Name: a rat model of ventricular fibrillation and resuscitation by conventional closed-chest technique
Uploaded: 2015-04-26T14:00:00
Description: Watch this Scientific Journal Video about A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique at JoVE.com

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&#8217;s disease and by a discretionary fund from the Department of Medicine at Rosalind Franklin University of Medicine and Science.

NOTE: The protocol was approved by the Institutional Animal Care and Use Committee at Rosalind Franklin University of Medicine and Science. All procedures were in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Research Council.
1. Experimental Setup and Anesthesia
<ol>
	<li>Perform calibrations of the various signals to be captured using a data acquisition system (pressures, temperature, piston displacement, electrocardiogram [ECG], ca...

Critical Steps in the protocol
There are critical steps in the protocol. When mastered, the preparation and protocol proceed as succinctly described below. The surgical preparation is expeditious, advancing catheters rapidly through small incisions triggering minimal or no vessel spasm and positioning the catheter tips as intended, followed by successful tracheal intubation after a single or a few attempt(s); thus, completing the preparation in &#8776; 90 min from the initial pentobar...

Close to 360,000 individuals in the United States1 and many more worldwide2 suffer an episode of sudden cardiac arrest every year. Attempts to restore life require not only that cardiac activity be reestablished but that damage to vital organs be prevented, minimized, or reversed. Current cardiopulmonary resuscitation techniques yield an initial resuscitation rate of approximately 30%; however, survival to hospital discharge is only 5%1. Myocardial dysfunction, neurological dysfunction, systemic inflammation, intercurrent illnesses, or a combination thereof occurring post-resuscitation account for the large proportion of patients who die in spite of initial return of circulation. Thus, greater understanding of the underlying pathophysiology and novel resuscitation approaches are urgently needed to increase the rate of initial resuscitation and subsequent survival with intact organ function.
Animal models of cardiac arrest play a critical role in the development of new resuscitation therapies by providing insights on the pathophysiology of cardiac arrest and resuscitation and offering practical means to conceptualize and test new interventions before they can be tested in humans3. The rat model of closed chest cardiopulmonary resuscitation (CPR) described here has played an important role. The model was developed in 1988 by Irene von Planta &#8211; a research fellow at the time &#8211; and her collaborators4 in the laboratory of late Professor Max Harry Weil M.D., Ph.D. at the University of Health Sciences (renamed Rosalind Franklin University of Medicine and Science in 2004) and has been extensively used in the field of resuscitation predominantly by fellows of Professor Weil and their trainees.
The model simulates an episode of sudden cardiac arrest with resuscitation attempted by conventional CPR techniques and thus includes induction of ventricular fibrillation (VF) by delivering an electrical current to the right ventricular endocardium and provision of closed chest CPR by a pneumatically driven piston device while concomitantly delivering positive pressure ventilation with oxygen-enriched gas. Termination of VF is accomplished by transthoracic delivery of electrical shocks. The rat model strikes a balance between models developed in large animals (e.g., swine) and models developed in smaller animals (e.g., mice) allowing exploration of new research concepts in a well-standardized, reproducible, and efficient manner with access to a robust inventory of pertinent measurements. The model is particularly useful in early stages of research to explore new concepts and examine the effects of confounders before conducting studies in larger animal models that are more costly, but of greater translational impact.
A Medline search for all peer-reviewed articles reporting a similar rat model having VF as the mechanism of cardiac arrest and some form of closed chest resuscitation revealed a total of 69 additional original studies using the model since it was first published in 19884. The research areas include pathophysiological aspects of resuscitation5-17, factors influencing outcomes18-30, the role of pharmacological interventions examining vasopressor agents31-43, buffer agents44, inotropic agents45, agents aimed at myocardial or cerebral protection46-70, and also the effects of mesenchymal stem cells71-73.
The model and protocol described in this article is currently being used at the Resuscitation Institute. Yet, there are multiple opportunities to &#8220;customize&#8221; the model based on the capabilities available to individual investigators and the goals of the studies.

