title: Remote ischaemic preconditioning suppresses endogenous plasma nitrite during ischaemia-reperfusion: a randomized controlled crossover pilot study.
abstract: The aim of this article is to test the hypothesis that remote ischaemic preconditioning (RIPC) increases circulating endogenous local and systemic plasma (nitrite) during RIPC and ischaemia-reperfusion (IR) as a potential protective mechanism against ischaemia-reperfusion injury (IRI).
  
  
  
  Six healthy male volunteers (mean age 29.5 ± 7.6 years) were randomized in a crossover study to initially receive either RIPC (4 × 5 min cycles) to the left arm, or no RIPC (control), both followed by an ischaemia-reperfusion (IR) sequence (20 min cuff inflation to 200 mmHg, 20 min reperfusion) to the right arm. The volunteers returned at least 7 days later for the alternate intervention. The primary outcome was the effect of RIPC vs. control on local and systemic plasma (nitrite).
  
  
  
  RIPC did not significantly change plasma (nitrite) in either the left or the right arm during the RIPC sequence. However, compared to control, RIPC decreased plasma (nitrite) during the subsequent IR sequence by ~26% (from 118 ± 9 to 87 ± 5 nmol l-1) locally in the left arm (P = 0.008) overall, with an independent effect of -58.70 nmol l-1(95% confidence intervals -116.1 to -1.33) at 15 min reperfusion, and by ~24% (from 109 ± 9 to 83 ± 7 nmol l-1) systemically in the right arm (P = 0.03).
  
  
  
  RIPC had no effect on plasma (nitrite) during the RIPC sequence, but instead decreased plasma (nitrite) by ~25% during IR. This would likely counteract the protective mechanisms of RIPC, and contribute to RIPC's lack of efficacy, as observed in recent clinical trials. A combined approach of RIPC with nitrite administration may be required.
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas' Hospital, London, SE1 7EH, UK.|Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.|Department of Anaesthetics, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Ashok
authors.initials: A
authors.lastname: Nair
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas' Hospital, London, SE1 7EH, UK.|Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Sitara
authors.initials: S
authors.lastname: Khan
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas' Hospital, London, SE1 7EH, UK.|Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Sami
authors.initials: S
authors.lastname: Omar
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas' Hospital, London, SE1 7EH, UK.|Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.|Ultrasound Department, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Pei
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas' Hospital, London, SE1 7EH, UK.|Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: McNeill
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas' Hospital, London, SE1 7EH, UK.|Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Phil
authors.initials: P
authors.lastname: Chowienczyk
authors.affiliation: King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas' Hospital, London, SE1 7EH, UK.|Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Andrew James
authors.initials: AJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D064368:Healthy Volunteers; D006801:Humans; D007511:Ischemia / Q000097:blood* / Q000150:complications; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009573:Nitrites / Q000097:blood*; D010865:Pilot Projects; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D009573:Nitrites
keywords: ischaemia reperfusion; nitrite; remote ischaemic preconditioning