The authors thank Kathy Gage for her editorial support. This study was supported by funds from the Department of Anesthesiology (Duke University Medical Center), American Heart Association grant (18CSA34080277), and National Institutes of Health (NIH) grants (NS099590, HL157354, NS117973, and NS127163).

All the procedures described here were conducted in accordance with the National Institutes of Health (NIH) guidelines for the care and use of animals in research, and the protocol was approved by the Duke Institute of Animal Care and Use Committee (IACUC). C57BL/6 male and female&#160;mice aged 8-10 weeks old were used for the present study.
1. Surgical preparation
<ol>
	<li>Weigh a mouse on a digital scale, and place it into a 4 in x 4 in x 7 in plexiglass anesthesia induction box.</li>
	<li>Adjust the anesthesia vaporizer to 5% isoflurane, the oxygen flow meter to 30, and the nitrogen flow meter to 70 (see Table of Materials).</li>
	<li>Take the animal out of the induction box, and lay it in a supine position on the surgical bench when its respiratory rate has decreased to 30-40 breaths per minute.</li>
	<li>Pull out the tongue with blunt forceps, and hold it using the non-dominant hand. Use the dominant&#160;hand to insert a laryngoscope (see Table of Materials) into the mouse&#39;s mouth and visualize the vocal cord.</li>
	<li>Use the non-dominant&#160;hand to insert a guide wire and 20 G intravenous catheter into the mouth. Gently insert the guide wire into the trachea.</li>
	<li>Push the catheter into the trachea until the wing part of the catheter is even with the nose tip. 
	NOTE: Do not intubate a mouse that is not fully anesthetized since this may injure the trachea and cause airway bleeding.</li>
	<li>Connect the intubated mouse to a small animal ventilator (see Table of Materials), and reduce the isoflurane to 1.5%.</li>
	<li>Input the mouse&#39;s body weight into the control panel of the ventilator to determine the tidal volume and respiratory rate.</li>
	<li>Keep the mouse in a supine position under a heat lamp, and maintain the rectal temperature at 37 &#176;C with a temperature controller.</li>
	<li>Shave the inguinal areas, disinfect the surgical area at least three times with iodine and alcohol&#160;(see Table of Materials),&#160;and cover the area with a sterile surgical drape.</li>
	<li>Apply eye ointment to both eyes and administer 5 mg/kg carprofen subcutaneously before surgery.</li>
	<li>Open the sterile instrument package for surgery. Make a 1 cm skin incision with surgical scissors to access the femoral arteries on both sides. Dissect and ligate the distal femoral artery with a single strand of 4-0 silk suture (see&#160;Table of Materials), and apply one drop of lidocaine.</li>
	<li>Apply an aneurysm clip at the proximal femoral artery&#160;and make a small cut on the artery distal to the clip. Insert a polyethylene 10 (PE-10, see Table of Materials) catheter into the left and the right femoral arteries. 
	NOTE: The left arterial line is used for blood pressure monitoring, while the right one is used for blood withdrawal and resuscitation mixture infusion.</li>
	<li>Inject 50 &#181;L of 1:10 heparinized saline into each arterial line to prevent clotting in the line.</li>
	<li>Turn the mouse to the prone position, and mount it on a stereotaxic head frame.</li>
	<li>Connect three needle electrodes (red, green, and black) to the left arm, left leg, and right arm for electrocardiogram (ECG, see Table of Materials) monitoring.</li>
	<li>Glue a flexible plastic fiber probe onto the intact temporal skull through a 0.5 cm skin incision for cerebral blood flow monitoring. This step is optional.</li>
	<li>Shave the top of the head,&#160;disinfect the surgical area at least three times with iodine and alcohol, and cover the area with a sterile surgical drapel.</li>
	<li>Cut a 2.5 cm midline skin incision, and use four small retractors to expose the entire skull surface for brain imaging.</li>
	<li>Place a monitoring imager (e.g., a laser speckle contrast imager, see Table of Materials) above the head. 
	NOTE: A few drops of saline can be added to the skull surface to facilitate laser speckle contrast imaging.</li>
</ol>
2. Induction of cardiac arrest
<ol>
	<li>Fill a 1 mL plastic syringe with 26 &#181;L of the resuscitation cocktail stock solution. 
	NOTE: Each milliliter of this solution contains 400 &#181;L of 1 mg/mL epinephrine, 500 &#181;L of 8.4% sodium bicarbonate, 50 &#181;L of 1,000 U/mL heparin, and 50 &#181;L of 0.9% sodium chloride (see Table of Materials).</li>
	<li>Wait until the body temperature reaches 37 &#176;C. Adjust the oxygen meter to 100% to oxygenate the blood for 2 min.</li>
	<li>Withdraw the oxygenated arterial blood up to 200 &#181;L via the right femoral artery into the prepared plastic syringe containing 26 &#181;L of resuscitation cocktail stock solution.</li>
	<li>Switch off the oxygen, and increase the nitrogen to 100% to induce anoxia. 
	NOTE: After approximately 45 s, the heart will fail to function, and the heart rate will rapidly decrease, indicating the onset of CA. After about 2 min of oxygen deprivation, the ECG monitoring will indicate an asystole, and there will be no measurable systemic blood pressure and negligible cerebral blood flow.</li>
	<li>Turn off the ventilator, isoflurane vaporizer, temperature controller, and nitrogen flowmeter. Adjust the oxygen to 100% in preparation for resuscitation.</li>
</ol>
3. Resuscitation procedure
<ol>
	<li>Turn the ventilator on at 8 min after CA onset.</li>
	<li>Immediately start to infuse the withdrawn oxygenated blood mixed with the resuscitation cocktail into the blood circulation via the right femoral artery in 1 min. 
	NOTE: The infusion leads to a gradual increase in the heart rate and the restoration of blood perfusion; eventually, the return of spontaneous circulation (ROSC) is achieved.</li>
</ol>
4. Post-CA recovery
<ol>
	<li>Place the mouse in the supine position after removing it from the stereotaxic frame, and remove&#160;the PE-10 catheters from the femoral arteries.</li>
	<li>Apply 0.25% bupivacaine to the skin incision, and suture the skin incisions using a 6-0 nylon suture (see Table of Materials). Apply antibiotic ointment to the surface of the skin incision.</li>
	<li>Disconnect the mouse ventilator when spontaneous respiration is restored.</li>
	<li>Transfer the mouse to a recovery chamber with a controlled temperature of 32 &#176;C.</li>
	<li>After 2 h of recovery, extubate the mouse, and return to the home cage. Inject 0.5 mL of normal saline subcutaneously to prevent dehydration.</li>
</ol>

