Este trabalho é apoiado pelo financiamento do Exército dos Estados Unidos, Medical Research e Materiel Command, Combate Care Program Perda de vida. Agradecemos LTC Kevin S. Akers, MD e Ms. Kristen R. Lye por sua assistência em fazer o vídeo.

Antes de qualquer procedimento humana, o Conselho de Revisão Institucional (IRB) deve aprovar o protocolo. O protocolo utilizado neste estudo foi aprovado pelo Medical Research Exército dos EUA e Comando de Material IRB. O protocolo é projetado para demonstrar as respostas fisiológicas de compensação a uma redução progressiva do volume sanguíneo central semelhante à vivida por indivíduos durante a hemorragia em curso em um ambiente controlado de laboratório e reprodutível. A temperatura ambiente de laboratório é controlada a 23 - 25 C. 1. Preparação Equipamento <ol><li> Ligue equipamentos e dispositivos que necessitam de warm-up e calibração. NOTA: Equipamentos e dispositivos incluem um sistema de aquisição de dados para gravar dados em 1 Hz; dois dispositivos separados que fornecem não invasivos, medições contínuas da pressão arterial artéria braquial e saturação arterial de oxigênio (SpO2), utilizando dois sensores infravermelhos dedo fotopletismografia de punho separadas 9-11; um capnograph para a medição de CO 2 ao final da expiração e freqüência respiratória; e um oxímetro de pulso dedo para adquirir formas de onda pulsátil arteriais periféricos para medir compensatória Reserve. </li><li> Sincronizar todos os instrumentos com relógios internos, ajustando o carimbo de tempo em cada um dos instrumentos para corresponder a um relógio mestre laboratório que vai ser utilizado para marcar o tempo durante a experiência. </li></ol> 2. Objecto Preparação <ol><li> Instrua o assunto para evitar a cafeína, álcool e extenuante exercício 24 h antes do ensaio, e evitar comer pelo menos 2 horas antes do protocolo, no caso de descompensação hemodinâmica induz náuseas. </li><li> Antes do início do protocolo, tem o médico realizar um exame de triagem médica para garantir o assunto atende aos requisitos de saúde mínimos, e garante a ausência de critérios de exclusão (uso de nicotina, hipertensão, disfunção autonômica, ou história de episódios de síncope). Desde a gravidez é um critério de exclusão paraparticipação, exigem que os participantes do sexo feminino para fazer um teste de gravidez de urina padrão no dia do estudo. NOTA: Para a segurança do assunto, o médico do estudo é certificada em suporte avançado de vida, e está presente durante o estudo. Um totalmente equipada &#39;carrinho de emergência&#39; está imediatamente disponível para apoiar o sujeito das vias aéreas, respiração e circulação em caso de perda de consciência ou uma arritmia cardíaca aguda ocorrendo durante o procedimento LBNP. </li><li> Informar a pessoa sobre o procedimento e obter consentimento por escrito para participar do estudo. NOTA: Explique ao assunto que o objetivo do estudo é aplicar LBNP até o início da descompensação cardiovascular (pré-síncope). Explique que há parâmetros cardiovasculares que definem este ponto, e LBNP será encerrada quando se observam estes parâmetros cardiovasculares. Informar a pessoa de que eles também podem experimentar sintomas tipicamente associados com pré-síncope durante o proce LBNPdure. Instrua o assunto para notificar o investigador se estes sintomas ocorrem e LBNP será imediatamente encerrado. </li><li> Coloque a saia neoprene LBNP sobre o assunto. Assegure-se que a saia é confortável em torno da cintura e torso, a fim de criar uma vedação estanque ao ar. </li><li> Instrua o assunto para estabelecer em decúbito dorsal sobre a cama da câmara LBNP enquanto montando um posto estacionária para fixar o torso no lugar durante LBNP. Instrua o assunto para relaxar a parte inferior do corpo durante a exposição LBNP. Fixar o sujeito dentro da câmara LBNP deslizando a cama para a câmara de fixação e a saia de neopreno para a abertura da câmara para criar uma vedação estanque ao ar. NOTA: A câmara LBNP fornece a capacidade de precisão (dentro de 0,1 mm Hg) que controla