作者没有致谢。

所有动物实验都是遵照德国动物保护法 (TierSchG) 进行的, 并得到当地动物福利委员会 (下萨克森国家消费者保护和食品安全办公室的批准, 协议TSA 14/1556)。适合该模型的小鼠的最小重量为25克. 
 1. 术前准备 注意: 所有的程序都在清洁、消毒的条件下进行, 并带有蒸压仪器. 
<ol> <li> 将 50-60 8 厘米长的丙烯中空纤维平行放置在试管中, 并与两侧的 T 型适配器连接。用胶水填充空心纤维和 T 型适配器的外部分支之间的空间. 
	<ol> <li> 允许至少24小时以使胶水变硬。使用标准切片切断从 T 型适配器延伸出来的中空纤维, 并将硅胶管拉到连接点. </li>
	</ol> </li> <li> 将27克金属针 (从 26G branule) 和 #160 插入一个2法郎的聚氨酯套管。使用显微镜下的手术刀片和微剪刀 (8-12X 放大), 使三至四 fenestrations, 每在远端三分之一的套管, 以确保最佳的静脉回流流量. 
	<ol> <li> 在完成时移除导线。用棉签对结构进行钝夹层和缩回。使用纱布拭子 (5 x 5 cm 2 ) 来吸收多余的液体, 以防止组织脱水. </li>
	</ol> </li> <li> 准备启动卷。为完成, 增加30单位肝素每毫升启动液和2.5% 伏/v 的8.4% 解决方案的 NaHCO 3 的缓冲。将此解决方案存储在4和 #176; C 直到使用. </li>
	<li> 填入 CPB 电路 (如: , 泵, 空气捕手, 油管和两个套管) 与850和 #181; 通过静脉导管启动溶液。一旦填充, 保持体外循环循环, 直到动物准备好插管. </li>
</ol> 2。动物麻醉 <ol> <li> 要进行麻醉, 请将该动物置于2.5% 伏/伏异氟烷/氧混合物的诱导室中。通过评估踏板撤退反射, 尾部捏反射, 和眼睛眨眼反射来确认正确的麻醉。应用兽医眼膏避免眼部干燥. </li>
	<li> 将动物置于温度调节功能的暖垫上。使用插入直肠的探头测量体温, 并连接到数据采集系统. </li>
	<li> 在完全麻醉完成后, 用20G 塑料 braunule 将动物 orotracheally 插管, 将其插入口腔, 并在视觉控制下将其推入气管。使用与鼠标呼吸器连接的异氟醚蒸发器启动机械通气。根据动物的重量, 调整通风, 使潮气量 250-350 和 #181; 我实现了. </li>
	<li> 确保完全镇痛, 注射5毫克/千克动物体重卡洛芬皮下注射。建议将异氟醚浓度保持在 1.3-2.5% 之间的氧。异氟醚浓度可根据手术阶段手动调节. </li>
</ol> 3。外科手术程序 <ol> <li> 在完全麻醉和插管完成后, 用锋利的细剪刀、以钝的方式分离肌肉、并暴露右颈静脉和左颈动脉, 在颈部进行中线皮肤切口。在制备过程中, 使用与双极性钳连接的兽医凝固将小血管凝固, 以确保最小的失血. </li>
	<li> 经颈静脉血管制备后, cranially 结扎左颈总动脉远端段使用8-0 丝缝合线进行分岔. </li>
	<li> 使用硅胶连接器 (0.5 mm ID, 1 mm 外径) 将27克套管的远端连接到动脉流入管上, 在动脉的近段处放置8-0 丝缝线滑动节, 并将套管尖端插入颈动脉. </li>
	<li> 在正确放置套管尖端后, 将套管尖端向前推进 3-4 毫米, 使其下部向主动脉弓。用8-0 丝结固定好套管的尖端. </li>
	<li> 使用显微外科钳和剪刀, 进行钝和尖锐的解剖, 暴露右颈静脉通过钝性准备组织侧向胸锁乳突肌, 接近锁骨, 并放置一个8-0 丝结在远端和一个8-0在近端循环. </li>
