Name: long-term blood pressure measurement in freely moving mice using telemetry
Uploaded: 2016-05-17T14:00:00.000+00:00
Duration: 7 min 54 s
Description: Watch this Scientific Journal Video about Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry at JoVE.com

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

Ethik-Anweisung: Alle Tier Verfahren in diesem Video-Artikel erwähnt wurden überprüft und von der Animal Care und Use Committee (IACUC) an der University of Tennessee Health Science Center genehmigt. Hinweis: Verwenden Sie sterile Mikro Instrumente während des chirurgischen Eingriffs. Chirurgische Instrumente sterilisiert werden können, einen Infrarot-Sterilisator in einem optimalen Sterilisationstemperatur von 1.500 ° F (815,6 ° C) verwendet. Entfernungsmesser kann wiederverwendet werden, jedoch, bevor es in das Tier sicher Einführen des gesamten Senders gemäß der Anweisungen des Herstellers, und dass die Spitze des Katheters mit einem speziellen Gel wurde vom Hersteller bereitgestellt nachgefüllt zu sterilisieren. 1. Versuchstiere <ol><li> Erhalten Sie IACUC Genehmigung für alle Experimente, die durchgeführt werden soll. Beratung bei institutionellen IACUC ist stark in Bezug auf Anforderungen empfohlen für die postoperative Analgesie nach diesem Verfahren. </li><li> Halten Sie die Tiere in clima kontrollierter Räume eine Umgebungstemperatur von 21 ° C, 60% relative Luftfeuchtigkeit, und eine 12-Stunden-Licht-Dunkel-Zyklus mit freiem Zugang zu Nahrung und Wasser. Anmerkung: Da die Mauskörper den Telemetriesonde aufzunehmen hat (annähernd 1 cm Durchmesser x 2 cm lang), es bevorzugt ist, Mäuse zu verwenden, die 20 g oder mehr wiegen. </li></ol> 2. Anästhesie und Operative Vorbereitung <ol><li> Wiegen Sie die Maus, um eine Präzisionswaage mit und notieren Sie sein Gewicht. Achten Sie darauf, das Tier sanft und leise zu behandeln. </li><li> Legen Sie das Tier in die Induktionskammer und schließen Sie es. Eingestellt Sauerstoffdurchflussrate von 0,5 L / min und eingestellt Isofluran-Konzentration bei 4 bis 5%. </li><li> Wenn die Maus das Bewusstsein verliert, legen Sie es auf eine Körperwärmeplatte bei 36 gehalten - 37 ° C. Pflegen Sie die Anästhesie über nosecone mit Isofluran-Set mit 2% (halten Durchfluss bei 0,5 l / min). </li><li> Bereiten Sie die Betriebsbereiche durch das Haar von der Rückseite des Halses zu entfernen und ter ventralen Seite des Halses durch Enthaarungscreme Anwendung. </li><li> Behandeln Sie die Inzisionsstelle mit 3-Anwendungen von chirurgischen Peeling (Betadin-Lösung) im Wechsel mit 70% Isopropylalkohol. </li></ol> 3. Chirurgie <ol><li> Platzieren Sie die Maus in Rückenlage. Prüfen Sie, ob Reflexe durch den Fuß Kneifen und Anästhesie anpassen, bis es keine Antwort gibt. Bilden eine in etwa 1 cm-Mittelschnitt unter dem Hals der Maus mit einem Skalpell. In der linken Seite des Schnitts einen subkutanen Raum schaffen, indem Sie vorsichtig die Haut von dem darunterliegenden Bindegewebe trennt. </li><li> Drehen Sie die Maus, und verwenden Sie ein Skalpell, um einen Hautschnitt von ca. 1,5 cm in der dorsalen linken Seite hinter dem Schulterblatt. Erstellen Sie eine subkutane Tasche entlang der Flanke des Tieres groß genug, um das Gerät aufzunehmen. Stecken Sie den Sender in die Tasche. </li><li> Legen Sie eine kleine hemostat Klemme in den Rücken Einschnitt und manövrieren sie subkutan in Richtung der vorderenHalsöffnung. Mit