This work was supported by the National Institutes of Health (NIH/NHLBI) [Grant no. HL114869] and the support from UTHSC to SM.

伦理学声明:此视频文章中提到的所有动物的程序进行了审查，并经动物护理和使用委员会（IACUC）在田纳西大学健康科学中心大学的认可。 注:整个手术过程中使用无菌器械显微外科。手术器械可以利用红外线消毒器在1500°F（815.6℃）的最佳的杀菌温度下进行灭菌。遥测能够但是重复使用，在动物插入之前确保根据生产商的指示和该导管的末端已被重新填充与由制造商提供的特殊凝胶灭菌整个发射机。 1.实验动物<ol><li>获得IACUC批准将要进行的所有实验。与机构IACUC咨询强烈建议对于此过程后，术后镇痛药的使用要求。 </li><li>保持动物在Climate受控室具有21℃，60％相对湿度，环境温度和自由摄取食物和水的12小时明暗周期。 注意:由于鼠标主体具有容纳遥测探针（近似直径为1厘米×2厘米长），它是优选使用重20克或更高的小鼠。 </li></ol> 2，麻醉和手术准备<ol><li>称量使用精密刻度鼠标并记录其重量。确保轻轻地，悄悄地处理动物。 </li><li>将动物进入感应室并关闭它。在0.5升/分钟设定氧流量，并在4设置的异氟烷浓度 - 5％。 </li><li>当鼠标失去知觉，将其放置在保持在36身体变暖板 - 37℃。保持通过用异氟烷组鼻锥麻醉在2％（保持流量在0.5升/分钟）。 </li><li>通过从颈部和叔背面去除毛发准备操作区域他通过应用脱毛膏颈部腹侧方面。 </li><li>手术擦洗（优碘溶液）用70％异丙醇的交替的3应用治疗切口部位。 </li></ol> 3.手术<ol><li>鼠标放置在仰卧位置。按捏脚检查反射，直到没有任何反应调整麻醉。使用手术刀鼠标的颈部下方约1厘米中线切口。在切割的左侧通过仔细分离下层的结缔组织皮肤创建皮下空间。 </li><li>翻转小鼠，并用手术刀做的约1.5厘米的皮肤切口在肩胛骨后面背侧左侧。创建沿着动物的侧翼大到足以容纳该设备的皮下囊袋。将发射器放入口袋。 </li><li>插入在后面的切口小止血钳和皮下操纵它朝向前领口。使用插入的-止血钳，轻轻抓住无毒聚乙烯管（4厘米长×1毫米的ID）。 <ol><li>通过在后面的隧道出横向切割拉止血背面直至管子从两个腹和背切口突出，从止血释放管。从背面，通过颈部插入导管传感器插入管隧道压力传感导管的尖端。从脖子前，拉并取出聚乙烯管，并使用金属夹关闭背侧切开。 </li></ol></li><li>仔细分离用无菌棉签涂抹下颌腺和使用弹性钩停留收回左上颚腺。用细尖弯钳，找到颈动脉沿气管左侧。保持手术部位放置和确保无菌的悬垂性不育。 <ol><li>小心隔离从周围组织容器并轻轻分开迷走神经（发白的颜色），它是沿着颈动脉从动脉远离。小心不要切断或损伤神经或动脉。 </li></ol></li><li>通过三片非吸收缝合线7-0的孤立的颈动脉部分下方。领带的颅缝以关闭血流量。拉缝线最接近胸骨暂时阻塞从主动脉血流量。 </li><li>请使用中间缝合线松散的结。这将用于固定导管的容器中。切一个小切口入颅，并使用微型剪刀胸骨缝合线之间的动脉。 </li><li>抓住特殊容器插管钳将导管，小心不要挤压导管，以防止探头凝胶损失。轻轻，抢用细尖弯曲的镊子镊子的动脉，检索导管，并通过小切口在容器插入。 </li><li>拧紧动脉周围的中间缝合节点，轻轻地推进猫海特。轻轻松开缝合线即最接近于胸骨和继续推进所述导管朝横向主动脉。 <ol><li>观察，让的导管需要多远插入近似指数导管的标志。一旦达到这一点，轻轻地拧紧两个较低和围绕导管上缝合。该导管是通过缝线结固定在颈动脉。 </li></ol></li><li>关闭与非吸收缝线5-0皮肤切口。一旦封闭，封闭与组织粘合剂切口。 </li></ol> 4.手术恢复和BP测量<ol><li>密切监测动物的正常姿势和行为的回报。期间由一名兽医人员24小时的手术后时期辖镇痛。 </li><li>一旦动物已恢复（5 - 7天手术后），在放置在遥测接收板顶部定期鼠笼分别容纳他们。 </li><li>打开植入TRansmitters"开"和"关"，通过使用磁性装置简要地定位成靠近所述动物从笼的外侧。 </li></ol>

