Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats

BackgroundWe previously have shown that glibenclamide (GBC), a sulfonylurea receptor 1–transient receptor potential M4 (SUR1‐TRPM4) channel inhibitor, improves survival and neurological outcome after asphyxial cardiac arrest and cardiopulmonary resuscitation (ACA/CPR). Here, we further compare the e...

Full description

Bibliographic Details
Main Authors: Kaibin Huang, Ziyue Wang, Yong Gu, Yafang Hu, Zhong Ji, Shengnan Wang, Zhenzhou Lin, Xing Li, Zuoshan Xie, Suyue Pan
Format: Article
Language:English
Published: Wiley 2016-07-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.116.003465
_version_ 1818393494852468736
author Kaibin Huang
Ziyue Wang
Yong Gu
Yafang Hu
Zhong Ji
Shengnan Wang
Zhenzhou Lin
Xing Li
Zuoshan Xie
Suyue Pan
author_facet Kaibin Huang
Ziyue Wang
Yong Gu
Yafang Hu
Zhong Ji
Shengnan Wang
Zhenzhou Lin
Xing Li
Zuoshan Xie
Suyue Pan
author_sort Kaibin Huang
collection DOAJ
description BackgroundWe previously have shown that glibenclamide (GBC), a sulfonylurea receptor 1–transient receptor potential M4 (SUR1‐TRPM4) channel inhibitor, improves survival and neurological outcome after asphyxial cardiac arrest and cardiopulmonary resuscitation (ACA/CPR). Here, we further compare the efficacy of GBC with target temperature management (TTM) and determine whether the efficacy of GBC is affected by TTM. Methods and ResultsMale Sprague‐Dawley rats (n=213) subjected to 10‐minute ACA/CPR were randomized to 4 groups after return of spontaneous circulation (ROSC): normothermia control (NT); GBC; TTM; and TTM+GBC. Survival, neurodeficit scores, histological injury, as well as the expressions of SUR1 and TRPM4 were evaluated. The 7‐day survival rate was 34.4% (11 of 32) in the NT group, 65% (13 of 20) in the GBC group, 50% (10 of 20) in the TTM group, and 70% (14 of 20) in the TTM+GBC group. Rats that received either GBC, TTM alone, or in combination showed less neurological deficit than NT control at 24, 48, and 72 hours and 7 days after ROSC. Moreover, TTM or GBC ameliorated neuronal degeneration and glial activation in the hippocampal CA1 region with similar efficacy, whereas the combination of them had a trend toward better effect. The subunits of SUR1‐TRPM4 heterodimers were both strongly upregulated after ACA/CPR and expressed in multiple types of brain cells, but partly suppressed by TTM. ConclusionsGBC is comparable to TTM in improving survival and neurological outcome after ACA/CPR. When GBC is given along with TTM, less histological injury tended to be achieved.
first_indexed 2024-12-14T05:46:13Z
format Article
id doaj.art-ead8bc2f4efc48a9b1da72888e7fa4b7
institution Directory Open Access Journal
issn 2047-9980
language English
last_indexed 2024-12-14T05:46:13Z
publishDate 2016-07-01
publisher Wiley
record_format Article
series Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
spelling doaj.art-ead8bc2f4efc48a9b1da72888e7fa4b72022-12-21T23:14:52ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-07-015710.1161/JAHA.116.003465Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in RatsKaibin Huang0Ziyue Wang1Yong Gu2Yafang Hu3Zhong Ji4Shengnan Wang5Zhenzhou Lin6Xing Li7Zuoshan Xie8Suyue Pan9Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaBackgroundWe previously have shown that glibenclamide (GBC), a sulfonylurea receptor 1–transient receptor potential M4 (SUR1‐TRPM4) channel inhibitor, improves survival and neurological outcome after asphyxial cardiac arrest and cardiopulmonary resuscitation (ACA/CPR). Here, we further compare the efficacy of GBC with target temperature management (TTM) and determine whether the efficacy of GBC is affected by TTM. Methods and ResultsMale Sprague‐Dawley rats (n=213) subjected to 10‐minute ACA/CPR were randomized to 4 groups after return of spontaneous circulation (ROSC): normothermia control (NT); GBC; TTM; and TTM+GBC. Survival, neurodeficit scores, histological injury, as well as the expressions of SUR1 and TRPM4 were evaluated. The 7‐day survival rate was 34.4% (11 of 32) in the NT group, 65% (13 of 20) in the GBC group, 50% (10 of 20) in the TTM group, and 70% (14 of 20) in the TTM+GBC group. Rats that received either GBC, TTM alone, or in combination showed less neurological deficit than NT control at 24, 48, and 72 hours and 7 days after ROSC. Moreover, TTM or GBC ameliorated neuronal degeneration and glial activation in the hippocampal CA1 region with similar efficacy, whereas the combination of them had a trend toward better effect. The subunits of SUR1‐TRPM4 heterodimers were both strongly upregulated after ACA/CPR and expressed in multiple types of brain cells, but partly suppressed by TTM. ConclusionsGBC is comparable to TTM in improving survival and neurological outcome after ACA/CPR. When GBC is given along with TTM, less histological injury tended to be achieved.https://www.ahajournals.org/doi/10.1161/JAHA.116.003465cardiopulmonary resuscitationglibenclamideheart arrestsulfonylurea receptor 1‐transient receptor potential M4 channeltarget temperature management
spellingShingle Kaibin Huang
Ziyue Wang
Yong Gu
Yafang Hu
Zhong Ji
Shengnan Wang
Zhenzhou Lin
Xing Li
Zuoshan Xie
Suyue Pan
Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cardiopulmonary resuscitation
glibenclamide
heart arrest
sulfonylurea receptor 1‐transient receptor potential M4 channel
target temperature management
title Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats
title_full Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats
title_fullStr Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats
title_full_unstemmed Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats
title_short Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats
title_sort glibenclamide is comparable to target temperature management in improving survival and neurological outcome after asphyxial cardiac arrest in rats
topic cardiopulmonary resuscitation
glibenclamide
heart arrest
sulfonylurea receptor 1‐transient receptor potential M4 channel
target temperature management
url https://www.ahajournals.org/doi/10.1161/JAHA.116.003465
work_keys_str_mv AT kaibinhuang glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats
AT ziyuewang glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats
AT yonggu glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats
AT yafanghu glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats
AT zhongji glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats
AT shengnanwang glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats
AT zhenzhoulin glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats
AT xingli glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats
AT zuoshanxie glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats
AT suyuepan glibenclamideiscomparabletotargettemperaturemanagementinimprovingsurvivalandneurologicaloutcomeafterasphyxialcardiacarrestinrats