	<li> 结扎颈静脉远端后, 将静脉导管尖端放置在右颈静脉, 朝向右心房进展, 并使用丝结固定。为了获得最佳的静脉回流, 可能需要将静脉尖端进入右心室. </li>
	<li> 一旦达到正确的插管位置, 通过直接静脉注射到颈静脉内, 将每克动物体重增加2.5 的肝素, 进行全身肝. </li>
	<li> 用于 real-time 侵入性压力监测, cannulate 左股动脉。在25X 放大倍数下, 暴露腹股沟区, 轻轻地将股股静脉和股神经分开. 
	<ol> <li> 结扎股动脉远端的部分。用微钳在前壁上临时咬合, 用滑结做一个小切口. </li>
		<li> 之后, 在股动脉中插入一根1法郎的聚氨酯套管, 用丝10-0 缝线固定。本套管用于抽取血液样本进行血气分析. </li>
	</ol> </li> <li> 在成功放置动脉和静脉套管后, 通过打开泵启动体外循环。从插管到 CPB 开始的时间大约是45分钟, 开始使用0.5 毫升/分钟的流速, 这取决于系统压力测量, 并增加泵的速度在2分钟内的全流量 (4-6 毫升/分钟) 的血流量. </li>
	<li> 在完全监视下, 使用锐剪刀从柄开始执行上部胸骨, 并在尾部方向上5毫米。立即凝固胸骨边缘以避免流血。通过在颅方向上拉右颈动脉来暴露主动脉弓. </li>
	<li> 为了获得最佳控制, 圆周从胸腺和周围组织中释放主动脉弓, 以便于夹紧。在升主动脉周围放置一个8-0 丝环。要将十字钳放置在心脏停搏液中, 在颅骨方向上拉上丝环, 以更好地暴露升主动脉. </li>
</ol> 4。体外循环与血气分析 <ol> 用于血气分析的 <li> , 使用玻璃毛细管收集 60-90 和 #181; 通过股动脉导管进行动脉血流. 
	<ol> <li> 在硅胶导管上使用一个小钳, 并将导管与导尿管分离。在钳上缓慢释放压力, 使毛细管控制充填. </li>
		<li> 将硅胶管重新连接到导管。将毛细管插入血气分析仪, 用于测量在以下时间点: 10 分钟后启动 CPB 通气 (BGA1)25分钟的 cpb 和15分钟的呼吸骤停 (BGA2) 后40分钟 cpb 和30分钟的呼吸骤停 (BGA3) 后55分钟, 45 分钟的呼吸, 20 分钟心跳骤停 (BGA4) </li> </ol> </li> <li> 在稳定的 CPB 流下, initia通过停止通气来呼吸骤停. </li>
	<li> 通风结束后, 将暖垫设置为28和 #186; c 和 #160; 开始局部冷却的动物到28和 #186; c 体温在第一20分钟内使用纱布浸泡在生理盐水中的呼吸骤停. </li>
	<li> 一旦体温为28和 #186; C 是达到, 并在总共30分钟的呼吸骤停后, 管理0.3 毫升的7.45% 氯化钾溶液进入 CPB 回路, 启动心脏停搏液. </li>
	<li> 对于主动脉的交叉夹紧, 将先前放置的丝环 (步骤 3.10) 置于颅骨方向, 以便更好地曝光, 并在主动脉的上升部分放置微 serrefine 钳. </li>
	<li> 共执行60分钟呼吸骤停和30分钟心跳骤停。从提升主动脉中取出微 serrefine 钳, 开始心脏再灌注。同时, re-ventilate 和温暖的动物到37和 #176; C. </li>
	<li> 在再灌注完成后, 动物已达到常温, 关闭泵, 并继续监测生理测量 ( 如 体温、心电图和侵入性血压) 20 分钟, 终止 CPB。
	<li> 在实验结束时, 血完全麻醉下的动物 (5% 异氟醚), 并收集血液和器官作进一步分析 14 . </li>
</ol>

