatur von 28 ° c erreicht wird, und nach insgesamt 30 min Atemstillstand, verwalten 0,3 mL 7,45 % KCl-Lösung in den Kreislauf der CPB Kardioplegie initiieren.</li>
	<li>Für überqueren Sie Klemmen der Aorta, ziehen Sie die zuvor platzierte Seide Schleife (Schritt 3.10) in Pfeilrichtung kranialen für bessere Belichtung und legen Sie eine Mikro-Serrefine Klammer auf den aufsteigenden Teil der Aorta.</li>
	<li>Führen Sie insgesamt 60 min Atemstillstand und 30 min von Herzstillstand. Entfernen Sie die Mikro-Serrefine-Klemme aus der Aorta ascendens, Reperfusion des Herzens zu initiieren. Gleichzeitig wieder lüften und wärmen Sie das Tier auf 37 ° c</li>
	<li>Nach Reperfusion abgeschlossen ist und das Tier Normothermie erreicht, kündigen die CPB durch das Ausschalten der Pumpe und weiterhin überwachen physiologische Messungen (z.B. Körpertemperatur, EKG, und invasive Blutdruckmessung) für 20 min.</li>
	<li>Am Ende des Experiments, das Tier in Vollnarkose (5 % Isofluran) aussaugen und sammeln Blut und Organe für die weitere Analyse 14.</li>
</ol>

<ol>
	<li>Edmunds, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiopulmonary+Bypass+after+50+Years.">Cardiopulmonary Bypass after 50 Years.</a> N. Engl. J. Med. 351 (16), 1601-1603 (2004).</li><li>Goto, T., Maekawa, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+dysfunction+after+coronary+artery+bypass+surgery.">Cerebral dysfunction after coronary artery bypass surgery.</a> J. Anesth. 28 (2), 242-248 (2014).</li><li>Uysal, S., Reich, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurocognitive+outcomes+of+cardiac+surgery.">Neurocognitive outcomes of cardiac surgery.</a> J. Cardiothorac. Vasc. Anesth. 27 (5), 958-971 (2013).</li><li>Ballaux, P. K., Gourlay, T., Ratnatunga, C. P., Taylor, K. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+literature+review+of+cardiopulmonary+bypass+models+for+rats.">A literature review of cardiopulmonary bypass models for rats.</a> Perfusion. 14 (6), 411-417 (1999).</li><li>Jungwirth, B., de Lange, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+cardiopulmonary+bypass:+development,+applications,+and+impact.">Animal models of cardiopulmonary bypass: development, applications, and impact.</a> Semin. Cardiothorac. Vasc. Anesth. 14 (2), 136-140 (2010).</li><li>G&#252;nzinger, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+rat+model+of+cardiopulmonary+bypass+with+cardioplegic+arrest+and+hemodynamic+assessment+by+conductance+catheter+technique.">A rat model of cardiopulmonary bypass with cardioplegic arrest and hemodynamic assessment by conductance catheter technique.</a> Basic Res Cardiol. 102 (6), 508-517 (2007).</li><li>Waterbury, T., Clark, T. J., Niles, S., Farivar, R. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rat+model+of+cardiopulmonary+bypass+for+deep+hypothermic+circulatory+arrest.">Rat model of cardiopulmonary bypass for deep hypothermic circulatory arrest.</a> J. Thorac. Cardiovasc. Surg. 141 (6), 1549-1551 (2011).</li><li>Schnoering, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+newly+developed+miniaturized+heart-lung+machine-expression+of+inflammation+in+a+small+animal+model.">A newly developed miniaturized heart-lung machine-expression of inflammation in a small animal model.</a> Artif. Organs. 34 (11), 911-917 (2010).</li><li>Kim, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+responses+of+tissues+from+the+brain,+heart,+kidney,+and+liver+to+resuscitation+following+prolonged+cardiac+arrest+by+examining+mitochondrial+respiration+in+rats.">The responses of tissues from the brain, heart, kidney, and liver to resuscitation following prolonged cardiac arrest by examining mitochondrial respiration in rats.</a> Oxid. Med. Cell. Longev. 2016, (2016).</li><li>Shappell, S. B., Gurpinar, T., Lechago, J., Suki, W. N., Truong, L. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+obstructive+uropathy+in+severe+combined+immunodeficient+(SCID)+mice:+lymphocyte+infiltration+is+not+required+for+progressive+tubulointerstitial+injury.">Chronic obstructive uropathy in severe combined immunodeficient (SCID) mice: lymphocyte infiltration is not required for progressive tubulointerstitial injury.</a> J. Am. Soc. Nephrol. 9 (6), 1008-1017 (1998).</li><li>Majzoub, J. A., Muglia, L. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Knockout+mice.">Knockout mice.</a> N. Engl. J. Med. , 904-907 (1996).</li><li>Houser, S. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+Models+of+Heart+Failure+A+Scientific+Statement+From+the+American+Heart+Association.">Animal Models of Heart Failure A Scientific Statement From the American Heart Association.</a> Circ. Res. 111 (1), 131-150 (2012).</li><li>Russell, J. C., Proctor, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small+animal+models+of+cardiovascular+disease:+tools+for+the+study+of+the+roles+of+metabolic+syndrome,+dyslipidemia,+and+atherosclerosis.">Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis.</a> Cardiovasc. Pathol. 15 (6), 318-330 (2006).</li><li>Iurascu-Gagea, M., Craig, S., Suckow, M. A., Stevens, K. A., Wilson, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Euthanasia+and+necropsy.">Euthanasia and necropsy.</a> The laboratory rabbit, guinea pig, hamster, and other rodents. , 117-141 (2012).</li></ol>

