这项工作是由美国陆军医学研究和装备司令部，作战伤员救护方案提供资金支持。我们感谢LTC凯文S.埃克斯，MD和克里斯汀R.碱液女士为他们制作的视频帮助。

在此之前任何人的过程中，机构审查委员会（IRB）必须批准该协议。在这项研究中使用的协议被批准由美国陆军医学研究和装备司令部IRB。该协议旨在演示在中央血容量逐步减少类似于在受控和可重复的实验室设置持续出血时由个人经历的补偿的生理反应。 25˚C - 实验室房间温度在23控制。 1.设备的准备<ol><li>打开设备并需要预热和校准设备。 注:设备和装置包括一个数据采集系统，记录在1赫兹的数据;这提供了使用两个单独的红外线手指光电容积袖带传感器9-11肱动脉血压和动脉血氧饱和度的非侵入性，连续测量（SPO 2）两个独立的设备;一个capnograpH值呼气末二氧化碳和呼吸频率的测量;和手指脉搏血氧计收购周边动脉搏动波形测量补偿储备。 </li><li>通过调整每个仪器时间戳匹配实验室主时钟将用于在实验过程中以标记时间同步所有与内部时钟的文书。 </li></ol> 2.除准备<ol><li>指示受试者避免咖啡因，酒精和剧烈运动24小时测试之前，并避免食用之前在血液动力学失代偿诱导恶心事件的协议，至少2小时。 </li><li>在此之前的协议开始，有医生进行体检检查，以确保符合题目最低卫生要求，并确保没有排除标准（尼古丁的使用，高血压，植物神经功能紊乱，或晕厥发作史）。由于怀孕是排除标准参与，要求女性参与者采取一个标准的尿妊娠试验在研究的当天。 注:有关主体的安全性，研究医生是高级生命支持认证，并在研究过程中存在。设备齐全的"急救车"可立即支持意识丧失或急性心律失常的LBNP过程中发生的事件中受到的气道，呼吸及循环。 </li><li>告知程序的问题，并取得书面同意参与这项研究。 注:解释给课题研究的目的是应用下体负压直到心血管失代偿（先兆）的发作。解释，有限定这一点心血管参数，并当观察这些心血管参数下体负压将被终止。告知他们也可以体验的症状通常有先兆的LBNP PROCE期间相关的主题杜热。责成主题，如果出现这些症状和下体负压将立即终止通知调查。 </li><li>广场上的主题氯丁橡胶下体负压裙子。确保该裙是为了创造一个气密密封围绕腰部和躯干贴身。 </li><li>责成主题，同时横跨固定后LBNP期间固定在躯干的地方，躺在下体负压室的床上平卧。指示主题LBNP暴露过程中放松下半身。通过滑动床进入室和附加氯丁橡胶裙到室开口以创建一个气密密封固定主体入下体负压室中。 注:下体负压室提供的准确的能力（0.1毫米汞柱内）手动或用一个计算机化信息控制从0到-100毫米汞柱的内部压力。该腔室包括一个可调节的鞍固定被检者的身体位置。透明的有机玻璃窗户让主体的腿的可视化。