resolvin-d1 and Postoperative-Complications

The magnitude of the perioperative inflammatory response plays a role in surgical outcomes. However, few studies have explored the mechanisms of the resolution of inflammation in the context of surgery. Here, we described the temporal kinetics of interleukin-6, cortisol, lipoxin A4, and resolvin D in patients who underwent oncologic liver resections.. All patients gave written informed consent. Demographic and perioperative surgical data were collected, along with blood samples, before surgery and on the mornings of postoperative days 1, 3, and 5. Interleukin-6, cortisol, lipoxin-A4, and resolvin D were measured in plasma. A P value < 0.05 was considered statistically significant.. Forty-one patients were included in the study. Liver resection for colorectal metastatic disease was the most commonly performed surgery. The plasma concentrations of interleukin-6 were highest on day 1 after surgery and remained higher than the baseline up to postoperative day 1. Postoperative complications occurred in 14 (24%) patients. Cortisol concentrations spiked on postoperative day 1. The concentrations of lipoxin A4 and resolvin D were lowest on day 1 after surgery.. The inflammatory response associated with hepatobiliary surgery is associated with low circulating concentrations of lipoxin A4 and resolvin D that mirror, in an opposite manner, the kinetics of interleukin 6 and cortisol.. NCT01438476.

Topics: Aged; Anti-Inflammatory Agents; Biliary Tract Surgical Procedures; Colorectal Neoplasms; Docosahexaenoic Acids; Female; Hepatectomy; Humans; Hydrocortisone; Inflammation; Interleukin-6; Lipoxins; Liver Neoplasms; Male; Middle Aged; Perioperative Period; Postoperative Complications; Prognosis; Time Factors; Treatment Outcome

Hospitalization for major surgery or critical illness often associates with cognitive decline. Inflammation and dysregulation of the innate immune system can exert broad effects in the periphery and central nervous system (CNS), yet the mechanisms underlying memory impairment after surgery remain poorly understood and without effective therapy. Endogenous regulation of acute inflammation is providing novel approaches to treat several disease states including sepsis, pain, obesity and diabetes. Resolvins are potent endogenous lipid mediators biosynthesized during the resolution phase of acute inflammation that display immunoresolvent actions. Here, using a mouse model of surgery-induced cognitive decline we report that orthopedic surgery affects hippocampal neuronal-glial function, including synaptic transmission and plasticity. Systemic prophylaxis with aspirin-triggered resolvin D1 (AT-RvD1: 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid, as little as 100 ng dose per mouse) improved memory decline following surgery and abolished signs of synaptic dysfunction. Moreover, delayed administration 24 h after surgery also attenuated signs of neuronal dysfunction postoperatively. AT-RvD1 also limited peripheral damage by modulating the release of systemic interleukin (IL)-6 and improved other clinical markers of tissue injury. Collectively, these results demonstrate a novel role of AT-RvD1 in modulating the proinflammatory milieu after aseptic injury and protecting the brain from neuroinflammation, synaptic dysfunction and cognitive decline. These findings provide novel and safer approaches to treat postoperative cognitive decline and potentially other forms of memory dysfunctions.

Topics: Animals; Aspirin; Brain; Cognition; Docosahexaenoic Acids; Electrophysiology; Immunohistochemistry; In Vitro Techniques; Locomotion; Long-Term Potentiation; Macrophages, Peritoneal; Male; Mice; Postoperative Complications; Superoxides