<ol>
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作者没有什么可透露的。

我们已经开发了一个完全功能性的临床相关模型的 CPB 在鼠标。由于有三十多株患有心血管疾病的小鼠, 我们的模型可以成为与 CPB 相关的新的前瞻性协议的发展起点。此外, 由于大量的鼠标特异试剂和 knockout-out 小鼠, 该模型不仅可以取代目前的大鼠 cpb 模型, 但将有助于解剖的分子机制参与与 cpb 相关的器官损害。到目前为止, CPB 还没有应用于小鼠, 因为在插管技术的显微外科挑战, 以及技术挑战, ?...

自体外循环 (cpb) 进入临床后, 它在心脏手术中起了重要作用1。在现代心脏手术中, 延长的 CPB 时间对进行广泛的主动脉重建和联合手术是必不可少的。尽管技术进步巨大, 外循环的使用与术后全身和局部脏器损伤有关2,3。
开发了大型动物模型来研究 CPB 在生理过程中的作用4,5。虽然这些模型提供了一些对 CPB 相关并发症的洞察力, 但它们是非常昂贵的, 分子工具 (例如, 抗体) 是非常有限的。一个更具成本效益的替代品已经在小动物身上得到了发展。自其发展以来, 进行了多项研究, 以优化大鼠和家兔的 CPB 模型5,6,7,8,9。这些模型为病理生理学疾病过程的测量提供了良好的基础;然而, 由于缺乏相关的抗体和试剂, 它们仍然不足以研究细胞和体液免疫学。这削弱了他们在这个研究领域的作用。
我们最近开发了一个鼠 CPB 模型。由于各种鼠标特异试剂和转基因小鼠, 小鼠模型一般是生理、分子和免疫学研究的选择模型10,11。因此, 我们的模型将促进研究 CPB 与各种并存, 因为有许多小鼠菌株可与临床相关的疾病12,13。因此, 本文详细介绍了如何在小鼠体内进行 CPB。在深部呼吸和循环停止后, 对氧和血流动力学参数进行严密监测。

<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

随着长期体外循环在心脏介入过程中变得越来越重要, 临床需求增加, 以进行程序优化, 并最大限度地减少因长期外循环而造成的器官损害。本文的目的是演示一个完整的功能和临床相关模型的体外循环在小鼠。我们报告的设备设计, 灌注电路优化, 和显微外科技术。该模型是一个急性模型, 这是不相容的生存, 由于需要多血图。由于可用于小鼠的工具范围 (例如、标记、敲除、等), 该模型将有助于研究器官损伤的分子机制和体外循环对其他并存.

本协议描述了在鼠 CPB 过程中的灌注回路、手术过程和生理参数的监测。当由一个充分熟练的 microsurgeon, 结果是一致和性获得。
为了保持足够的组织灌注, 平均动脉压力始终保持在40和60柱通过调整 CPB 血流量和增加额外的体积。根据动物的重量, 它的体积状况和体温, 外血流维持在 2.3-6.5 毫升/分钟. 在实验过程中, 通过增加0.1 毫...

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

本文介绍了如何在小鼠体内进行体外循环手术。这种新型模型将有助于研究器官损伤的分子机制。

小鼠体外循环模型: 一种新方法

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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Research

JoVE Journal

Medicine

10.8K 次观看.  Hannover Medical School. 本文介绍了如何在小鼠体内进行体外循环手术。这种新型模型将有助于研究器官损伤的分子机制。

视频: 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.

血管闭塞包涵体肌炎培训：一种新的治疗方法

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

科研

医学

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.

支气管Thermoplasty:严重哮喘的一种新的治疗方法

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.

多光子成像在口腔鳞状细胞癌原位小鼠模型的肿瘤细胞的侵袭

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.

常温心脏骤停和心肺复苏术:缺血再灌注损伤的小鼠模型

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.

空肠Roux-en-Y胃搭桥手术大鼠

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.

一种新的手术方法气管内注射生物活性剂在胎鼠模型

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.

评价一种新型激光辅助冠状动脉吻合口连接器 - 三位一体夹 - 在猪非体外循环旁路模式

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.

应急方案和设置药物和液体管理的新方法

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.

静脉介入型号:研究旁路移植通畅一个合适的模型

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.

用线 Myography 测定小鼠肠系膜动脉的等轴收缩力

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