dem eingefügten hemostat Klemme, greifen Sie sanft ein ungiftiges Polyethylenrohr (4 cm Länge x 1 mm ID). <ol><li> Ziehen Sie den hemostat zurück durch den Tunnel aus dem lateralen Einschnitt in den Rücken, bis der Schlauch von beiden Bauch- und Dorsalschnitt ragt, lassen Sie den Schlauch vom hemostat. Von der Rückseite, legen Sie die Katheter-Sensor in das Rohr Tunnel die Spitze des Drucksensorkatheter durch den Hals. Vom Hals vorderen, ziehen und den Polyethylenschlauch entfernen und den Dorsalschnitt mit Metallklammern schließen. </li></ol></li><li> Trennen Sie sorgfältig die Mandibeldrüsen mit sterilen Spitze Applikatoren Baumwolle und Einfahren der linken Kieferdrüse einen elastischen Aufenthalt Haken verwenden. Mit feinen bestückte gebogenen Pinzette, suchen Sie die Arteria carotis auf der linken Seite der Trachea. Halten Sie die Operationsstelle steril, indem und eine sterile Abdeckung zu sichern. <ol><li> Sorgfältig isolieren, das Schiff aus dem umgebenden Gewebe und trennen sanft dieVagusnerv (weißlich), die entlang der A. carotis von der Arterie entfernt ist. Achten Sie darauf, nicht zu schneiden oder die Nerven oder die Arterie beschädigt werden. </li></ol></li><li> Führen Sie drei Stücke von nicht resorbierbaren 7-0 Naht unterhalb der isolierten Arteria carotis Abschnitt. Binden Sie die Schädelnaht zu verschließen Blutfluss. Ziehen Sie die Naht, die am nächsten an der Brustbeins ist, um vorübergehend den Blutfluss aus der Aorta zu verschließen. </li><li> Machen Sie einen lockeren Knoten in der Mitte Naht verwendet wird. Dies wird verwendet, um den Katheter in dem Gefäß zu befestigen. Schneiden Sie einen kleinen Einschnitt in die Arterie zwischen der Schädel und den sternal Nähte mit Mikro-Schere. </li><li> Ergreifen Sie den Katheter mit Spezialschiff Kanülierung Zange, wobei darauf geachtet, den Katheter nicht zu quetschen Gel Verlust von der Sonde zu verhindern. Sanft mit einer feinen Spitze gebogenen Pinzette Pinzette die Arterie greifen, um den Katheter abzurufen und es in dem Gefäß durch den kleinen Einschnitt ein. </li><li> Ziehen Sie die mittlere Nahtknoten um die Arterie und sanft die Katze voranheter. Vorsichtig lassen Sie die Naht, die mit dem Brustbein proximal und weiterhin den Katheter in Richtung der Quer Aorta zu fördern. <ol><li> Beachten Sie die Markierung auf dem Katheter, der eine ungefähre Index gibt, wie weit der Katheter eingeführt werden soll. Sobald der Punkt erreicht ist, sanft ziehen sowohl die untere und die obere Naht um den Katheter. Der Katheter wird in die Arteria carotis durch Naht Knoten gesichert. </li></ol></li><li> Schließen Sie den Hautschnitt mit nicht resorbierbaren 5-0 Naht. Einmal geschlossen, dichten den Einschnitt mit Gewebekleber. </li></ol> 4. Chirurgische Erholung und BP-Messungen <ol><li> Monitor-Tier eng für die Rückkehr der normalen Körperhaltungen und Verhaltensweisen. Während der 24 Stunden nach der Operation Zeitraum verabreichen Analgesie, wie durch einen Mitarbeiter Tierarzt gerichtet. </li><li> Sobald die Tiere erholt haben (5 bis 7 Tage nach der Operation), Das Haus sie einzeln in einem regelmäßigen Käfig Maus auf der Oberseite des Telemetrie-Empfänger Platte gelegt. </li><li> Drehen Sie den implantierten transmitters &quot;on&quot; und &quot;off&quot; durch eine Magnetvorrichtung kurz nahe Verwendung von der Außenseite des Käfigs zu dem Tier positioniert ist. </li></ol>