A Mouse Model to Study Brain Physiology During Cardiac Arrest

<ol>
	<li>Smith, A., Masters, S., Ball, S., Finn, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+incidence+and+outcomes+of+out-of-hospital+cardiac+arrest+in+metropolitan+versus+rural+locations:+A+systematic+review+and+meta-analysis.">The incidence and outcomes of out-of-hospital cardiac arrest in metropolitan versus rural locations: A systematic review and meta-analysis.</a> Resuscitation. 185, 109655 (2022).</li><li>Amacher, S. A., 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=Predicting+neurological+outcome+in+adult+patients+with+cardiac+arrest:+systematic+review+and+meta-analysis+of+prediction+model+performance.">Predicting neurological outcome in adult patients with cardiac arrest: systematic review and meta-analysis of prediction model performance.</a> Critical Care. 26 (1), 382 (2022).</li><li>Matsuyama, T., Ohta, B., Kiyohara, K., Kitamura, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intra-arrest+partial+carbon+dioxide+level+and+favorable+neurological+outcome+after+out-of-hospital+cardiac+arrest:+A+nationwide+multicenter+observational+study+in+Japan+(the+JAAM-OHCA+registry).">Intra-arrest partial carbon dioxide level and favorable neurological outcome after out-of-hospital cardiac arrest: A nationwide multicenter observational study in Japan (the JAAM-OHCA registry).</a> European Heart Journal of Acute Cardiovascular Care. 12 (1), 14-21 (2023).</li><li>Takahagi, M., Sawano, H., Moriyama, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+neurological+outcome+of+extracorporeal+cardiopulmonary+resuscitation+for+out-of-hospital+cardiac+arrest+patients+with+nonshockable+rhythms:+A+single-center,+consecutive,+retrospective+observational+study.">Long-term neurological outcome of extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest patients with nonshockable rhythms: A single-center, consecutive, retrospective observational study.</a> The Journal of Emergency Medicine. 63 (3), 367-375 (2022).</li><li>Mork, S. R., Botker, M. T., Christensen, S., Tang, M., Terkelsen, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Survival+and+neurological+outcome+after+out-of-hospital+cardiac+arrest+treated+with+and+without+mechanical+circulatory+support.">Survival and neurological outcome after out-of-hospital cardiac arrest treated with and without mechanical circulatory support.</a> Resuscition Plus. 10, 100230 (2022).</li><li>Koenig, M. A., Kaplan, P. W., Thakor, N. 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A., 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=Multimodal+monitoring+including+early+EEG+improves+stratification+of+brain+injury+severity+after+pediatric+cardiac+arrest.">Multimodal monitoring including early EEG improves stratification of brain injury severity after pediatric cardiac arrest.</a> Resuscitation. 167, 282-288 (2021).</li><li>Beekman, R., 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=Bedside+monitoring+of+hypoxic+ischemic+brain+injury+using+low-field,+portable+brain+magnetic+resonance+imaging+after+cardiac+arrest.">Bedside monitoring of hypoxic ischemic brain injury using low-field, portable brain magnetic resonance imaging after cardiac arrest.</a> Resuscitation. 176, 150-158 (2022).</li><li>Sinha, N., Parnia, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Monitoring+the+brain+after+cardiac+arrest:+A+new+era.">Monitoring the brain after cardiac arrest: A new era.</a> Current Neurology Neuroscience Report. 17 (8), 62 (2017).</li><li>Reis, C., 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=Pathophysiology+and+the+monitoring+methods+for+cardiac+arrest+associated+brain+injury.">Pathophysiology and the monitoring methods for cardiac arrest associated brain injury.</a> International Journal of Molecular Sciences. 18 (1), 129 (2017).</li><li>Zhou, H., Lin, C., Liu, J., Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+monitoring+of+brain+perfusion+by+cerebral+oximetry+after+spontaneous+return+of+circulation+in+cardiac+arrest:+A+case+report.">Continuous monitoring of brain perfusion by cerebral oximetry after spontaneous return of circulation in cardiac arrest: A case report.