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	<li>Danaei, G., 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+preventable+causes+of+death+in+the+United+States:+comparative+risk+assessment+of+dietary,+lifestyle,+and+metabolic+risk+factors.">The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors.</a> PLoS Med. 6 (4), e1000058 (2009).</li><li>Dornas, W. C., Silva, M. E. <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+for+the+study+of+arterial+hypertension.">Animal models for the study of arterial hypertension.</a> J Biosci. 36 (4), 731-737 (2011).</li><li>Henze, M., 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=Persistent+alterations+in+heart+rate+variability,+baroreflex+sensitivity,+and+anxiety-like+behaviors+during+development+of+heart+failure+in+the+rat.">Persistent alterations in heart rate variability, baroreflex sensitivity, and anxiety-like behaviors during development of heart failure in the rat.</a> Am J Physiol Heart Circ Physiol. 295 (1), H29-H38 (2008).</li><li>Hoffmann, D. S., 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=Chronic+tempol+prevents+hypertension,+proteinuria,+and+poor+feto-placental+outcomes+in+BPH/5+mouse+model+of+preeclampsia.">Chronic tempol prevents hypertension, proteinuria, and poor feto-placental outcomes in BPH/5 mouse model of preeclampsia.</a> Hypertension. 51 (4), 1058-1065 (2008).</li><li>Lerman, L. O., Chade, A. R., Sica, V., Napoli, C. <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+hypertension:+an+overview.">Animal models of hypertension: an overview.</a> J Lab Clin Med. 146 (3), 160-173 (2005).</li><li>Johns, C., Gavras, I., Handy, D. 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G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+simultaneous+measurement+of+mouse+systolic+arterial+blood+pressure+by+radiotelemetry+and+tail-cuff+methods.">Comparison of simultaneous measurement of mouse systolic arterial blood pressure by radiotelemetry and tail-cuff methods.</a> Am J Physiol Heart Circ Physiol. 286 (6), H2408-H2415 (2004).</li><li>Kurtz, T. W., 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=Recommendations+for+blood+pressure+measurement+in+humans+and+experimental+animals.+Part+2:+Blood+pressure+measurement+in+experimental+animals:+a+statement+for+professionals+from+the+subcommittee+of+professional+and+public+education+of+the+American+Heart+Association+council+on+high+blood+pressure+research.">Recommendations for blood pressure measurement in humans and experimental animals. Part 2: Blood pressure measurement in experimental animals: a statement for professionals from the subcommittee of professional and public education of the American Heart Association council on high blood pressure research.</a> Hypertension. 45 (2), 299-310 (2005).</li><li>Kurtz, T. 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The authors have nothing to disclose.

植入无线电遥测已经在过去十年显著改善;较小的探针尺寸使得所述植入物为动物创伤小，延长电池寿命有助于降低成本，并独立遥测频率消除接收器之间的串扰。遥测被认为是国家的最先进的方法为自由移动的动物而不使用约束，人际交往，或者麻醉由其他技术8,9所需的相关文物收集的各种生理参数。 然而，他的一些技术的缺点的用仪器和软件的初始成本相关联。发射机是脆弱的，容易受到损害，并在电池最终不会用完电并需要更换。虽然公司提供了翻新成本更低的损坏探头，成本可能仍然望而却步一些实验室。此外，该过程可以是技术上具有挑战性和实践要求达到可靠的血压测量。最后，还有相关的死亡率一些手术后，这在我们手中的5％左右。这可以大大增加，如果一个特定的处理，必须进行测试，或者如果一个基因操作损害鼠标健康。 以下关键因素是对过程的成功执行必不可少的:用无菌生理盐水保持组织水合整个过程。务必使用非常谨慎，发送器;避免由压力传感器保持它，因为这可能导致凝胶漏出或损坏变送器。当插入导管，配合中央的缝合带双结，因为不这样做将导致导管退出容器。导管的所需长度具有在颈动脉中插入可以按照在该particu使用的小鼠品系和重量改变LAR研究。因此，强烈建议运行一些初步试验来确定导管需要有多深要插入以避免主动脉的闭塞。最后，每日监测动物，并确保发射机上方的皮肤没有被拉伸或坏死。如果扩展的坏死或感染时，根据机构的政策安乐死的动物。

