Diese Arbeit wurde durch Grant 5-U24-DK059637-10 der Vanderbilt Maus Metabolic Phänotypisierung Center unterstützt.

<ol>
	<li>Ayala, J. E., Bracy, D. P., McGuinness, O. P., Wasserman, D. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Considerations+in+the+design+of+hyperinsulinemic-euglycemic+clamps+in+the+conscious+mouse.">Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse.</a> Diabetes. 55, 390-397 (2006).</li><li>Berglund, E. D., Li, C. Y., Poffenberger, G., Ayala, J. E., Fueger, P. T., Willis, S. E., Jewell, M. M., Powers, A. C., Wasserman, D. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glucose+metabolism+in+vivo+in+four+commonly+used+inbred+mouse+strains.">Glucose metabolism in vivo in four commonly used inbred mouse strains.</a> Diabetes. 57, 1790-1799 (2008).</li><li>Niswender, K. D., Shiota, M., Postic, C., Cherrington, A. D., Magnuson, M. 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Die hyperinsulinämische-euglykämische Clamp-oder Insulin-Clamp, gilt weithin als der &quot;Goldstandard&quot;-Methode zur Beurteilung der Wirkung von Insulin in vivo. Diese Technik hat mehrere Arten einschließlich des Menschen, Hunde, Ratten und Mäusen angewendet worden. Angesichts der wachsenden Zahl von transgenen Mausmodellen für Stoffwechselerkrankungen, hat die Miniaturisierung der Technik für den Einsatz in der Maus bedeutende Fortschritte zu metabolischer Forschung zur Verfügung gestellt. Während die Konzepte hinter den Insulin-Clamp unkompliziert sind, in der Praxis gibt es verschiedene Ansätze für die Durchführung von Insulin Clamp-Experimenten. Dies ist kein trivialer Punkt, denn die Art und Weise, in der das Experiment durchgeführt wird beeinflusst Ergebnisse 1. Hier präsentieren wir Ihnen das Protokoll von der Vanderbilt MMPC verwendet. Der wesentliche Unterschied zwischen unserem Protokoll und das der anderen ist, dass wir einen arteriellen Katheter verwenden für den Erhalt von Blutproben. Dies ist im Gegensatz zu den weiter verbreitete Ansatz der obtaining Blutproben durch Abtrennen der Spitze des Schwanzes 4, 7, 11, 12, 14-17. Der Vorteil der Entnahme aus einem arteriellen Katheter ist, dass das Experiment in einer bewussten und hemmungslos Maus durchgeführt wird. Probenahme aus dem Schwanz erfordert oft Zurückhaltung und erhöht Indizes von Stress, wenn große Blut-Proben 1 erworben werden. Stress Hormone stimulieren endogenen Glukose-Produktion und beeinträchtigen Glucoseverwertung 18, 19, möglicherweise, um den Eindruck einer Insulin-resistenten Phänotyp. Probenahme aus den abgetrennten Schwanz benötigen möglicherweise spezielle Institutional Animal Care und Verwenden Ausschusses Genehmigung wegen ihrer stressigen Natur. Die arterielle Katheterisierung Verfahren wurde entwickelt, um die Belastung der Maus Abtrennen des Schwanzes zu vermeiden. Ein wesentlicher Aspekt der Durchführung Insulin Klammern ist die Fähigkeit, Normoglykämie aufrecht zu erhalten. Es gibt keine Algorithmen, die korrekt vorhersagen können, wie die GIR basierend auf Blutzuckerwerte angepasst werden sollte. Wie die Chirurgie,Personal führt Insulin Clamp-Experimenten wird tüchtig in die Aufrechterhaltung angemessener Normoglykämie nur durch Erfahrung. Es ist wichtig zu beachten, dass aufgrund ihrer höheren Stoffwechselrate die Daten von der Maus-Studien gewonnen werden grundsätzlich laut. Dies macht die komplette Präsentation von Daten, einschließlich Zeit-Verläufe von Glukose und GIR und absolute Werte