Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Feb 4, 2018; 7(1): 1-8
Published online Feb 4, 2018. doi: 10.5492/wjccm.v7.i1.1
Effects of mineralocorticoid receptor antagonists on responses to hemorrhagic shock in rats
Kanako Yamamoto, Takashi Yamamoto, Masayuki Takamura, Soichiro Usui, Hisayoshi Murai, Shuichi Kaneko, Takumi Taniguchi
Kanako Yamamoto, Masayuki Takamura, Soichiro Usui, Hisayoshi Murai, Shuichi Kaneko, Department of System Biology, Kanazawa University Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa 920-8641, Japan
Takashi Yamamoto, Takumi Taniguchi, Department of Anesthesiology and Intensive Care Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Japan
Author contributions: All authors contributed to this manuscript.
Institutional review board statement: The protocol was approved by the ethical committee of Kanazawa University (AP-153421).
Institutional animal care and use committee statement: All animal protocol was performed according to the Guide for the Care and Use of Laboratory Animals in Kanazawa University, which strictly conforms to the Guide for the Care and Use of Laboratory Animals, published by the US National Institutes of Health (NIH, Bethesda, MD). The protocol was approved by the ethical committee of Kanazawa University (AP-153421).
Conflict-of-interest statement: All authors have no conflicts of interest to declare.
Data sharing statement: All data are available from the corresponding author at mtakamura@m-kanazawa.jp.
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: Masayuki Takamura, MD, PhD, Doctor, Senior Lecturer, Department of System Biology, Kanazawa University Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, 13-1, Takara-machi, Kanazawa 920-8641, Japan. mtakamura@m-kanazawa.jp
Telephone: +81-76-2652233 Fax: +81-76-2344250
Received: September 16, 2017
Peer-review started: September 17, 2017
First decision: November 27, 2017
Revised: December 3, 2017
Accepted: December 14, 2017
Article in press: December 14, 2017
Published online: February 4, 2018
Processing time: 138 Days and 21.2 Hours
ARTICLE HIGHLIGHTS
Research background

Clinically, mineralocorticoid receptor (MR) antagonists such as spironolactone (SPL) and eplerenone (EP) are often administered to hypertensive patients to control blood pressure. However, it is not clear whether MR antagonists have beneficial effects when patients administered MR antagonists become hemorrhagic shock (HS) state caused by trauma and intraoperative bleeding.

Research motivation

It is very important for perioperative management to clarify the influence of MR antagonist administration before HS state caused by trauma and intraoperative bleeding.

Research objectives

The effects of pretreatment of MR antagonists on mortality and inflammatory responses after HS were evaluated in rats.

Research methods

HS was induced by the removal of blood by using rats which MR antagonists were administered or were not administered. The effects of pretreatment of MR antagonists were evaluated by mortality, hemodynamics, plasma TNF-α concentrations, arterial blood gas and liver TNF-α, IL-6, IL-1β and ICAM-1 mRNA expression after HS recovery.

Research results

There were no significant differences among the three groups in survival rate, plasma TNF-α concentrations, arterial blood gas and liver TNF-α, IL-6, IL-1β and ICAM-1 mRNA expression. Systolic arterial pressure (SAP) after HS recovery did not decrease in rats of EP group in comparison with control groups. After HS recovery, the reason why blood pressure was maintained in rats of EP group is the problems that remain to be solved, in this research.

Research conclusions

Pretreatment with MR antagonists did not improve mortality or cytokine responses in the liver after HS recovery in rats. The HS model in the present study was made during general anesthesia after pretreatment of MR antagonists. This model is similar to the clinical situation when patients administered MR antagonists become HS state during operation. The present study suggested that MR antagonists may not be worsen the recovery of HS state and may not need to be withdrawn before the operations.

Research perspectives

The present study used normal SD rats. In clinical settings, MR antagonists are generally administered to hypertensive patients. Further investigations by using hypertensive rats which MR antagonists were administered will be needed. The present study, SAPs of the EP treatment group did not decrease in comparison with the SAP of the control group, so further studies are needed to evaluate relations of blood corticosterone or aldosterone and blood pressure in hemorrhagic shock by using rats which MR antagonists were administered.