a pressão interna de 0 a -100 mmHg, quer manualmente ou com um perfil computadorizado. A câmara inclui uma sela ajustável para fixar a posição do corpo do sujeito. janelas de plexiglas permitir a visualização das pernas do sujeito.Uma placa de alumínio cintura ajustável permite uma vedação estanque ao ar a ser criado por uma saia de neoprene usado pelo sujeito e a câmara de LBNP ao nível da crista ilíaca (Figura 1). </li><li> Lugar eletrocardiograma (ECG) eletrodos no lado direito e articulações humorais-clavicular esquerda e à direita e à esquerda costelas inferiores (total de 4) em uma configuração modificada chumbo II (Figura 1) para a medição contínua da frequência cardíaca. </li><li> Posicione os braços do sujeito no descansa braço, ajustada de modo que as mãos são suportados ao nível do coração. Usando algemas dedo tamanho adequado, colocar um dedo fotopletismografia infravermelha &#160; dispositivo sobre os dedos médios esquerda e da direita para a medição contínua não invasiva batimento a batimento da pressão arterial. </li><li> Anexar as algemas dos dedos para os monitores de pressão. Calibrar a pressão dispositivos e sangue registro de acordo com as instruções do fabricante. 12 Digite informações sobre o assunto (idade, sexo, height, e peso) para permitir que os pressupostos apropriados para o cálculo (estimativa) de volume sistólico, débito cardíaco e resistência vascular periférica pelo algoritmo Modelflow se desejado. 13,14 </li><li> Coloque o oxímetro de pulso dedo no dedo indicador direito para a medição contínua da reserva de compensação 1,12 (Figura 2). </li><li> Coloque uma cânula nasal sobre o assunto e instruir o sujeito a respirar pelo nariz para assegurar reflexões sensíveis em inspiração e expiração. amostragem de ar nasal permitirá que o sujeito para falar livremente para o auto-relato de sintomas em desenvolvimento. Conectar-se a cânula nasal à capnografia para a medição contínua da respiração e terminar CO maré 2. </li></ol> 3. Executando o Protocolo LBNP <ol><li> Iniciar a gravação de dados, clicando no botão &quot;Iniciar&quot; no sistema de aquisição de dados. dados de base de registro para 5 min. Iniciado o primeiro nível de hypovole Centralmia ligando o motor de vácuo e definindo pressão negativa para -15 mmHg, e mantenha esta pressão durante 5 min. Figura 3 descreve o protocolo. </li><li> Aumentar a LBNP para -30 mmHg, e mantenha esta pressão durante 5 min. </li><li> Aumentar a LBNP para -45 mmHg, e mantenha esta pressão durante 5 min. </li><li> Aumentar a LBNP para -60 mmHg, e mantenha esta pressão durante 5 min. </li><li> Aumentar a LBNP para -70 mmHg, e mantenha esta pressão durante 5 min. </li><li> Continuar a aumentar os níveis de LBNP -10 mmHg por cada 5 min, até ao final do protocolo (5 min a -100 mmHg LBNP) ou o ponto de descompensação hemodinâmica. Rescindir o LBNP pressionando o botão de liberação de pressão na câmara de LBNP. NOTA: hemodinâmica descompensação é identificado por uma queda abrupta na pressão arterial sistólica abaixo de 80 mmHg, ou o assunto relatando sintomas pré-síncope, tais como cinza-out (perda de visão de cores), visão em túnel, sudorese, náuseas ou vertigens (Figura 4). </li><li>Continue dados de registro no sistema de aquisição de dados durante 10 min após a cessação das LBNP (postLBNP recuperação). </li><li> Parar de gravar dados no final do período de recuperação de 10 min, clicando no botão &quot;Stop&quot; no sistema de aquisição de dados. </li><li> Retire toda a instrumentação do assunto e remover o assunto da câmara LBNP. Peça ao sujeito para se sentar depois de pisar para baixo a partir da plataforma LBNP para garantir que eles estão livres de sintomas antes de sair do laboratório. O estudo está agora completa. </li><li> Arquivos de download de dados do sistema de aquisição para a extração do Índice compensatória Reserve (CRI), pressão arterial média (PAM), frequência cardíaca, e SpO 2 valores. 1,15,16 </li></ol>

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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.