<ol>
	<li>Danaei, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+preventable+causes+of+death+in+the+United+States:+comparative+risk+assessment+of+dietary,+lifestyle,+and+metabolic+risk+factors.">The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors.</a> PLoS Med. 6 (4), e1000058 (2009).</li><li>Dornas, W. C., Silva, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+for+the+study+of+arterial+hypertension.">Animal models for the study of arterial hypertension.</a> J Biosci. 36 (4), 731-737 (2011).</li><li>Henze, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persistent+alterations+in+heart+rate+variability,+baroreflex+sensitivity,+and+anxiety-like+behaviors+during+development+of+heart+failure+in+the+rat.">Persistent alterations in heart rate variability, baroreflex sensitivity, and anxiety-like behaviors during development of heart failure in the rat.</a> Am J Physiol Heart Circ Physiol. 295 (1), H29-H38 (2008).</li><li>Hoffmann, D. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+tempol+prevents+hypertension,+proteinuria,+and+poor+feto-placental+outcomes+in+BPH/5+mouse+model+of+preeclampsia.">Chronic tempol prevents hypertension, proteinuria, and poor feto-placental outcomes in BPH/5 mouse model of preeclampsia.</a> Hypertension. 51 (4), 1058-1065 (2008).</li><li>Lerman, L. O., Chade, A. R., Sica, V., Napoli, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+hypertension:+an+overview.">Animal models of hypertension: an overview.</a> J Lab Clin Med. 146 (3), 160-173 (2005).</li><li>Johns, C., Gavras, I., Handy, D. E., Salomao, A., Gavras, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Models+of+experimental+hypertension+in+mice.">Models of experimental hypertension in mice.</a> Hypertension. 28 (6), 1064-1069 (1996).</li><li>Vatner, S. F., Braunwald, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiovascular+control+mechanisms+in+the+conscious+state.">Cardiovascular control mechanisms in the conscious state.</a> N Engl J Med. 293 (19), 970-976 (1975).</li><li>Zhao, X., 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=Arterial+Pressure+Monitoring+in+Mice.">Arterial Pressure Monitoring in Mice.</a> Curr Protoc Mouse Biol. 1, 105-122 (2011).</li><li>Whitesall, S. E., Hoff, J. B., Vollmer, A. P., D'Alecy, L. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+simultaneous+measurement+of+mouse+systolic+arterial+blood+pressure+by+radiotelemetry+and+tail-cuff+methods.">Comparison of simultaneous measurement of mouse systolic arterial blood pressure by radiotelemetry and tail-cuff methods.</a> Am J Physiol Heart Circ Physiol. 286 (6), H2408-H2415 (2004).</li><li>Kurtz, T. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recommendations+for+blood+pressure+measurement+in+humans+and+experimental+animals.+Part+2:+Blood+pressure+measurement+in+experimental+animals:+a+statement+for+professionals+from+the+subcommittee+of+professional+and+public+education+of+the+American+Heart+Association+council+on+high+blood+pressure+research.">Recommendations for blood pressure measurement in humans and experimental animals. Part 2: Blood pressure measurement in experimental animals: a statement for professionals from the subcommittee of professional and public education of the American Heart Association council on high blood pressure research.</a> Hypertension. 45 (2), 299-310 (2005).</li><li>Kurtz, T. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recommendations+for+blood+pressure+measurement+in+animals:+summary+of+an+AHA+scientific+statement+from+the+Council+on+High+Blood+Pressure+Research,+Professional+and+Public+Education+Subcommittee.">Recommendations for blood pressure measurement in animals: summary of an AHA scientific statement from the Council on High Blood Pressure Research, Professional and Public Education Subcommittee.</a> Arterioscler Thromb Vasc Biol. 25 (3), 478-479 (2005).</li></ol>

The authors have nothing to disclose.

Implantierbare Radio-Telemetrie hat sich in den letzten zehn Jahren verbessert; kleinere Sondengröße macht weniger das Implantat traumatische für das Tier, verlängert die Lebensdauer der Batterie hilft, die Kosten und unabhängige Entfernungsmesser Frequenzen beseitigen Übersprechens zwischen den Empfängern zu reduzieren. Telemetrie wird der state-of-the-art - Verfahren betrachtet zum Sammeln einer Vielzahl von physiologischen Parametern von frei Tiere ohne die Artefakte , die mit der Verwendung von Rückhalte, me...

Bluthochdruck ist einer der wichtigsten Risikofaktoren für Herz - Kreislauf - Erkrankungen, wohl ist es ein wichtiges Problem der öffentlichen Gesundheit sowohl in Industrie- und Entwicklungsländern 1. Mehreren Tiermodellen experimenteller Hypertonie wurden beim Menschen 2 hypertensiven Reaktionen wie die beobachtet nachzuahmen entwickelt. Unter anderem stellt die ambulante Maus ein hervorragendes Modell , um die Entstehung und das Fortschreiten der Hypertonie zu untersuchen ermöglicht in vivo Analyse der Folgen einer chronischen Exposition bei Hypertonie. Der Blutdruck (BP) Überwachung bei Mäusen hat Forscher dazu beigetragen , verschiedene Mechanismen in der Physiologie und Pathophysiologie von Erkrankungen wie Bluthochdruck und Herzinsuffizienz 3, 4 beteiligt zu entwirren. Tatsächlich Manipulation der Maus - Genom erlaubt Erzeugung transgener oder Gen-Targeting geeignete Modelle für das Studium Hypertension 5, 6. Aber auch sanfte Manipulationbewußter Mäusen induziert Aufregungen , die möglicherweise Artefakte während der Datenerfassung einführen kann, während die Verwendung von Sedierung oder tief Tranquilizer Blutdruck 7 beeinflussen. Diese Aspekte sind besonders wichtig und muss in Betracht gezogen werden, wenn langfristige BP Überwachung versuchen. Es gibt mehrere Möglichkeiten BP in Mäusen zu erfassen, und ein Vergleich zwischen den gebräuchlichsten Techniken , die derzeit verfügbar diskutiert wurde an anderer Stelle 8, 9. Allerdings schlossen die AHA Empfehlungen für BP - Messung , dass die intraarterielle Messung von BP werden in der Regel wegen ihrer Fähigkeit bevorzugt direkt BP über einen längeren Zeitraum 10 messen. Radio-Telemetrie gekoppelt mit der direkten Messung des arteriellen Drucks ist die State-of-the-art Verfahren zur Überwachung physiologischer Funktionen in wach und frei Labortiere zu bewegen , während Stress zu minimieren und umweltassoziierten Artefakte 9, 11.Radio-Telemetrie bietet die Möglichkeit, automatisch Blutdruck, Herzfrequenz, Körpertemperatur und Tieraktivität von mehreren wachen Tieren sammeln. Obwohl diese Methode ist in vielen Labors immer sehr beliebt, Radio-Telemetrie-Implantation in Mäuse können technisch anspruchsvoll sein. Hier zeigen wir einen Schritt-für-Schritt-Protokoll, das zeigt, wie ein Druckwandler in Mäusen zu implantieren. Die Technik beinhaltet subkutane Einführen der Sonde in dem Mausgehäuse, kanalisieren, um den Katheter an den Hals und nach vorne in der Nähe des Aortenbogens über die linke Arteria carotis. Remotely erfassten Daten werden live auf dem Computer-Monitor angezeigt. Die Daten werden auch für &quot;off-line&quot; Analyse gespeichert.

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

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

Bei der Entwicklung von neuen vasoaktiven Mitteln, arterielle Blutdrucküberwachung von entscheidender Bedeutung für die Wirksamkeit der vorgeschlagenen neuen Medikamenten zu bewerten. Tatsächlich Forschung auf die Entdeckung neuer potentielle therapeutische Targets konzentriert genetisch veränderte Mäuse verwendet, erfordert eine zuverlässige, langfristige Beurteilung der systemischen arteriellen Druckschwankung. Derzeit ist der Goldstandard Langzeitmessungen des Blutdrucks in der ambulanten Mäuse verwendet implantierbare Radiosender für den Erhalt, die Arterie Kanülierung erfordern. Diese Technik eliminiert die Notwendigkeit für Tethering, Bändigen, oder die Tiere zu betäuben, die Stress und Artefakte während der Datensampling einzuführen. Jedoch kann arterielle Blutdruckmessung in Mäusen über Katheterisierung ziemlich schwierig sein, aufgrund der geringen Größe der Arterien. Hier präsentieren wir eine Schritt-für-Schritt-Anleitung, die entscheidenden Schlüsselstellen für eine erfolgreiche subkutane Implantation von Radiosendern und Arteria carotis c illustrierenAnellierung in Mäusen. Wir sind auch Beispiele für Langzeit-Blutdruckaktivität von sich frei bewegenden Mäusen entnommen nach einer Zeit der postoperative Genesung. Im Anschluss an dieses Verfahren ermöglicht zuverlässige direkten Blutdruckaufzeichnungen von mehreren Tieren gleichzeitig.

Die Daten können von einem Empfänger erfasst remote; Spuren werden auf einem Computer - Bildschirm für die Qualitätskontrolle (Abbildung 1a) sichtbar gemacht . Details wie Tier ID, ​​der diastolische Blutdruck und der systolische Blutdruck werden auch (1b) gezeigt ist . Arterial BP kontinuierlich (24/7) aufgenommen werden können, oder für kurze programmierten Intervallen (dh 60 sec Akquisitions jede Stunde). Daten können automatisch a...

Watch this Scientific Journal Video about Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry at JoVE.com

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

Langzeit-Blutdruckmessung in sich frei bewegenden Mäuse Telemetrie

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

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

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

Research

JoVE Journal

Medicine

18.7K Aufrufe.  University of Tennessee Health Sciences Center. The goal of this protocol is to assess systemic blood pressure in conscious freely moving mice using implantable radio-telemetry devices.

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

Implantation of Radiotelemetry Transmitters Yielding Data on ECG, Heart Rate, Core Body Temperature and Activity in Free-moving Laboratory Mice

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a manageable size and relatively easy to house. These factors, together with the availability of a wealth of spontaneous and experimentally induced mutants, make laboratory mice ideally suited to a wide variety of research areas.
In cardiovascular, pharmacological and toxicological research, accurate measurement of parameters relating to the circulatory system of laboratory animals is often required. Determination of heart rate, heart rate variability, and duration of PQ and QT intervals are based on electrocardiogram (ECG) recordings. However, obtaining reliable ECG curves as well as physiological data such as core body temperature in mice can be difficult using conventional measurement techniques, which require connecting sensors and lead wires to a restrained, tethered, or even anaesthetized animal. Data obtained in this fashion must be interpreted with caution, as it is well known that restraining and anesthesia can have a major artifactual influence on physiological parameters1, 2.
Radiotelemetry enables data to be collected from conscious and untethered animals. Measurements can be conducted even in freely moving animals, and without requiring the investigator to be in the proximity of the animal. Thus, known sources of artifacts are avoided, and accurate and reliable measurements are assured. This methodology also reduces interanimal variability, thus reducing the number of animals used, rendering this technology the most humane method of monitoring physiological parameters in laboratory animals3, 4. Constant advancements in data acquisition technology and implant miniaturization mean that it is now possible to record physiological parameters and locomotor activity continuously and in realtime over longer periods such as hours, days or even weeks3, 5.
Here, we describe a surgical technique for implantation of a commercially available telemetry transmitter used for continuous measurements of core body temperature, locomotor activity and biopotential (i.e. onelead ECG), from which heart rate, heart rate variability, and PQ and QT intervals can be established in freeroaming, untethered mice. We also present pre-operative procedures and protocols for post-operative intensive care and pain treatment that improve recovery, well-being and survival rates in implanted mice5, 6.

A surgical technique for implantation of commercially available telemetry transmitters used for continuous measurement of biopotential (one-lead ECG), heart rate, core body temperature and locomotor activity in freely moving mice is shown. Recommendations and protocols for post-operative care and pain relief, improving recovery, well being and survival rate are also presented.

Die Implantation von Radiotelemetrie Sender Nachgeben Daten über EKG, Herzfrequenz, Körpertemperatur und Aktivität in frei bewegliche Labormäusen

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a ...

Forschung

Medizin

Measuring Blood Pressure in Mice using Volume Pressure Recording, a Tail-cuff Method

The CODA 8-Channel High Throughput Non-Invasive Blood Pressure system measures the blood pressure in up to 8 mice or rats simultaneously. The CODA tail-cuff system uses Volume Pressure Recording (VPR) to measure the blood pressure by determining the tail blood volume. A specially designed differential pressure transducer and an occlusion tail-cuff measure the total blood volume in the tail without the need to obtain the individual pulse signal. Special attention is afforded to the length of the occlusion cuff in order to derive the most accurate blood pressure readings. VPR can easily obtain readings on dark-skinned rodents, such as C57BL6 mice and is MRI compatible. The CODA system provides you with measurements of six (6) different blood pressure parameters; systolic and diastolic blood pressure, heart rate, mean blood pressure, tail blood flow, and tail blood volume. Measurements can be made on either awake or anesthetized mice or rats. The CODA system includes a controller, laptop computer, software, cuffs, animal holders, infrared warming pads, and an infrared thermometer. There are seven different holder sizes for mice as small as 8 grams to rats as large as 900 grams.

The CODA 8-Channel High Throughput Non-Invasive Blood Pressure system measures the blood pressure in up to 8 mice or rats simultaneously. This tail-cuff system uses Volume Pressure Recording (VPR) to measure the blood pressure by determining the tail blood volume.

Blutdruckmessung in Mäuse mit Volume Druck Recording, ein Tail-Manschette Methode

The CODA 8-Channel High Throughput Non-Invasive Blood Pressure system measures the blood pressure in up to 8 mice or rats simultaneously. The CODA ...

Biologie

Monitoring of Systemic and Hepatic Hemodynamic Parameters in Mice

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. However, due to the small size of the mouse, technical details of the intraoperative monitoring procedure suitable for the mouse were rarely described. Previously we have reported a monitoring procedure to obtain hemodynamic parameters for rats. Now, we adapted the procedure to acquire systemic and hepatic hemodynamic parameters in mice, a species ten-fold smaller than rats. This film demonstrates the instrumentation of the animals as well as the data acquisition process needed to assess systemic and hepatic hemodynamics in mice. Vital parameters, including body temperature, respiratory&#160;rate&#160;and heart&#160;rate were recorded throughout the whole procedure. Systemic hemodynamic parameters consist of carotid artery pressure (CAP) and central venous pressure (CVP). Hepatic perfusion parameters include portal vein pressure (PVP), portal flow rate as well as the flow rate of the common hepatic artery (table 1). Instrumentation and data acquisition to record the normal values was completed within 1.5 h. Systemic and hepatic hemodynamic parameters remained within normal ranges during this procedure.
This procedure is challenging but feasible. We have already applied this procedure to assess hepatic hemodynamics in normal mice as well as during 70% partial hepatectomy and in liver lobe clamping experiments. Mean PVP after resection (n= 20), was 11.41&#177;2.94 cmH2O which was significantly higher (P&#60;0.05) than before resection (6.87&#177;2.39 cmH2O). The results of liver lobe clamping experiment indicated that this monitoring procedure is sensitive and suitable for detecting small changes in portal pressure and portal flow rate. In conclusion, this procedure is reliable in the hands of an experienced micro-surgeon but should be limited to experiments where mice are absolutely needed.

This film demonstrates how to acquire systemic and hepatic hemodynamics in mice. The whole monitoring includes acquisition of vital parameters, systemic blood pressure, central venous pressure, common hepatic artery flow rate, and portal vein pressure as well as the portal flow rate in mice.

Überwachung der System und Leber hämodynamischen Parameter in Mäuse

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. ...

Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

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

Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

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

Intrauterine Telemetrie zur Maus Kontraktionsdruck messen<em&gt; In-vivo-</em

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

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 ...

Simultaneous Electrocardiography Recording and Invasive Blood Pressure Measurement in Rats

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

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

Gleichzeitige Elektrokardiographie Aufnahme und Invasive Blut Druckmessung bei Ratten

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

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. ...

Long-Term Continuous Measurement of Renal Blood Flow in Conscious Rats

The kidneys play a crucial role in maintaining the homeostasis of body fluids. The regulation of renal blood flow (RBF) is essential to the vital functions of filtration and metabolism in kidney function. Many acute studies have been carried out in anesthetized animals to measure RBF under various conditions to determine mechanisms responsible for the regulation of kidney perfusion. However, for technical reasons, it has not been possible to measure RBF continuously (24 h/day) in unrestrained unanesthetized rats over prolonged periods. These methods allow the continuous determination of RBF over many weeks while also simultaneously recording blood pressure (BP) with implanted catheters (fluid-filled or by telemetry). RBF monitoring is carried out with rats placed in a circular servo-controlled rat cage that enables the unrestrained movement of the rat throughout the study. At the same time, the tangling of cables from the flow probe and arterial catheters is prevented. Rats are first instrumented with an ultrasonic flow probe placement on the left renal artery and an arterial catheter implanted in the right femoral artery. These are routed subcutaneously to the nape of the neck, and connected to the flowmeter and pressure transducer, respectively, to measure RBF and BP. Following surgical implantation, rats are immediately placed in the cage to recover for at least one week and stabilize the ultrasonic probe recordings. Urine collection is also feasible in this system. The surgical and post-surgical procedures for continuous monitoring are demonstrated in this protocol.

The present protocol describes a long-term continuous measurement of renal blood flow in conscious rats and simultaneously recording blood pressure with implanted catheters (fluid-filled or by telemetry).

Kontinuierliche Langzeitmessung des renalen Blutflusses bei bewussten Ratten

The kidneys play a crucial role in maintaining the homeostasis of body fluids. The regulation of renal blood flow (RBF) is essential to the vital ...

Multiple Intravenous Bolus Dosing and Invasive Hemodynamic Assessment in a Hypoxia-Induced Mouse Pulmonary Artery Hypertension Model

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease, primarily affecting small pulmonary arterioles of the lung. Currently, there is no cure for PAH. It is important to discover new compounds that can be used to treat PAH. The mouse hypoxia-induced PAH model is a widely used model for PAH research. This model recapitulates human clinical manifestations of PAH Group 3 disease and is an important research tool to evaluate the effectiveness of new experimental therapies for PAH. Research using this model often requires the administration of compounds in mice. For a compound that needs to be given directly into the bloodstream, optimizing intravenous (IV) administration is a key part of the experimental procedures. Ideally, the IV injection system should permit multiple injections over a set time course. Although the mouse hypoxia-induced PAH model is very popular in many laboratories, it is technically challenging to perform multiple IV bolus dosing and invasive hemodynamic assessment in this model. In this protocol, we present step-by-step instructions on how to carry out multiple IV bolus dosing via mouse jugular vein and perform arterial and right ventricle catheterization for hemodynamic assessment in mouse hypoxia-induced PAH model.

This protocol provides a step-by-step procedure for executing multiple intravenous bolus dose administration and invasive hemodynamic monitoring in mice. Investigators can use this protocol for future therapeutic compound screening for pulmonary artery hypertension.

Multiple intravenöse Bolusdosierung und invasive hämodynamische Beurteilung in einem Hypoxie-induzierten Mausmodell für pulmonalarterielle Hypertonie

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease, primarily affecting small pulmonary arterioles of the lung. Currently, ...

Simple Continuous Glucose Monitoring in Freely Moving Mice

Mice are a common model organism used to study metabolic diseases such as diabetes mellitus. Glucose levels are typically measured by tail-bleeding, which requires handling the mice, causes stress, and does not provide data on freely behaving mice during the dark cycle. State-of-the-art continuous glucose measurement in mice requires inserting a probe into the aortic arch of the mouse, as well as a specialized telemetry system. This challenging and expensive method has not been adopted by most labs. Here, we present a simple protocol involving the utilization of commercially available continuous glucose monitors used by millions of patients to measure glucose continuously in mice as a part of basic research. The glucose-sensing probe is inserted into the subcutaneous space in the back of the mouse through a small incision to the skin and is held in place tightly using a couple of sutures. The device is sutured to the mouse skin to ensure it remains in place. The device can measure glucose levels for up to 2 weeks and sends the data to a nearby receiver without any need to handle the mice. Scripts for the basic data analysis of glucose levels recorded are provided. This method, from surgery to computational analysis, is cost-effective and potentially very useful in metabolic research.

Here, we describe a simple method to implant a commercial continuous glucose monitor designed for patients onto mice and provide the scripts to analyze the results.

Einfache kontinuierliche Glukosemessung bei frei beweglichen Mäusen

Mice are a common model organism used to study metabolic diseases such as diabetes mellitus. Glucose levels are typically measured by tail-bleeding, which ...