Yazarlar hiçbir katkıda bulunanlar var.

tüm hayvan deneyleri Alman hayvan koruma kanunu (TierSchG) uygun olarak gerçekleştirilen ve yerel hayvan refahı Komitesi (alt Saksonya eyalet ofis için tüketicinin korunması ve gıda güvenliği, iletişim kuralı tarafından kabul edildi TSA 14/1556). Fare bu model için uygun en az kilo 25 yaşında g.
 1. Preoperatif hazırlıklar Not: tüm yordamları temiz, steril olmayan koşullar altında autoclaved araçlarıyla yapılmaktadır.
<ol><li>Yer 50-60 8 cm uzun propilen liflerin paralel bir tüp oyuk ve her iki tarafta bir T-adaptör ile bağlayın. Yapıştırıcı ile içi boş elyaf ve T-adaptör dış dalı arasındaki boşluğu doldurmak.
	<ol><li>İzin ver en az 24 tutkal sertleşmesine s. Dışarı uzanan T-standart bir microtome kullanarak bağdaştırıcısından boş lifler kesme ve bağlantı yerleri silikon tüp kenara.</li>
	</ol></li> <li>Bir 27 G metal iğneden (26 G branule) 2 Fr poliüretan kanül yerleştirin. Cerrahi bir bıçak kullanın ve mikro-makas (8-12 X büyütme) 3-4 fenestrations yaklaşık 0.15 cm her sağlamak için kanül distal üçüncü içinde en uygun Venöz yapmak için mikroskop altında geri akışı.
	<ol><li>Kaldır tamamlandığında tel. Pamuk temizleme bezi künt disseksiyon ve retraksiyon yapıları için kullanın. Doku su kaybı önlemek için aşırı sıvı emmek için gazlı bez temizleme bezi (5 x 5 cm 2) kullanın.</li>
	</ol></li> <li>Astar birim hazırlamak. Tamamlamak için heparin çözüm ve % 2.5 v/v % 8.4 çözümünün tamponlama için NaHCO 3 priming mL başına 30 IU ekleyin. Bu çözüm kullanana kadar 4 ° C'de depolayın.</li>
	<li>Doldurmak KPB devre (yani, pompa, hava avcı, boru ve her iki Kanüller) 850 µL astar eriyik yolu ile Venöz kanül ile. Hayvan cannulation için hazır olması ne kadar KPB dolaşan dolu bir kez tutmak.</li>
</ol> 2. Hayvan anestezi anestezi yönetmek, hayvan indüksiyon odasında altında %2.5 yer için <ol><li>v/v isoflurane/oksijen karışımı. Uygun anestezi tarafından değerlendirilmesi pedal çekilme refleks, kuyruk tutam refleks ve göz kırpma refleksi onaylayın. Göz kuruluğu önlemek için veteriner göz merhem uygulamak.</li>
	<li>Sıcaklık düzenleyen fonksiyonu ile ısınma bir yastık üzerinde hayvan yer. Rektal eklenen ve veri toplama sistemine bağlı bir sonda ile vücut ısısını ölçmek.</li>
	Tam anestezi elde sonra <li>bir 20 G plastik braunule kullanarak, sözlü olarak ekleme ve görsel kontrol altında nefes borusu içine iterek hayvan orotracheally Tüp takacağım. Mekanik havalandırma bir fare vantilatöre bağlı bir isoflurane Buharlaştırıcı kullanarak başlatın. 250-350 µL gelgit hacmi elde havalandırma hayvan ağırlık bağlı olarak ayarlayın.</li>
	Tam analjezi sağlamak için <li>5 mg/kg vücut ağırlığı hayvan carprofen subkutan enjekte et. Bu isoflurane konsantrasyonu % oksijen 1.3-2.5 arasında tutulması önerilir. Isoflurane konsantrasyon el ile ayarlanabilir prosedür Sahne bağlı olarak.</li>
</ol> 3. Cerrahi <ol><li>sonra tam anestezi ve entübasyon, Ensizyon deri boyun için keskin iyi makas ile gerçekleştirmek, ayrı bir künt moda kaslarda ve Sağ juguler ven ve sol Karotis arter açığa. Hazırlık sırasında küçük gemiler en az kan kaybı emin olmak için iki kutuplu forseps için bağlı bir veteriner coagulator kullanarak koagüle.</li>
	<li>Şah damarları hazırlanması sonra cranially sol ortak Karotid arter ile 8-0 ipek sütür kullanma, çatallanma distal segment ligate.</li>
	<li>Kullanarak bir silikon konektörü (0,5 mm kimliği, 1 mm OD), yer 8-0 ipek sütür kayma Arteryel girişi boru için 27 G kanül distal sonu knot, arter ve INSERT Karotid arter içine kanül ucu proksimal segmentin bağlan.</li>
	<li>3-4 mm proksimale aort bırakır böylece kanül ucu kanül ucu doğru yerleşimini sonra ilerlemek. 8-0 ipek deniz mili ile güvenli hale getirme kanül ucu düzeltmek.</li>
	<li>Kullanma mikrocerrahi forseps ve makas, künt ve keskin diseksiyon gerçekleştirmek, Sağ juguler ven yanal için köprücük, yakın boyun kas dokusunun künt hazırlık tarafından ortaya çıkarmak ve distal uç ve bir 8-0 8-0 ipek düğüm yerleştirin döngü proksimal ucunda.</li>
