Clinical investigations have revealed that this opioid-induced respiratory depression is less severe in patients with chronic pain, but the mechanisms that underlie this phenomenon are unknown. Therefore, the present study was designed to examine the influence of chronic pain on morphine-induced respiratory depression. Respiration was detected by double-chamber, flow-through whole-body plethysmography. Respiratory
frequency was dose-dependently and significantly decreased after morphine administration. This effect peaked at 30 min after administration and lasted 3 h. In contrast, tidal volume was increased. Minute volume was significantly decreased by morphine at a higher dose, but not a lower dose. In nerve-ligated mice, a morphine-induced decrease in respiratory frequency was observed, whereas the increase of tidal volume was more prominent. A decrease in minute volume was not observed in nerve-ligated mice. This attenuation of the morphine-induced selleck products decrease in minute volume in nerve-ligated mice was reversed by treatment
with the serotonin (5-HT)4a receptor antagonist GR125487. Moreover, treatment with the 5-HT4 receptor agonist mosapride antagonized the morphine-induced decrease in minute volume, due to the enhancement of tidal volume. Finally, the expression of 5-HT4a receptor in the brainstem was enhanced in nerve-ligated mice compared to that in sham-operated mice. These results suggest that the decrease in morphine-induced respiratory depression under chronic pain this website is mediated by the enhancement of 5-HT4a receptor systems in the brainstem. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Background: Patients with critical limb ischemia (CLI) have a high rate Forskolin cell line of adverse cardiovascular events, particularly when undergoing surgery. We sought to determine the effect of surgery and vascular disease on platelet and monocyte activation in vivo in patients with CLI.
Methods. An observational,
cross-sectional study was performed at a tertiary referral hospital in the southeast of Scotland. Platelet and monocyte activation were measured in whole blood in patients with CLI scheduled for mfrainguinal bypass and compared with matched healthy controls, patients with chronic intermittent claudication, patients with acute myocardial infarction, and those undergoing arthroplasty (n = 30 per group). Platelet and monocyte activation were quantified using flow cytometric assessment of platelet-monocyte aggregation, platelet P-selectin expression, plateletderived microparticles, and monocyte CD40 and CD11b expression.
Results: Compared with those with intermittent claudication, subjects with CLI had increased platelet-monocyte aggregates (41.7% +/- 12.2% vs 32.6% +/- 8.5%, respectively), platelet microparticles (178.7 +/- 106.9 vs 116.9 +/- 53.4), and monocytc CD40 expression (70.0% +/- 12.2% vs 52.4% +/- 15.2%; P < .001 for all).