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Neuromodulation of innate immunity by remote ischaemic conditioning in humans: Experimental cross-over study.
May, Shaun M; Chiang, Eric; Reyes, Anna; Martir, Gladys; Patel, Amour; Karmali, Shamir; Patel, Sanjiv; West, Simeon; Del Arroyo, Ana Gutierrez; Gourine, Alexander V; Ackland, Gareth L.
Afiliação
  • May SM; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
  • Chiang E; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
  • Reyes A; University College Hospital NHS Trust, London, UK.
  • Martir G; University College Hospital NHS Trust, London, UK.
  • Patel A; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
  • Karmali S; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
  • Patel S; University College Hospital NHS Trust, London, UK.
  • West S; University College Hospital NHS Trust, London, UK.
  • Del Arroyo AG; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
  • Gourine AV; Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, University College London, UK.
  • Ackland GL; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
Brain Behav Immun Health ; 16: 100299, 2021 Oct.
Article em En | MEDLINE | ID: mdl-34589791
Experimental animal studies on the mechanisms of remote ischaemic conditioning (RIC)-induced cardioprotection against ischaemia/reperfusion injury demonstrate involvement of both neuronal and humoral pathways. Autonomic parasympathetic (vagal) pathways confer organ protection through both direct innervation and/or immunomodulation, but evidence in humans is lacking. During acute inflammation, vagal release of acetylcholine suppresses CD11b expression, a critical ß2-integrin regulating neutrophil adhesion to the endothelium and transmigration to sites of injury. Here, we tested the hypothesis that RIC recruits vagal activity in humans and has an anti-inflammatory effect by reducing neutrophil CD11b expression. Participants (age:50 â€‹± â€‹19 years; 53% female) underwent ultrasound-guided injection of local anaesthetic within the brachial plexus before applying 3 â€‹× â€‹8 min cycles of brachial artery occlusion using a blood pressure cuff (RICblock). RIC was repeated 6 weeks later without brachial plexus block. Masked analysers quantified vagal activity (heart rate, heart rate variability (HRV)) before, and 10 â€‹min after, the last cycle of RIC. RR-interval increased after RIC (reduced heart rate) by 40 â€‹ms (95% confidence intervals (95%CI):13-66; n â€‹= â€‹17 subjects; P â€‹= â€‹0.003). RR-interval did not change after brachial plexus blockade (mean difference: 20 â€‹ms (95%CI:-11 to 50); P â€‹= â€‹0.19). The high-frequency component of HRV was reduced after RICblock, but remained unchanged after RIC (P â€‹< â€‹0.001), indicating that RIC preserved vagal activity. LPS-induced CD16+CD11b+ expression in whole blood (measured by flow cytometry) was reduced by RIC (3615 median fluorescence units (95%CI:475-6754); P = 0.026), compared with 2331 units (95%CI:-3921 to 8582); P = 0.726) after RICblock. These data suggest that in humans RIC recruits vagal cardiac and anti-inflammatory mechanisms via ischaemia/reperfusion-induced activation of sensory nerve fibres that innervate the organ undergoing RIC.
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Texto completo: 1 Bases de dados: MEDLINE Tipo de estudo: Clinical_trials Idioma: En Revista: Brain Behav Immun Health Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Tipo de estudo: Clinical_trials Idioma: En Revista: Brain Behav Immun Health Ano de publicação: 2021 Tipo de documento: Article