</a> BMC Neurology. 22 (1), 365 (2022).</li><li>Takegawa, R., 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=Real-time+brain+monitoring+by+near-infrared+spectroscopy+predicts+neurological+outcome+after+cardiac+arrest+and+resuscitation+in+rats:+A+proof+of+concept+study+of+a+novel+prognostic+measure+after+cardiac+arrest.">Real-time brain monitoring by near-infrared spectroscopy predicts neurological outcome after cardiac arrest and resuscitation in rats: A proof of concept study of a novel prognostic measure after cardiac arrest.</a> Journal Clinical Medicine. 11 (1), 131 (2021).</li><li>Zhang, C., 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=Invasion+of+peripheral+immune+cells+into+brain+parenchyma+after+cardiac+arrest+and+resuscitation.">Invasion of peripheral immune cells into brain parenchyma after cardiac arrest and resuscitation.</a> Aging and Disease. 9 (3), 412-425 (2018).</li><li>Duan, 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=Cervical+vagus+nerve+stimulation+improves+neurologic+outcome+after+cardiac+arrest+in+mice+by+attenuating+oxidative+stress+and+excessive+autophagy.">Cervical vagus nerve stimulation improves neurologic outcome after cardiac arrest in mice by attenuating oxidative stress and excessive autophagy.</a> Neuromodulation. 25 (3), 414-423 (2022).</li><li>Liu, H., 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=Novel+modification+of+potassium+chloride+induced+cardiac+arrest+model+for+aged+mice.">Novel modification of potassium chloride induced cardiac arrest model for aged mice.</a> Aging and Disease. 9 (1), 31-39 (2018).</li><li>Shen, Y., 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=Aging+is+associated+with+impaired+activation+of+protein+homeostasis-related+pathways+after+cardiac+arrest+in+mice.">Aging is associated with impaired activation of protein homeostasis-related pathways after cardiac arrest in mice.</a> Journal of American Heart Association. 7 (17), e009634 (2018).</li><li>Wang, P., 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=Manganese+porphyrin+promotes+post+cardiac+arrest+recovery+in+mice+and+rats.">Manganese porphyrin promotes post cardiac arrest recovery in mice and rats.</a> Biology. 11 (7), 957 (2022).</li><li>Wang, 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=Development+and+evaluation+of+a+novel+mouse+model+of+asphyxial+cardiac+arrest+revealed+severely+impaired+lymphopoiesis+after+resuscitation.">Development and evaluation of a novel mouse model of asphyxial cardiac arrest revealed severely impaired lymphopoiesis after resuscitation.</a> Journal of American Heart Association. 10 (11), e019142 (2021).</li><li>Li, R., 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=Activation+of+the+XBP1s/O-GlcNAcylation+pathway+improves+functional+outcome+after+cardiac+arrest+and+resuscitation+in+young+and+aged+mice.">Activation of the XBP1s/O-GlcNAcylation pathway improves functional outcome after cardiac arrest and resuscitation in young and aged mice.</a> Shock. 56 (5), 755-761 (2021).</li><li>Shen, Y., 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=Activation+of+the+ATF6+(activating+transcription+factor+6)+signaling+pathway+in+neurons+improves+outcome+after+cardiac+arrest+in+mice.">Activation of the ATF6 (activating transcription factor 6) signaling pathway in neurons improves outcome after cardiac arrest in mice.</a> Journal American Heart Association. 10 (12), e020216 (2021).</li><li>Jiang, 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=MCC950,+a+selective+NLPR3+inflammasome+inhibitor,+improves+neurologic+function+and+survival+after+cardiac+arrest+and+resuscitation.">MCC950, a selective NLPR3 inflammasome inhibitor, improves neurologic function and survival after cardiac arrest and resuscitation.</a> Journal of Neuroinflammation. 17 (1), 256 (2020).</li><li>Zhao, Q., 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=Cardiac+arrest+and+resuscitation+activates+the+hypothalamic-pituitary-adrenal+axis+and+results+in+severe+immunosuppression.">Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.</a> Journal of Cerebral Blood Flow &amp; Metabolism. 41 (5), 1091-1102 (2021).</li></ol>