für Plasma-Insulin, Endora, Rd und Rg entscheidend für die Fähigkeit von jedem Leser die Ergebnisse zu interpretieren. Die hohe Glukose-Flussraten in der Maus (ca. 5-mal höher als die Rate bei Menschen) garantieren eine hohe Frequenz von Glukose Probenahme. Während das Blutvolumen der Maus beschränkt ist, ist ein Minimum Sampling-Frequenz von einmal alle 10 Minuten notwendig, um sicher sein, dass eine ausreichende Klammer erreicht worden ist. Wie in Abbildung 4 dargestellt ist, kann Klemme Insulinspiegel werden unterschiedlich zwischen den Gruppen. Faktoren wie Ernährung Interventionen transgenen Manipulationen oder Unterschiede in der Hintergrund-Stämme können sich auf fasting Insulinspiegel, die anschließend beeinflussen können Klemme Insulinspiegel. Interpretation der Ergebnisse, wenn Klemme Insulinspiegel unterschiedlich sind problematisch sein kann. Dies kann experimentell, indem Pilotversuchen zur Insulin-Infusion Preise erzielen, die entsprechende Klemme Insulinspiegel zwischen den Gruppen zu erreichen wählen Sie angesprochen werden. Alternativ können Somatostatin zur Pankreas-Sekretion hemmen und Insulin und Glukagon kann experimentell kontrollierten Raten ersetzt werden. Dieser Ansatz wird häufig auch in Insulin-Klemmen an Ratten als Mäuse getan. Wenn dieser experimentellen Ansätze nicht getroffen werden, kann der Steady-State-GIR der Klemme Insulinspiegel normalisiert werden, oder eine Insulin-Empfindlichkeit-Index (S I) kann von Clamp-Daten wie S I = GIR / (G • DELTA), wo abgeleitet werden G ist die Steady-State-Glucose-Konzentration und DELTA ist der Unterschied zwischen Fasten und Klemme Insulin-Konzentrationen. Eine Annahme entweder mit Ansatzes ist, dass die Klemme Insulin erreicht wirdinnerhalb des Bereichs, wo die Insulinsensitivität linear auf den Insulinspiegel ist nach der Gruppe untersucht verwandt. Diese letztere Annahme ist nicht anwendbar, beim Vergleich von Insulin resistent und Insulin empfindlicher Gruppen. Idealerweise sollte ein Insulin-Dosis-Wirkungs-Kurve generiert, um die entsprechenden Insulin-Infusion zu wählen. Da jedoch die Voraussetzung für weitere Experimente, ist dies selten getan. Die Vielseitigkeit von arteriellen Katheter zur Verfügung gestellt erstreckt sich auf experimentelle Ansätze jenseits euglykämische Klammern. Zum Beispiel kann hyperglycemic Klammern, in denen Glukose bei einem variablen Zinssatz zu Hyperglykämie gegenüber Nüchternglukose halten infundiert wird, verwendet werden, um endogenen Pankreasfunktion in vivo 2, 20, 21 zu beurteilen. Die Messung der ersten Phase der Insulinsekretion bei diesem Test erfordert häufige Übernahme von Blutproben (dh alle 2-5 min), was nicht machbar ist, wenn den Erhalt einer Probe von der Spitze des Schwanzes. Darüber hinauserhöhten Katecholaminen aus tail Probenahme beeinträchtigen können Insulinsekretion und erhöhen Glucagonsekretion 22. Das Insulin Clamp-Protokoll kann auch so modifiziert, dass für die Glukosewerte zu relativen Hypoglykämien fallen zu Gegen-regulatorische Antwort 2, 23, 24 zu beurteilen. Arterielle Katheter können auch verwendet werden, um die Dynamik des Glukosestoffwechsels während des Trainings 25-30 beurteilen. Das ist deutlich vorteilhaft gegenüber herkömmlichen Ansätzen bei einzelnen Zeitpunkten durchgeführt Pre-und Post-Sport oder in isolierten Muskeln ex vivo. Die hier vorgestellten Verfahren kann auch verwendet werden, um nicht nur Glukose, aber auch Fettsäure-Stoffwechsel 31 zu beurteilen.

