Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Feb 4, 2015; 4(1): 1-12
Published online Feb 4, 2015. doi: 10.5492/wjccm.v4.i1.1
Modeling cardiac arrest and resuscitation in the domestic pig
Brandon H Cherry, Anh Q Nguyen, Roger A Hollrah, Albert H Olivencia-Yurvati, Robert T Mallet
Brandon H Cherry, Anh Q Nguyen, Roger A Hollrah, Albert H Olivencia-Yurvati, Robert T Mallet, Department of Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, United States
Brandon H Cherry, Anh Q Nguyen, Roger A Hollrah, Robert T Mallet, Department of Integrative Physiology and Anatomy Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, United States
Brandon H Cherry, Robert T Mallet, Institute of Aging and Alzheimer’s Disease Research, University of North Texas Health Science Center, Fort Worth, TX 76107, United States
Albert H Olivencia-Yurvati, Department of Surgery Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, United States
Author contributions: Cherry BH, Nguyen AQ, Hollrah RA and Mallet RT researched the literature, wrote and edited the manuscript and prepared the figures; Olivencia-Yurvati AH reviewed and edited the manuscript for clinical accuracy.
Supported by Grants from The United States National Institute of Neurological Disorders and Stroke, No. R01 NS076975-03; a predoctoral fellowship from the United States National Institute of Aging, Training in the Neurobiology of Aging, No. T31 AG020494; and a predoctoral fellowship from the University of North Texas Health Science Center’s Physician Scientist Program.
Conflict-of-interest: The authors declare that they have no competing interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Robert T Mallet, PhD, Department of Integrative Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, United States. robert.mallet@unthsc.edu
Telephone: +1-817-7352260 Fax: +1-817-7355084
Received: August 8, 2014
Peer-review started: August 8, 2014
First decision: October 31, 2014
Revised: November 3, 2014
Accepted: November 27, 2014
Article in press: November 27, 2014
Published online: February 4, 2015
Processing time: 187 Days and 14.7 Hours
Abstract

Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca2+ overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation (CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.

Keywords: Acidemia; Asphyxia; Cardiopulmonary resuscitation; Countershocks; Hyperoxia; Vasopressin; Ventricular fibrillation

Core tip: Cardiac arrest remains a leading cause of death worldwide, despite tremendous improvements in emergency medical care and increased public delivery of bystander cardiopulmonary resuscitation (CPR). But progress is being achieved, thanks to the joint efforts of biomedical scientists, physicians and emergency medical personnel to translate laboratory discoveries to the ambulance and hospital. The domestic pig has proven to be a superb preclinical model of cardiac arrest, yielding a wealth of mechanistic insights and practical strategies to refine the delivery of CPR and to test promising treatments. This review examines pivotal factors in modeling cardiac arrest and CPR in the pig.