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Background The glycocalyx layer is a key structure in the endothelium. Tourniquet-induced ischemic periods are used during orthopedic surgery, and the reactive oxygen species generated after ischemia-reperfusion may mediate the shedding of the glycocalyx. Here, we describe the effects of tourniquet-induced ischemia-reperfusion and compare the effects of sevoflurane and propofol on the release of endothelial biomarkers after ischemia-reperfusion in knee-ligament surgery. Methods This pilot, single-center, blinded, randomized, controlled trial included 16 healthy patients. After spinal anesthesia, hypnosis was achieved with sevoflurane or propofol according to randomization. During the perioperative period, five venous blood samples were collected for quantification of syndecan-1, heparan sulfate, and thrombomodulin from blood serum by using ELISA assays kits. Sample size calculation was performed to detect a 25% change in the mean concentration of syndecan-1 with an alpha of 0.05 and power of 80%. Results For our primary outcome, a two-way ANOVA with post-hoc Bonferroni correction analysis showed no differences in syndecan-1 concentrations between the sevoflurane and propofol groups at any time point. In the sevoflurane group, we noted an increase in syndecan-1 concentrations 90 min after tourniquet release in the sevoflurane group from 34.6 ± 24.4 ng/mL to 47.9 ± 29.8 ng/mL (Wilcoxon test, p < 0.01) that was not observed in patients randomized to the propofol group. The two-way ANOVA showed no intergroup differences in heparan sulfate and thrombomodulin levels. Conclusions Superficial endothelial damage without alterations in the cell layer integrity was observed after tourniquet knee-ligament surgery. There was no elevation in serum endothelial biomarkers in the propofol group patients. Sevoflurane did not show the protective effect observed in in vitro and in vivo studies. Trial registration The trial was registered in www.clinicaltrials.gov (ref: NCT03772054, Registered 11 December 2018).

Aging is a gradual biological process characterized by a decrease in cell and organism functions. Gingival wound healing is one of the impaired processes found in old rats. Here, we studied the in vivo wound healing process using a gingival repair rat model and an in vitro model using human gingival fibroblast for cellular responses associated to wound healing. To do that, we evaluated cell proliferation of both epithelial and connective tissue cells in gingival wounds and found decreased of Ki67 nuclear staining in old rats when compared to their young counterparts. We next evaluated cellular responses of primary gingival fibroblast obtained from young subjects in the presence human blood serum of individuals of different ages. Eighteen to sixty five years old masculine donors were classified into 3 groups: “young” from 18 to 22 years old, “middle-aged” from 30 to 48 years old and “aged” over 50 years old. Cell proliferation, measured through immunofluorescence for Ki67 and flow cytometry for DNA content, was decreased when middle-aged and aged serum was added to gingival fibroblast compared to young serum. Myofibroblastic differentiation, measured through alpha-smooth muscle actin (α-SMA), was stimulated with young but not middle-aged or aged serum both the protein levels and incorporation of α-SMA into actin stress fibers. High levels of PDGF, VEGF, IL-6R were detected in blood serum from young subjects when compared to middle-aged and aged donors. In addition, the pro-inflammatory cytokines MCP-1 and TNF were increased in the serum of aged donors. In old rat wound there is an increased of staining for TNF compared to young wound. Moreover, healthy gingiva (non injury) shows less staining compared to a wound site, suggesting a role in wound healing. Moreover, serum from middle-aged and aged donors was able to stimulate cellular senescence in young cells as determined by the expression of senescence associated beta-galactosidase and histone H2A.X phosphorylated at Ser139. Moreover, we detected an increased frequency of γ-H2A.X-positive cells in aged rat gingival tissues. The present study suggests that serum factors present in middle-aged and aged individuals may be responsible, at least in part, for the altered responses observed during wound healing in aging.

BACKGROUND: Patients with low cognitive performance are thought to have a higher risk of postoperative neurocognitive disorders. Here we analyzed the relationship between preoperative cognition and anesthesia-induced brain dynamics. We hypothesized that patients with low cognitive performance would be more sensitive to anesthetics and would show differences in electroencephalogram (EEG) activity consistent with a brain anesthesia overdose. METHODS: This is a retrospective analysis from a previously reported observational study. We evaluated cognitive performance using the Montreal cognitive assessment (MoCA) test. All patients received general anesthesia maintained with sevoflurane or desflurane during elective major abdominal surgery. We analyzed the EEG using spectral, coherence, and phase-amplitude modulation analyses. RESULTS: Patients were separated into a low MoCA group (<26 points, n = 12) and a high MoCA group (n = 23). There were no differences in baseline EEG, nor end-tidal age-corrected minimum alveolar concentration (MACage). However, under anesthesia, the low MoCA group had lower α-β power (high MoCA: 2.9 [interquartile range {IQR}: 0.6–5.8 dB] versus low MoCA: −1.2 [IQR: −2.1 to 0.6 dB], difference 4.1 [1.0–5.7]) and a lower α peak frequency (high MoCA: 9.0 [IQR: 8.3–9.8 Hz] versus low MoCA: 7.5 [IQR: 6.3–9.0 Hz], difference 1.5 [0–2.3]) compared to the high MoCA group. The low MoCA group also had a lower α band coherence and a stronger peak-max phase–amplitude coupling (PAC). Finally, patients in the low MoCA group had longer emergence times (high MoCA 663 ± 345 seconds versus low MoCA: 960 ± 352 seconds, difference 297 [15–578]). Multiple linear regression shows up that both age and MoCA scores are independently associated with intraoperative α-β power. CONCLUSIONS: All these EEG features, together with a prolonged emergence time, are consistent with the possibility that older patients with low cognitive performance are receiving a brain anesthesia overdose compare to cognitive normal patients.

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