hyperinsulinemic-euglycemic clamps in conscious, unrestrained mice

Typ 2 Diabetes ist durch einen Defekt in der Insulin-Wirkung gekennzeichnet. Die hyperinsulinämische-euglykämische Clamp-oder Insulin-Clamp, gilt weithin als der &quot;Goldstandard&quot;-Methode zur Beurteilung der Wirkung von Insulin in vivo. Während einer Insulin-Clamp ist Hyperinsulinämie durch einen konstanten Insulin-Infusion erreicht. Normoglykämie wird über eine gleichzeitige Glukose-Infusion mit einer variablen Rate beibehalten. Diese Variable Glukose Infusionsrate (GIR) wird durch die Messung des Blutzuckers in kurzen Abständen während des gesamten Experiments und die Anpassung der GIR entsprechend bestimmt. Die GIR ist bezeichnend für die Ganzkörper-Insulinwirkung, wie die Mäuse mit erhöhter Wirkung von Insulin erfordern eine größere GIR. Das Insulin Clamp kann die Verabreichung von Isotopen-2 greifen [14 C] Desoxyglucose zu beurteilen, Gewebe-spezifische Glukoseaufnahme und [3 bis 3 H]-Glucose auf die Fähigkeit von Insulin, um die Rate der endogenen Glukose Aussehen (Endora) zu unterdrücken, einem Marker der Beurteilung Glukoneogenese in der Leber und zur Anregung derRate der Ganzkörper-Glukose Verschwinden (Rd). Die Miniaturisierung der Insulin-Clamp für den Einsatz in der genetischen Mausmodellen der Stoffwechselkrankheit zu erheblichen Fortschritten in der Diabetes-Forschung führte. Methoden zur Durchführung von Insulin Klammern variieren zwischen den Labors. Es ist wichtig zu beachten, dass die Art und Weise, ein Insulin-Clamp durchgeführt wird, kann erhebliche Auswirkungen auf die erzielten Ergebnisse. Wir haben eine umfassende Bewertung der verschiedenen Ansätze zur Durchführung von Insulin Klemmen in bewusster Mäusen 1 sowie eine Bewertung der metabolischen Reaktion von vier häufigsten verwendeten Inzucht-Mausstämme mit verschiedenen Clamp-Technik 2 veröffentlicht. Hier präsentieren wir ein Protokoll für die Durchführung von Insulin Klemmen auf bewusste, hemmungsloser Mäusen durch die Vanderbilt Maus Metabolic Phänotypisierung Center (MMPC; URL: www.mc.vanderbilt.edu / MMPC) entwickelt. Dies umfasst eine Beschreibung der Verfahren zum Implantieren Katheter während der Insulin Clamp verwendet. Das Protokoll, das von den BeschäftigtenVanderbilt MMPC nutzt ein einzigartiges Zwei-Katheter-System 3. Ein Katheter wird in die Jugularvene für Infusionen eingesetzt. Ein zweiter Katheter wird in die Halsschlagader, die zur Blutentnahme ermöglicht, ohne die Notwendigkeit, zurückzuhalten oder Griff mit der Maus eingefügt. Diese Technik bietet einen wesentlichen Vorteil für die am weitesten verbreitete Methode zur Gewinnung von Blutproben während der Insulin-Klemmen, die aus dem abgetrennten Spitze des Schwanzes Probe. Im Gegensatz zu dieser letzteren Methode, Probenahme aus einem arteriellen Katheter ist nicht belastend für die Maus 1. Wir beschreiben auch Verfahren zur Verwendung Isotopen-Tracer-Infusionen, um Gewebe-spezifische Wirkung von Insulin zu bewerten. Wir bieten auch Richtlinien für die angemessene Präsentation der Ergebnisse aus der Insulin-Klemmen erhalten.

