A MultiCenter Pilot Randomized Controlled Trial of Remote Ischemic Preconditioning in Major Vascular Surgery

Healy, Donagh; Boyle, E.; McCartan, Damian; Bourke, Michael; Medani, Mekki; Ferguson, John; Yagoub, Hatim; Bashar, Khalid; O'Donnell, M; Newell, John; Canning, Catriona; McMonagle, Morgan; Dowdall, Joseph; Cross, Simon S.; O'Daly, S.; Manning, Brian J.; Fulton, Gregory J.; Kavanagh, Eamon G.; Burke, P.; Grace, Pierce A.; Moloney, Mary; Walsh, Stewart R.

doi:10.1177/1538574415614404

“…In astrocytes, HIF-1 also induces the expression of P450 2C11, an arachidonic acid epoxygenase, which is protective against ischemia-reperfusion injury in multiple organ systems [22], and contributes to IPC-mediated protection [22]. HIF-1 controls the glycolytic response of immune cells and profoundly alters inflammatory responses under conditions of hypoxia [23].…”

Section: Molecular Mediators Of Preconditioningmentioning

confidence: 99%

“…HIF-1 is an upstream regulator for a series of hypoxiaresponsive genes, including glucose transporter (GLUT) 1 and vascular endothelial growth factor (VEGF), and is upregulated by hypoxic preconditioning [4,22,69]. In astrocytes, HIF-1 also induces the expression of P450 2C11, an arachidonic acid epoxygenase, which is protective against ischemia-reperfusion injury in multiple organ systems [22], and contributes to IPC-mediated protection [22].…”

Section: Molecular Mediators Of Preconditioningmentioning

confidence: 99%

“…Regulates metabolic genes to protect against hypoxia Multiple CNS cells [17,22], peripheral immune cells [23] Type 1 IFNs Regulate neuroimmune function Microglia [11], peripheral macrophages [24,25] Refractive microRNAs Modulate gene expression post-translationally Multiple CNS cells [18,26] Polycomb group proteins Induce lasting alterations of gene-transcription programs…”

Section: Hif-1mentioning

confidence: 99%

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Neuroimmune Response in Ischemic Preconditioning

McDonough

¹

,

Weinstein

²

2016

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Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon in which a brief period of cerebral ischemia confers transient tolerance to subsequent ischemic challenge. Research on IPC has implicated cellular, molecular, and systemic elements of the immune response in this phenomenon. Potent molecular mediators of IPC include innate immune signaling pathways such as Toll-like receptors and type 1 interferons. Brain ischemia results in release of proand anti-inflammatory cytokines and chemokines that orchestrate the neuroinflammtory response, resolution of inflammation, and transition to neurological recovery and regeneration. Cellular mediators of IPC include microglia, the resident central nervous system immune cells, astrocytes, and neurons. All of these cell types engage in cross-talk with each other using a multitude of signaling pathways that modulate activation/ suppression of each of the other cell types in response to ischemia. As the postischemic neuroimmune response evolves over time there is a shift in function toward provision of trophic support and neuroprotection. Peripheral immune cells infiltrate the central nervous system en masse after stroke and are largely detrimental, with a few subtypes having beneficial, protective effects, though the role of these immune cells in IPC is largely unknown. The role of neural progenitor cells in IPC-mediated neuroprotection is another active area of investigation as is the role of microglial proliferation in this setting. A mechanistic understanding of these molecular and cellular mediators of IPC may not only facilitate more effective direct application of IPC to specific clinical scenarios, but also, more broadly, reveal novel targets for therapeutic intervention in stroke.

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“…The relative ease of administration, low cost, and potential wide generalizability of RIPC make the concept a particularly attractive clinical strategy for select populations of patients that are at high risk for cerebral ischemic events in the immediate (hours to days) future. This would include patients that are about to undergo major cardiac [32,33] or carotid artery [34] surgery, as well as possibly patients with subarachnoid hemorrhage that are at high risk of developing cerebral vasospasm and accompanying delayed cerebral ischemia [35,36]. The pioneering papers in the RIPC field suggest that neuroprotection is induced rapidly [30,31,37]; however, the duration of protection has not been determined [37,38].…”

Section: Remote Preconditioningmentioning

confidence: 99%

Correction to: Neuroimmune Response in Ischemic Preconditioning

McDonough

¹

,

Weinstein

²

2018

View full text Add to dashboard Cite

Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon in which a brief period of cerebral ischemia confers transient tolerance to subsequent ischemic challenge. Research on IPC has implicated cellular, molecular, and systemic elements of the immune response in this phenomenon. Potent molecular mediators of IPC include innate immune signaling pathways such as Tolllike receptors and type 1 interferons. Brain ischemia results in release of pro-and anti-inflammatory cytokines and chemokines that orchestrate the neuroinflammatory response, resolution of inflammation, and transition to neurological recovery and regeneration. Cellular mediators of IPC include microglia, the resident central nervous system immune cells, astrocytes, and neurons. All of these cell types engage in cross-talk with each other using a multitude of signaling pathways that modulate activation/ suppression of each of the other cell types in response to ischemia. As the postischemic neuroimmune response evolves over time there is a shift in function toward provision of trophic support and neuroprotection. Peripheral immune cells infiltrate the central nervous system en masse after stroke and are largely detrimental, with a few subtypes having beneficial, protective effects, though the role of these immune cells in IPC is largely unknown. The role of neural progenitor cells in IPC-mediated neuroprotection is another active area of investigation as is the role of microglial proliferation in this setting. A mechanistic understanding of these molecular and cellular mediators of IPC may not only facilitate more effective direct application of IPC to specific clinical scenarios, but also, more broadly, reveal novel targets for therapeutic intervention in stroke. Keywords PreconditioningIschemic preconditioning (IPC) is an experimental phenomenon in which a brief period of ischemia confers robust neuroprotection against subsequent ischemic events [1-3]. It is important to note that preconditioning does not reduce the incidence of stroke, but rather ameliorates the pathophysiologic response to cerebral ischemia and results in a smaller infarct volume and improved poststroke recovery [4][5][6]. Clinical studies suggest that patients with stroke who suffered a recent prior transient ischemic attack have better outcomes than those who did not, implying that a human correlate to experimental IPC exists [7,8]. Elucidating the mechanisms of IPC is considered a critical challenge in stroke research [9,10]. Recent literature has implicated innate immune pathways, including Toll-like receptors (TLRs) [11,12] and type 1 interferon (IFN) signaling [5,11,13] in IPC-mediated protection.Due to a technical error in the production process, the earlier version of this article contained numerous errors in the reference numbering. We are reprinting the entire article in the correction for readabilityThe online version of the original article can be found at https://doi

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“…To date, trials assessing the effect of RIPC in vascular surgery have used either propofol anaesthesia, 4e11 or provided no information about the anaesthetic protocol. 2,3,12 However, no clinical trial has been conducted that was specifically designed to investigate the influence of an anaesthetic regimen with propofol on the effectiveness of RIPC. Consequently, the evidence from experimental studies remains the closest estimation and a recent experimental study directly designed to investigate the adverse effects of the anaesthetic regimen on RIPC demonstrated that the use of propofol reserved the protective effect of RIPC, while protective effects were observed in animal groups receiving pentobarbital or sevoflurane/remifentanil for the induction and maintenance of anaesthesia.…”

mentioning

confidence: 99%