Beneficial Effect of Sodium Nitrite on EEG Ischaemic Markers in Patients with Subarachnoid Haemorrhage

Translational Stroke Research ◽

10.1007/s12975-021-00939-9 ◽

2021 ◽

Author(s):

Alexander Luettich ◽

Edit Franko ◽

Desiree B. Spronk ◽

Catherine Lamb ◽

Rufus Corkill ◽

...

Keyword(s):

Subarachnoid Haemorrhage ◽

Sodium Nitrite ◽

Cerebral Ischaemia ◽

Cerebral Metabolism ◽

Early Brain Injury ◽

Saline Infusion ◽

Experimental Medicine ◽

No Donor

AbstractSubarachnoid haemorrhage (SAH) is associated with long-term disability, serious reduction in quality of life and significant mortality. Early brain injury (EBI) refers to the pathological changes in cerebral metabolism and blood flow that happen in the first few days after ictus and may lead on to delayed cerebral ischaemia (DCI). A disruption of the nitric oxide (NO) pathway is hypothesised as a key mechanism underlying EBI. A decrease in the alpha-delta power ratio (ADR) of the electroencephalogram has been related to cerebral ischaemia. In an experimental medicine study, we tested the hypothesis that intravenous sodium nitrite, an NO donor, would lead to increases in ADR. We studied 33 patients with acute aneurysmal SAH in the EBI phase. Participants were randomised to either sodium nitrite or saline infusion for 1 h. EEG measurements were taken before the start of and during the infusion. Twenty-eight patients did not develop DCI and five patients developed DCI. In the patients who did not develop DCI, we found an increase in ADR during sodium nitrite versus saline infusion. In the five patients who developed DCI, we did not observe a consistent pattern of ADR changes. We suggest that ADR power changes in response to nitrite infusion reflect a NO-mediated reduction in cerebral ischaemia and increase in perfusion, adding further evidence to the role of the NO pathway in EBI after SAH. Our findings provide the basis for future clinical trials employing NO donors after SAH.

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Delayed cerebral ischaemia in patients with aneurysmal subarachnoid haemorrhage: Functional outcome and long‐term mortality

Acta Anaesthesiologica Scandinavica ◽

10.1111/aas.13412 ◽

2019 ◽

Vol 63 (9) ◽

pp. 1191-1199 ◽

Cited By ~ 3

Author(s):

Markus Harboe Olsen ◽

Matias Orre ◽

Anna Cold Winge Leisner ◽

Rune Rasmussen ◽

Søren Bache ◽

...

Keyword(s):

Subarachnoid Haemorrhage ◽

Functional Outcome ◽

Cerebral Ischaemia ◽

Aneurysmal Subarachnoid Haemorrhage ◽

Delayed Cerebral Ischaemia ◽

Long Term Mortality

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The Selectin Superfamily: The Role of Selectin Adhesion Molecules in Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage

Brain Edema XI ◽

10.1007/978-3-7091-6346-7_11 ◽

2000 ◽

pp. 55-60

Author(s):

J. J. Nissen ◽

D. Mantle ◽

A. Blackburn ◽

J. Barnes ◽

T. Wooldridge ◽

...

Keyword(s):

Subarachnoid Haemorrhage ◽

Adhesion Molecules ◽

Cerebral Ischaemia ◽

Aneurysmal Subarachnoid Haemorrhage ◽

Delayed Cerebral Ischaemia

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Neuroprotective Role of the Nrf2 Pathway in Subarachnoid Haemorrhage and Its Therapeutic Potential

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6218239 ◽

2019 ◽

Vol 2019 ◽

pp. 1-21 ◽

Cited By ~ 12

Author(s):

Ardalan Zolnourian ◽

Ian Galea ◽

Diederik Bulters

Keyword(s):

Subarachnoid Haemorrhage ◽

Therapeutic Potential ◽

Early Brain Injury ◽

Dimethyl Fumarate ◽

Protective Effects ◽

Nrf2 Pathway ◽

Nrf2 Knockout ◽

Microcirculatory Disturbances ◽

Knockout Animals

The mechanisms underlying poor outcome following subarachnoid haemorrhage (SAH) are complex and multifactorial. They include early brain injury, spreading depolarisation, inflammation, oxidative stress, macroscopic cerebral vasospasm, and microcirculatory disturbances. Nrf2 is a global promoter of the antioxidant and anti-inflammatory response and has potential protective effects against all of these mechanisms. It has been shown to be upregulated after SAH, and Nrf2 knockout animals have poorer functional and behavioural outcomes after SAH. There are many agents known to activate the Nrf2 pathway. Of these, the actions of sulforaphane, curcumin, astaxanthin, lycopene,tert-butylhydroquinone, dimethyl fumarate, melatonin, and erythropoietin have been studied in SAH models. This review details the different mechanisms of injury after SAH including the contribution of haemoglobin (Hb) and its breakdown products. It then summarises the evidence that the Nrf2 pathway is active and protective after SAH and finally examines the evidence supporting Nrf2 upregulation as a therapy after SAH.