Watch this Scientific Journal Video about Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice at JoVE.com

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Die hyperinsulinämische-euglykämische Clamp-oder Insulin-Clamp, ist der Goldstandard für die Beurteilung der Wirkung von Insulin<em&gt; In vivo</em&gt;. Ein Verfahren zur Durchführung von Insulin Klemmen bei Mäusen beschrieben. Dieser umfasst ein Verfahren zum arteriellen Katheter, dass Experimente in bewusste, hemmungsloser Mäusen mit minimalem Stress durchgeführt werden ermöglicht.

Hyperinsulinämische-euglykämische Schellen in dem Bewusstsein, Unrestrained Mäuse

Type 2 diabetes is characterized by a defect in insulin action. The hyperinsulinemic-euglycemic clamp, or insulin clamp, is widely considered the "gold ...

hyperinsulinemic-euglycemic-clamps-in-conscious-unrestrained-mice

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93.9K Aufrufe.  Sanford-Burnham Medical Research Institute at Lake Nona. Die hyperinsulinämische-euglykämische Clamp-oder Insulin-Clamp, ist der Goldstandard für die Beurteilung der Wirkung von Insulin In vivo. Ein Verfahren zur Durchführung von Insulin Klemmen bei Mäusen beschrieben. Dieser umfasst ein Verfahren zum arteriellen Katheter, dass Experimente in bewusste, hemmungsloser Mäusen mit minimalem Stress durchgeführt werden ermöglicht.

Serie: Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Transthoracic Echocardiography in Mice

In recent years, murine models have become the primary avenue for studying the molecular mechanisms of cardiac dysfunction resulting from changes in gene expression. Transgenic and gene targeting methods can be used to generate mice with altered cardiac size and function,1-3 and as a result, in vivo techniques are needed to evaluate their cardiac phenotype. Transthoracic echocardiography, pulse wave Doppler (PWD), and tissue Doppler imaging (TDI) can be used to provide dimensional measurements of the mouse heart and to quantify the degree of cardiac systolic and diastolic performance. Two-dimensional imaging is used to detect abnormal anatomy or movements of the left ventricle, whereas M-mode echo is used for quantification of cardiac dimensions and contractility.4,5 In addition, PWD is used to quantify localized velocity of turbulent flow,6 whereas TDI is used to measure the velocity of myocardial motion.7 Thus, transthoracic echocardiography offers a comprehensive method for the noninvasive evaluation of cardiac function in mice.

Transthoracic echocardiography offers a noninvasive method for the evaluation of cardiac function in mice. A combination of ultrasound and Doppler imaging modalities can be used to obtain dimensional measurements of the heart and intracardiac blood flow, which together provide an assessment of cardiac systolic and diastolic performance.

Transthorakale Echokardiographie in Mäuse

In recent years, murine models have become the primary avenue for studying the molecular mechanisms of cardiac dysfunction resulting from changes in gene ...

