lithium-chloride and Postoperative-Complications

Postoperative cognition impairment is a perishing complication in elderly patients undergone surgeries. Lithium is widely used in psychiatric patients for its role in neuronal protection, whereas whether or not it could attenuate surgery-associated postoperative cognition dysfunction used prophylactically is not well defined. After approval by the Institutional Animal Care and Use Committee, 48 male Sprague-Dawley rats aged 18months old were randomly divided into three groups with 16 each: i, no surgeries and drugs were given; ii, surgical procedures were performed only without drug delivery; iii, prophylactic 2mM/kg lithium chloride was given intraperitoneally once a day for seven days before surgeries. The change in spatial memory was assessed with Morris Water Maze (MWM), and the activation of PI3K/AKT/mTOR pathway was detected, and the levels of hippocampal glycogen synthase kinase-3β (p-GSK-3β) phosphorylation at serine 9 and interleukin-1β (IL-1β) were measured. The MWM detection showed that both swimming latency and distance were considerably prolonged by the surgeries, but these changes could be markedly shortened by prophylactic lithium administration. Meanwhile, the changes in the hippocampal PI3K cascades and p-GSK-3β and IL-1β expression displayed corresponding changes that were parallel to the alterations of spatial memory, and inhibition of PI3K and GSK-3β suggested upstream PI3K activation leads to downstream change in p-GSK-3β and IL-1β. These results indicate, at least in part, that prophylactic lithium can alleviate surgery-associated impairment of the spatial memory in aged rats which is strongly associated with the reduced levels of hippocampal p-GSK-3β and IL-1β resulted from the activation of PI3K/AKT/mTORC2 pathway.

Topics: Aging; Animals; Cognition; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hippocampus; Injections, Intraperitoneal; Interleukin-1beta; Lithium Chloride; Male; Memory Disorders; Neuroprotective Agents; Phosphorylation; Postoperative Complications; Primary Prevention; Rats; Rats, Sprague-Dawley; Surgical Procedures, Operative

1. Postoperative cognitive dysfunction has become more prevalent in recent years. We used a splenectomized rat model with postoperative spatial learning and memory deficits to investigate the role of tau hyperphosphorylation and glycogen synthase kinase-3β (GSK-3β) within the hippocampus. 2. Cognitive function was assessed in a Y-maze 1 day before and 1, 3 and 7 days after surgery. We measured site-specific phosphorylation of hippocampal tau (Thr-205 and Ser-396), GSK-3β activity and expression of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3β inhibitor. 3. Splenectomy was associated with learning and memory impairment 3 days later, as well as a rapid and massive hyperphosphorylation of hippocampal tau at Thr-205 and Ser-396, activated GSK-3β, and increased IL-1β and TNF-α expression. LiCl completely restored tau hyperphosphorylation to control levels. 4. These data from the splenectomized rat model suggest that inflammatory factors affect tau pathology through the GSK-3β signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits.

Topics: Animals; Biomarkers; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Inflammation Mediators; Lithium Chloride; Male; Maze Learning; Memory Disorders; Neuroprotective Agents; Phosphorylation; Postoperative Complications; Rats; Rats, Sprague-Dawley; Signal Transduction; Splenectomy; tau Proteins; Treatment Outcome

To study adult patients in the immediate postoperative period after cardiac surgery and determine whether cardiac output (CO) and systemic vascular resistance (SVR) are generally within normal limits and whether clinical assessment of CO provides an adequate approximation to guide treatment.. Prospective study.. Overnight intensive recovery unit, St Thomas' Hospital, London.. Fifty patients who had undergone cardiac surgery within the previous 5 hours and whose COs were not being measured.. The physician (if present) or nurse managing the patient was asked to make a clinical estimate (as low, normal, or high) of CO and of SVR. CO was measured by lithium dilution. The clinically estimated values were compared with the measured values, after adjusting for patient size.. In 29 of 50 (58%) patients, cardiac index (CI) (20 of 50 [40%] patients) or systemic vascular resistance index (SVRI) (22 of 50 [44%] patients) was outside normal limits (CI, 2.7 (plus minus 30%) L/min/m(2); SVRI, 2,500 (plus minus 30%) dyne center dot sec center dot cm(minus sign 5)/m(2)). When CI was outside the normal range, the clinical estimate was usually wrong (13 of 20 [65%]); when SVRI was outside the normal range, the clinical estimate was also usually wrong (16 of 22 [73%]).. In the early postoperative period after cardiac surgery, clinical assessment of the circulatory state is frequently misleading, and there should be a low threshold for measuring CO.

Topics: Aged; Blood Pressure; Cardiac Output; Cardiac Surgical Procedures; Humans; Indicator Dilution Techniques; Lithium Chloride; Middle Aged; Postoperative Complications; Postoperative Period; Prospective Studies; Reference Values; Vascular Resistance