The authors have no conflicts of interest.

In experimental CA studies, asphyxia, potassium chloride injections, or electrical current-derived ventricular fibrillation have been used to induce CA16,17,18,19,20,21,22,23. Normally, CPR is required for resuscitation in these CA models, especially in mic...

Cardiac arrest (CA) remains a global public health crisis1. More than 356,000 out-of-hospital and 290,000 in-hospital CA cases are reported annually in the US alone, and most CA victims are over 60 years old. Notably, post-CA neurologic impairments are common among survivors, and these represent a major challenge for CA management2,3,4,5. To understand post-CA brain pathologic changes and their effects on neurologic outcomes, various neurophysiologic monitoring and brain tissue monitoring techniques have been applied in patients6,7,8,9,10,11,12. Using near-infrared spectroscopy, real-time brain monitoring has also been performed in CA rats to predict neurologic outcomes13.
However, in murine CA models, such an imaging approach has been complicated by the need for chest compressions to restore spontaneous circulation, which always entails substantial physical motion and, thus, hinders delicate imaging procedures. Moreover, CA models are normally performed with mice in a supine position, whereas the mice must be turned to the prone position for many brain imaging modalities. Thus, a mouse model with minimal body movement during the surgery is required in many cases in order to perform real-time imaging/monitoring of the brain during the whole CA procedure, spanning from pre-CA to post-resuscitation.
Previously, Zhang et al. reported a mouse CA model that could be useful for brain imaging14. In their model, CA was induced by bolus injections of vecuronium and esmolol followed by the cessation of mechanical ventilation. They showed that after 5 min of CA, resuscitation could be achieved by infusing a resuscitation mixture. Notably, however, circulatory arrest in their model occurred only about 10 s after the esmolol injection. Thus, this model does not recapitulate the progression of asphyxia-induced CA in patients, including hypercapnia and tissue hypoxia during the prearrest period.
The overall goal of the current surgical procedure is to model clinical asphyxia CA in mice followed by resuscitation without chest compressions. This CA model, therefore, allows the use of complex imaging techniques to study brain physiology in mice15.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr >
			<td >Adrenalin</td>
			<td >Par Pharmaceutical</td>
			<td >NDC 42023-159-01</td>
			<td ></td>
		</tr>
		<tr >
			<td >Alcohol swabs</td>
			<td >BD</td>
			<td >326895</td>
			<td></td>
		</tr>
		<tr >
			<td >Animal Bio Amp</td>
			<td >ADInstruments</td>
			<td >FE232</td>
			<td></td>
		</tr>
		<tr >
			<td >BP transducer</td>
			<td >ADInstruments</td>
			<td >MLT0699</td>
			<td></td>
		</tr>
		<tr >
			<td >Bridge Amp</td>
			<td >ADInstruments</td>
			<td >FE117</td>
			<td></td>
		</tr>
		<tr >
			<td >Heparin sodium injection, USP</td>
			<td >Fresenius Kabi</td>
			<td >NDC 63323-540-05</td>