Forschung

Medizin

Hyperinsulinemic-Euglycemic Clamp in the Conscious Rat

Type 2 diabetes (T2D) is rapidly rising in prevalence. Characterized by either inadequate insulin production or the inability to utilize insulin produced, T2D results in elevated blood glucose levels. The "gold-standard" in assessing insulin sensitivity is a hyperinsulinemic-euglycemic clamp or insulin clamp. In this procedure, insulin is infused at a constant rate resulting in a drop in blood glucose. To maintain blood glucose at a constant level, exogenous glucose (D50) is infused into the venous circulation. The amount of glucose infused to maintain homeostasis is indicative of insulin sensitivity. Here, we show the basic clamp procedure in the chronically catheterized, unrestrained, conscious rat. This model allows blood to be collected with minimal stress to the animal. Following the induction of anesthesia, a midline incision is made and the left common carotid artery and right jugular vein are catheterized. Inserted catheters are flushed with heparinized saline, then exteriorized and secured. Animals are allowed to recover for 4-5 days prior to experiments, with weight gain monitored daily. Only those animals who regain weight to pre-surgery levels are used for experiments. On the day of the experiment, rats are fasted and connected to pumps containing insulin and D50. Baseline glucose is assessed from the arterial line and used a benchmark throughout the experiment (euglycemia). Following this, insulin is infused at a constant rate into the venous circulation. To match the drop in blood glucose, D50 is infused. If the rate of D50 infusion is greater than the rate of uptake, a rise in glucose will occur. Similarly, if the rate is insufficient to match whole body glucose uptake, a drop will occur. Titration of glucose continues until stable glucose readings are achieved. Glucose levels and glucose infusion rates during this stable period are recorded and reported. Results provide an index of whole body insulin sensitivity. The technique can be refined to meet specific experimental requirements. It is further enhanced by the use of radioactive tracers that can determine tissue specific insulin-stimulated glucose uptake as well as whole body glucose turnover.

The hyperinsulinemic-euglycemic clamp is the "gold standard" for the assessment of insulin action. Insulin is infused at a constant rate stimulating glucose uptake. The amount of exogenous glucose infused to counter this drop is indicative of insulin sensitivity. Here the procedure is performed on a conscious, unrestrained rat.

Hyperinsulinämische-euglykämische Clamp in der Conscious Rat

Type 2 diabetes (T2D) is rapidly rising in prevalence. Characterized by either inadequate insulin production or the inability to utilize insulin produced, ...

Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures, Infusions and Blood Sampling in a Conscious Rat Model

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. Intra-tracheal inoculation of a known amount of bacteria has been successfully used to reproduce the pathogenesis of pneumonia which then develops into sepsis. Monitoring hemodynamic parameters and providing standard clinical treatment including infusion of antibiotics, fluids and drugs to maintain blood pressure is critical to simulate routine supportive care in this model but to do so requires both arterial and venous vascular access. The video details the surgical technique for implanting carotid artery and common jugular vein catheters in an anesthetized rat. Following a 72 hr recovery period, the animals will be re-anesthetized and connected to a tether and swivel setup attached to the rodent housing which connects the implanted catheters to the hemodynamic monitoring system. This setup allows free movement of the rat during the study while continuously monitoring pressures, infusing fluids and drugs (antibiotics, vasopressors) and performing blood sampling.

Vascular accesses to measure hemodynamics, provide fluids and perform blood sampling are important to any small animal model study. We present a technique for implanting catheters into the carotid artery and the common jugular vein in an anesthetized rat for connecting to a system to perform monitoring, infusions and sampling.

Katheterisierung der Halsschlagader und Vena jugularis zur hämodynamischen Maßnahmen im Conscious Rattenmodell durchführen, Infusionen und Blutentnahme

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse&#8217;s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.

This method was developed with the goal of delivering a steady drug solution via the carotid artery, to assess the pharmacokinetics of novel drugs in mouse models.

Halsschlagader Infusionen für pharmakokinetischen und pharmakodynamischen Analyse von Taxanen in Mäusen

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

Transcutaneous Assessment of Renal Function in Conscious Rodents

Glomerular filtration rate (GFR) is the gold standard to assess overall kidney function. However, traditional methods to evaluate GFR are cumbersome and time-consuming. In addition, serial blood or urine samples are required, with the associated stress for the experimental animals. A recent technique significantly reduces the investment in time and resources, minimizing the invasiveness and the animal stress, but being equally valid as the traditional approaches. The method measures transcutaneously renal function. Using an optical device and the exogenous renal marker fluorescein isothiocyanate (FITC)-sinistrin, this technique is capable of measuring the elimination kinetics of the marker through the skin. With neither blood nor urine samples nor the associated laboratory assays needed, the results of the transcutaneous measurement are almost instantaneously available. The method has been already validated in different species and successfully applied in several models of renal pathology. Moreover, due to its minimally invasive characteristics, it is suitable for sequential measurements within the same animal. Here is provided a detailed protocol to carry out the transcutaneous assessment of renal function in rodents.