高血压是心血管疾病的主要危险因素之一，它无疑是一个重大的公共卫生问题无论是在发达国家和发展中国家1。实验性高血压几种动物模型已经发展到模仿像那些在人体2观察到的高血压反应。其中，门诊鼠标代表了一个很好的模型来研究的起源与高血压，允许在长期暴露于高血压的后果体内分析的进展。 血压（BP）的小鼠监测已经帮助研究人员解开参与生理学和疾病，如高血压和心脏衰竭3,4病理生理学几种机制。事实上，小鼠基因组的操纵允许代转基因或基因靶向模型合适的用于研究高血压5,6。然而，即使是温和的操作清醒小鼠的诱导兴奋，能够在数据采集过程可能引进假象，而使用镇静剂或镇静剂的深刻影响血压7。这些方面是特别重要的，必须在考虑尝试长期血压监测时作出。 有几种方法在小鼠中以记录血压，和目前最常用的技术之间的比较已在别处讨论8,9。然而，对于测量血压的AHA建议的结论是，BP的动脉内测量通常是优选的，因为它们直接测量血压在一段10长时间的能力。加之动脉压的直接测量无线电遥测是监测生理功能清醒和自由活动的实验动物，同时尽量减少压力和环保相关的人为9，11国家的最先进的方法。无线电遥测提供自动收集血压，心脏速率，体温和动物活动来自多个清醒动物的能力。 虽然这种方法已成为很受欢迎，在许多实验室，在小鼠无线电遥测植入可以技术上具有挑战性。这里，我们显示了一步一步的协议，阐释如何植入在小鼠一压力传感器。该技术涉及在小鼠体内的探针的皮下插入，引导导管到颈部并通过左侧颈动脉附近的主动脉弓转发。远程捕获的数据显示活在电脑显示器上。数据也存储为"离线"的分析。

