Evidence map›Paper›PMID 33030094›Full record

ArticleJournal of the American Heart Association2020

Role of Endothelial Nitric Oxide Synthase in Isoflurane Conditioning-Induced Neurovascular Protection in Subarachnoid Hemorrhage.

Umeshkumar Athiraman, Keshav Jayaraman, Meizi Liu, Tusar Giri, Jane Yuan, Gregory J Zipfel

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Inhaled Anesthetics: Beyond the Operating Room.Journal of clinical medicine · 2024
    Review
  4. Observational
  5. Conditioning-based therapeutics for aneurysmal subarachnoid hemorrhage - A critical review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Review
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  9. Review
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  14. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Umeshkumar AthiramanDepartment of Anesthesiology Washington University St. Louis MO.
Keshav JayaramanDepartment of Neurological surgery Washington University St. Louis MO.
Meizi LiuDepartment of Anesthesiology Washington University St. Louis MO.
Tusar GiriDepartment of Anesthesiology Washington University St. Louis MO.
Jane YuanDepartment of Neurological surgery Washington University St. Louis MO.
Gregory J ZipfelDepartment of Neurological surgery Washington University St. Louis MO.
Hope Center for Neurological Disorders · USWashington University in St. Louis · US

Funding

TRAINING PROGRAM IN ANESTHESIOLOGY RESEARCHT32GM108539 · NIGMS · WASHINGTON UNIVERSITY · PI Aaron J Norris · 2014 to 2026
$4.9M
Translating Endogenous Vascular Protective Cascades into Therapy for Aneurysmal Subarachnoid HemorrhageR01NS091603 · NINDS · WASHINGTON UNIVERSITY · PI ZIPFEL, GREGORY J · 2015 to 2019
$2.5M
WASHINGTON UNIVERSITY NEUROSURGERY RESIDENT RESEARCH EDUCATION PROGRAMR25NS090978 · NINDS · WASHINGTON UNIVERSITY · PI ZIPFEL, GREGORY J · 2015 to 2023
$2.1M
NIGMS NIH HHS T32 GM108539NINDS NIH HHS R01 NS091603NINDS NIH HHS R25 NS090978
6 · The paper itself

Abstract

Background Delayed cerebral ischemia remains a common and profound risk factor for poor outcome after subarachnoid hemorrhage (SAH). The aim of our current study is to define the role of endothelial nitric oxide synthase (eNOS) in isoflurane conditioning-induced neurovascular protection after SAH. Methods and Results Ten- to 14-week-old male wild-type mice (C57BL/6) as controls and eNOS knockout male mice (strain # 002684) were obtained for the study. Animals underwent either sham surgery, SAH surgery, or SAH with isoflurane conditioning. Anesthetic post conditioning was performed with isoflurane 2% for 1 hour, 1 hour after SAH. Normothermia was maintained with the homeothermic blanket. In a separate cohort, nitric oxide synthase was inhibited by a pan nitric oxide synthase inhibitor, L-nitroarginine methyl ester. Vasospasm measurement was assessed 72 hours after SAH and neurological function was assessed daily. Isoflurane-induced changes in the eNOS protein expression were measured. eNOS protein expression was significantly increased by isoflurane conditioning in naïve mice as well as mice subjected to SAH. Vasospasm of the middle cerebral artery and neurological deficits were evident following SAH versus sham surgery, both in wild-type mice and eNOS knockout mice. Isoflurane conditioning attenuated vasospasm and neurological deficits in wild-type mice. This delayed cerebral ischemia protection was lost in L-nitroarginine methyl ester -administered mice and eNOS knockout mice. Conclusions Our data indicate isoflurane conditioning provides robust protection against SAH-induced vasospasm and neurological deficits, and that this delayed cerebral ischemia protection is critically mediated via isoflurane-induced augmentation of eNOS.

Indexed as

Brain IschemiaAnesthetics, InhalationAnimalsDisease Models, AnimalEndothelium, VascularIschemic PostconditioningIschemic PreconditioningIsofluraneMiceMice, Inbred C57BLMice, KnockoutNeuroprotectionNitric Oxide Synthase Type IIISubarachnoid HemorrhageAnesthetics, InhalationIsofluraneNitric Oxide Synthase Type IIIaneurysmal subarachnoid hemorrhagedelayed cerebral ischemiaendothelial nitric oxide synthaseisoflurane conditioning

Identifiers

PMID33030094
PMCPMC7763369
OpenAlexW3092219022

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.