一个可调节的铝腰部板允许通过由主体和在髂嵴（ 图1）的水平的下体负压室佩戴的氯丁橡胶裙创建一个气密密封。 </li><li>在右侧和左侧体液锁骨关节，并在正确的地方心电图（ECG）电极，并在修改后的铅II组态左下肋（总共4个）（ 图1）对心脏速率的连续测量。 </li><li>在扶手，调整，使得手是在心脏水平支撑位置主体的怀抱。使用适当大小的手指袖口，将一个手指红外光电容积描记&#160;装置上的左和右中指的连续无创逐次心跳的测量血压。 </li><li>附加手指袖口到压力监视器。根据制造商的说明进行校准的装置和记录血压。12输入对象信息（年龄，性别，HEIGHT和重量），如果需要的话，使每搏量，心输出量和外周血管阻力由Modelflow算法计算（估计）在适当的假设。13,14 </li><li>广场上的右手食指为赔偿准备金1,12（ 图2）的连续测量手指脉搏血氧仪。 </li><li>广场上的主题鼻导管，并指示主体通过鼻子呼吸，以确保在吸气和呼气敏感的思考。鼻的空气采样将使主题为发展中国家症状的自我报告畅所欲言。鼻插管连接到二氧化碳监测仪对呼吸的连续测量和呼气末CO 2。 </li></ol> 3.执行LBNP协议<ol><li>通过点击数据采集系统的"开始"按钮，开始记录数据。 5分钟记录基线数据。启动中央hypovole的第一级MIA转动真空电机上和负压力设定到-15毫米汞柱，并保持该压力5分钟。 图3概括了协议。 </li><li>增加LBNP至-30毫米汞柱，并保持该压力5分钟。 </li><li>增加LBNP到-45毫米汞柱，并保持该压力5分钟。 </li><li>增加LBNP到-60毫米汞柱，并保持该压力5分钟。 </li><li>增加LBNP至-70毫米汞柱，并保持该压力5分钟。 </li><li>继续由-10毫米汞柱，每5分钟，以增加下体负压水平直到的协议（5分钟于-100毫米汞柱下体负压）的端部或血液动力学失代偿的点。通过按LBNP室中的压力释放按钮终止下体负压。 注:血流动力学失代偿由急剧下降，动脉收缩压低于80毫米汞柱，或主题报告晕厥前症状，如灰了（色觉丧失），隧道视野，出汗，恶心或头晕（ 图4）确定。 </li><li>下体负压停止（postLBNP恢复）后的10分钟内继续进行数据采集系统上记录数据。 </li><li>停止通过点击数据采集系统上的"停止"按钮，10分钟恢复期末记录数据。 </li><li>从分离问题的所有仪器，并从下体负压室的主题。让拍摄对象从下体负压平台下台，以确保它们没有症状离开实验室之前后坐。这项研究现已完成。 </li><li>从用于补偿储备指数（CRI），平均动脉压（MAP），心脏率和血氧饱和度值的提取采集系统下载数据文件。1,15,16 </li></ol>