			<td></td>
		</tr>
		<tr >
			<td >Isoflurane</td>
			<td >Covetrus</td>
			<td >NDC 11695-6777-2</td>
			<td></td>
		</tr>
		<tr >
			<td >Laser Doppler perfusion monitor</td>
			<td >Moor Instruments</td>
			<td >moorVMS-LDF1</td>
			<td></td>
		</tr>
		<tr >
			<td >Laser speckle imaging system</td>
			<td >RWD</td>
			<td >RFLSI III</td>
			<td></td>
		</tr>
		<tr >
			<td >Lubricant eye ointment</td>
			<td >Bausch + Lomb</td>
			<td >339081</td>
			<td></td>
		</tr>
		<tr >
			<td >Micro clip</td>
			<td >Roboz</td>
			<td >RS-5431</td>
			<td></td>
		</tr>
		<tr >
			<td >Mouse rectal probe</td>
			<td >Physitemp</td>
			<td >RET-3</td>
			<td></td>
		</tr>
		<tr >
			<td >Needle electrode</td>
			<td >ADInstruments</td>
			<td >MLA1213</td>
			<td>29 Ga, 1.5 mm socket</td>
		</tr>
		<tr >
			<td >Nitrogen</td>
			<td >Airgas</td>
			<td >UN1066</td>
			<td></td>
		</tr>
		<tr >
			<td >Optic plastic fibre</td>
			<td >Moor Instruments</td>
			<td >POF500</td>
			<td></td>
		</tr>
		<tr >
			<td >Otoscope</td>
			<td >Welchallyn</td>
			<td >728</td>
			<td>2.5 mm Speculum</td>
		</tr>
		<tr >
			<td >Oxygen</td>
			<td >Airgas</td>
			<td >UN1072</td>
			<td></td>
		</tr>
		<tr >
			<td >PE-10 tubing</td>
			<td >BD</td>
			<td >427401</td>
			<td>Polyethylene tubing</td>
		</tr>
		<tr >
			<td >Povidone-iodine</td>
			<td >CVS</td>
			<td >955338</td>
			<td></td>
		</tr>
		<tr >
			<td >PowerLab 8/35</td>
			<td >ADInstruments</td>
			<td ></td>
			<td></td>
		</tr>
		<tr >
			<td >Rimadyl (carprofen)</td>
			<td >Zoetis</td>
			<td >6100701</td>
			<td>Injectable 50 mg/ml</td>
		</tr>
		<tr >
			<td >Small animal ventilator</td>
			<td >Kent Scientific</td>
			<td >RoVent Jr.</td>
			<td></td>
		</tr>
		<tr >
			<td >Temperature controller</td>
			<td >Physitemp</td>
			<td >TCAT-2DF</td>
			<td></td>
		</tr>
		<tr >
			<td >Triple antibioric &#38; pain relief</td>
			<td >CVS</td>
			<td >NDC 59770-823-56</td>
			<td></td>
		</tr>
		<tr >
			<td >Vaporizer</td>
			<td >RWD</td>
			<td >R583S</td>
			<td></td>
		</tr>
		<tr >
			<td >0.25% bupivacaine</td>
			<td >Hospira</td>
			<td >NDC 0409-1159-18</td>
			<td></td>
		</tr>
		<tr >
			<td >0.9% sodium chroride</td>
			<td >ICU Medical</td>
			<td >NDC 0990-7983-03</td>
			<td></td>
		</tr>
		<tr >
			<td >1 mL plastic syringe</td>
			<td >BD</td>
			<td >309659</td>
			<td></td>
		</tr>
		<tr >
			<td >4-0 silk suture</td>
			<td >Look</td>
			<td >SP116</td>
			<td>Black braided silk</td>
		</tr>
		<tr >
			<td >6-0 nylon suture</td>
			<td >Ethilon</td>
			<td >1698G</td>
			<td></td>
		</tr>
		<tr >
			<td >8.4% sodium bicarbonate Inj., USP</td>
			<td >Hospira</td>
			<td >NDC 0409-6625-02</td>
			<td></td>
		</tr>
		<tr >
			<td >20 G IV catheter</td>
			<td >BD</td>
			<td >381534</td>
			<td>20GA 1.6 IN</td>
		</tr>
		<tr >
			<td >30 G PrecisionGlide needle</td>
			<td >BD</td>
			<td >305106</td>
			<td>30 G X 1/2</td>
		</tr>
	</tbody>
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mouse cardiac arrest model for brain imaging and brain physiology monitoring during ischemia and resuscitation