	<li>Sonra ligasyonu juguler ven distal ucunun Sağ juguler ven ve sağ Kulakçık doğru ilerleme Venöz kanül ucu yeri ve ipek düğüm kullanarak güvenli. En uygun Venöz dönüş için Venöz uç sağ ventrikül ilerlemek gerekli olabilir.</li>
	<li>Doğru kanül pozisyonu elde sonra sistemik heparinization heparin juguler ven içine direkt intravenöz enjeksiyon yolu ile hayvan vücut ağırlığı gram başına 2.5 IU ekleyerek devam.</li>
	<li>Gerçek zamanlı invaziv basınç kontrolü için sol femoral arter cannulate. Kasık bölgesinde ortaya çıkarmak ve yavaşça femoral ven ve 25 X büyütme altında femoral sinir ortak femoral arter ayırın.
	<ol><li>Ligate distal femoral arter parçası. Geçici olarak bir kayma-düğüm ile proksimal bölümü doldurmak ve mikro-forseps kullanarak anterior duvarda küçük bir insizyon attım olun.</li>
		<li>Daha sonra 1 Fr poliüretan kanül femoral arter yerleştirin ve 10-0 sütür ipek ile sabitleyin. Bu kanül kan gaz analiz için kan örnekleri ayıklamak için kullanılır.</li>
	</ol></li> <li>Sonra başarılı yerleşim Arteryel ve venöz Kanüller, Kardiyopulmoner bypass pompayı çevirerek başlatmak. KPB ile başlayan entübasyon üzerinden yaklaşık 45 dk. Pompa hızı artırarak bir akış hızı 0.5 mL/dk, sistemik basınç ölçümleri ve artış kan akımı tam akış (4-6 mL/dak) için 2 dk içinde bağlı olarak kullanarak başlangıç zamanıdır.</li>
	<li>Tam kontrolü altında gerçekleştirmek ağız sapı başlayan ve 5 mm Kaudal yönde gidiyor keskin makas kullanarak üst bir yöntemdir. Hemen kanama önlemek için göğüs kenarları koagüle. Aort kranial yönde şu Şah damarı çekerek ortaya çıkarmak.</li>
	<li>İçin en uygun denetimi, çepeçevre aort timus ve çevresindeki doku sıkma kolaylaştırmak için ücretsiz. Artan aort çevresine bir 8-0 ipek daire yerleştirin. Minikardiyopleji yöntemi için çapraz klemp yerleştirmek için daha iyi maruz için kranial yönde ipek döngü artan aort çekin.</li>
</ol> 4. Kardiyopulmoner baypas gerektirmeyen ve kan gazı analizi <ol><li>kan gaz analizi (BGA) için cam kılcal tüpler femoral arter kateter yolu ile 60-90 µL arteryel kan toplamak için kullanın.
	<ol><li>Silikon tüp üzerinde küçük bir mengene kullanın ve sonda gelen boru ayır. Serbest yavaş yavaş kelepçe Kılcal Boru kontrollü dolum izin vermek için baskıyı.</li>
		<li>Kateter silikon tüp takın. Kan gazı analyzer aşağıdaki zaman noktalarda ölçümler için kılcal tüpler yerleştirin: 10 dakika sonra KPB inisiyasyon havalandırma (BGA1) ile 25 min CPB ve solunum durması (BGA2) 15 dk sonra 40 dk CPB ve solunum durması (BGA3) 30 dk sonra KPB 55 dk., 45 dk solunum ve kalp durması (BGA4) 20 dk sonra</li></ol></li> <li>istikrarlı KPB akışı, baş altında Havalandırma durdurma tarafından te solunum tutuklama.</li>
	<li>Havalandırma sona ermesi sonra ısınma yastık için 28 ºC ayarlayın ve topikal hayvan 28 ºC vücut ısısı solunum durması soğuk salin batırılmış gazlı bez kullanarak ilk 20 dk içinde için soğutma başlatın.</li>
	<li>Kez bir vücut sıcaklığı 28 ºC elde ve toplam solunum tutuklama 30 dak sonra 0.3 mL %7,45 KCl çözeltisi Minikardiyopleji yöntemi başlatmak için KPB devre yönetmek.</li>
	<li>İçin aort damarı sıkma çapraz, daha önce yerleştirilmiş ipek döngü (Adım 3.10) daha iyi maruz kranial yönde çekin ve bir mikro-serrefine kelepçe aort artan parçası yerleştirin.</li>
	<li>Toplam 60 dk solunum ve kalp durması 30 dk gerçekleştirin. Mikro-serrefine kelepçe reperfüzyon kalp başlatmak için artan aort kaldırın. Aynı anda, yeniden havalandırın ve hayvan 37 sıcak ° C.</li>
	<li>Reperfüzyon tamamladıktan ve hayvan normothermia, ulaştı sonra KPB pompası kapatarak sonlandırmak ve fizyolojik ölçümleri (örneğin vücut ısısı, EKG ve invaziv kan basıncı) 20 dakika süreyle izlemeye devam edin</li>
	<li>Deneme sonunda hayvan tam anestezi (%5 isoflurane) altında exsanguinate ve toplamak kan ve organları daha fazla analiz 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. 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Yazarlar ifşa gerek yok.

