title: Helium induces preconditioning in human endothelium in vivo.
abstract: OBJECTIVE
  Helium protects myocardium by inducing preconditioning in animals. We investigated whether human endothelium is preconditioned by helium inhalation in vivo.
  
  
  RESULTS
  Forearm ischemia-reperfusion (I/R) in healthy volunteers (each group n = 10) was performed by inflating a blood pressure cuff for 20 min. Endothelium-dependent and endothelium-independent responses were measured after cumulative dose-response infusion of acetylcholine and sodium nitroprusside, respectively, at baseline and after 15 min of reperfusion using strain-gauge, venous occlusion plethysmography. Helium preconditioning was applied by inhalation of helium (79% helium, 21% oxygen) either 15 min (helium early preconditioning [He-EPC]) or 24 h before I/R (helium late preconditioning). Additional measurements of He-EPC were done after blockade of endothelial nitric oxide synthase. Plasma levels of cytokines, adhesion molecules, and cell-derived microparticles were determined. Forearm I/R attenuated endothelium-dependent vasodilation (acetylcholine) with unaltered endothelium-independent response (sodium nitroprusside). Both He-EPC and helium late preconditioning attenuated I/R-induced endothelial dysfunction (max increase in forearm blood flow in response to acetylcholine after I/R was 180 ± 24% [mean ± SEM] without preconditioning, 573 ± 140% after He-EPC, and 290 ± 32% after helium late preconditioning). Protection of helium was comparable to ischemic preconditioning (max forearm blood flow 436 ± 38%) and was not abolished after endothelial nitric oxide synthase blockade. He-EPC did not affect plasma levels of cytokines, adhesion molecules, or microparticles.
  
  
  CONCLUSIONS
  Helium is a nonanesthetic, nontoxic gas without hemodynamic side effects, which induces early and late preconditioning of human endothelium in vivo. Further studies have to investigate whether helium may be an instrument to induce endothelial preconditioning in patients with cardiovascular risk factors.
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Centre, Meibergdreef Amsterdam, The Netherlands.
authors.forename: Kirsten F
authors.initials: KF
authors.lastname: Smit
authors.forename: Gezina T M L
authors.initials: GT
authors.lastname: Oei
authors.forename: Daniel
authors.initials: D
authors.lastname: Brevoord
authors.forename: Erik S
authors.initials: ES
authors.lastname: Stroes
authors.forename: Rienk
authors.initials: R
authors.lastname: Nieuwland
authors.forename: Wolfgang S
authors.initials: WS
authors.lastname: Schlack
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.forename: Nina C
authors.initials: NC
authors.lastname: Weber
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000328:Adult; D015815:Cell Adhesion Molecules / Q000097:blood; D016207:Cytokines / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005542:Forearm / Q000098:blood supply / Q000502:physiology; D006371:Helium / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage; D010991:Plethysmography / Q000379:methods; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D014665:Vasodilator Agents; D009599:Nitroprusside; D006371:Helium; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D010100:Oxygen