Die Autoren haben nichts preisgeben.

Wir haben eine voll funktionsfähige klinisch relevante Modell des CPB in eine Maus entwickelt. Mit mehr als 30 Stämme von Mäusen mit Herz-Kreislauf-Krankheiten wäre unser Modell einen Ausgangspunkt für die Entwicklung neuer Interessenten Protokolle im Zusammenhang mit CPB. Darüber hinaus aufgrund der Fülle von Maus-spezifischen Reagenzien und Ko-Out Mäuse, dieses Modell kann nicht nur die aktuellen Rattenmodell der CPB ersetzen aber erleichtert Sezieren von den molekularen Mechanismen CPB-bezogene Organschäden. ...

Seit der Einführung der kardiopulmonalen Bypass (CPB) in die Klinik hat es eine wesentliche Rolle in der Herzchirurgie1gespielt. In der modernen Herzchirurgie unbedingt längere CPB Zeit umfangreiche Aorten Rekonstruktionen und kombinierte Verfahren durchführen. Technologische Fortschritte enorm gewesen, die Verwendung des intravasalen Umlauf wird im Zusammenhang mit Intra- und postoperativen systemische und lokale Orgel Schaden2,3.
Große Tier-Modelle wurden entwickelt, um die Rolle des CPB auf physiologische Prozesse4,5zu untersuchen. Obwohl diese Modelle zur Verfügung, einen Einblick in die CPB Komplikationen verbunden gestellt haben, sie sind extrem teuer und molekulare Werkzeuge (z. B. Antikörper) sind sehr begrenzt. Bei kleinen Tieren wurde eine kostengünstigere Alternative entwickelt. Seit ihrer Entwicklung wurden mehrere Studien durchgeführt, um ein Modell der CPB in Ratten und Kaninchen5,6,7,8,9zu optimieren. Diese Modelle bieten eine gute Grundlage für Messungen der pathophysiologischen Krankheitsprozesse; Sie sind jedoch noch nicht ausreicht, um zelluläre und humorale Immunologie aufgrund des Fehlens von entsprechenden Antikörper und Reagenzien zu untersuchen. Dies beeinträchtigt ihre Rolle in diesem Bereich der Forschung.
Wir haben vor kurzem ein Maus-Modell der CPB entwickelt. Durch eine Vielzahl von Maus-spezifischen Reagenzien und genetisch veränderte Mäuse sind Maus-Modellen im Allgemeinen das Modell der Wahl für physiologische, molekularen und immunologischen Forschung10,11. Daher wird unser Modell die Studie von CPB in Bezug auf verschiedenen Komorbiditäten erleichtern, da gibt es viele Mäuse Stämme mit klinisch relevanten Krankheiten12,13. Entsprechend beschreibt dieses Papier im Detail, wie CPB an Mäusen durchgeführt. Sauerstoff und hämodynamischen Parameter sind genau nach Tiefe Atem-und Kreislauf überwacht.

