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...
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Format: | Article |
Language: | English |
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Wiley
2016-07-01
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Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.116.003465 |
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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. |
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language | English |
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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 |
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