Bir tam işlev gören klinik olarak ilgili model KPB bir fare geliştirdik. Kalp-damar hastalıkları olan fareler otuzdan fazla suşları ile bizim model geliştirme için KPB ile ilgili yeni potansiyel iletişim kuralları için bir başlangıç noktası olabilir. Ayrıca, fare özgü reaktifler ve nakavt-out fareler bolluk, nedeniyle bu model sadece KPB geçerli fare modelinin yerini alamaz ama moleküler mekanizmaları KPB ile ilgili organ hasarı dahil diseksiyon kolaylaştıracaktır. Bugüne kadar KPB mikrocerrahi...

Klinik içine Kardiyopulmoner bypass (KPB) giriş beri kalp cerrahisi1' de önemli bir rol oynamıştır. Modern kardiyak cerrahi, uzamış CPB süresi geniş aort rekonstrüksiyonu ve kombine yordamları gerçekleştirmek için önemlidir. Teknolojik gelişmeler çok büyük olmasına rağmen extracorporal kan dolaşımı ile içi - ve ameliyat sonrası sistemik ilişkili ve yerel organ zarar2,3.
Büyük hayvan modeller fizyolojik süreçleri4,5KPB rolünü araştırmak için geliştirilmiştir. Her ne kadar bu modeller KPB bazıları içgörü komplikasyonlar ilgili sağlamış, onlar son derece pahalı ve moleküler araçları (örneğin, antikorlar) çok sınırlıdır. Daha maliyet etkin bir alternatif küçük hayvanlarda geliştirmiştir. Gelişimleri beri fare ve tavşan5,6,7,8,9KPB modelinde en iyi duruma getirmek için birden fazla çalışmalar yapılmıştır. Bu modeller patofizyolojik hastalığı süreçleri ölçümleri için iyi bir temel sağlamak; Ancak, onlar hala hücresel ve humoral İmmünoloji ilgili antikorlar ve Kimyasalları eksikliği nedeniyle araştırmak yetersizdir. Bu araştırma Bu alan içindeki rollerine bozar.
Biz son zamanlarda KPB bir fare modeli geliştirdik. Genetik olarak değiştirilmiş fare ve fare özgü reaktifler çok çeşitli nedeniyle, fare modelleri genel olarak tercih ettiği fizyolojik, moleküler ve immünolojik araştırma10,11modeli vardır. Bu nedenle, birçok fare suşların klinik olarak ilgili hastalıklar12,13ile kullanılabilir olduğundan modelimiz KPB çalışma ile ilgili olarak çeşitli comorbidities kolaylaştıracaktır. Buna göre bu kağıt, ayrıntılı olarak KPB fareler nasıl gerçekleştirileceği açıklanır. Oksijen ve hemodinamik parametreler derin solunum ve dolaşım tutuklandıktan sonra yakından izlenir.

