ABSTRACT
Objective: Several lines of evidence demonstrated the role of anesthetic drugs in cognitive functions. Some anesthetic agents have been confirmed to be associated with long-term spatial memory and learning in aged animal models. Methods: C57BL/6 mice were divided into four different groups based on different concentrations of remimazolam treatments. Behavioral phenotype was observed by open field, rota rod, Morris water maze, and elevated plus maze test. Western blot was performed to see the expression pattern of different proteins. Confocal microscopy images were taken for neuronal and glial cells to see the effect of remimazolam on CNS cells. Results: We showed that remimazolam, a new anesthetic drug, impaired cognitive behavior. Repetitive doses of remimazolam have been found to induce neuronal loss with a significant change in morphology. Here, we showed that a higher concentration of remimazolam had a significant effect on CNS cell activation. We showed that remimazolam caused memory dysfunction by inducing neuronal apoptosis via glutamate excitotoxicity. It also exhibited amyloid ß plaque in the brain via abnormal phosphorylation of tau protein. Remimazolam-mediated regulation of glial cells in mouse cortex was observed and robust activation of astrocytes and microglial cells was found. Finally, we assessed the behavioral phenotype of mice and found that treatment with remimazolam induced significant behavioral changes and memory dysfunction. Conclusions: This study provides insight into the mechanism of anesthetic drug-induced memory deficits and may help improve the therapeutic effects of anesthesia agents in clinical applications.
ABSTRACT
OBJECTIVE: The purpose of this study was to investigate the effects of acute hypervolemic fluid infusion (AHFI) of 6% hydroxyethyl starch (HES) 130/0.4 or 4% succinylated gelatin (GEL) on hemostasis and the possible mechanisms. METHODS: Thirty-six gastric cancer patients were randomized to receive AHFI of either HES, GEL or lactated Ringer's (RL) solution at the rate of 30 mL x kg(-1) x h( -1) from 20 minutes before to 40 minutes after induction of general anesthesia. RESULTS: Group HES and GEL had significantly prolonged PT and aPTT, decreased VIII:C and vWF immediately after AHFI. Statistically prolonged reaction time and coagulation time, and decreased growth angle were seen immediately after HES infusion. Maximum amplitude decreased significantly in group HES and GEL immediately after and 4 hours after AHFI. CONCLUSION: Gelatin reduced clot quality associated with derangements of fibrin polymerization and HES 130/0.4 delayed initiation of sufficient thrombin generation to convert fibrinogen to fibrin and impaired platelet function.
Subject(s)
Gelatin/administration & dosage , Hemostasis/drug effects , Hydroxyethyl Starch Derivatives/administration & dosage , Plasma Substitutes/administration & dosage , Stomach Neoplasms/blood , Stomach Neoplasms/surgery , Succinates/administration & dosage , Adult , Anesthesia, General , Blood Coagulation Tests , Blood Loss, Surgical/prevention & control , Blood Platelets/physiology , Blood Volume/drug effects , Female , Fibrin/metabolism , Fluid Therapy , Gastrectomy , Humans , Isotonic Solutions/administration & dosage , Male , Middle Aged , Ringer's Lactate , Thrombelastography/drug effects , Thrombin/metabolismABSTRACT
Artificial colloids are used in situations with a high risk of bleeding such as trauma or during surgery. Although more efficacious than crystalloids, colloids can be associated with derangements of the haemostatic system and may also interfere with normal haemostasis via a number of different mechanisms.
