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

Summary

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.

Abstract

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality^1-4 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

Protocol

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 & Science University Institutional Animal Care and Use Committee.

1. Surgical Preparation

1. 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 maintained using 1.5-2.5% isoflurane in air/oxygen mixture.
2. Lubricate the eyes and position the animal supine on a heating pad. Immobilize 4 e....

Discussion

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.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Potassium Chloride	Abbott Laboratories	06653-5
Isoflurane	Abbott Laboratories	05260-05 (and others)
Epinephrine HCl	Multiple Suppliers	Multiple
Digi-Sense temperature controller	Cole-Parmer	EW-89000-00
Angiocath IV Cath	VWR international	381134
Frova angled airway introducer	Cook	G27282
MicroVent Ventilator for Mice	Harvard Apparatus	733591