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©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Minocycline fails to improve neurologic and histologic outcome after ventricular fibrillation cardiac arrest in rats
Andreas Janata, Ingrid AM Magnet, Kristin L Schreiber, Caleb D Wilson, Jason P Stezoski, Keri Janesko-Feldman, Patrick M Kochanek, Tomas Drabek
Andreas Janata, Ingrid AM Magnet, Kristin L Schreiber, Caleb D Wilson, Jason P Stezoski, Keri Janesko-Feldman, Patrick M Kochanek, Tomas Drabek, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States
Andreas Janata, Jason P Stezoski, Keri Janesko-Feldman, Patrick M Kochanek, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States
Andreas Janata, Emergency Department, KA Rudolfstiftung, Vienna 1030, Austria
Ingrid AM Magnet, Department of Emergency Medicine, Vienna General Hospital, Medical University of Vienna, Vienna 1090, Austria
Kristin L Schreiber, Jason P Stezoski, Tomas Drabek, Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States
Kristin L Schreiber, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States
Caleb D Wilson, Wyoming Otolaryngology, Wyoming Medical Center, Casper, WY 82604, United States
Author contributions: Janata A, Magnet IAM, Drabek T, and Kochanek PM designed the study; Janata A, Magnet IAM, and Drabek T conducted the study and collected the data; Janata A, Magnet IAM, Drabek T, Schreiber KL, Wilson CD, and Janesko-Feldman K analyzed the data; Janata A, Magnet IAM, Drabek T, Schreiber KL, Wilson CD, Stezoski JP, and Janesko-Feldman K prepared the manuscript; Stezoski JP performed the experiments and collected the biochemical and neurobehavioral data; Janesko-Feldman K prepared the histological slides; Kochanek PM coordinated the research.
Supported by the Laerdal Foundation for Acute Medicine to Janata A; the Erwin Schroedinger Stipend by the Austrian Science Fund (#J 2931-818) to Janata A; Medical Student Anesthesia Research Foundation Award from the International Anesthesia Research Society to Wilson CD; Seed Grant from The Department of Anesthesiology, University of Pittsburgh to Drabek T; Starter Grant from the Society of Cardiovascular Anesthesiologists to Drabek T; the Laerdal Foundation for Acute Medicine to Drabek T.
Institutional review board statement: The study protocol was approved by the Institutional Animal Care and Use Committee of the University of Pittsburgh on February 12, 2013 (Protocol #13021161).
Institutional animal care and use committee statement: The study protocol was approved by the Institutional Animal Care and Use Committee of the University of Pittsburgh on February 12, 2013 (Protocol #13021161). Principal Investigator: Tomas Drabek. Protocol Title: Neuroinflammation after prolonged cardiac arrest.
Conflict-of-interest statement: Dr Drabek reports grants from Society of Cardiovascular Anesthesiolgists, grants from The Laerdal Foundation for Acute Medicine, grants from Department of Anesthesiology, University of Pittsburgh, during the conduct of the study.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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/
Corresponding author: Tomas Drabek, MD, PhD, Associate Professor, Research Scientist, FASA, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, United States. drabekt@anes.upmc.edu
Telephone: +1-412-6471687 Fax: +1-412-6240943
Received: June 21, 2019
Peer-review started: June 26, 2019
First decision: August 2, 2019
Revised: September 17, 2019
Accepted: October 27, 2019
Article in press: October 27, 2019
Published online: November 19, 2019
ARTICLE HIGHLIGHTS
Research background
Outcomes from cardiac arrest (CA) are suboptimal and survivors are often left with significant neuro-cognitive disabilities. No pharmacological adjuncts have been shown to improve outcomes after CA in a clinical setting. Exploration of novel therapeutical adjuncts for neuroprotection in clinically relevant animal models is thus warranted.
Research motivation
Minocycline has been shown to be neuroprotective in several models of ischemia-reperfusion, attenuating microglial activation as a dominant effect. Minocycline seemed a promising candidate to be tested in an experimental CA model that is characterized by extensive neuronal degeneration and microglial activation.
Research objectives
We tested the hypothesis that early treatment with minocycline at a sufficient dose would improve survival rate, survival time, neurologic outcome and histological damage in adult male rats subjected to prolonged CA.
Research methods
Rats were subjected to CA and randomized to either minocycline treatment or control group, treated with vehicle, for 72 h. Minocycline treatment regimen was selected based on prior studies that demonstrated benefits.
Research results
Minocycline did not improve survival rate, survival time, neurologic outcome or histological damage (neuronal degeneration or microglial proliferation) in multiple selectively vulnerable brain regions.
Research conclusions
Minocycline did not provide a breakthrough beneficial effect on neurologic injury or histological damage resulting from prolonged experimental CA.
Research perspectives
Alternative pharmacological strategies should be explored to augment the outcome from CA.