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L., 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+compensatory+reserve+for+early+and+accurate+prediction+of+hemodynamic+compromise:+case+studies+for+clinical+utility+in+acute+care+and+physical+performance.">The compensatory reserve for early and accurate prediction of hemodynamic compromise: case studies for clinical utility in acute care and physical performance.</a> J Special Op. Med. 16, 6-13 (2016).</li></ol>

The authors declare that they have no competing financial interests. The views expressed herein are the private views of the authors and are not to be construed as representing those of the US Department of the Army or the US Department of Defense.

用下体负压引起中央血容量进步和不断的减少，我们能够诱导血液动力学失代偿的主题典型的响应，其特点是低血压和心动过缓（ 图7）突然发作。理解到出血集成代偿反应是非常复杂的是很重要的，19从而在公差失血显著个体变异。1同样地，一些个体具有相对响应的补偿机制，而其他不那样有效地补偿。因此，在该协议中的关键步骤是在实验进行到心血管失代偿的?...

心血管系统的最重要的功能是足够的灌注（血流量和氧输送）到身体的所有组织中，通过动脉血压稳态调节控制。补偿各种机制（ 例如 ，自主神经系统的活动，心率和收缩，静脉回流，血管收缩，呼吸）有助于维持在组织氧气的正常生理水平1的减少在循环血液量例如那些引起出血可以妥协心血管补偿机制的能力，并最终导致低动脉血压，认真组织缺氧，循环性休克，可以是致命的。 严重出血（ 即出血性休克）引起的循环性休克是死亡的主要原因是由于创伤。2一个防止病人从最具挑战性的方面发展的冲击是我们的没有认识到它的早期发病。朝向休克的发展进展的早期和准确的评估目前在临床上由提供在失血因为人体的众多代偿的早期阶段变化很小的生命体征测量技术（ 即，医疗监视器）限定对调节血压的机制。3-6因此，衡量的总和身体的储备，以弥补血液流失的能力代表组织灌注状态的最准确的反映和发展电击的危险。1该储备金被称为。它可以通过改变实时测量动脉波形的特点准确地评估代偿储备代偿储备的枯竭1复制的危重患者低血压突然发作观察到的终端心血管功能不稳定;被称为血液动力学装饰的条件mpensation 7 在人类持续失血期间代偿储备和调节血压的利用之间的关系可以用一套完整的生理测量的实验室证明（ 如血压，心脏率，动脉血氧饱和度，每搏输出量，心输出量，血管阻力，呼吸，脉搏的性格，精神状态，呼气末二氧化碳 ，组织氧）期间，中央血容量相似出血期间发生持续逐步削减通过标准生理监测提供。降低的中心血量可以无创性与下体负压逐步增加（LBNP）诱发。8使用生理测量和下体负压，如何评价人体的补偿减少中央血量可以很容易地能力概念理解的这种组合恶魔trated。该研究描述了实验预习制备，模拟出血期间相对于其他生理反应代偿性反应的示范，和结果的postlab评价。用于做出补偿准备金的测量实验技术证实在人类志愿者。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Dynamic Research Evaluation Workstation (DREW) data acquisition syetem</td>
			<td>NA</td>
			<td>NA</td>
			<td>Custom Built by ISR personnel.&#160; The DREW allows for time synchronization of both digital and analog signal data collection from up to 16 independent instruments with a sampling rate of 1000 Hz.</td>
		</tr>
		<tr>
			<td>Finometer</td>
			<td>Finapress Medical Systems (FMS)</td>
			<td>Model 1</td>
			<td>Device that provides non-invasive, continuous measurements of brachial artery blood pressure and arterial oxygen saturation (SpO2) using two separate infrared finger photophlethymography cuff sensors.</td>
		</tr>
		<tr>
			<td>BCI Capnocheck Plus</td>
			<td>Smith Medical PM Inc.</td>
			<td>9004</td>
			<td>Capnograph used to measure&#160; end tidal CO2 and respiration rate</td>
		</tr>
		<tr>
			<td>CipherOX&#160;</td>
			<td>Flashback Technologies Inc.</td>
			<td>R200</td>
			<td>Investigational device used to calculate Compensatory Reserve Index (CRI)</td>
		</tr>
		<tr>
			<td>Nonin 9560 Pulse Oximeter</td>
			<td>Nonin</td>
			<td>9560</td>
			<td>finger pulse oximeter</td>
		</tr>
		<tr>
			<td>Lower Body Negative Pressure Chamber (LBNP)</td>
			<td>NASA</td>
			<td>79K32632-1</td>
			<td>Custom Chamber built by NASA</td>
		</tr>
		<tr>
			<td>ECG Biotach</td>
			<td>Gould</td>
			<td>13-6615-65</td>
			<td>Electrocardiograph for measuring ECG</td>
		</tr>
		<tr>
			<td>Nasal CO2 Sample Line</td>
			<td>Salter Labs</td>
			<td>REF 4000</td>
			<td>Latex free nasal cannula for sampling expired air</td>
		</tr>
	</tbody>
</table>

integrated compensatory responses in a human model of hemorrhage

出血是创伤有关的死亡的首要原因，部分是由于失血的严重性的早期诊断是困难的。出血的患者的评估是困难的，因为目前的临床工具提供的生命体征，由于代偿机制仍然期间出血的早期阶段稳定的措施。因此，有必要了解和测量的该补偿减少循环血液量，以及他们如何持续渐进出血时改变机构的总积分。人体的储备，以弥补减少循环血容量被称为"补偿性储备"。代偿储备可以在动脉波形与使用一个高功率的计算机的测量的特征的变化的实时测量来精确地进行评价。下体负压（LBNP）已经显示出模拟许多生理反应的与出血相关的人类，并且是用来研究对出血的代偿性反应。这项研究的目的是演示过程中中央血量逐步削减与下体负压为出血的模拟储备代偿如何评估。

