All procedures described are conducted in accordance with the National Institutes of Health guidelines for the care and use of animals in research and all animal protocols were approved by the Oregon Health &amp; Science University Institutional Animal Care and Use Committee.
1. Surgical Preparation
<ol>
 <li>Weigh the mouse. The procedure described is performed on C57BL/6 mice weighing between 20 and 25 g. Anesthesia is induced in an induction box using 3-4% 
 isoflurane, and subsequently...

<ol>
	<li>Chertow, G. M., Lazarus, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Predictors+of+mortality+and+the+provision+of+dialysis+in+patients+with+acute+tubular+necrosis.+the+auriculin+anaritide+acute+renal+failure+study+group.">Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. the auriculin anaritide acute renal failure study group.</a> J Am Soc Nephrol. 9, 692-698 (1998).</li><li>Lassnigg, A., Schmidlin, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Minimal+changes+of+serum+creatinine+predict+prognosis+in+patients+after+cardiothoracic+surgery:+A+prospective+cohort+study.">Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: A prospective cohort study.</a> J Am Soc Nephrol. 15, 1597-1605 (2004).</li><li>Lassnigg, A., Donner, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lack+of+renoprotective+effects+of+dopamine+and+furosemide+during+cardiac+surgery.">Lack of renoprotective effects of dopamine and furosemide during cardiac surgery.</a> J Am Soc Nephrol. 11, 97-104 (2000).</li><li>Metnitz, P. G., Krenn, C. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+acute+renal+failure+requiring+renal+replacement+therapy+on+outcome+in+critically+ill+patients.">Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients.</a> Crit Care Med. 30, 2051-2058 (2002).</li><li>Uchino, S., Kellum, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+renal+failure+in+critically+ill+patients:+A+multinational,+multicenter+study.">Acute renal failure in critically ill patients: A multinational, multicenter study.</a> JAMA. 294, 813-818 (2005).</li><li>Mehta, R. L., Pascual, M. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spectrum+of+acute+renal+failure+in+the+intensive+care+unit:+The+PICARD+experience.">Spectrum of acute renal failure in the intensive care unit: The PICARD experience.</a> Kidney Int. 66, 1613-1621 (2004).</li><li>Zager, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Partial,+aortic+ligation:+A+hypoperfusion+model+of+ischemic+acute+renal+failure+and+a+comparison+with+renal+artery+occlusion.">Partial, aortic ligation: A hypoperfusion model of ischemic acute renal failure and a comparison with renal artery occlusion.</a> J Lab Clin Med. 110, 396-405 (1987).</li><li>Zager, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adenine,+nucleotide+changes+in+kidney,+liver,+and+small+intestine+during+different+forms+of+ischemic+injury.">Adenine, nucleotide changes in kidney, liver, and small intestine during different forms of ischemic injury.</a> Circ Res. 68, 185-196 (1991).</li><li>Oliver, J., MacDowell, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+pathogenesis+of+acute+renal+failure+associated+with+traumatic+and+toxic+injury;+renal+ischemia,+nephrotoxic+damage+and+the+ischemic+episode.">The pathogenesis of acute renal failure associated with traumatic and toxic injury; renal ischemia, nephrotoxic damage and the ischemic episode.</a> J Clin Invest. 30, 1307-1439 (1951).</li><li>Phillips, R. A., Dole, V. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+acute+hemorrhage+and+traumatic+shock+on+renal+function+in+dogs.">Effects of acute hemorrhage and traumatic shock on renal function in dogs.</a> Am J Physiol. 145, 314-336 (1945).</li><li>Klocke, R., Tian, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+animal+models+of+heart+failure+related+to+coronary+heart+disease.">Surgical animal models of heart failure related to coronary heart disease.</a> Cardiovasc Res. 74, 29-38 (2007).</li><li>Traystman, R. J. <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+focal+and+global+cerebral+ischemia.">Animal models of focal and global cerebral ischemia.</a> ILAR J. 44, 85-95 (2003).</li><li>Burne-Taney, M. J., Kofler, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+renal+failure+after+whole+body+ischemia+is+characterized+by+inflammation+and+T+cell-mediated+injury.">Acute renal failure after whole body ischemia is characterized by inflammation and T cell-mediated injury.</a> Am J Physiol Renal Physiol. 285, 87-94 (2003).</li><li>Hutchens, M. P., Nakano, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Estrogen+is+renoprotective+via+a+non-receptor+dependent+mechanism+after+cardiac+arrest+in+vivo.">Estrogen is renoprotective via a non-receptor dependent mechanism after cardiac arrest in vivo.</a> Anesthesiology. 112, 395-405 (2010).</li><li>Hutchens, M. P., Nakano, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Soluble+epoxide+hydrolase+gene+deletion+reduces+survival+after+cardiac+arrest+and+cardiopulmonary+resuscitation.">Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation.</a> Resuscitation. 76, 89-94 (2007).</li><li>Planta, I. v. o. n., Weil, M. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiopulmonary+resuscitation+in+the+rat.">Cardiopulmonary resuscitation in the rat.</a> J Appl Physiol. 65, 2641-2647 (1988).</li><li>Cobb, L. A., Fahrenbruch, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+cardiopulmonary+resuscitation+prior+to+defibrillation+in+patients+with+out-of-hospital+ventricular+fibrillation.">Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation.</a> JAMA. 281, 1182-1188 (1999).</li><li>Aufderheide, T. P., Lurie, K. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Death+by+hyperventilation:+A+common+and+life-threatening+problem+during+cardiopulmonary+resuscitation.">Death by hyperventilation: A common and life-threatening problem during cardiopulmonary resuscitation.</a> Crit Care Med. 32, 345-351 (2004).</li><li>Aufderheide, T. P., Sigurdsson, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperventilation-induced+hypotension+during+cardiopulmonary+resuscitation.">Hyperventilation-induced hypotension during cardiopulmonary resuscitation.</a> Circulation. 109, 1960-1965 (2004).</li></ol>