Usando LBNP para causar reduções progressivas e contínuas no volume sanguíneo central, fomos capazes de induzir uma resposta típica de descompensação hemodinâmica no assunto, caracterizada por um início súbito de hipotensão e bradicardia (Figura 7). É importante compreender que a resposta compensatória integrada a hemorragia é muito complexo, 19 resultando em variabilidade individual significativa da tolerância à perda de sangue. 1 Como tal, alguns indivíduos possu...

A função mais importante do sistema cardiovascular é o controlo da perfusão adequada (fluxo sanguíneo e entrega de oxigénio) para todos os tecidos do corpo por meio da regulação homeostática da pressão sanguínea arterial. Vários mecanismos de compensação (por exemplo, a atividade do sistema nervoso autônomo, freqüência cardíaca e contratilidade, o retorno venoso, vasoconstrição, respiração) contribuir para manter os níveis fisiológicos normais de oxigênio nos tecidos. 1 Reduções no volume de sangue circulante tais como as causadas por hemorragia pode comprometer a capacidade de mecanismos compensatórios cardiovasculares e, finalmente, levar à baixa pressão arterial, hipóxia tecidual grave e choque circulatório, que pode ser fatal. Choque circulatório causado por hemorragia grave (ie, choque hemorrágico) é uma das principais causas de morte por trauma. 2 Um dos aspectos mais difíceis de prevenir um paciente de desenvolver choque é nossaincapacidade de reconhecer seu início precoce. A avaliação precoce e rigorosa da progressão para o desenvolvimento de choque está actualmente limitada na prática clínica por tecnologias (por exemplo, monitores médicos) que fornecem medições de sinais vitais que mudam muito pouco nos primeiros estágios de perda de sangue devido a numerosos compensatória do organismo mecanismos de regulação da pressão arterial. 3-6 Como tal, a capacidade de medir a soma total de reserva do corpo para compensar a perda de sangue representa o reflexo mais preciso do estado de perfusão tecidual e o risco de desenvolvimento de choque. 1 Esta reserva é chamado o . reserva de compensação que pode ser avaliada com precisão por medições em tempo real das mudanças em características da forma de onda arterial 1 Esgotamento da reserva de compensação replica a instabilidade cardiovascular do terminal observado em pacientes criticamente doentes com início súbito de hipotensão; uma condição conhecida como hemodinâmica decompensation. 7 A relação entre a utilização da reserva de compensação e regulação da pressão arterial durante a perda contínua de sangue em seres humanos pode ser demonstrada em laboratório, utilizando um conjunto abrangente de medidas fisiológicas (por exemplo, pressão arterial, freqüência cardíaca, saturação de oxigênio no sangue arterial, o volume sistólico, débito cardíaco, resistência vascular, taxa de respiração, caráter de pulso, estado mental, CO corrente final 2, oxigênio nos tecidos) fornecidas pelo monitoramento fisiológico normal durante reduções progressivas contínuos no volume sanguíneo central semelhantes aos que ocorrem durante a hemorragia. Volume sanguíneo central reduziu pode ser induzida de forma não invasiva com aumentos progressivos em Lower Body pressão negativa (LBNP). 8 Usando esta combinação de medições fisiológicas e LBNP, o entendimento conceitual de como avaliar a capacidade do corpo para compensar o volume de sangue central reduziu pode ser facilmente demôniostrados. Este estudo descreve a preparação pré-laboratório, a demonstração de resposta compensatória em relação a outras respostas fisiológicas durante hemorragia simulada, e a avaliação dos resultados postlab. As técnicas experimentais necessárias para a tomada de medidas de reserva de compensação são demonstrados em um voluntário humano.