该下体负压过程会导致在周围的下部躯干和腿的空气压力降低。作为这种真空逐渐增加，从头部和上部躯干在下体血容量移位来创建中央血容量不足的状态。在中央血容量逐步减少（ 即 ，LBNP）产生与红外线手指光体积描记（ 图5）测量的动脉波形的特征显著改变。该补偿储备指数（CRI）是从采用了独特的机器学习算法，其分析在波形特性的变化来计算...

Watch this Scientific Journal Video about Integrated Compensatory Responses in a Human Model of Hemorrhage at JoVE.com

Integrated Compensatory Responses in a Human Model of Hemorrhage

该协议的目的是证明的技术用于使用下体负压作为可用于定量的人类代偿机制血容量赤字总积分的人类出血的非侵入性的实验模型测量减少中央血容量代偿反应。

在出血的人体模型集成的代偿反应

Hemorrhage is the leading cause of trauma-related deaths, partly because early diagnosis of the severity of blood loss is difficult. Assessment of ...

integrated-compensatory-responses-in-a-human-model-of-hemorrhage

Research

JoVE Journal

Medicine

12.4K 次观看.  JBSA Fort Sam Houston. 该协议的目的是证明的技术用于使用下体负压作为可用于定量的人类代偿机制血容量赤字总积分的人类出血的非侵入性的实验模型测量减少中央血容量代偿反应。 

视频: Integrated Compensatory Responses in a Human Model of Hemorrhage

Stem Cell Transplantation in an in vitro Simulated Ischemia/Reperfusion Model

Stem cell transplantation protocols are finding their way into clinical practice1,2,3. Getting better results, making the protocols more robust, and finding new sources for implantable cells are the focus of recent research4,5. Investigating the effectiveness of cell therapies is not an easy task and new tools are needed to investigate the mechanisms involved in the treatment process6. We designed an experimental protocol of ischemia/reperfusion in order to allow the observation of cellular connections and even subcellular mechanisms during ischemia/reperfusion injury and after stem cell transplantation and to evaluate the efficacy of cell therapy. H9c2 cardiomyoblast cells were placed onto cell culture plates7,8. Ischemia was simulated with 150 minutes in a glucose free medium with oxygen level below 0.5%. Then, normal media and oxygen levels were reintroduced to simulate reperfusion. After oxygen glucose deprivation, the damaged cells were treated with transplantation of labeled human bone marrow derived mesenchymal stem cells by adding them to the culture. Mesenchymal stem cells are preferred in clinical trials because they are easily accessible with minimal invasive surgery, easily expandable and autologous. After 24 hours of co-cultivation, cells were stained with calcein and ethidium-homodimer to differentiate between live and dead cells. This setup allowed us to investigate the intercellular connections using confocal fluorescent microscopy and to quantify the survival rate of postischemic cells by flow cytometry. Confocal microscopy showed the interactions of the two cell populations such as cell fusion and formation of intercellular nanotubes. Flow cytometry analysis revealed 3 clusters of damaged cells which can be plotted on a graph and analyzed statistically. These populations can be investigated separately and conclusions can be drawn on these data on the effectiveness of the simulated therapeutical approach.

Stem Cell Transplantation in an in vitro Simulated Ischemia/Reperfusion Model

We demonstrate how to set up an in vitro ischemia/reperfusion model and how to evaluate the effect of stem cell therapy on postischemic cardiac cells.

在干细胞移植在体外模拟缺血/再灌注模型

Stem cell transplantation protocols are finding their way into clinical practice1,2,3. Getting better results, making the protocols more robust, and ...