Determination of glomerular filtration rate (GFR) is the gold standard to assess overall kidney function. However, traditional procedures to measure this parameter are cumbersome and require a large investment of time. Here we describe a faster and minimally invasive method to determinate GFR transcutaneously.

Transkutane Beurteilung der Nierenfunktion in Conscious Nagetiere

Glomerular filtration rate (GFR) is the gold standard to assess overall kidney function. However, traditional methods to evaluate GFR are cumbersome and ...

Novel Approach for Simultaneous Recording of Renal Sympathetic Nerve Activity and Blood Pressure with Intravenous Infusion in Conscious, Unrestrained Mice.

Renal sympathetic nerves contribute significantly to both physiological and pathophysiological phenomena. Evaluating renal sympathetic nerve activity (RSNA) is of great interest in many areas of research such as chronic kidney disease, hypertension, heart failure, diabetes and obesity. Unequivocal assessment of the role of the sympathetic nervous system is thus imperative for proper interpretation of experimental results and understanding of disease processes. RSNA has been traditionally measured in anesthetized rodents, including mice. However, mice usually exhibit very low systemic blood pressure and hemodynamic instability for several hours during anesthesia and surgery. Meaningful interpretation of RSNA is confounded by this non-physiological state, given the intimate relationship between sympathetic nervous tone and cardiovascular status. To address this limitation of traditional approaches, we developed a new method for measuring RSNA in conscious, freely-moving mice. Mice were chronically instrumented with radio-telemeters for continuous monitoring of blood pressure as well as a jugular venous infusion catheter and custom-designed bipolar electrode for direct recording of RSNA. Following a 48-72 hour recovery period, survival rate was 100% and all mice behaved normally. At this time-point, RSNA was successfully recorded in 80% of mice, with viable signals acquired up to 4 and 5 days post-surgery in 70% and 50% of mice, respectively. Physiological blood pressures were recorded in all mice (116&plusmn;2 mmHg; n=10). Recorded RSNA increased with eating and grooming, as well-established in the literature. Furthermore, RSNA was validated by ganglionic blockade and modulation of blood pressure with pharmacological agents. Herein, an effective and manageable method for clear recording of RSNA in conscious, freely-moving mice is described.

Anesthetized mice exhibit non-physiological systemic blood pressure, which precludes meaningful assessment of autonomic tone given the intimate relationship between blood pressure and the autonomic nervous system. Thus, a novel method to simultaneously record renal sympathetic nerve activity and blood pressure with intravenous infusion in conscious mice is outlined.

Neuer Ansatz zur gleichzeitigen Erfassung von renalen sympathischen Nerven-Aktivität und Blutdruck mit intravenösen Infusion in dem Bewusstsein, hemmungslose Mäuse.

Renal sympathetic nerves contribute significantly to both physiological and pathophysiological phenomena. Evaluating renal sympathetic nerve activity ...

Assessment of Respiratory Function in Conscious Mice by Double-chamber Plethysmography

Air volume changes created by a conscious subject breathing spontaneously within a body box are at the basis of plethysmography, a technique used to non-invasively assess some features of the respiratory function in humans as well as in laboratory animals. The present article focuses on the application of the double-chamber plethysmography (DCP) in small animals. It provides background information on the methodology as well as a detailed step-by-step procedure to successfully assess respiratory function in conscious, spontaneously breathing animals in a non-invasive manner. The DCP can be used to monitor the respiratory function of multiple animals in parallel, as well as to identify changes induced by aerosolized substances over a chosen time period and in a repeated manner. Experiments on control and allergic mice are used herein to demonstrate the utility of the technique, explain the associated outcome parameters, as well as to discuss the related advantages and shortcomings. Overall, the DCP provides valid and theoretically sound readouts that can be trusted to evaluate the respiratory function of conscious small animals both at baseline and after challenges with aerosolized substances.

