Summary

نموذج فأر من الرجفان البطيني والإنعاش التي كتبها التقليدية مغلقة الصدر تقنية

Published: April 26, 2015
doi:

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

بالقرب من 360،000 شخص في الولايات المتحدة 1 وغيرها الكثير في جميع أنحاء العالم يعانون 2 حلقة من سكتة قلبية مفاجئة كل عام. محاولات لإعادة الحياة تتطلب لا يمكن منع فقط أن النشاط القلبي يتم إعادة تأسيس ولكن هذا الضرر إلى الأعضاء الحيوية، التقليل أو عكسه. تقنيات الإنعاش القلبي الحالية تسفر عن معدل الإنعاش الأولي من حوالي 30٪. ومع ذلك، البقاء على قيد الحياة إلى الخروج من المستشفى ليست سوى 5٪ 1. ضعف عضلة القلب، خلل عصبي، التهاب النظامية، والأمراض داغل، أو أن يحدث خلطا يحدث الاعتبار ما بعد الإنعاش لنسبة كبيرة من المرضى الذين يموتون على الرغم من عودة الأولية من التداول. وبالتالي، هناك حاجة إلى فهم أكبر لالفيزيولوجيا المرضية والإنعاش رواية النهج الأساسية على وجه السرعة لزيادة معدل الإنعاش الأولي والبقاء على قيد الحياة لاحق مع وظيفة الجهاز سليمة.

وضع الحيوانليرة سورية من السكتة القلبية تلعب دورا حاسما في تطوير علاجات جديدة الإنعاش من خلال توفير رؤى على الفيزيولوجيا المرضية للسكتة قلبية والإنعاش وتقديم الوسائل العملية لوضع تصور واختبار تدخلات جديدة قبل أن يتم اختباره على البشر 3. نموذج الفئران من الصدر مغلقة الإنعاش القلبي الرئوي (CPR) وصفت هنا قد لعبت دورا هاما. وقد تم تطوير هذا النموذج في عام 1988 من قبل إيرين فون بلانتا – زميل باحث في ذلك الوقت – ومعاونيها 4 في مختبر البروفيسور الراحل هاري ماكس ويل MD، دكتوراه في جامعة العلوم الصحية (التي أعيدت تسميتها روزاليند فرانكلين جامعة الطب والعلوم في عام 2004)، وقد استخدمت على نطاق واسع في مجال الإنعاش في الغالب من قبل زملاء البروفيسور ويل والمتدربين.

نموذج يحاكي حلقة من سكتة قلبية مفاجئة مع الإنعاش حاول من خلال تقنيات CPR التقليدية، وبالتالي يشمل جندأيون من الرجفان البطيني (VF) من خلال توفير تيار كهربائي إلى اليمين البطانة البطين وتوفير CPR الصدر المغلق بواسطة جهاز المكبس مدفوعة هوائيا بينما كان يلقى بالتزامن التهوية بالضغط الإيجابي مع غاز الأكسجين التخصيب. ويتم إنجاز إنهاء VF قبل تسليم عبر الصدر الصدمات الكهربائية. نموذج الفئران توازنا بين النماذج المتقدمة في الحيوانات الكبيرة (على سبيل المثال، والخنازير) ونماذج المتقدمة في الحيوانات الصغيرة (مثل الفئران) مما يتيح استكشاف مفاهيم جديدة للبحث بطريقة جيدة موحدة، قابلة للتكرار، وكفاءة مع الوصول إلى قوية جرد من القياسات ذات الصلة. هذا النموذج هو مفيدة بشكل خاص في المراحل الأولى من البحث لاستكشاف مفاهيم جديدة ودراسة آثار الإرباك قبل إجراء الدراسات في النماذج الحيوانية الكبيرة التي هي أكثر تكلفة، ولكن من تأثير أكبر متعدية.

بحث ميدلاين لجميع المواد لاستعراض الأقران الإبلاغ كمانموذج الفئران imilar وجود VF كآلية من السكتة القلبية، ونوعا من الإنعاش الصدر مغلقة كشف ما مجموعه 69 دراسات إضافية الأصلية باستخدام نموذج منذ نشر لأول مرة في عام 1988 (4). وتشمل مجالات البحوث الجوانب المرضية في جسم المريض لإنعاش 5-17، العوامل المؤثرة على النتائج 18-30، ودور التدخلات الدوائية فحص وكلاء الرافعة للضغط 31-43، وكلاء عازلة 44، وكلاء مؤثر في التقلص العضلي 45، وكلاء تهدف إلى عضلة القلب أو حماية الدماغية 46-70، وأيضا تأثيرات الخلايا الجذعية الوسيطة 71-73.

ويجري حاليا استخدام نموذج وبروتوكول الموضحة في هذه المقالة في معهد الإنعاش. ومع ذلك، وهناك فرص متعددة ل"تخصيص" نموذج يقوم على الإمكانات المتاحة للمحققين الفردية وأهداف الدراسات.

Protocol

ملاحظة: تمت الموافقة على البروتوكول من قبل لجنة رعاية واستخدام الحيوان المؤسسي في روزاليند فرانكلين جامعة الطب والعلوم. وكانت جميع الإجراءات وفقا لدليل لرعاية واستخدام الحيوانات المختبرية نشرت من قبل المجلس القومي للبحوث. 1…

Representative Results

نموذج الفئران الموصوفة هنا كانت تستخدم في الآونة الأخيرة لمقارنة آثار اثنين من مثبطات للsarcolemmal الصوديوم والهيدروجين مبادل شكل الإسوي 1 (NHE-1) على وظيفة عضلة القلب والدورة الدموية أثناء ضغط الصدر وما بعد الإنعاش 61. وقد ذكرت سابقا أن NHE-1 مثبطات تخفيف الاصابة ضخه عض?…

Discussion

خطوات حاسمة في البروتوكول

هناك خطوات حاسمة في البروتوكول. عندما يتقن، وإعداد وبروتوكول تشرع صفها بأنها بإيجاز أدناه. إعداد الجراحي هو على وجه السرعة، والنهوض القسطرة بسرعة من خلال شقوق صغيرة مما اثار الحد الأدنى أو أي سفينة…

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

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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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