科研

医学

Assessing Teratogenic Changes in a Zebrafish Model of Fetal Alcohol Exposure

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, including mental retardation due to disordered and damaged brain development. Fetal alcohol spectrum disorder (FASD) is a term used to cover a continuum of birth defects that occur due to maternal alcohol consumption, and occurs in approximately 4% of children born in the United States. With 50% of child-bearing age women reporting consumption of alcohol, and half of all pregnancies being unplanned, unintentional exposure is a continuing issue2. In order to best understand the damage produced by ethanol, plus produce a model with which to test potential interventions, we developed a model of developmental ethanol exposure using the zebrafish embryo. Zebrafish are ideal for this kind of teratogen study3-8. Each pair lays hundreds of eggs, which can then be collected without harming the adult fish. The zebrafish embryo is transparent and can be readily imaged with any number of stains. Analysis of these embryos after exposure to ethanol at different doses and times of duration and application shows that the gross developmental defects produced by ethanol are consistent with the human birth defect. Described here are the basic techniques used to study and manipulate the zebrafish FAS model.

In order to understand the molecular mechanisms of the ethanol-induced developmental damage, we have developed a zebrafish model of ethanol exposure and are exploring the physical, cellular, and genetic alterations that occur after ethanol exposure1. We then seek to find potential interventions and rapidly test them in this animal model.

在斑马鱼模型的胎儿酒精暴露评估致畸的变化

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, ...

A Low Mortality Rat Model to Assess Delayed Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage

Objective: To characterize and establish a reproducible model that demonstrates delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) in rats, in order to identify the initiating events, pathophysiological changes and potential targets for treatment.
Methods: Twenty-eight male Sprague-Dawley rats (250 - 300 g) were arbitrarily assigned to one of two groups - SAH or saline control. Rat subarachnoid hemorrhage in the SAH group (n=15) was induced by double injection of autologous blood, 48 hr apart, into the cisterna magna. Similarly, normal saline (n=13) was injected into the cisterna magna of the saline control group. Rats were sacrificed on day five after the second blood injection and the brains were preserved for histological analysis. The degree of vasospasm was measured using sections of the basilar artery, by measuring the internal luminal cross sectional area using NIH Image-J software. The significance was tested using Tukey/Kramer's statistical analysis.
Results: After analysis of histological sections, basilar artery luminal cross sectional area were smaller in the SAH than in the saline group, consistent with cerebral vasospasm in the former group. In the SAH group, basilar artery internal area (.056 &mu;m &plusmn; 3) were significantly smaller from vasospasm five days after the second blood injection (seven days after the initial blood injection), compared to the saline control group with internal area (.069 &plusmn; 3; p=0.004). There were no mortalities from cerebral vasospasm.
Conclusion: The rat double SAH model induces a mild, survivable, basilar artery vasospasm that can be used to study the pathophysiological mechanisms of cerebral vasospasm in a small animal model. A low and acceptable mortality rate is a significant criterion to be satisfied for an ideal SAH animal model so that the mechanisms of vasospasm can be elucidated 7, 8. Further modifications of the model can be made to adjust for increased severity of vasospasm and neurological exams.

Aneurysmal subarachnoid hemorrhage (SAH) is bleeding that occurs into the subarachnoid space when an aneurysm ruptures. While the morbidity and mortality from this event has been on a decline due to improved treatment approaches, the risk of vasospasm after subarachnoid hemorrhage continues to be the same as it was several years ago. The importance of establishing a comprehensive and reproducible animal model to identify initiating events of cerebral vasospasm has been the focus of research since the first use of rats in an experimental vasospasm model in 1979 by Barry et al. Early work in rats demonstrated that a single injection of autologous blood into the cisterna magna led to acute (within minutes) but not delayed cerebral vasospasm 3, 6, 14. Here we characterize a low mortality SAH rat model that results in reproducible delayed vasospasm.