<table border="0" cellpadding="0" cellspacing="0" width="1191">
	<tbody>
		<tr height="23">
			<td height="23" style="height:23px;width:297px;">Sterofundin</td>
			<td style="width:279px;">B.Braun Petzold GmbH</td>
			<td style="width:181px;">PZN:8609189</td>
			<td style="width:435px;">priming volume, 1:1 with Tetraspan</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">Tetraspan 6% HES Solution</td>
			<td style="width:279px;">B. Braun Melsungen AG</td>
			<td style="width:181px;">PZN: 05565416</td>
			<td>priming volume, 1:1 with Sterofundin</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">Heparin Natrium 25.000</td>
			<td style="width:279px;">Ratiopharm GmbH</td>
			<td style="width:181px;">PZN: 3029843</td>
			<td>2.5 IU per ml of priming solution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">NaHCO3 8,4% Solution</td>
			<td style="width:279px;">B. Braun Melsungen AG</td>
			<td style="width:181px;">PZN: 1579775</td>
			<td>3% in priming solution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">KCL 7,45 % Solution</td>
			<td style="width:279px;">B. Braun Melsungen AG</td>
			<td style="width:181px;">PZN: 2418577</td>
			<td>0.1 ml for cardioplegia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">Carprofen</td>
			<td style="width:279px;">Zoetis Inc., USA</td>
			<td>PZN:00289615 08859153</td>
			<td>5 mg/kg/BW</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">1 Fr PU Catheter</td>
			<td style="width:279px;">Instechlabs INC., USA</td>
			<td style="width:181px;">C10PU-MCA1301</td>
			<td>carotid artery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">2 Fr PU Catheter</td>
			<td style="width:279px;">Instechlabs INC., USA</td>
			<td style="width:181px;">C20PU-MJV1302</td>
			<td>jugular vein</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Vasofix Safety catheter 20G</td>
			<td style="width:279px;">B.Braun Medical</td>
			<td style="width:181px;">4268113S-01</td>
			<td>orotracheal intubation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">8-0 Silk suture braided</td>
			<td>Ashaway Line &#38; Twine Mfg. Co., USA</td>
			<td style="width:181px;">75290</td>
			<td>ligature</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">Isoflurane</td>
			<td style="width:279px;">Piramal Critical Care Deutschland GmbH</td>
			<td style="width:181px;">PZN:9714675</td>
			<td>narcosis</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">CLINITUBES blood capillaries</td>
			<td style="width:279px;">Radiomed GmbH</td>
			<td style="width:181px;">51750132</td>
			<td>blood sampling 60 - 95 microliter</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Spring Scissors - 6mm Blades</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">15020-15</td>
			<td>instruments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Spring Scissors - 2mm Blades</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">15000-03</td>
			<td>instruments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Halsted-Mosquito Hemostat</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">13009-12</td>
			<td>instruments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Dumont #55 Forceps</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">11295-51</td>
			<td>instruments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Castroviejo Micro Needle Holder - 9cm</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">12060-02</td>
			<td>instruments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Micro Serrefines</td>
			<td>Fine Science Tools GmbH</td>
			<td>18555-01</td>
			<td>instruments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Bulldog Serrefine</td>
			<td>Fine Science Tools GmbH</td>
			<td style="width:181px;">18050-28</td>
			<td>instruments</td>
		</tr>
		<tr height="23">
			<td height="23" style="height:23px;width:297px;">MiniVent Ventilator for Mice (Model 845)</td>
			<td style="width:279px;">Harvard Apparatus</td>
			<td style="width:181px;">73-0044</td>
			<td>mechanical ventilation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">Isoflurane Vaporizer Drager 19.1</td>
			<td style="width:279px;">Dr&#228;gerwerk AG &#38; Co. KGaA</td>
			<td style="width:181px;"></td>
			<td>anesthesia 1.3 -2.5%</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">PowerLab data acquisition device 4/35</td>
			<td>ADInstruments Ltd, New Zealand</td>
			<td style="width:181px;">PL3504</td>
			<td>invasive pressure, ECG, temperature</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">ABL 800 Flex</td>
			<td>Radiometer GmbH</td>
			<td style="width:181px;"></td>
			<td>blood gas analysis</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:297px;">NMRI mice</td>
			<td style="width:279px;">Charles River Laboratories</td>
			<td style="width:181px;">Crl:NMRI(Han)</td>
			<td>male, 30-35 g, 12 weeks old, housed at least 1 week before the experiment</td>
		</tr>
	</tbody>
</table>

