Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation

Michael Hutchens, Takaaki Nakano, Jennifer Dunlap, Richard J. Traystman, Patricia D. Hurn, Nabil Alkayed

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 arachidonic acid epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH). Pharmacological inhibition and gene deletion of sEH protect against ischemia/reperfusion injury in brain and heart, and against hypertension-related end-organ damage in kidney. We tested the hypothesis that sEH gene deletion improves survival, recovery of renal function and pathologic ischemic renal damage following transient whole-body ischemia induced by cardiac arrest (CA) and resuscitation. Mice with targeted deletion of sEH (sEH knockout, sEHKO) and C57Bl/6 wild-type control mice were subjected to 10-min CA, followed by cardiopulmonary resuscitation (CPR). Survival in wild-type mice was 93% and 80% at 10 min and 24 h after CA/CPR (n = 15). Unexpectedly, survival in sEHKO mice was significantly lower than WT. Only 56% of sEHKO mice survived for 10 min (n = 15, p = 0.014 compared to WT) and no mice survived for 24 h after CA/CPR (p <0.0001 versus WT). We conclude that sEH plays an important role in cardiovascular regulation, and that reduced sEH levels or function reduces survival from cardiac arrest.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalResuscitation
Volume76
Issue number1
DOIs
StatePublished - Jan 2008

Fingerprint

Epoxide Hydrolases
Cardiopulmonary Resuscitation
Gene Deletion
Heart Arrest
Kidney
Knockout Mice
Induced Heart Arrest
Eicosanoids
Recovery of Function
Reperfusion Injury
Arachidonic Acid
Resuscitation
Cytochrome P-450 Enzyme System
Ischemia
Pharmacology
Hypertension
Acids
Brain

Keywords

  • Blood pressure
  • Cardiac arrest
  • CPR
  • EPHX2
  • Epoxyeicosatrienoic acids
  • Ischemia
  • P450 epoxygenase
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Nursing(all)

Cite this

Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation. / Hutchens, Michael; Nakano, Takaaki; Dunlap, Jennifer; Traystman, Richard J.; Hurn, Patricia D.; Alkayed, Nabil.

In: Resuscitation, Vol. 76, No. 1, 01.2008, p. 89-94.

Research output: Contribution to journalArticle

@article{0c2a8918b0784c00926def4e66bfe54a,
title = "Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation",
abstract = "The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 arachidonic acid epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH). Pharmacological inhibition and gene deletion of sEH protect against ischemia/reperfusion injury in brain and heart, and against hypertension-related end-organ damage in kidney. We tested the hypothesis that sEH gene deletion improves survival, recovery of renal function and pathologic ischemic renal damage following transient whole-body ischemia induced by cardiac arrest (CA) and resuscitation. Mice with targeted deletion of sEH (sEH knockout, sEHKO) and C57Bl/6 wild-type control mice were subjected to 10-min CA, followed by cardiopulmonary resuscitation (CPR). Survival in wild-type mice was 93{\%} and 80{\%} at 10 min and 24 h after CA/CPR (n = 15). Unexpectedly, survival in sEHKO mice was significantly lower than WT. Only 56{\%} of sEHKO mice survived for 10 min (n = 15, p = 0.014 compared to WT) and no mice survived for 24 h after CA/CPR (p <0.0001 versus WT). We conclude that sEH plays an important role in cardiovascular regulation, and that reduced sEH levels or function reduces survival from cardiac arrest.",
keywords = "Blood pressure, Cardiac arrest, CPR, EPHX2, Epoxyeicosatrienoic acids, Ischemia, P450 epoxygenase, Soluble epoxide hydrolase",
author = "Michael Hutchens and Takaaki Nakano and Jennifer Dunlap and Traystman, {Richard J.} and Hurn, {Patricia D.} and Nabil Alkayed",
year = "2008",
month = "1",
doi = "10.1016/j.resuscitation.2007.06.031",
language = "English (US)",
volume = "76",
pages = "89--94",
journal = "Resuscitation",
issn = "0300-9572",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation

AU - Hutchens, Michael

AU - Nakano, Takaaki

AU - Dunlap, Jennifer

AU - Traystman, Richard J.

AU - Hurn, Patricia D.

AU - Alkayed, Nabil

PY - 2008/1

Y1 - 2008/1

N2 - The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 arachidonic acid epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH). Pharmacological inhibition and gene deletion of sEH protect against ischemia/reperfusion injury in brain and heart, and against hypertension-related end-organ damage in kidney. We tested the hypothesis that sEH gene deletion improves survival, recovery of renal function and pathologic ischemic renal damage following transient whole-body ischemia induced by cardiac arrest (CA) and resuscitation. Mice with targeted deletion of sEH (sEH knockout, sEHKO) and C57Bl/6 wild-type control mice were subjected to 10-min CA, followed by cardiopulmonary resuscitation (CPR). Survival in wild-type mice was 93% and 80% at 10 min and 24 h after CA/CPR (n = 15). Unexpectedly, survival in sEHKO mice was significantly lower than WT. Only 56% of sEHKO mice survived for 10 min (n = 15, p = 0.014 compared to WT) and no mice survived for 24 h after CA/CPR (p <0.0001 versus WT). We conclude that sEH plays an important role in cardiovascular regulation, and that reduced sEH levels or function reduces survival from cardiac arrest.

AB - The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 arachidonic acid epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH). Pharmacological inhibition and gene deletion of sEH protect against ischemia/reperfusion injury in brain and heart, and against hypertension-related end-organ damage in kidney. We tested the hypothesis that sEH gene deletion improves survival, recovery of renal function and pathologic ischemic renal damage following transient whole-body ischemia induced by cardiac arrest (CA) and resuscitation. Mice with targeted deletion of sEH (sEH knockout, sEHKO) and C57Bl/6 wild-type control mice were subjected to 10-min CA, followed by cardiopulmonary resuscitation (CPR). Survival in wild-type mice was 93% and 80% at 10 min and 24 h after CA/CPR (n = 15). Unexpectedly, survival in sEHKO mice was significantly lower than WT. Only 56% of sEHKO mice survived for 10 min (n = 15, p = 0.014 compared to WT) and no mice survived for 24 h after CA/CPR (p <0.0001 versus WT). We conclude that sEH plays an important role in cardiovascular regulation, and that reduced sEH levels or function reduces survival from cardiac arrest.

KW - Blood pressure

KW - Cardiac arrest

KW - CPR

KW - EPHX2

KW - Epoxyeicosatrienoic acids

KW - Ischemia

KW - P450 epoxygenase

KW - Soluble epoxide hydrolase

UR - http://www.scopus.com/inward/record.url?scp=36849019028&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36849019028&partnerID=8YFLogxK

U2 - 10.1016/j.resuscitation.2007.06.031

DO - 10.1016/j.resuscitation.2007.06.031

M3 - Article

VL - 76

SP - 89

EP - 94

JO - Resuscitation

JF - Resuscitation

SN - 0300-9572

IS - 1

ER -