<table border="0" cellpadding="0" cellspacing="0" width="595">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Name of Material/ Equipment</td>
			<td style="width:93px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:167px;">Comments/Description</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Sodium pentobarbital</td>
			<td style="width:93px;">Sigma Aldrich</td>
			<td style="width:119px;">P3761</td>
			<td style="width:167px;">http://www.sigmaaldrich.com/catalog/product/sigma/p3761?lang=en&#38;region=US</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Rectal thermistor</td>
			<td style="width:93px;">BIOPAC Systems, INC</td>
			<td style="width:119px;">TSD202A</td>
			<td style="width:167px;">http://www.biopac.com/fast-response-thermistor</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Needle electrode biopolar concentric 25 mm TP</td>
			<td style="width:93px;">BIOPAC Systems, INC</td>
			<td style="width:119px;">EL451</td>
			<td style="width:167px;">http://www.biopac.com/needle-electrode-concentric-25mm</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">PE25 polyethylene tubing&#160;</td>
			<td style="width:93px;">Solomon Scientific</td>
			<td style="width:119px;">BPE-T25</td>
			<td style="width:167px;">http://www.solsci.com/products/polyethylene-pe-tubing</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">26GA female luer stub adapter</td>
			<td style="width:93px;">Access Technologies</td>
			<td style="width:119px;">LSA-26</td>
			<td style="width:167px;">http://www.norfolkaccess.com/needles.html</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Stopcocks with luer connections; 3-way; male lock, non-sterile</td>
			<td style="width:93px;">Cole-Parmer</td>
			<td style="width:119px;">UX-30600-02</td>
			<td style="width:167px;">http://www.coleparmer.com/Product/Large_bore_3_way 
			_male_lock_stopcocks 
			_10_pack_Non_sterile/EW-30600-23</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">TruWave disposable pressure transducer</td>
			<td style="width:93px;">Edwards Lifesciences</td>
			<td style="width:119px;">PX600I&#160;</td>
			<td style="width:167px;">http://www.edwards.com/products/pressuremonitoring/Pages/truwavemodels.aspx?truwave=1</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Type-T thermocouple</td>
			<td style="width:93px;">Physitemp Instruments</td>
			<td style="width:119px;">IT-18</td>
			<td style="width:167px;">http://www.physitemp.com/products/probesandwire/flexprobes.html</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Central venous pediatric catheter&#160;</td>
			<td style="width:93px;">Cook Medical&#160;</td>
			<td style="width:119px;">C-PUM-301J</td>
			<td style="width:167px;">https://www.cookmedical.com/product/-/catalog/display?ds=cc_pum1lp_webds</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Abbocath-T subclavian I.V. catheter (14g x 5 1/2&#34;)</td>
			<td style="width:93px;">Hospira</td>
			<td style="width:119px;">453527</td>
			<td style="width:167px;">http://www.hospira.com/products_and_services/iv_sets/045350427</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Novametrix Medical Systems, Infrared CO2 monitor</td>
			<td style="width:93px;">Soma Technology, Inc.</td>
			<td style="width:119px;">7100 CO2SMO&#160;</td>
			<td style="width:167px;">http://www.somatechnology.com/MedicalProducts/novametrix_respironics_co2smo_ 
			7100.asp</td>
		</tr>
		<tr height="147">
			<td height="147" style="height:147px;width:216px;">Harvard Model 683 small animal ventilator</td>
			<td style="width:93px;">Harvard Apparatus</td>
			<td style="width:119px;">555282</td>
			<td style="width:167px;">http://www.harvardapparatus.com/webapp/wcs/stores/servlet/haisku2_10001_11051_44453_-1_ 
			HAI_ProductDetail_N_37322_37323</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Double-flexible tipped wire guides</td>
			<td style="width:93px;">Cook Medical&#160;</td>
			<td style="width:119px;">C-DOC-15-40-0-2</td>
			<td style="width:167px;">https://www.cookmedical.com/product/-/catalog/display?ds=cc_doc_webds</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">High accuracy AC LVDT displacement sensor</td>
			<td style="width:93px;">Omega Engineering</td>
			<td style="width:119px;">LD320-25</td>
			<td style="width:167px;">http://www.omega.com/pptst/LD320.html</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">HeartStart XL defibrillator/monitor</td>
			<td style="width:93px;">Phillips Medical Systems</td>
			<td style="width:119px;">M4735A</td>
			<td style="width:167px;">http://www.healthcare.philips.com/main/products/resuscitation/products/xl/</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Graefe micro dissection forceps 4 inches</td>
			<td style="width:93px;">Roboz&#160;</td>
			<td style="width:119px;">RS-5135</td>
			<td style="width:167px;">http://shopping.roboz.com/Surgical-Instrument-Online-Shopping?search=RS-5135</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Graefe micro dissection forceps 4 inches with teeth</td>
			<td style="width:93px;">Roboz&#160;</td>
			<td style="width:119px;">RS-5157</td>
			<td style="width:167px;">http://shopping.roboz.com/Surgical-Instrument-Online-Shopping?search=RS-5157</td>
		</tr>
		<tr height="147">
			<td height="147" style="height:147px;width:216px;">Extra fine micro dissection scissors 4 inches</td>
			<td style="width:93px;">Roboz&#160;</td>
			<td style="width:119px;">RS-5882</td>
			<td style="width:167px;">http://shopping.roboz.com/micro-scissors-micro-forceps-groups/micro-dissecting-scissors/Micro-Dissecting-Scissors-4-Straight-Sharp-Sharp</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Heiss tissue retractor</td>
			<td style="width:93px;">Fine Science Tools&#160;</td>
			<td style="width:119px;">17011-10</td>
			<td style="width:167px;">http://www.finescience.com/Special-Pages/Products.aspx?ProductId=321&#38;CategoryId=134&#38; 
			lang=en-US</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Crile curve tip hemostats</td>
			<td style="width:93px;">Fine Science Tools&#160;</td>
			<td style="width:119px;">13005-14</td>
			<td style="width:167px;">http://www.finescience.com/Special-Pages/Products.aspx?ProductId=372</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Visistat skin stapler&#160;</td>
			<td style="width:93px;">Teleflex Incorporated</td>
			<td style="width:119px;">528135</td>
			<td style="width:167px;">http://www.teleflexsurgicalcatalog.com/weck/products/9936</td>
		</tr>
		<tr height="147">
			<td height="147" style="height:147px;width:216px;">Braided silk suture, 3-0</td>
			<td style="width:93px;">Harvard Apparatus</td>
			<td style="width:119px;">517706</td>
			<td style="width:167px;">http://www.harvardapparatus.com/webapp/wcs/stores/servlet/haisku2_10001_11051_43051_-1_ 
			HAI_ProductDetail_N_37916_37936</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Betadine solution</td>
			<td style="width:93px;">Butler Schein</td>
			<td style="width:119px;">3660</td>
			<td style="width:167px;">https://www.henryscheinvet.com/</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Sterile saline, 250 ml bags</td>
			<td style="width:93px;">Fisher</td>
			<td style="width:119px;">50-700-069</td>
			<td style="width:167px;">http://www.fishersci.com/ecomm/servlet/itemdetail?catnum=50700069&#38;storeId=10652</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Heparin sodium injection, USP</td>
			<td style="width:93px;">Fresenius Kabi</td>
			<td style="width:119px;">504201</td>
			<td style="width:167px;">http://fkusa-products-catalog.com/files/assets/basic-html/page25.html</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Loxicom (meloxicam)</td>
			<td style="width:93px;">Butler Schein</td>
			<td style="width:119px;">045-321</td>
			<td style="width:167px;">https://www.henryscheinvet.com/</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Thermodilution cardiac output computer for small animals</td>
			<td style="width:93px;">N/A</td>
			<td style="width:119px;">N/A</td>
			<td style="width:167px;">Custom-developed at the Resuscitation Institute using National Instruments hardware and LabVIEW software</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Analog-to-digital data acquisition and analysis system</td>
			<td style="width:93px;">N/A</td>
			<td style="width:119px;">N/A</td>
			<td style="width:167px;">Custom-developed at the Resuscitation Institute using National Instruments hardware and LabVIEW software</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Pneumatically-driven and electronically controlled piston device for chest compression in small animals</td>
			<td style="width:93px;">N/A</td>
			<td style="width:119px;">N/A</td>
			<td style="width:167px;">Custom-developed at the Weil Institute of Critical Care Medicine</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">60 Hz alternating current generator</td>
			<td style="width:93px;">N/A</td>
			<td style="width:119px;">N/A</td>
			<td style="width:167px;">Custom-developed at the Weil Institute of Critical Care Medicine</td>
		</tr>
	</tbody>
</table>