cardiopulmonary bypass in a mouse model: a novel approach

Während längerer kardiopulmonalen Bypass bei kardiologischen Eingriffen wichtiger wird, entsteht ein zunehmender klinischer Bedarf zur Optimierung der Verfahren und zur Minimierung der Organschäden, die aus dem längeren intravasalen Verkehr. Das Ziel dieser Arbeit war eine voll funktionsfähige und klinisch relevante Modell der kardiopulmonalen Bypass in einer Maus zu demonstrieren. Wir berichten über das Gerätedesign, Perfusion Schaltung Optimierung und mikrochirurgischen Techniken. Dieses Modell ist ein akuter Modell, das mit überleben aufgrund des Bedarfs an mehreren Blut Zeichnungen nicht kompatibel ist. Wegen der Auswahl an Tools für die Mäuse (z.B., Marker, Knockouts, etc.) wird dieses Modell Untersuchung über die molekularen Mechanismen der Organschäden und die Wirkung der kardiopulmonalen Bypass im Vergleich zu anderen erleichtern. Begleiterkrankungen.

Dieses Protokoll beschreibt die Perfusion Schaltung, chirurgische Eingriffe und die Überwachung der physiologischen Parameter während CPB einer Maus. Wenn von einem angemessen qualifizierten Mikrochirurg durchgeführt, werden die Ergebnisse konstant und reproduzierbar erzielt.
Um ausreichende Gewebedurchblutung zu erhalten, wird der mittlere arterielle Druck immer zwischen 40 und 60 MmHg durch Anpassung des CPB Blutfluss und H...

Watch this Scientific Journal Video about Cardiopulmonary Bypass in a Mouse Model: A Novel Approach at JoVE.com

Cardiopulmonary Bypass in a Mouse Model: A Novel Approach

Dieses Papier beschreibt die kardiopulmonalen Bypass bei Mäusen durchführen. Dieses neue Modell erleichtert die Untersuchung der molekularen Mechanismen Organschäden.

Kardiopulmonalen Bypass in einem Mausmodell: ein neuer Ansatz

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization ...

cardiopulmonary-bypass-in-a-mouse-model-a-novel-approach

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10.8K Aufrufe.  Hannover Medical School. Dieses Papier beschreibt die kardiopulmonalen Bypass bei Mäusen durchführen. Dieses neue Modell erleichtert die Untersuchung der molekularen Mechanismen Organschäden.

Serie: Cardiopulmonary Bypass in a Mouse Model: A Novel Approach

Vascular Occlusion Training for Inclusion Body Myositis: A Novel Therapeutic Approach

Inclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy. It is known to produces remarkable muscle weakness and to greatly compromise function and quality of life. Moreover, clinical practice suggests that, unlike other inflammatory myopathies, the majority of IBM patients are not responsive to treatment with immunosuppressive or immunomodulatory drugs to counteract disease progression1. Additionally, conventional resistance training programs have been proven ineffective in restoring muscle function and muscle mass in these patients2,3. Nevertheless, we have recently observed that restricting muscle blood flow using tourniquet cuffs in association with moderate intensity resistance training in an IBM patient produced a significant gain in muscle mass and function, along with substantial benefits in quality of life4. Thus, a new non-pharmacological approach for IBM patients has been proposed. Herein, we describe the details of a proposed protocol for vascular occlusion associated with a resistance training program for this population.

The present article presents the details pertaining to the application of resistance training associated to vascular occlusion in IBM patients.

Gefäßverschluss Training für Inclusion Body Myositis: einen neuen therapeutischen Ansatz

Inclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy. It is known to produces remarkable muscle weakness and to greatly compromise ...

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Medizin

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks. Bronchial thermoplasty is delivered by the Alair System and is performed in three outpatient procedure visits, each scheduled approximately three weeks apart. The first procedure treats the airways of the right lower lobe, the second treats the airways of the left lower lobe and the third and final procedure treats the airways in both upper lobes. After all three procedures are performed the bronchial thermoplasty treatment is complete.
Bronchial thermoplasty is performed during bronchoscopy with the patient under moderate sedation. All accessible airways distal to the mainstem bronchi between 3 and 10 mm in diameter, with the exception of the right middle lobe, are treated under bronchoscopic visualization. Contiguous and non-overlapping activations of the device are used, moving from distal to proximal along the length of the airway, and systematically from airway to airway as described previously. Although conceptually straightforward, the actual execution of bronchial thermoplasty is quite intricate and procedural duration for the treatment of a single lobe is often substantially longer than encountered during routine bronchoscopy. As such, bronchial thermoplasty should be considered a complex interventional bronchoscopy and is intended for the experienced bronchoscopist. Optimal patient management is critical in any such complex and longer duration bronchoscopic procedure. This article discusses the importance of careful patient selection, patient preparation, patient management, procedure duration, postoperative care and follow-up to ensure that bronchial thermoplasty is performed safely.
Bronchial thermoplasty is expected to complement asthma maintenance medications by providing long-lasting asthma control and improving asthma-related quality of life of patients with severe asthma. In addition, bronchial thermoplasty has been demonstrated to reduce severe exacerbations (asthma attacks) emergency rooms visits for respiratory symptoms, and time lost from work, school and other daily activities due to asthma.