<table>
	<tbody>
		<tr>
			<td>Small animal anesthesia system</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td></td>
			<td>low-Flow small animal anesthesia system</td>
		</tr>
		<tr>
			<td>Pad warmer and mouse termometer</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td></td>
			<td>allows monitoring body temperature,&#160; and homeothermic control in small animals.</td>
		</tr>
		<tr>
			<td>Binocular Microscope</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td>KSCXTS-1121</td>
			<td>binocular body with boom stand pole and top LED.</td>
		</tr>
		<tr>
			<td>Hemostat Forceps</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td>INS750451</td>
			<td>used to clamp blood vessels or tag sutures</td>
		</tr>
		<tr>
			<td>Small metal Clips, 7mm, Stainless Steel</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td>INS750344</td>
			<td>used for skin closure</td>
		</tr>
		<tr>
			<td>Betadine solution</td>
			<td>Purdue Products L.P., Stamford, CT, USA</td>
			<td>NDC-67618-150-01</td>
			<td>10% povidone iodine topical solution</td>
		</tr>
		<tr>
			<td>Normal saline solution</td>
			<td>Abott Laboratories</td>
			<td>04930-04-10</td>
			<td>Needed for preventing tissue from drying.</td>
		</tr>
		<tr>
			<td>Nair (Hair remover lotion)</td>
			<td></td>
			<td></td>
			<td>Needed for fur removal from the site of incision/surgery.</td>
		</tr>
		<tr>
			<td>Braide silk suture</td>
			<td>Teleflex Medical OEM, Coventry, Connecticut, USA</td>
			<td></td>
			<td>Size 5.0, 6.0, 7.0</td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td></td>
			<td>2716</td>
			<td>70% ethanol for disinfection</td>
		</tr>
		<tr>
			<td>Spring scissors&#160;</td>
			<td>Fine Science Tool</td>
			<td>15000-10</td>
			<td>for minor dissection</td>
		</tr>
		<tr>
			<td>Scissors (angled to side)</td>
			<td>Fine Science Tool</td>
			<td>14063-011</td>
			<td>No. 3 handle</td>
		</tr>
		<tr>
			<td>Scalpel blade</td>
			<td></td>
			<td>2976-0</td>
			<td>No. 10</td>
		</tr>
		<tr>
			<td>Forceps (curved)</td>
			<td>Fine Science Tool</td>
			<td>11150-10</td>
			<td>for holding tissue</td>
		</tr>
		<tr>
			<td>Forceps (straight)</td>
			<td>Fine Science Tool</td>
			<td>11151-10</td>
			<td>for holding tissue</td>
		</tr>
		<tr>
			<td>Needle holder&#160;</td>
			<td>Fine Science Tool</td>
			<td>12002-12</td>
			<td>for suturing</td>
		</tr>
		<tr>
			<td>Fine needle nose Forceps</td>
			<td>Fine Science Tool</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Henry Schein&#160;Animal Health, Melville, New York, USA</td>
			<td></td>
			<td>a general inhalation anesthetic agent</td>
		</tr>
		<tr>
			<td>Sterilizer</td>
			<td>Benchmark Scientific, 116 Corporate Blvd, South Plainfield, NJ, USA</td>
			<td>B1000</td>
			<td>sterilize surgical tools&#160;in 5-10 seconds using infrared heating</td>
		</tr>
		<tr>
			<td>Gauze Pads</td>
			<td>Johnson &#38; Johnson, New Brunswick, NJ, USA</td>
			<td>JJ8513</td>
			<td>to use for wound cleaning, prepping, scrubbin or dressing.</td>
		</tr>
		<tr>
			<td>Telemetry Device</td>
			<td>Data Sciences International, St. Paul, MN, USA</td>
			<td>DSI-PA-C10</td>
			<td>to record blood pressure in freely moving mice</td>
		</tr>
		<tr>
			<td>Telemetry receiver system&#160; coumpled with a PC</td>
			<td>Data Sciences International, St. Paul, MN, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>small Tubing</td>
			<td>Instech Laboratories, Plymouth Meeting, PA USA</td>
			<td>BTPE-90</td>
			<td></td>
		</tr>
		<tr>
			<td>Vessel Cannulation Forceps, 13cm, 0.5mm OD</td>
			<td>World Precision Instruments</td>
			<td>503374</td>
			<td>special vessel cannulation forceps.</td>
		</tr>
		<tr>
			<td>Tissue adhesive</td>
			<td>3M Animal Care Products, St. Paul, MN, USA</td>
			<td>NAC No.:&#160;11380041</td>
			<td>&#160;use to close minor wounds, often eliminating the need for sutures and/or bandages</td>
		</tr>
		<tr>
			<td>Weighing scale&#160;</td>
			<td></td>
			<td>BB300</td>
			<td>&#160;Precision Analytical Laboratory Balance</td>
		</tr>
	</tbody>
</table>

long-term blood pressure measurement in freely moving mice using telemetry

中的新血管活性药物的发展，动脉血压监测是用于评价新提出的药物的功效的关键。事实上，研究集中在新的潜在的治疗靶标使用基因改变的小鼠中发现需要全身动脉压力变化的可靠，长期评估。目前，金标准获得门诊老鼠血压长期测量采用植入无线电发射器，这就需要动脉插管。这种技术消除了对束缚，抑制，或麻醉的数据采样期间引入应力和工件的动物。然而，在经由导管小鼠动脉血压监测可以是相当有挑战性由于动脉的小尺寸。在这里，我们提出一个一步一步的指导，说明了无线电发射器和颈动脉C的成功皮下植入的关键钥匙通道环中的小鼠。我们还包括了一周期手术后恢复的后自由移动小鼠的长期血压活性的实例。根据这一程序将允许同时从多个可靠的动物直接血压记录。