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Long-term co-administration of sodium nitrite and sodium hydrosulfide inhibits hepatic gluconeogenesis in male type 2 diabetic rats: Role of PI3K-Akt-eNOS pathway

Life Sciences ◽

10.1016/j.lfs.2020.118770 ◽

2021 ◽

Vol 265 ◽

pp. 118770

Author(s):

Sajad Jeddi ◽

Sevda Gheibi ◽

Mattias Carlström ◽

Khosrow Kashfi ◽

Asghar Ghasemi

Keyword(s):

Sodium Nitrite ◽

Diabetic Rats ◽

Hepatic Gluconeogenesis ◽

Sodium Hydrosulfide ◽

Male Type ◽

Type 2 Diabetic

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The role of haptoglobin and hemopexin in the prevention of delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a review of current literature

Neurosurgical Review ◽

10.1007/s10143-019-01169-2 ◽

2019 ◽

Vol 43 (5) ◽

pp. 1273-1288

Author(s):

Sean Griffiths ◽

Jeremy Clark ◽

Alexios A Adamides ◽

James Ziogas

Keyword(s):

Subarachnoid Haemorrhage ◽

Current Literature ◽

Cerebral Ischaemia ◽

Aneurysmal Subarachnoid Haemorrhage ◽

Delayed Cerebral Ischaemia

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Efficacy and safety of cilostazol-nimodipine combined therapy on delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a prospective, randomised, double-blinded, placebo-controlled trial protocol

BMJ Open ◽

10.1136/bmjopen-2019-036217 ◽

2020 ◽

Vol 10 (10) ◽

pp. e036217

Author(s):

Troy Dawley ◽

Chad F Claus ◽

Doris Tong ◽

Sina Rajamand ◽

Diana Sigler ◽

...

Keyword(s):

Subarachnoid Haemorrhage ◽

Cerebral Ischaemia ◽

Controlled Trial ◽

Combined Therapy ◽

Aneurysmal Subarachnoid Haemorrhage ◽

Delayed Cerebral Ischaemia ◽

Symptomatic Vasospasm ◽

Institutional Review ◽

Double Blinded

IntroductionDelayed cerebral ischaemia (DCI) due to cerebral vasospasm (cVS) remains the foremost contributor to morbidity and mortality following aneurysmal subarachnoid haemorrhage (aSAH). Past efforts in preventing and treating DCI have failed to make any significant progress. To date, our most effective treatment involves the use of nimodipine, a calcium channel blocker. Recent studies have suggested that cilostazol, a platelet aggregation inhibitor, may prevent cVS. Thus far, no study has evaluated the effect of cilostazol plus nimodipine on the rate of DCI following aSAH.Methods and analysisThis is a multicentre, double-blinded, randomised, placebo-controlled superiority trial investigating the effect of cilostazol on DCI. Data concerning rates of DCI, symptomatic and radiographic vasospasm, length of intensive care unit stay, and long-term functional and quality-of-life (QoL) outcomes will be recorded. All data will be collected with the aim of demonstrating that the use of cilostazol plus nimodipine will safely decrease the incidence of DCI, and decrease the rates of both radiographic and symptomatic vasospasm with subsequent improvement in long-term functional and QoL outcomes when compared with nimodipine alone.Ethics and disseminationEthical approval was obtained from all participating hospitals by the Ascension Providence Hospital Institutional Review Board. The results of this study will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04148105

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Advances in the understanding of delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage

F1000Research ◽

10.12688/f1000research.6635.1 ◽

2015 ◽

Vol 4 ◽

pp. 1200 ◽

Cited By ~ 7

Author(s):

Liam Flynn ◽

Peter Andrews

Keyword(s):

Subarachnoid Haemorrhage ◽

Cerebral Ischaemia ◽

Early Brain Injury ◽

Causative Factor ◽

Aneurysmal Subarachnoid Haemorrhage ◽

Substantial Evidence ◽

Cerebral Vessel ◽

Delayed Cerebral Ischaemia ◽

Common Definition ◽

Definition Of

Delayed cerebral ischaemia has been described as the single most important cause of morbidity and mortality in patients who survive the initial aneurysmal subarachnoid haemorrhage. Our understanding of the pathophysiology of delayed cerebral ischaemia is meagre at best and the calcium channel blocker nimodipine remains the only intervention to consistently improve functional outcome after aneurysmal subarachnoid haemorrhage. There is substantial evidence to support cerebral vessel narrowing as a causative factor in delayed cerebral ischaemia, but contemporary research demonstrating improvements in vessel narrowing has failed to show improved functional outcomes. This has encouraged researchers to investigate other potential causes of delayed cerebral ischaemia, such as early brain injury, microthrombosis, and cortical spreading depolarisation. Adherence to a common definition of delayed cerebral ischaemia is needed in order to allow easier assessment of studies using multiple different terms. Furthermore, improved recognition of delayed cerebral ischaemia would not only allow for faster treatment but also better assessment of interventions. Finally, understanding nimodipine’s mechanism of action may allow us to develop similar agents with improved efficacy.

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