Most cardiac arrest (CA) survivors experience varying degrees of neurologic deficits. To understand the mechanisms that underpin CA-induced brain injury and, subsequently, develop effective treatments, experimental CA research is essential. To this end, a few mouse CA models have been established. In most of these models, the mice are placed in the supine position in order to perform chest compression for cardiopulmonary resuscitation (CPR). However, this resuscitation procedure makes the real-time imaging/monitoring of brain physiology during CA and resuscitation challenging. To obtain such critical knowledge, the present protocol presents a mouse asphyxia CA model that does not require the chest compression CPR step. This model allows for the study of dynamic changes in blood flow, vascular structure, electrical potentials, and brain tissue oxygen from the pre-CA baseline to early post-CA reperfusion. Importantly, this model applies to aged mice. Thus, this mouse CA model is expected to be a critical tool for deciphering the impact of CA on brain physiology.

Author Spotlight: A Unique Mouse Model of Asphyxia-Induced Cardiac Arrest 

Mouse Cardiac Arrest Model for Brain Imaging and Brain Physiology Monitoring During Ischemia and Resuscitation

Cardiac arrest affects over half a million people in the US every year, leading to impaired neurological function primarily caused by hypoxic-ischemic brain injury. To develop better treatments, we aim to understand how cardiac arrest affects brain physiology, including microcirculatory blood flow and oxygen use, through experimental research. Advanced imaging and the monitoring methods have been established to investigate the cerebral blood flow after cardiac arrest.However, obtaining a complete image of cerebral circulation during cardiac arrest and early resuscitation remains challenging. Our protocol involves simulating clinical asphyxia-induced cardiac arrest in mice, followed by recitation without chest compressions. This model enables the use of advanced imaging methods to study brain physiology in mice throughout the cardiac arrest process.This model does not require complex surgical interventions, and is relatively easier to perform. More importantly, during cardiac arrest and resuscitation, animals can be kept in prone proposition with minimal animal movement, which greatly facilitates the use of various imaging modalities. The impact of cardiac arrest and its treatment strategies, such as epinephrine administration, brain hemodynamics and the neurological function, is not yet fully understood.Our mouse model is ideal for investigating the dynamic alterations in brain circulation, vascular responses, and brain tissue oxygenation that occur during a cardiac arrest and resuscitation.

To induce CA, the mouse was anesthetized with 1.5% isoflurane and ventilated with 100% nitrogen. This condition led to severe bradycardia in 45 s (Figure 1). Following 2 min of anoxia, the heart rate dramatically reduced (Figure 2), the blood pressure decreased below 20 mmHg, and the cerebral blood flow ceased completely (Figure 1).&#160;As the isoflurane was turned off, the body temperature was no longer managed and slowly dropped ...

