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.

Pharmaceutical integrated stress response enhancement protects oligodendrocytes and provides a potential multiple sclerosis therapeutic

“…The ISR is known to affect T cell cytokine production 50 , such that sustained activation of the ISR in the presence of guanabenz could help explain the noted alteration to T cell activity in the treated animals. Moreover, independent from its ISR effects, guanabenz is also an α2-adrenergic receptor agonist, and other drugs with similar activity have been demonstrated to modulate the inflammatory response 51 52 . The full effects of guanabenz on the clinical and histopathologic response of EAE are likely a combination of its oligodendrocyte-protective effects in combination with modest immunomodulatory activities.…”

The neutrophil-to-lymphocyte ratio (NLR) after surgery for hip fracture (HF)

“…Firstly, the acute inflammatory response can be observed minutes after a vascular lesion or an acute ischemic event (Gourdin et al, 2012). This response is characterized by increases in IL-1beta and IL-6 secretion, at least partially by activated neutrophils (Mann & Young, 1994;Torre-Amione et al, 1996;Wang, Chen, & Chen, 2011).…”

Septic encephalopathy: does inflammation drive the brain crazy?

“…The administration of norepinephrine reuptake inhibitors (NRIs) inhibits LPS-induced expression of cytokines, chemokines and endothelial activation, 99 probably increasing norepinephrine availability to glial cells. In addition, a2-adrenoceptor stimulation decreases vascular endothelial cell permeability 77 and reduces production of inflammatory mediators. 78 Supporting this view, dopexamine, an a2-adrenoceptor and dopamine 1 and 2 receptor agonist, protects against cerebral edema induced by sepsis, and the co-administration of an a2-adrenoceptor antagonist blunted this effect.…”