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks.

Bronchial Thermoplastie: einen neuen therapeutischen Ansatz bis schwerem Asthma

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled ...

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient management strategies. Orthotopic mouse models of oral cancer have been developed to facilitate the study of factors that impact invasion and serve as model system for evaluating anti-tumor therapeutics. In these systems, visualization of disseminated tumor cells within oral cavity tissues has typically been conducted by either conventional histology or with in vivo bioluminescent methods. A primary drawback of these techniques is the inherent inability to accurately visualize and quantify early tumor cell invasion arising from the primary site in three dimensions. Here we describe a protocol that combines an established model for squamous cell carcinoma of the tongue (SCOT) with two-photon imaging to allow multi-vectorial visualization of lingual tumor spread. The OSC-19 head and neck tumor cell line was stably engineered to express the F-actin binding peptide LifeAct fused to the mCherry fluorescent protein (LifeAct-mCherry). Fox1nu/nu mice injected with these cells reliably form tumors that allow the tongue to be visualized by ex-vivo application of two-photon microscopy. This technique allows for the orthotopic visualization of the tumor mass and locally invading cells in excised tongues without disruption of the regional tumor microenvironment. In addition, this system allows for the quantification of tumor cell invasion by calculating distances that invaded cells move from the primary tumor site. Overall this procedure provides an enhanced model system for analyzing factors that contribute to SCOT invasion and therapeutic treatments tailored to prevent local invasion and distant metastatic spread. This method also has the potential to be ultimately combined with other imaging modalities in an in vivo setting.

A comprehensive overview of the techniques involved in generating a mouse model of oral cancer and quantitative monitoring of tumor invasion within the tongue through multi-photon microscopy of labeled cells is presented. This system can serve as a useful platform for the molecular assessment and drug efficacy of anti-invasive compounds.

Multi-Photonen-Imaging der Tumorzellinvasion in einem orthotopen Mausmodell des oralen Plattenepithelkarzinoms

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient ...

Normothermic Cardiac Arrest and Cardiopulmonary Resuscitation: A Mouse Model of Ischemia-Reperfusion Injury

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused by whole-body hypoperfusion.5,6 Successful reproduction of whole-body hypoperfusion in rodent models has been fraught with 
difficulty.7-9,9,10 Models which employ focal ischemia have repeatedly demonstrated results which do not translate to the clinical setting, and larger 
animal models which allow for whole body hypoperfusion lack access to the full toolset of genetic manipulation possible in the mouse.11,12 However, in recent 
years a mouse model of cardiac arrest and cardiopulmonary resuscitation has emerged which can be adapted to model AKI.13 This model reliably reproduces 
physiologic, functional, anatomic, and histologic outcomes seen in clinical AKI, is rapidly repeatable, and offers all of the significant advantages of a murine surgical 
model, including access to genetic manipulative techniques, low cost relative to large animals, and ease of use. Our group has developed extensive experience 
with use of this model to assess a number of organ-specific outcomes in AKI.14,15

A powerful model for perioperative and critical care related acute kidney injury is presented. Using whole body hypoperfusion induced by cardiac arrest it is possible to nearly replicate the histologic and functional changes of clinical AKI.

Normothermen Herzstillstand und Herz-Lungen: Ein Maus-Modell der Ischämie-Reperfusionsschaden

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused ...