Watch this Scientific Journal Video about A Unique Mouse Model of Asphyxia-Induced Cardiac Arrest at JoVE.com

This protocol demonstrates a unique mouse model of asphyxia cardiac arrest that does not require chest compression for resuscitation. This model is useful for monitoring and imaging the dynamics of brain physiology during cardiac arrest and resuscitation.

Most cardiac arrest (CA) survivors experience varying degrees of neurologic deficits. To understand the mechanisms that underpin CA-induced brain injury ...

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Research

JoVE Journal

Neuroscience

﻿Cardiac Arrest and Resuscitation Procedure in a Murine Model

Cardiac Arrest and Resuscitation Procedure in a Murine Model  

To begin, lay the eight to 10-week-old, anesthetized C57 black 6 mouse on the surgical bench. Using blunt forceps, pull out the tongue and hold it. Insert a laryngoscope into the mouth and visualize the vocal cord.Insert a guide wire into a 20 gauge intravenous catheter. Then gently push the catheter into the trachea until its wing part is even with the nose tip. Connect the mouse to the ventilator, and place it in a supine position under a heat lamp.Maintain the rectal temperature at 37 degrees Celsius. After shaving and disinfecting the surgical area, make a one centimeter skin incision on the left and right inguinal areas to access the femoral arteries. Then disinfect and ligate the distal femoral artery, and apply one drop of lidocaine.Place a clip on the proximal femoral artery, and make a small cut on the artery distal to the clip. Insert a polyethylene 10 catheter into both the left and right femoral arteries. Inject 50 microliters of one to 10 heparinized saline into each arterial line.To prevent clotting in the line, turn the mouse to the prone position, and mount it on a stereotaxic head frame. Connect three needle electrodes to the left arm, left leg, and right arm for electrocardiogram monitoring. Then shave the top of the head and sterilize it with three alternating rounds of iodine and alcohol swabs.Make a 2.5 centimeter midline skin incision, and use four small retractors to expose the entire skull surface for brain imaging. Then place a Laser Speckle Contrast Imager above the head. Adjust the Laser Speckle Imager to see the baseline of cerebral blood vessels before cardiac arrest.Before inducing cardiac arrest, fill a one milliliter plastic syringe with 26 microliters of the resuscitation cocktail stock solution. Once the body temperature reaches 37 degrees Celsius, adjust the oxygen meter to 100%to oxygenate the blood for two minutes. Then draw up to 200 microliters of blood through the right femoral artery into the plastic syringe containing the resuscitation cocktail.To induce cardiac arrest, switch off the oxygen and increase the nitrogen to 100%to induce anoxia. Turn off the ventilator, isoflurane vaporizer, temperature controller, and nitrogen flow meter. Confirm the absence of brain blood flow during cardiac arrest.By observing the laser speckle image, adjust the oxygen to 100%and turn on the ventilator eight minutes after cardiac arrest onset. Immediately infuse the withdrawn oxygenated blood mixed with the resuscitation cocktail into blood circulation through the right femoral artery in one minute to restore vitals such as heart rate and blood pressure. See the Laser Speckle Image to confirm successful reperfusion of the brain.For postoperative recovery, remove the retractors from the head, apply 0.25%bupivacaine to the skin incision, and close the incision using a 6-0 nylon suture thread. Then apply antibiotic ointment on the closed skin incision surface. Induction of cardiac arrest in the mouse led to severe bradycardia within 45 seconds.Following two minutes of an anoxia, the heart rate significantly reduced. The blood pressure decreased below 20 millimeters of mercury and the cerebral blood flow ceased. Also, the body temperature slowly dropped to about 32 degrees Celsius at the end of the cardiac arrest.After injecting the blood resuscitation mixture, all vital functions started to recover. Laser Speckle Contrast Imaging confirmed the complete absence of blood flow in the brain during cardiac arrest, the photoacoustic images enabled the identification of changes in blood flow, structure, and oxygenation during the cardiac arrest procedure.

1.2K Views.  Duke University Medical Center.  This protocol demonstrates a unique mouse model of asphyxia cardiac arrest that does not require chest compression for resuscitation. This model is useful for monitoring and imaging the dynamics of brain physiology during cardiac arrest and resuscitation.

A Mouse Model to Study Brain Physiology During Cardiac Arrest

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