The objective of the present article is to provide a detailed description of the recommended procedures to evaluate respiratory function in conscious mice by double-chamber plethysmography.

Beurteilung der Atemfunktion in bewusste Mäuse durch Doppel-Kammer-Plethysmographie

Air volume changes created by a conscious subject breathing spontaneously within a body box are at the basis of plethysmography, a technique used to ...

Repeated Orotracheal Intubation in Mice

The literature describes several methods for mouse intubation that either require visualization of the glottis through the oral cavity or incision in the ventral neck for direct confirmation of cannula placement in the trachea. The relative difficulty or the tissue trauma induced to the subject by such procedures can be an impediment to an investigator&#8217;s ability to perform longitudinal studies. This article illustrates a technique in which physical manipulation of the mouse following the use of a depilatory to remove hair from the ventral neck permits transcutaneous visualization of the trachea for orotracheal intubation regardless of degree of skin pigmentation. This method is innocuous to the subject and easily achieved with a limited understanding of murine anatomy. This refined approach facilitates repeated intubation, which may be necessary for monitoring progression of disease or instillation of treatments. Using this method may result in a reduction of the number of animals and technical skill required to measure lung function in mouse models of respiratory disease.

The goal of this article is to describe a refined method of intubation of the laboratory mouse. The method is noninvasive and, therefore, ideal for studies that require serial monitoring of respiratory function and/or instillation of treatments into the lung.

Wiederholte orotracheale Intubation bei Mäusen

The literature describes several methods for mouse intubation that either require visualization of the glottis through the oral cavity or incision in the ...

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.

Implantation von kombinierten telemetrischen EKG- und Blutdrucktransmittern zur Bestimmung der spontanen Baroreflexsensitivität bei bewussten Mäusen

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

Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits

Patients with ion channelopathies are at a high risk of developing seizures and fatal cardiac arrhythmias. There is a higher prevalence of heart disease and arrhythmias in people with epilepsy (i.e., epileptic heart.) Additionally, cardiac and autonomic disturbances have been reported surrounding seizures. 1:1,000 epilepsy patients/year die of sudden unexpected death in epilepsy (SUDEP). The mechanisms for SUDEP remain incompletely understood. Electroencephalograms (EEG) and electrocardiograms (ECG) are two techniques routinely used in the clinical setting to detect and study the substrates/triggers for seizures and arrhythmias. While many studies and descriptions of this methodology are in rodents, their cardiac electrical activity differs significantly from humans. This article provides a description of a non-invasive method for recording simultaneous video-EEG-ECG-oximetry-capnography in conscious rabbits. As cardiac electrical function is similar in rabbits and humans, rabbits provide an excellent model of translational diagnostic and therapeutic studies. In addition to outlining the methodology for data acquisition, we discuss the analytical approaches for examining neuro-cardiac electrical function and pathology in rabbits. This includes arrhythmia detection, spectral analysis of EEG and a seizure scale developed for restrained rabbits.

Using simultaneous video-EEG-ECG-oximetry-capnography, we developed a methodology to evaluate the susceptibility of rabbit models to develop provoked arrhythmias and seizures. This novel recording system establishes a platform to test the efficacy and safety of therapeutics and can capture the complex cascade of multi-system events that culminate in sudden death.

Multisystem-Monitoring zur Identifizierung von Anfällen, Arrhythmien und Apnoe bei bewusst zurückhaltenden Kaninchen

Patients with ion channelopathies are at a high risk of developing seizures and fatal cardiac arrhythmias. There is a higher prevalence of heart disease ...