No conflicts of interest declared.

The normothermic model of cardiac arrest and cardiopulmonary resuscitation in the mouse offers multiple avenues of evaluation in a model which replicates the pathophysiology and morphology of the most common clinical cause of AKI, whole-body hypoperfusion. Hypothesis testing may be aided by access to a panoply of genetic manipulation techniques and the well-understood and characterized anatomy and physiology of the laboratory mouse.
As described here, survival in experienced hands is 80%. A...

<table border="1">
	<tbody>
		<tr>
			<th>Name of the reagent</th>
			<th>Company</th>
			<th>Catalogue number</th>
		</tr>
		<tr>
			<td>Potassium Chloride</td>
			<td>Abbott Medical</td>
			<td>06653-5</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Abbott Medical</td>
			<td>05260-05 (and others)</td>
		</tr>
		<tr>
			<td>Epinephrine HCl</td>
			<td>Multiple</td>
			<td>Multiple</td>
		</tr>
		<tr>
			<td>Digi-Sense temperature controller</td>
			<td>Cole-Palmer</td>
			<td>EW-89000-00</td>
		</tr>
		<tr>
			<td>Angiocath IV Cath</td>
			<td>VWR</td>
			<td>381134</td>
		</tr>
		<tr>
			<td>Frova angled airway introducer</td>
			<td>Cook</td>
			<td>G27282</td>
		</tr>
		<tr>
			<td>MicroVent Ventilator for Mice</td>
			<td>Harvard Apparatus</td>
			<td>733591</td>
		</tr>
	</tbody>
</table>

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 by whole-body hypoperfusion.5,6 Successful reproduction of whole-body hypoperfusion in rodent models has been fraught with 
difficulty.7-9,9,10 Models which employ focal ischemia have repeatedly demonstrated results which do not translate to the clinical setting, and larger 
animal models which allow for whole body hypoperfusion lack access to the full toolset of genetic manipulation possible in the mouse.11,12 However, in recent 
years a mouse model of cardiac arrest and cardiopulmonary resuscitation has emerged which can be adapted to model AKI.13 This model reliably reproduces 
physiologic, functional, anatomic, and histologic outcomes seen in clinical AKI, is rapidly repeatable, and offers all of the significant advantages of a murine surgical 
model, including access to genetic manipulative techniques, low cost relative to large animals, and ease of use. Our group has developed extensive experience 
with use of this model to assess a number of organ-specific outcomes in AKI.14,15

Watch this Scientific Journal Video about Normothermic Cardiac Arrest and Cardiopulmonary Resuscitation: A Mouse Model of Ischemia-Reperfusion Injury at JoVE.com

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

A powerful model for perioperative and critical care related acute kidney injury is presented. Using whole body hypoperfusion induced by cardiac arrest it is possible to nearly replicate the histologic and functional changes of clinical AKI.

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 ...

normothermic-cardiac-arrest-cardiopulmonary-resuscitation-mouse-model

Research

JoVE Journal

Medicine

17.9K Görüntüleme.  Oregon Health & Sciences University. Perioperatif ve yoğun bakım ile ilgili akut böbrek hasarı için güçlü bir model sundu. Neredeyse, klinik AKI, histolojik ve fonksiyonel değişiklikleri çoğaltmak mümkündür kardiyak arrest ile indüklenen tüm vücut hipoperfüzyon kullanma.