<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

A hemorragia é a causa principal de mortes relacionadas com o trauma, em parte porque o diagnóstico precoce da gravidade da perda de sangue é difícil. A avaliação dos pacientes hemorrágicas é difícil porque as ferramentas clínicas atuais fornecem medidas de sinais vitais que se mantêm estáveis ​​durante os primeiros estágios de hemorragia devido a mecanismos compensatórios. Consequentemente, existe uma necessidade de compreender e medir a integração total de mecanismos que compensem reduzido volume de sangue circulante e como eles mudam durante hemorragia progressiva em curso. A reserva do corpo para compensar a redução do volume de sangue circulante é chamado de &quot;reserva de compensação&quot;. A reserva de compensação pode ser avaliado de forma precisa com medições em tempo real de mudanças nas características da forma de onda arterial medida com a utilização de um computador de alta potência. Parte inferior do corpo de pressão negativa (LBNP) foi mostrado para simular muitas das respostas fisiológicas em humanos associados com hemorragia,e é usado para estudar a resposta compensatória à hemorragia. O objetivo deste estudo é demonstrar como reserva compensatória é avaliado durante reduções progressivas no volume sanguíneo central com LBNP como uma simulação de hemorragia.

O procedimento LBNP provoca uma redução na pressão de ar em torno da parte inferior do tronco e pernas. Como este vácuo é progressivamente aumentada, as mudanças de volume de sangue da cabeça e parte superior do tronco para a parte inferior do corpo para criar um estado de hipovolemia central. A redução progressiva do volume sanguíneo central (ou seja, LBNP) produz alterações significativas nas características da forma de onda arterial medida com o photoplethysmogra...

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

O objectivo deste protocolo é demonstrar as técnicas para medir respostas compensatórias para o volume de sangue central reduziu utilizando menor pressão negativa corpo como um modelo experimental não-invasivo de hemorragia humana que pode ser usado para quantificar a integração total de mecanismos compensatórios para déficit de volume de sangue em seres humanos .

Respostas compensatórias integrados em um modelo humano de hemorragia

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 visualizações.  JBSA Fort Sam Houston.  O objectivo deste protocolo é demonstrar as técnicas para medir respostas compensatórias para o volume de sangue central reduziu utilizando menor pressão negativa corpo como um modelo experimental não-invasivo de hemorragia humana que pode ser usado para quantificar a integração total de mecanismos compensatórios para déficit de volume de sangue em seres humanos . 

Vídeo: 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.

Transplante de Células-tronco em um In vitro Modelo de isquemia / reperfusão Simulated

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

Medicina

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.

Um Modelo de Rato Baixa Mortalidade para Avaliar vasoespasmo cerebral adiada após hemorragia subaracnóide Experimental

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.

Um modelo murino de hemorragia subaracnóide

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.

Excitotóxico Estimulação do Microslices cérebro como um<em&gt; In vitro</em&gt; Modelo de AVC

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.

Respostas Bexiga Distensão Evocado Visceromotor como um modelo para Bexiga dor em camundongos

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.

O coelho Modelo Blood-shunt para o Estudo da aguda e tardia Sequelas de hemorragia subaracnóidea: Aspectos Técnicos

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.

Rato Pneumonectomia modelo de crescimento compensatório pulmonar

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.

Indução de Aterosclerose Acelerada em Camundongos: O Modelo de "Lesão por Fio"

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.

Medição de contratilidade isométrica da artéria mesentérica Mouse usando fio miografia

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

A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the pathophysiological mechanism and to develop effective therapeutic strategy for this devastating neurological disorder. Intraparenchymal hemorrhage and post-traumatic inflammatory response induced by initial physical impact can aggravate microglia/macrophage activation and neuroinflammation which subsequently worsen brain pathology. We provide here a controlled cortical impact (CCI) protocol that can reproduce experimental cortical contusion in mice by using a pneumatic impactor system to deliver mechanical force with controllable magnitude and velocity onto the dural surface. This preclinical model allows researchers to induce moderately severe focal cerebral contusion in mice and to investigate a wide range of post-traumatic pathological progressions including hemorrhage contusion, microglia/macrophage activation, iron toxicity, axonal injury, as well as short-term and long-term neurobehavioral deficits. The present protocol can be useful for exploring the long-term effects of and potential interventions for cerebral contusion.

<meta charset="utf8"></head><body>Um modelo pré-clínico de impacto cortical controlado para hemorragia traumática, contusão e neuroinflamação

Intraparenchymal hemorrhage and neuroinflammation accompanied by cerebral contusion can trigger severe secondary brain injury. This protocol details a mouse controlled cortical impact (CCI) model allowing researchers to study hemorrhage contusion and post-traumatic immune responses and explore potential therapeutics.