Roux-en-Y Gastric Bypass Operation in Rats

Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality benefit is bariatric surgery1,2. Consequently, there has been a steady rise in the number of bariatric operations done worldwide in recent years with the Roux-en-Y gastric bypass (gastric bypass) being the most commonly performed operation3. Against this background, it is important to understand the physiological mechanisms by which gastric bypass induces and maintains body weight loss. These mechanisms are yet not fully understood, but may include reduced hunger and increased satiation4,5, increased energy expenditure6,7, altered preference for food high in fat and sugar8,9, altered salt and water handling of the kidney10 as well as alterations in gut microbiota11. Such changes seen after gastric bypass may at least partly stem from how the surgery alters the hormonal milieu because gastric bypass increases the postprandial release of peptide-YY (PYY) and glucagon-like-peptide-1 (GLP-1), hormones that are released by the gut in the presence of nutrients and that reduce eating12.
During the last two decades numerous studies using rats have been carried out to further investigate physiological changes after gastric bypass. The gastric bypass rat model has proven to be a valuable experimental tool not least as it closely mimics the time profile and magnitude of human weight loss, but also allows researchers to control and manipulate critical anatomic and physiologic factors including the use of appropriate controls. Consequently, there is a wide array of rat gastric bypass models available in the literature reviewed elsewhere in more detail 13-15. The description of the exact surgical technique of these models varies widely and differs e.g. in terms of pouch size, limb lengths, and the preservation of the vagal nerve. If reported, mortality rates seem to range from 0 to 35%15. Furthermore, surgery has been carried out almost exclusively in male rats of different strains and ages. Pre- and postoperative diets also varied significantly.
Technical and experimental variations in published gastric bypass rat models complicate the comparison and identification of potential physiological mechanisms involved in gastric bypass. There is no clear evidence that any of these models is superior, but there is an emerging need for standardization of the procedure to achieve consistent and comparable data. This article therefore aims to summarize and discuss technical and experimental details of our previously validated and published gastric bypass rat model.

Numerous studies using gastric bypass rat models have been recently conducted to uncover the underlying physiological mechanisms of Roux-en-Y gastric bypass operations. This article aims to demonstrate and discuss the technical and experimental details of our published gastric bypass rat model to understand advantages and limitations of this experimental tool.

Roux-en-Y-Magenbypass Operation in Ratten

Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality ...

A Novel Surgical Approach for Intratracheal Administration of Bioactive Agents in a Fetal Mouse Model

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and acquired diseases. Apart from congenital or inherited abnormalities with the requirement for long-term expression of the delivered gene, several non-inherited perinatal conditions, where short-term gene expression or pharmacological intervention is sufficient to achieve therapeutic effects, are considered as potential future indications for this kind of approach. Candidate diseases for the application of short-term prenatal therapy could be the transient neonatal deficiency of surfactant protein B causing neonatal respiratory distress syndrome1,2 or hyperoxic injuries of the neonatal lung3. Candidate diseases for permanent therapeutic correction are Cystic Fibrosis (CF)4, genetic variants of surfactant deficiencies5 and &alpha;1-antitrypsin deficiency6.
Generally, an important advantage of prenatal gene therapy is the ability to start therapeutic intervention early in development, at or even prior to clinical manifestations in the patient, thus preventing irreparable damage to the individual. In addition, fetal organs have an increased cell proliferation rate as compared to adult organs, which could allow a more efficient gene or stem cell transfer into the fetus. Furthermore, in utero gene delivery is performed when the individual's immune system is not completely mature. Therefore, transplantation of heterologous cells or supplementation of a non-functional or absent protein with a correct version should not cause immune sensitization to the cell, vector or transgene product, which has recently been proven to be the case with both cellular and genetic therapies7.
In the present study, we investigated the potential to directly target the fetal trachea in a mouse model. This procedure is in use in larger animal models such as rabbits and sheep8, and even in a clinical setting9, but has to date not been performed before in a mouse model. When studying the potential of fetal gene therapy for genetic diseases such as CF, the mouse model is very useful as a first proof-of-concept because of the wide availability of different transgenic mouse strains, the well documented embryogenesis and fetal development, less stringent ethical regulations, short gestation and the large litter size.
Different access routes have been described to target the fetal rodent lung, including intra-amniotic injection10-12, (ultrasound-guided) intrapulmonary injection13,14 and intravenous administration into the yolk sac vessels15,16 or umbilical vein17. Our novel surgical procedure enables researchers to inject the agent of choice directly into the fetal mouse trachea which allows for a more efficient delivery to the airways than existing techniques18.

We developed a novel surgical approach for intratracheal administration of bioactive agents into the mouse fetus. The delivery route is more efficient in targeting the fetal mouse lungs than the commonly used intra-amniotic injection. This procedure has to date not been described in a mouse model.