数据可以远程由接收机获取;痕迹显现在电脑屏幕的质量控制（ 图1a）上。细节如动物的ID，舒张压和收缩压也示（ 图1b）。动脉压可连续（24/7）记录，或简称设定的时间间隔（ 即 ，60秒收购每隔一小时）。数据可以被自动存储在硬盘用于以后的分析。平均的从3天的连续记录血压数据示（ 图2），也能够欣赏黑暗和光照周期之间的昼夜节律变化。的压力变化和心脏率平均分别计算与时间作图。 <img alt="图1" src="/files/ftp_upload/53991/53991fig1.jpg" /> 图1.典型的血压描记 </str与遥测装置植入4不同的鼠标翁&gt;。 （A）描记显示，在5分钟的间隔实时动脉血压的变化（毫米汞柱）。数据被植入后第5天，从四个不同的成年小鼠同时采集的。 （B）在从A提取时间分辨率高跟踪，就可以体会到血压的收缩压和舒张压值，BP周期的持续时间和心脏率。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53991/53991fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图2" src="/files/ftp_upload/53991/53991fig2.jpg" /> 图2. 长期动脉血压显示昼夜节律变化。场均压力数据说明了（A）收缩压（SP），（B）舒张压（DP），（C），平均动脉压（MAP），值（D）心脏RATE在次/分表示。数据来自白天（光照周期，L）或夜间（黑暗周期，D）采取连续录音中提取。录音开始7天手术后。所有数据都表示为平均值±SEM（N = 4只小鼠）。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53991/53991fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

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Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry

自由活动小鼠使用遥测长期血压测量

The goal of this protocol is to assess systemic blood pressure in conscious freely moving mice using implantable radio-telemetry devices.

During the development of new vasoactive agents, arterial blood pressure monitoring is crucial for evaluating the efficacy of the new proposed drugs. ...

long-term-blood-pressure-measurement-freely-moving-mice-using

Nanyang Technological University

Research

JoVE Journal

Medicine

18.3K 次观看.  University of Tennessee Health Sciences Center. The goal of this protocol is to assess systemic blood pressure in conscious freely moving mice using implantable radio-telemetry devices.

视频: Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion.

A murine model for ventilator induced lung injury is an important tool to study an acute lung injury in vivo. Here, we report an easy applicable in situ model for acute lung injury using high-pressure mechanical ventilation to induce acute failure of the lung.

压力控制通气诱导小鼠急性肺损伤

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged ...

科研

医学

Epidural Intracranial Pressure Measurement in Rats Using a Fiber-optic Pressure Transducer

Elevated intracranial pressure (ICP) is a significant problem in several forms of ischemic brain injury including stroke, traumatic brain injury and cardiac arrest. This elevation may result in further neurological injury, in the form of transtentorial herniation1,2,3,4, midbrain compression, neurological deficit or increased cerebral infarct2,4. Current therapies are often inadequate to control elevated ICP in the clinical setting5,6,7 . Thus there is a need for accurate methods of ICP measurement in animal models to further our understanding of the basic mechanisms and to develop new treatments for elevated ICP.
In both the clinical and experimental setting ICP cannot be estimated without direct measurement. Several methods of ICP catheter insertion currently exist. Of these the intraventricular catheter has become the clinical 'gold standard' of ICP measurement in humans8. This method involves the partial removal of skull and the instrumentation of the catheter through brain tissue. Consequently, intraventricular catheters have an infection rate of 6-11%9. For this reason, subdural and epidural cannulations have become the preferred methods in animal models of ischemic injury. 
Various ICP measurement techniques have been adapted for animal models, and of these, fluid-filled telemetry catheters10 and solid state catheters are the most frequently used11,12,13,14,15. The fluid-filled systems are prone to developing air bubbles in the line, resulting in false ICP readings. Solid state probes avoid this problem (Figure 1). An additional problem is fitting catheters under the skull or into the ventricles without causing any brain injury that might alter the experimental outcomes. Therefore, we have developed a method that places an ICP catheter contiguous with the epidural space, but avoids the need to insert it between skull and brain. 
An optic fibre pressure catheter (420LP, SAMBA Sensors, Sweden) was used to measure ICP at the epidural location because the location of the pressure sensor (at the very tip of the catheter) was found to produce a high fidelity ICP signal in this model. There are other manufacturers of similar optic fibre technologies13 that may be used with our methodology. Alternative solid state catheters, which have the pressure sensor located at the side of the catheter tip, would not be appropriate for this model as the signal would be dampened by the presence of the monitoring screw. 
Here, we present a relatively simple and accurate method to measure ICP. This method can be used across a wide range of ICP related animal models.