死亡率低大鼠模型的实验性蛛网膜下腔出血后迟发性脑血管痉挛评估

Objective: To characterize and establish a reproducible model that demonstrates delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) ...

A Murine Model of Subarachnoid Hemorrhage

In this video publication a standardized mouse model of subarachnoid hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of Willis perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a homogenous blood distribution in subarachnoid spaces surrounding the arterial circulation and cerebellar fissures is achieved. Animal physiology is maintained by intubation, mechanical ventilation, and continuous on-line monitoring of various physiological and cardiovascular parameters: body temperature, systemic blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral perfusion pressure can be tightly monitored resulting in a less variable volume of extravasated blood. This allows a better standardization of endovascular filament perforation in mice and makes the whole model highly reproducible. Thus it is readily available for pharmacological and pathophysiological studies in wild type and genetically altered mice.

A standardized mouse model of subarachnoid hemorrhage by intraluminal Circle of Willis perforation is described. Vessel perforation and subarachnoid bleeding are monitored by intracranial pressure monitoring. In addition various vital parameters are recorded and controlled to maintain physiologic conditions.

蛛网膜下腔出血的小鼠模型

In this video publication a standardized mouse model of subarachnoid  hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of  Willis ...

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As such, primary or &#39;neuronal-like&#39; cell culture systems are commonly utilized. While&#160;these systems are relatively easy to work with, and are useful model systems in which various functional outcomes (such as cell death) can be readily quantified, the examined outcomes and pathways in cultured immature neurons (such as excitotoxicity-mediated cell death pathways) are not necessarily the same as those observed in mature brain, or in intact tissue. Therefore, there is the need to develop models in which cellular mechanisms in mature neural tissue can be examined. We have developed an in vitro technique that can be used to investigate a variety of molecular pathways in intact nervous tissue. The technique described herein utilizes rat cortical tissue, but this technique can be adapted to use tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken) or brain regions (for example, hippocampus, striatum, etc.). Additionally, a variety of stimulations/treatments can be used (for example, excitotoxic, administration of inhibitors, etc.). In conclusion, the brain slice model described herein can be used to examine a variety of molecular mechanisms involved in excitotoxicity-mediated brain injury.

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

We have developed a brain slice model which can be used to examine molecular mechanisms involved in excitotoxicity-mediated brain injury.&#160;This technique generates viable mature brain tissue and reduces animal numbers required for experimentation, whilst keeping the neuronal circuitry, cellular interactions, and postsynaptic compartments partly intact.

脑Microslices的兴奋性刺激作为<em&gt;在体外</em&gt;中风模型

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As ...

Urinary Bladder Distention Evoked Visceromotor Responses as a Model for Bladder Pain in Mice

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized by increased urgency and frequency of urination, as well as nocturia and general pelvic pain, especially upon bladder filling or voiding. Despite years of research, the cause of IC/BPS remains elusive and treatment strategies are unable to provide complete relief to patients. In order to study nervous system contributions to the condition, many animal models have been developed to mimic the pain and symptoms associated with IC/BPS. One such murine model is urinary bladder distension (UBD). In this model, compressed air of a specific pressure is delivered to the bladder of a lightly anesthetized animal over a set period of time. Throughout the procedure, wires in the superior oblique abdominal muscles record electrical activity from the muscle. This activity is known as the visceromotor response (VMR) and is a reliable and reproducible measure of nociception. Here, we describe the steps necessary to perform this technique in mice including surgical manipulations, physiological recording, and data analysis. With the use of this model, the coordination between primary sensory neurons, spinal cord secondary afferents, and higher central nervous system areas involved in bladder pain can be unraveled. This basic science knowledge can then be clinically translated to treat patients suffering from IC/BPS.

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized in part by pelvic pain. In order to study nervous system contributions to the condition, a physiological model of urinary bladder pain is used in mice and rats.