a rat model of ventricular fibrillation and resuscitation by conventional closed-chest technique

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 &#8211; but is not limited to &#8211; 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.

The rat model described here was recently used to compare the effects of two inhibitors of the sarcolemmal sodium-hydrogen exchanger isoform 1 (NHE-1) on myocardial and hemodynamic function during chest compression and post-resuscitation61. It was previously reported that NHE-1 inhibitors attenuate myocardial reperfusion injury by limiting sodium-induced cytosolic and mitochondrial calcium overload, and thereby help preserve left ventricular distensibility during chest compression and attenuate post-resuscitat...

Watch this Scientific Journal Video about A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique at JoVE.com

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

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.

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic ...

Research

JoVE Journal

Medicine

Normothermic Cardiac Arrest and Cardiopulmonary Resuscitation: A Mouse Model of Ischemia-Reperfusion Injury

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused ...

A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion

Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ...

Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved ...

A Closed-chest Model to Induce Transverse Aortic Constriction in Mice

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to ...

The Perinatal Asphyxiated Lamb Model: A Model for Newborn Resuscitation

Birth asphyxia accounts for nearly one million deaths worldwide each year, and is one of the primary causes of early neonatal morbidity and mortality. ...

Ultrasonographic Assessment During Cardiopulmonary Resuscitation

The US-CAB (Ultrasound, Circulation/Airway/Breathing) protocol integrates several sonographic techniques into a structured assessment of the circulation, ...

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen

Acute liver failure (ALF) is a clinical condition caused by various etiologies resulting in the loss of metabolic, biochemical, synthesizing, and ...

Standardized Model of Ventricular Fibrillation and Advanced Cardiac Life Support in Swine

Cardiopulmonary resuscitation after cardiac arrest, independent of its origin, is a regularly encountered medical emergency in hospitals as well as ...

Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) ...

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&#246;ttingen Minipigs and Landrace Pigs

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in GÃƒÆ’Ã‚Â¶ttingen Minipigs and Landrace Pigs

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an ...