A novel technique to record the pressures within the skull is described. The minimally invasive method uses a fibre-optic pressure sensing system to accurately measure intracranial pressure (ICP) in anaesthetized rats without causing significant brain trauma. The technique may be used in a wide range of experimental models.

硬膜外颅内压测量中使用的光纤压力传感器的大鼠

Elevated intracranial pressure (ICP) is a significant problem in several forms of ischemic brain injury including stroke, traumatic brain injury and ...

Measurement of the Pressure-volume Curve in Mouse Lungs

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential phenotypic changes are best assessed by measurement of the changes in lung elasticity. To best understand specific mechanisms underlying such pathologies in mice, it is essential to make functional measurements that can reflect the developing pathology. Although there are many ways to measure elasticity, the classical method is that of the total lung pressure-volume (PV) curve done over the whole range of lung volumes. This measurement has been made on adult lungs from nearly all mammalian species dating back almost 100 years, and such PV curves also played a major role in the discovery and understanding of the function of pulmonary surfactant in fetal lung development. Unfortunately, such total PV curves have not been widely reported in the mouse, despite the fact that they can provide useful information on the macroscopic effects of structural changes in the lung. Although partial PV curves measuring just the changes in lung volume are sometimes reported, without a measure of absolute volume, the nonlinear nature of the total PV curve makes these partial ones very difficult to interpret. In the present study, we describe a standardized way to measure the total PV curve. We have then tested the ability of these curves to detect changes in mouse lung structure in two common lung pathologies, emphysema and fibrosis. Results showed significant changes in several variables consistent with expected structural changes with these pathologies. This measurement of the lung PV curve in mice thus provides a straightforward means to monitor the progression of the pathophysiologic changes over time and the potential effect of therapeutic procedures.

Here we present a protocol to simply and reliably measure the lung pressure-volume curve in mice, showing that it is sufficiently sensitive to detect phenotypic parenchymal changes in two common lung pathologies, pulmonary fibrosis and emphysema. This metric provides a means to quantify the lung&#8217;s structural changes with developing pathology.

在小鼠肺压力容积曲线的测量

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential ...

Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

A complex integration of molecular and electrical signals is needed to transform a quiescent uterus into a contractile organ at the end of pregnancy. Despite the discovery of key regulators of uterine contractility, this process is still not fully understood. Transgenic mice provide an ideal model in which to study parturition. Previously, the only method to study uterine contractility in the mouse was ex vivo isometric tension recordings, which are suboptimal for several reasons. The uterus must be removed from its physiological environment, a limited time course of investigation is possible, and the mice must be sacrificed. The recent development of radiometric telemetry has allowed for longitudinal, real-time measurements of in vivo intrauterine pressure in mice. Here, the implantation of an intrauterine telemeter to measure pressure changes in the mouse uterus from mid-pregnancy until delivery is described. By comparing differences in pressures between wild type and transgenic mice, the physiological impact of a gene of interest can be elucidated. This technique should expedite the development of therapeutics used to treat myometrial disorders during pregnancy, including preterm labor.

Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

This manuscript provides a protocol for implanting telemeters in the mouse for the purpose of measuring intrauterine pressures during pregnancy.

宫内遥测来衡量鼠标收缩压力<em&gt;在体内</em

A complex integration of molecular and electrical signals is needed to transform a quiescent uterus into a contractile organ at the end of pregnancy. ...

Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early cardiopulmonary dysfunction is difficult to diagnose, particularly in animal models, as cardiopulmonary function is often measured invasively, requiring anesthesia. As many anesthetic agents are cardiodepressive, subtle changes in cardiovascular function may be masked. In contrast, chronic instrumentation allows for measurement of cardiopulmonary function in the awake state, so that measurements can be obtained under quiet resting conditions, without the effects of anesthesia and acute surgical trauma. Furthermore, when animals are properly trained, measurements can also be obtained during graded treadmill exercise.
Flow probes are placed around the aorta or pulmonary artery for measurement of cardiac output and around the left anterior descending coronary artery for measurement of coronary blood flow. Fluid-filled catheters are implanted in the aorta, pulmonary artery, left atrium, left ventricle and right ventricle for pressure measurement and blood sampling. In addition, a 20 G&#160;catheter is positioned in the anterior interventricular vein to allow coronary venous blood sampling.
After a week of recovery, swine are placed on a motor-driven treadmill, the catheters are connected to pressure and flow meters, and swine are subjected to a five-stage progressive exercise protocol, with each stage lasting 3 min. Hemodynamic signals are continuously recorded and blood samples are taken during the last 30 sec of each exercise stage.
The major advantage of studying chronically instrumented animals is that it allows serial assessment of cardiopulmonary function, not only at rest but also during physical stress such as exercise. Moreover, cardiopulmonary function can be assessed repeatedly during disease development and during chronic treatment, thereby increasing statistical power and hence limiting the number of animals required for a study.

Here we present a protocol to assess cardiopulmonary function in awake swine, at rest and during graded treadmill exercise. Chronic instrumentation allows for repeated hemodynamic measurements uninfluenced by cardiodepressive anesthetic agents.

导管手术放置了长期的心血管运动试验猪

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early ...

Transdermal Measurement of Glomerular Filtration Rate in Mice

Transdermal analysis of glomerular filtration rate (GFR) is an established technique that is used to assess renal function in mouse and rat models of acute kidney injury and chronic kidney disease. The measurement system consists of a miniaturized fluorescence detector that is directly attached to the skin on the back of conscious, freely moving animals, and measures the excretion kinetics of the exogenous GFR tracer, fluorescein-isothiocyanate (FITC) conjugated sinistrin (an inulin analog). This system has been described in detail in rats. However, because of their smaller size, measurement of transcutaneous GFR in mice presents additional technical challenges. In this paper we therefore provide the first detailed practical guide to the use of transdermal GFR monitors in mice based on the combined experience of three different investigators who have been performing this assay in mice over a number of years.

Here we describe a protocol to measure glomerular filtration rate (GFR) in conscious, freely moving mice using a transdermal GFR monitor.

小鼠肾小球滤过率的透皮测定

Transdermal analysis of glomerular filtration rate (GFR) is an established technique that is used to assess renal function in mouse and rat models of ...

Simultaneous Electrocardiography Recording and Invasive Blood Pressure Measurement in Rats

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. Research focusing on cardiovascular disease models, potential cardiovascular therapeutic targets or pharmaceutical agents requires assessment of systemic arterial pressure and heart rhythm changes. In situations where radio telemetry systems are not available or affordable, the technique of femoral artery cannulation is an alternative way to obtain intra-arterial pressure waveform recordings and systemic BP measurements. This technique is economical and can be performed with standard equipment in animal facilities. However, invasive arterial pressure recording requires cannulation of small arteries, which can be a challenging surgical skill. Here, we present step-by-step protocols for femoral artery cannulation procedures. Key procedures include the calibration of the data acquisition system, tissue dissection and femoral artery cannulation, and setup of the arterial cannulation system for pressure recording. Surface electrocardiography recording procedures are also included. We also present examples of BP recordings from normotensive and hypertensive rats. This protocol allows reliable direct recordings of systemic BP with simultaneous electrocardiography.

Here, we describe a setup for simultaneous recording of electrocardiography and intra-arterial blood pressure (BP) in experimental rats, which can be done with standard equipment in animal facilities and can be applied to physiological or pharmacological studies to investigate pathogenic or therapeutic mechanisms in cardiovascular medicine.

大鼠同时心电图记录及侵入性血压测量

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. ...

Blood Collection Through Subclavian Vein Puncture in Mice

The mouse is the foremost mammalian model for studying human disease and human health. However, blood sample collection from mice is challenging in research work. Tail blood collection is a popular method when a small amount of blood sample is needed. Orbital artery could be considered if a large amount of blood is needed but this blood collection method has ethical issues. Formerly, we demonstrated the feasibility and safety of blood sample collection through subclavian vein puncture in rats, and here we investigate whether this method could be used in mice. We report that this method is safe and practical for blood collection in mice. Blood collection through the subclavian vein puncture in mice can be a convenient method in daily research works.

