title: The effect of clonidine, an alpha-2 adrenergic receptor agonist, on inflammatory response and postischemic endothelium function during early reperfusion in healthy volunteers.
abstract: Ischemia-reperfusion disturbs endothelial physiology and generates a proinflammatory state. Animal studies showed that clonidine administered prior hypoxia improves posthypoxic endothelial function. To investigate this effect in human, we have assessed the postischemic endothelium function and the proinflammatory state in healthy volunteers with and without clonidine. Seven volunteers were included. Each subject underwent the experimental protocol (15 minutes nondominant forearm ischemia) with and without clonidine. Endothelial function was assessed by flow-mediated dilatation (FMD) in the brachial artery before ischemia (FMDPI), immediately after ischemia (FMDIAI), and 15 minutes after ischemia (FMD15AI). Neutrophil (CD11b/CD18) and platelet (CD42b) activations were measured by flow cytometry during reperfusion in blood samples from ischemic (local) and nonischemic (systemic) forearms. Proinflammatory state was assessed by serum concentration of interleukin (IL)-1β and -6. Clonidine does not influence baseline FMD (P = 0.118) but improves FMDIAI (P = 0.018) and FMD15AI (P = 0.018). It increases platelet activation in systemic circulation (P = 0.003) during reperfusion but not in local circulation (P = 0.086). Clonidine increases neutrophil activation in local circulation (P = 0.001) but not in systemic circulation (P = 0.642). In local circulation, clonidine decreases IL-6 (P = 0.044) but does not influence IL-1β (P = 0.113). By contrast, it decreases both IL-6 (P = 0.026) and IL-1β (P = 0.027) concentrations in systemic circulation. In conclusion, clonidine improves endothelial function and modulates inflammation during reperfusion.
authors.affiliation: Department of Anesthesiology, Université Catholique de Louvain, Centre Hospitalier Universitaire UCL de Mont-Godinne, Yvoir, Belgium. maximilien.gourdin@uclouvain.be
authors.forename: Maximilien
authors.initials: M
authors.lastname: Gourdin
authors.forename: Philippe
authors.initials: P
authors.lastname: Dubois
authors.forename: Francois
authors.initials: F
authors.lastname: Mullier
authors.forename: Bernard
authors.initials: B
authors.lastname: Chatelain
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
authors.forename: Baudouin
authors.initials: B
authors.lastname: Marchandise
authors.forename: Jacques
authors.initials: J
authors.lastname: Jamart
authors.forename: Marc
authors.initials: M
authors.lastname: De Kock
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use*; D000328:Adult; D001530:Belgium; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D039481:CD11b Antigen / Q000097:blood; D018821:CD18 Antigens / Q000097:blood; D003000:Clonidine / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D005434:Flow Cytometry; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis; D015424:Reperfusion; D015427:Reperfusion Injury / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D014111:Tourniquets; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D015415:Biomarkers; D039481:CD11b Antigen; D018821:CD18 Antigens; C508600:IL6 protein, human; C509295:ITGAM protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D019038:Platelet Glycoprotein GPIb-IX Complex; D003000:Clonidine