膀胱胀诱发内脏运动反应为膀胱疼痛小鼠模型

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition ...

The Rabbit Blood-shunt Model for the Study of Acute and Late Sequelae of Subarachnoid Hemorrhage: Technical Aspects

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and controllable animal models that simulate both conditions are presently uncommon. Therefore, new models are needed in order to mimic human pathophysiological conditions resulting from SAH.
This report describes the technical nuances of a rabbit blood-shunt SAH model that enables control of intracerebral pressure (ICP). An extracorporeal shunt is placed between the arterial system and the subarachnoid space, which enables examiner-independent SAH in a closed cranium. Step-by-step procedural instructions and necessary equipment are described, as well as technical considerations to produce the model with minimal mortality and morbidity. Important details required for successful surgical creation of this robust, simple and consistent ICP-controlled SAH rabbit model are described.

The experimental intracranial pressure-controlled blood shunt subarachnoid hemorrhage (SAH) model in the rabbit combines the standard procedures &#8212; subclavian artery cannulation and transcutaneous cisterna magna puncture, which enables close mimicking of human pathophysiological conditions after SAH. We present step-by-step instructions and discuss key surgical points for successful experimental SAH creation.

蛛网膜下腔出血急性和后遗症的研究兔血分流型号:技术问题

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and ...

Mouse Pneumonectomy Model of Compensatory Lung Growth

In humans, disrupted repair and remodeling of injured lung contributes to a host of acute and chronic lung disorders which may ultimately lead to disability or death. Injury-based animal models of lung repair and regeneration are limited by injury-specific responses making it difficult to differentiate changes related to the injury response and injury resolution from changes related to lung repair and lung regeneration. However, use of animal models to identify these repair and regeneration signaling pathways is critical to the development of new therapies aimed at improving pulmonary function following lung injury. The mouse pneumonectomy model utilizes compensatory lung growth to isolate those repair and regeneration signals in order to more clearly define mechanisms of alveolar re-septation. Here, we describe our technique for performing mouse pneumonectomy and sham pneumonectomy. This technique may be utilized in conjunction with lineage tracing or other transgenic mouse models to define molecular and cellular mechanism of lung repair and regeneration.

Mouse pneumonectomy is a commonly employed model of compensatory lung growth. This procedure can be used in conjunction with lineage tracing or transgenic mouse models to elucidate underlying mechanisms.

补偿性增长龙鼠标肺切除型号

In humans, disrupted repair and remodeling of injured lung contributes to a host of acute and chronic lung disorders which may ultimately lead to ...

Induction of Accelerated Atherosclerosis in Mice: The "Wire-Injury" Model

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. Moreover, by rupture of the defective vascular wall, atherosclerosis induces occlusive thrombus formation, which represents the main cause of myocardial infarction or stroke and the most frequent cause of death. Despite the advances in the cardiovascular field, many questions remain unanswered, and additional basic research is essential to improve our understanding of the molecular mechanisms during atherosclerosis and its effects. Due to limited clinical studies, there is a need for representative animal models recreating atherosclerotic conditions such as neointima formation after stent implantation, balloon angioplasty, or endarterectomy. Since the mouse presents many advantages and is the most frequently used model for studying molecular processes, the current study proposes an invasive procedure of endothelial denudation, also known as the wire-injury model, which is representative of the human condition of neointima formation in arteries after revascularization procedures.

This study describes an invasive procedure for the induction of accelerated atherosclerosis in mice. In comparison to other methods using electric- or cryo-induced injury, mechanical-induced injury mimics the human condition of restenosis after revascularization therapies and is ideal for the study of the molecular mechanisms involved.

小鼠加速动脉硬化的诱导:"电线损伤"模型

Atherosclerosis is a proliferative fibro-inflammatory disease developing in the arterial wall, inducing a deficient blood flow or a lack of blood flow. ...

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 ...