Here, we present a protocol to take blood samples from the subclavian vein of mice.

小鼠锁骨下静脉穿刺采血

The mouse is the foremost mammalian model for studying human disease and human health. However, blood sample collection from mice is challenging in ...

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. The baroreflex is a key homeostatic mechanism to counteract acute, short-term changes in arterial BP and to maintain BP in a relatively narrow physiological range. BP is sensed by baroreceptors located in the aortic arch and carotid sinus. When BP changes, signals are transmitted to the central nervous system and are then communicated to the parasympathetic and sympathetic branches of the autonomic nervous system to adjust HR. A rise in BP causes a reflex decrease in HR, a drop in BP causes a reflex increase in HR.
Baroreflex sensitivity (BRS) is the quantitative relationship between changes in arterial BP and corresponding changes in HR. Cardiovascular diseases are often associated with impaired baroreflex function. In various studies reduced BRS has been reported in e.g., heart failure, myocardial infarction, or coronary artery disease. 
Determination of BRS requires information from both BP and HR, which can be recorded simultaneously using telemetric devices. The surgical procedure is described beginning with the insertion of the pressure sensor into the left carotid artery and positioning of its tip in the aortic arch to monitor arterial pressure followed by the subcutaneous placement of the transmitter and ECG electrodes. We also describe postoperative intensive care and analgesic management. After a two-week period of post-surgery recovery long-term ECG and BP recordings are performed in conscious and unrestrained mice. Finally, we include examples of high-quality recordings and the analysis of spontaneous baroreceptor sensitivity using the sequence method.

The baroreflex is a heart-rate regulation mechanism by the autonomic nervous system in response to blood-pressure changes. We describe a surgical technique to implant telemetry transmitters for continuous and simultaneous measurement of electrocardiogram and blood pressure in mice. This can determine spontaneous baroreflex sensitivity, an important prognostic marker for cardiovascular disease.

植入遥测心电图和血压递质组合以确定意识小鼠的自发压力反射敏感性

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. ...

Analyzing Long-Term Electrocardiography Recordings to Detect Arrhythmias in Mice

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ineffective in many patients. To improve patient care, novel and innovative therapeutic concepts causally targeting arrhythmia mechanisms are needed. To study the complex pathophysiology of arrhythmias, suitable animal models are necessary, and mice have been proven to be ideal model species to evaluate the genetic impact on arrhythmias, to investigate fundamental molecular and cellular mechanisms, and to identify potential therapeutic targets.
Implantable telemetry devices are among the most powerful tools available to study electrophysiology in mice, allowing continuous ECG recording over a period of several months in freely moving, awake mice. However, due to the huge number of data points (&gt;1 million QRS complexes per day), analysis of telemetry data remains challenging. This article describes a step-by-step approach to analyze ECGs and to detect arrhythmias in long-term telemetry recordings using the software, Ponemah, with its analysis modules, ECG Pro and Data Insights, developed by Data Sciences International (DSI). To analyze basic ECG parameters, such as heart rate, P wave duration, PR interval, QRS interval, or QT duration, an automated attribute analysis was performed using Ponemah to identify P, Q, and T waves within individually adjusted windows around detected R waves. 
Results were then manually reviewed, allowing adjustment of individual annotations. The output from the attribute-based analysis and the pattern recognition analysis was then used by the Data Insights module to detect arrhythmias. This module allows an automatic screening for individually defined arrhythmias within the recording, followed by a manual review of suspected arrhythmia episodes. The article briefly discusses challenges in recording and detecting ECG signals, suggests strategies to improve data quality, and provides representative recordings of arrhythmias detected in mice using the approach described above.

Here we present a step-by-step protocol for a semiautomated approach to analyze murine long-term electrocardiography (ECG) data for basic ECG parameters and common arrhythmias. Data are obtained by implantable telemetry transmitters in living and awake mice and analyzed using Ponemah and its analysis modules.

分析长期心电图记录以检测小鼠心律失常

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ...