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Abstract
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Medicine

Ein Rattenmodell von Kammerflimmern und Reanimation durch konventionelle Closed-Brust-Technik

Published: April 26, 2015
doi:
10.3791/52413
, ,
1Resuscitation Institute,Rosalind Franklin University of Medicine and Science

Summary

This article describes a rat model of electrically-induced ventricular fibrillation and resuscitation by chest compression, ventilation, and delivery of electrical shocks that simulates an episode of sudden cardiac arrest and conventional cardiopulmonary resuscitation. The model enables gathering insights on the pathophysiology of cardiac arrest and exploration of new resuscitation strategies.

Abstract

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic components of cardiopulmonary resuscitation in humans is herein described. The model was developed in 1988 and has been used in approximately 70 peer-reviewed publications examining a myriad of resuscitation aspects including its physiology and pathophysiology, determinants of resuscitability, pharmacologic interventions, and even the effects of cell therapies. The model featured in this presentation includes: (1) vascular catheterization to measure aortic and right atrial pressures, to measure cardiac output by thermodilution, and to electrically induce ventricular fibrillation; and (2) tracheal intubation for positive pressure ventilation with oxygen enriched gas and assessment of the end-tidal CO2. A typical sequence of intervention entails: (1) electrical induction of ventricular fibrillation, (2) chest compression using a mechanical piston device concomitantly with positive pressure ventilation delivering oxygen-enriched gas, (3) electrical shocks to terminate ventricular fibrillation and reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic and metabolic function, and (5) assessment of survival and recovery of organ function. A robust inventory of measurements is available that includes – but is not limited to – hemodynamic, metabolic, and tissue measurements. The model has been highly effective in developing new resuscitation concepts and examining novel therapeutic interventions before their testing in larger and translationally more relevant animal models of cardiac arrest and resuscitation.

Introduction

In der Nähe von 360.000 Personen in den Vereinigten Staaten ein und viele mehr leiden weltweit 2 Episoden plötzlichen Herzstillstand jedes Jahr. Versuche, Leben wiederherzustellen erfordern nicht nur, daß die Herzaktivität wiederhergestellt werden, doch dass die Schädigung lebenswichtiger Organe verhindert werden, minimiert wird, oder umgekehrt. Aktuelle Reanimation Techniken ergeben eine erste Wiederbelebungsrate von ca. 30%; jedoch ist das Überleben bis zur Krankenhausentlassung nur 5% 1. Myokardiale Dysfunktion, neurologische Funktionsstörung, systemische Entzündung, Begleiterkrankungen, oder eine Kombination davon auftreten Postreanimationskonto für den Großteil der Patienten, die trotz anfänglicher Rückzirkulations sterben. So besseres Verständnis der Pathophysiologie und neuartige Reanimation Ansätze sind dringend erforderlich, um die Rate der ersten Reanimation und anschließende Überleben mit intakter Organfunktion zu erhöhen.

Tiermodusls von Herzstillstand eine entscheidende Rolle in der Entwicklung neuer Therapien Reanimation durch Einblicke in die Pathophysiologie von Herzstillstand und Reanimation und bietet praktische Hilfe zu konzipieren und zu testen, neue Interventionen, bevor sie beim Menschen 3 getestet werden. Das Rattenmodell der geschlossenen Brust kardiopulmonalen Reanimation (CPR) beschriebenen hat eine wichtige Rolle gespielt. Wissenschaftlicher Mitarbeiter an der Zeit – – 4 im Labor des verstorbenen Professor Max Harry Weil MD, Ph.D., und ihre Mitarbeiter Das Modell wurde 1988 von Irene von Planta entwickelt an der Universität für Gesundheitswissenschaften (umbenannt Rosalind Franklin Universität für Medizin und Wissenschaft im Jahr 2004) und wurde umfangreich im Bereich der Reanimation überwiegend von Stipendiaten der Professor Weil und ihre Auszubildenden eingesetzt.

Das Modell simuliert eine Episode von plötzlichen Herzstillstand mit Reanimation durch konventionelle CPR Techniken versucht und umfasst somit inductIonen des Kammerflimmerns (VF) durch die Bereitstellung eines elektrischen Stroms an der rechten ventrikulären Endokard und Bereitstellung der geschlossenen Brust CPR durch einen pneumatisch angetriebenen Kolben-Vorrichtung, während gleichzeitig liefern positive Druckventilation mit Sauerstoff angereicherten Gases. Beendigung der VF wird durch transthorakale Lieferung von elektrischen Schlägen erreicht. Die Ratten-Modell schafft ein Gleichgewicht zwischen Modellen in großen Tieren (zB Schweine) und Modelle in kleineren Tieren entwickelt entwickelt (zB Mäuse) ermöglicht die Erkundung neuer Forschungskonzepte in einem gut standardisiert, reproduzierbar und effizient mit Zugang zu einem robusten Bestandsaufnahme der einschlägigen Messungen. Das Modell ist besonders nützlich in einem frühen Stadium der Forschung, um neue Konzepte der Auswirkungen der Störgrößen vor der Durchführung von Untersuchungen in größeren Tiermodelle, kostspieliger zu erforschen und zu untersuchen, aber von größerer translationalen Einfluss.

Eine Medline-Suche für alle Peer-Review-Artikel Berichterstattungimilar Rattenmodell mit VF als Mechanismus der Herzstillstand und einer Form der geschlossenen Brust-Wiederbelebung wurden insgesamt 69 zusätzliche Originalstudien mit Hilfe des Modells, da sie erstmals im Jahr 1988 4 veröffentlicht. Die Forschungsschwerpunkte sind pathophysiologische Aspekte der Wiederbelebung von 5 bis 17, Einflussfaktoren auf die Ergebnisse von 18 bis 30, die Rolle der pharmakologische Interventionen untersuchen Vasopressoren 31-43, Puffermittel 44, inotropen Mitteln 45, Stoffe bei der myokardialen oder zerebralen Schutz 46-70 gerichtet, und auch die Auswirkungen von mesenchymalen Stammzellen 71-73.

Die in diesem Artikel beschriebenen Modells und Protokoll wird derzeit an der Wiederbelebung Institut eingesetzt. Dennoch gibt es mehrere Möglichkeiten, "Anpassen" das Modell auf der Grundlage der für einzelne Forscher und die Ziele der Studien-Fähigkeiten.

Protocol

HINWEIS: Das Protokoll wurde von der Institutional Animal Care und Verwenden Ausschuss bei Rosalind Franklin Universität für Medizin und Wissenschaft genehmigt. Alle Verfahren wurden in Übereinstimmung mit dem Leitfaden für die Pflege und Verwendung von Labortieren durch die National Research Council veröffentlicht. 1. Versuchsaufbau und Anästhesie Kalibrierungen der verschiedenen Signale mit einem Datenerfassungssystem (Druck, Temperatur, Hubvolumen, Elektrokardiog…

Representative Results

Die hier beschriebenen Rattenmodell wurde kürzlich verwendet, um die Wirkungen von zwei Inhibitoren des Natrium-sarkolemmalen Wasserstoffaustauschers Isoform 1 (NHE-1) auf die myokardiale und hämodynamische Funktion während der Herzdruckmassage und Post-Reanimations 61 zu vergleichen. Es wurde bereits berichtet, dass NHE-1-Hemmer verringern den myokardialen Reperfusionsschaden indem Natrium-induzierten cytosolischen und mitochondrialen Calciumüberladung und damit zur Erhaltung der linksventrikulären Dehn…

Discussion

Kritische Schritte im Protokoll

Es gibt kritische Schritte in dem Protokoll. Wenn beherrscht, gehen Sie die Vorbereitung und Protokoll als lapidar unten beschrieben. Das Operationsvorbereitung ist schnell, schnell fortschreit Katheter durch kleine Einschnitte Auslösung minimale oder gar keine Gefäßspasmen und Positionieren der Katheterspitzen, wie beabsichtigt, gefolgt von erfolgreichen Intubation nach einer einzigen oder wenigen Versuch (e); damit Abschluss der Vorbereitung in ?…

Disclosures

The authors have nothing to disclose.

Acknowledgements

The authors would like to acknowledge Dr. Wanchun Tang MD, MCCM, FCCP, FAHA and Jena Cahoon of the Weil Institute of Critical Care Medicine in Rancho Mirage, CA. for their contributions to the resuscitation protocol outline and for having helped train the rodent surgeon (LL). The preparation of this article was in part supported by a gift in memory of US Navy Retired SKC Robert W. Ply by Ms. Monica Ply for research in heart disease and Parkinson’s disease and by a discretionary fund from the Department of Medicine at Rosalind Franklin University of Medicine and Science.

Materials

Name of Material/ Equipment Company Catalog Number Comments/Description
Sodium pentobarbital Sigma Aldrich P3761 http://www.sigmaaldrich.com/catalog/product/sigma/p3761?lang=en&region=US
Rectal thermistor BIOPAC Systems, INC TSD202A http://www.biopac.com/fast-response-thermistor
Needle electrode biopolar concentric 25 mm TP BIOPAC Systems, INC EL451 http://www.biopac.com/needle-electrode-concentric-25mm
PE25 polyethylene tubing  Solomon Scientific BPE-T25 http://www.solsci.com/products/polyethylene-pe-tubing
26GA female luer stub adapter Access Technologies LSA-26 http://www.norfolkaccess.com/needles.html
Stopcocks with luer connections; 3-way; male lock, non-sterile Cole-Parmer UX-30600-02 http://www.coleparmer.com/Product/Large_bore_3_way
_male_lock_stopcocks
_10_pack_Non_sterile/EW-30600-23
TruWave disposable pressure transducer Edwards Lifesciences PX600I  http://www.edwards.com/products/pressuremonitoring/Pages/truwavemodels.aspx?truwave=1
Type-T thermocouple Physitemp Instruments IT-18 http://www.physitemp.com/products/probesandwire/flexprobes.html
Central venous pediatric catheter  Cook Medical  C-PUM-301J https://www.cookmedical.com/product/-/catalog/display?ds=cc_pum1lp_webds
Abbocath-T subclavian I.V. catheter (14g x 5 1/2") Hospira 453527 http://www.hospira.com/products_and_services/iv_sets/045350427
Novametrix Medical Systems, Infrared CO2 monitor Soma Technology, Inc. 7100 CO2SMO  http://www.somatechnology.com/MedicalProducts/novametrix_respironics_co2smo_
7100.asp
Harvard Model 683 small animal ventilator Harvard Apparatus 555282 http://www.harvardapparatus.com/webapp/wcs/stores/servlet/haisku2_10001_11051_44453_-1_
HAI_ProductDetail_N_37322_37323
Double-flexible tipped wire guides Cook Medical  C-DOC-15-40-0-2 https://www.cookmedical.com/product/-/catalog/display?ds=cc_doc_webds
High accuracy AC LVDT displacement sensor Omega Engineering LD320-25 http://www.omega.com/pptst/LD320.html
HeartStart XL defibrillator/monitor Phillips Medical Systems M4735A http://www.healthcare.philips.com/main/products/resuscitation/products/xl/
Graefe micro dissection forceps 4 inches Roboz  RS-5135 http://shopping.roboz.com/Surgical-Instrument-Online-Shopping?search=RS-5135
Graefe micro dissection forceps 4 inches with teeth Roboz  RS-5157 http://shopping.roboz.com/Surgical-Instrument-Online-Shopping?search=RS-5157
Extra fine micro dissection scissors 4 inches Roboz  RS-5882 http://shopping.roboz.com/micro-scissors-micro-forceps-groups/micro-dissecting-scissors/Micro-Dissecting-Scissors-4-Straight-Sharp-Sharp
Heiss tissue retractor Fine Science Tools  17011-10 http://www.finescience.com/Special-Pages/Products.aspx?ProductId=321&CategoryId=134&
lang=en-US
Crile curve tip hemostats Fine Science Tools  13005-14 http://www.finescience.com/Special-Pages/Products.aspx?ProductId=372
Visistat skin stapler  Teleflex Incorporated 528135 http://www.teleflexsurgicalcatalog.com/weck/products/9936
Braided silk suture, 3-0 Harvard Apparatus 517706 http://www.harvardapparatus.com/webapp/wcs/stores/servlet/haisku2_10001_11051_43051_-1_
HAI_ProductDetail_N_37916_37936
Betadine solution Butler Schein 3660 https://www.henryscheinvet.com/
Sterile saline, 250 ml bags Fisher 50-700-069 http://www.fishersci.com/ecomm/servlet/itemdetail?catnum=50700069&storeId=10652
Heparin sodium injection, USP Fresenius Kabi 504201 http://fkusa-products-catalog.com/files/assets/basic-html/page25.html
Loxicom (meloxicam) Butler Schein 045-321 https://www.henryscheinvet.com/
Thermodilution cardiac output computer for small animals N/A N/A Custom-developed at the Resuscitation Institute using National Instruments hardware and LabVIEW software
Analog-to-digital data acquisition and analysis system N/A N/A Custom-developed at the Resuscitation Institute using National Instruments hardware and LabVIEW software
Pneumatically-driven and electronically controlled piston device for chest compression in small animals N/A N/A Custom-developed at the Weil Institute of Critical Care Medicine
60 Hz alternating current generator N/A N/A Custom-developed at the Weil Institute of Critical Care Medicine
DOWNLOAD MATERIALS LIST

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Keywords: Rat ModelVentricular FibrillationCardiac ResuscitationClosed-chest TechniqueCardiopulmonary ResuscitationVascular CatheterizationTracheal IntubationPositive Pressure VentilationElectrical ShocksHemodynamic MeasurementsMetabolic MeasurementsResuscitation ConceptsTherapeutic InterventionsCardiac Arrest
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Lamoureux, L., Radhakrishnan, J., Gazmuri, R. J. A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique. J. Vis. Exp. (98), e52413, doi:10.3791/52413 (2015).
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