Cerebral and myocardial mitochondrial injury differ in a rat model of cardiac arrest and cardiopulmonary resuscitation

Xianfei Ji; Jennifer L. Bradley; Guanghui Zheng; Weiwei Ge; Jing Xu; Juntao Hu; Fenglian He; Rabiya Shabnam; Mary Ann Peberdy; Joseph P. Ornato; Qun Chen; Edward J. Lesnefsky; Wanchun Tang

Biomedicine & Pharmacotherapy (Aug 2021)

Cerebral and myocardial mitochondrial injury differ in a rat model of cardiac arrest and cardiopulmonary resuscitation

Xianfei Ji,
Jennifer L. Bradley,
Guanghui Zheng,
Weiwei Ge,
Jing Xu,
Juntao Hu,
Fenglian He,
Rabiya Shabnam,
Mary Ann Peberdy,
Joseph P. Ornato,
Qun Chen,
Edward J. Lesnefsky,
Wanchun Tang

Affiliations

Xianfei Ji: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China; Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA
Jennifer L. Bradley: Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA
Guanghui Zheng: Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA
Weiwei Ge: Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA
Jing Xu: Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA
Juntao Hu: Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA
Fenglian He: Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA
Rabiya Shabnam: McGuire Research Institute, Richmond, VA, USA
Mary Ann Peberdy: Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA; Departments of Internal Medicine and Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA, USA; Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University Health System, Richmond, VA, USA
Joseph P. Ornato: Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA; Department of Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA, USA
Qun Chen: Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University Health System, Richmond, VA, USA
Edward J. Lesnefsky: Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University Health System, Richmond, VA, USA; Medical Service, McGuire Department of Veterans Affairs Medical Center, Richmond, VA, USA; McGuire Research Institute, Richmond, VA, USA
Wanchun Tang: Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA; Department of Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA, USA; Correspondence to: Weil Institute of Emergency and Critical Care Research at VCU, Department of Emergency Medicine, VCU School of Medicine, Box 980266, Sanger Hall, 1101 E. Marshall St., Richmond, VA 23298-0279, USA.

Journal volume & issue: Vol. 140
p. 111743

Abstract

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Brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Complex I in the electron transport chain (ETC) is sensitive to ischemic injury and is a major control point of the rate of ADP stimulated oxygen consumption. The purpose of this study was to explore whether changes in cerebral and myocardial mitochondria differ after cardiac arrest. Animals were randomized into 4 groups (n = 6): 1) Sham 2) VF 3) VF+CPR 4) ROSC 1hr. Ventricular Fibrillation (VF) was induced through a guide wire advanced from the right jugular vein into the ventricle and untreated for 8 min. Resuscitation was attempted with a 4J defibrillation after 8 min of cardiopulmonary resuscitation (CPR). Brain mitochondria and cardiac mitochondrial subpopulations were isolated. Calcium retention capacity was measured to assess susceptibility to mitochondrial permeability transition pore opening. ADP stimulated oxygen consumption and ETC activity assays were performed. Brain mitochondria are far more sensitive to injury during cardiac arrest and resuscitation compared to cardiac mitochondria. Complex I is highly sensitive to injury in brain mitochondria. With markedly decreased calcium retention capacity, mitochondria contribute to cerebral reperfusion injury. Therapeutic preservation of cerebral mitochondrial activity and mitochondrial function during cardiac arrest may improve post-resuscitation neurologic function.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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