A Novel Surgical Ansatz intratracheale Verabreichung von Wirkstoffen in einem Fetal Mouse Model

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and ...

Evaluation of a Novel Laser-assisted Coronary Anastomotic Connector - the Trinity Clip - in a Porcine Off-pump Bypass Model

To simplify and facilitate beating heart (i.e., off-pump), minimally invasive coronary artery bypass surgery, a new coronary anastomotic connector, the Trinity Clip, is developed based on the excimer laser-assisted nonocclusive anastomosis technique. The Trinity Clip connector enables simplified, sutureless, and nonocclusive connection of the graft to the coronary artery, and an excimer laser catheter laser-punches the opening of the anastomosis. Consequently, owing to the complete nonocclusive anastomosis construction, coronary conditioning (i.e., occluding or shunting) is not necessary, in contrast to the conventional anastomotic technique, hence simplifying the off-pump bypass procedure. Prior to clinical application in coronary artery bypass grafting, the safety and quality of this novel connector will be evaluated in a long-term experimental porcine off-pump coronary artery bypass (OPCAB) study. In this paper, we describe how to evaluate the coronary anastomosis in the porcine OPCAB model using various techniques to assess its quality. Representative results are summarized and visually demonstrated.

This paper describes a novel nonocclusive coronary anastomotic connector in a porcine off-pump coronary artery bypass (OPCAB) model. This easy-to-use coronary connector has intrinsic potential to facilitate minimally invasive OPCAB surgery.

Evaluierung eines neuartigen Lasergestützte Koronare Anastomotische Steckverbinder - Dreifaltigkeit Clip - in einem Schweine Off-Pumpe Bypass-Modell

To simplify and facilitate beating heart (i.e., off-pump), minimally invasive coronary artery bypass surgery, a new coronary anastomotic connector, the ...

A Novel Approach for the Administration of Medications and Fluids in Emergency Scenarios and Settings

The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or intraosseous routes, but in many patients, particularly in the emergency or critical care settings, these routes are often unavailable or time-consuming to access. A novel device is now available that offers an easy route for administration of medications or fluids via rectal mucosal absorption (also referred to as proctoclysis in the case of fluid administration and subsequent absorption). Although originally intended for the palliative care market, the utility of this device in the emergency setting has recently been described. Specifically, reports of patients being treated for dehydration, alcohol withdrawal, vomiting, fever, myocardial infarction, hyperthyroidism, and cardiac arrest have shown success with administration of a wide variety of medications or fluids (including water, aspirin, lorazepam, ondansetron, acetaminophen, methimazole, and buspirone). Device placement is straightforward, and based on the observation of expected effects from the medication administrations, absorption is rapid. The rapidity of absorption kinetics are further demonstrated in a recent report of the measurement of phenobarbital pharmacokinetics. We describe here the placement and use of this device, and demonstrate methods of pharmacokinetic measurements of medications administered by this method.

This study presents a novel device that offers an easy route to quickly provide medications and fluids in patients with limited or difficult IV access. This small-diameter device is placed in the distal third of the rectum, allowing for ongoing medication and fluids administration.

Ein neuer Ansatz für die Verabreichung von Medikamenten und Flüssigkeiten in Notfallszenarien und Einstellungen

The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or ...

Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. Research models for bypass graft failure are essential for a better understanding of pathobiological and pathophysiological processes during graft patency loss. Large animal models, such as pigs or sheep, resemble human anatomical structures but require special facilities and equipment. This video describes a rat vein interposition model to investigate vein graft patency loss. Rats are inexpensive and easy to handle. Compared to mouse models, the convenient size of rats permits better operability and enables a sufficient amount of material to be obtained for further diverse analysis. In brief, the inferior epigastric vein of a donor rat is harvested and used to replace a segment of the femoral artery. Anastomosis is conducted via single stitches and sealed with fibrin glue. Graft patency can be monitored non-invasively using duplex sonography. Myointimal hyperplasia, which is the main cause for graft patency loss, develops progressively over time and can be calculated from histological cross sections.

This video demonstrates a model to study the development of myointimal hyperplasia after venous interposition surgery in rats.

Vein Interposition Modell: ein geeignetes Modell zur Untersuchung Bypass Graft Durchgängigkeit

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

Messung der isometrischen Kontraktilität der Maus mesenterialen Arterie mit Draht Myographie

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...