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The Effect of Clonidine, an Alpha-2 Adrenergic Receptor Agonist, on Inflammatory Response and Postischemic Endothelium Function During Early Reperfusion in Healthy Volunteers

Gourdin, Maximilien MD*; Dubois, Philippe MD*; Mullier, Francois PharmD, PhD; Chatelain, Bernard Pharm Biol; Dogné, Jean-Michel PharmD, PhD; Marchandise, Baudouin MD§; Jamart, Jacques MD, MSc; De Kock, Marc MD, PhD

Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0b013e31827303fa
Original Article
Abstract

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.

Author Information

*Department of Anesthesiology, Université Catholique de Louvain, Centre Hospitalier Universitaire UCL de Mont-Godinne, Yvoir, Belgium

Department of Hematology, Namur Thrombosis and Hemostasis Centre–NAmur Research Institute for LIfe Sciences, Université Catholique de Louvain, Cliniques Universitaires UCL de Mont-Godinne, Yvoir, Belgium

Department of Pharmacy, NAmur Research Institute for LIfe Sciences, Facultés Universitaires Notre-Dame de la Paix, Namur Thrombosis and Hemostasis Centre, University of Namur, Rue de Bruxelles, Namur, Belgium

§Department of Cardiology, Université Catholique de Louvain, Centre Hospitalier Universitaire Université Catholique de Louvain de Mont-Godinne, Yvoir, Belgium

Department of Biostatistics, Université Catholique de Louvain, Centre Hospitalier Universitaire Université Catholique de Louvain de Mont-Godinne, Yvoir, Belgium

Department of Anesthesiology, Université Catholique de Louvain, Cliniques Universitaires Université Catholique de Louvain Saint-Luc, Brussels, Belgium.

Reprints: Maximilien Gourdin, MD, Department of Anesthesiology, Université Catholique de Louvain, Centre Hospitalier Universitaire de Mont-Godinne, 1 Avenue Dr Therasse, 5530, Yvoir, Belgium (e-mail: maximilien.gourdin@uclouvain.be).

Disclosure: This work was supported by institutional and departmental funds provided by the Department of Anaesthesiology of Centre Hospitalier Universitaire UCL Mont-Godinne, 1 Avenue Dr Therasse, 5530, Yvoir, Belgium and by the Department of Pharmacy, Facultés Universitaires Notre-Dame de la Paix, University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium.

The authors declare no conflicts of interest.

Received May 5, 2012

Accepted September 5, 2012

© 2012 Lippincott Williams & Wilkins, Inc.