<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

Uzun süreli Kardiyopulmoner bypass sırasında kalp müdahaleler daha gerekli hale geldikçe, artan bir klinik talep yordam en iyi duruma getirme ve uzun süreli extracorporal dolaşımdan kaynaklanan organ hasarı en aza indirmek için ortaya çıkar. Bu kağıt amacı tamamen fonksiyonel ve klinik manken Kardiyopulmoner baypas gerektirmeyen bir Mouse göstermekti. Biz cihaz tasarımı, perfüzyon devre optimizasyonu ve mikrocerrahi teknikleri raporu. Bu model birden çok kan çizimi için ihtiyaç nedeniyle hayatta kalma ile uyumlu değildir akut bir modeldir. Fareler için (örneğin, işaretçileri, altını gizleme vb.)araçları yelpazesi nedeniyle, bu modeli moleküler mekanizmaları üzerindeki araştırmasını organ hasarı ve Kardiyopulmoner bypass ile ilgili olarak diğer etkisini kolaylaştıracak comorbidities.

Bu iletişim kuralı perfüzyon devre, cerrahi işlemler açıklanır ve fizyolojik parametrelerinin bir fare CPB sırasında izleme. Yeterince yetenekli bir microsurgeon tarafından gerçekleştirilen, sonuçları sürekli ve tekrarlanarak alınır.
Ortalama arter basıncı yeterli doku perfüzyon korumak için her zaman KPB kan akışını ayarlama ve ilave hacmi ekleyerek 40 ve 60 mmHg arasında tutulur. Hayvan, birim durumu ...

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

Bu kağıt, Kardiyopulmoner bypass farelerde gerçekleştirmek açıklar. Bu yeni modeli moleküler mekanizmaları organ hasarı dahil incelenmesi kolaylaştıracaktır.

Kardiyopulmoner baypas gerektirmeyen bir fare modeli: yeni bir yaklaşım

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

Research

JoVE Journal

Medicine

10.8K Görüntüleme.  Hannover Medical School. Bu kağıt, Kardiyopulmoner bypass farelerde gerçekleştirmek açıklar. Bu yeni modeli moleküler mekanizmaları organ hasarı dahil incelenmesi kolaylaştıracaktır.

Video: 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.

Damar Tıkanıklığı Eğitim İçerme Vücut Miyozit: Yeni Bir Tedavi Yaklaşımı

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

Tıp

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.

Bronş Thermoplasty: Şiddetli Astım Yeni Bir Tedavi Yaklaşımı

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.

Oral Skuamöz Hücre Karsinomu Ortotopik Fare Modeli Tümör Hücre Invasion Multi-foton Görüntüleme

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.

Normotermik Kardiyak Arrest ve Kardiyopulmoner Resusitasyon: İskemi-Reperfüzyon Hasarı Fare Modeli

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.

Sıçanlarda Roux-en-Y Gastrik Bypass Operasyonu

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.

Bir Fetal Fare Modelinde Biyoaktif Ajan intratrakeal Yönetimi İçin Yeni Bir Cerrahi Yaklaşım

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.

Trinity Clip - - Roman Lazer destekli Koroner Anastomoz Connector Değerlendirilmesi Domuz Off-pompa Bypass Modeli

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.

Acil Senaryoları ve Ayarlar İlaçlar ve Sıvılar İdaresi Yeni Bir Yaklaşım

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.

Ven interpozisyonu Model: baypas açıklığının Eğitim için uygun bir model

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.

İzometrik Contractility ölçüm tel Myography kullanarak fare mezenterik arter

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