The New Orientation of Postoperative Analgesia: Remote Ischemic Preconditioning.

Purpose of Review: Postoperative analgesia is currently a significant topic in anesthesiology. Currently, the predominant approach for achieving multimodal analgesia involves the utilization of pharmacotherapy and regional anesthesia procedures. The primary objectives of this approach are to mitigate postoperative pain, enhance patient satisfaction, and diminish overall opioid usage. Nevertheless, there is a scarcity of research on the use of remote ischemia preconditioning aimed at mitigating postoperative pain. Recent Findings: Transient stoppage of blood flow to an organ has been found to elicit remote ischemia preconditioning (RIPC), which serves as a potent intrinsic mechanism for protecting numerous organs. In addition to its established role in protecting against reperfusion injury, RIPC has recently been identified as having potential benefits in the context of postoperative analgesia. Summary: In addition to traditional perioperative analgesia, RIPC provides perioperative analgesia and organ protection.

Propofol postconditioning alleviates diabetic myocardial ischemia­reperfusion injury via the miR­200c­3p/AdipoR2/STAT3 signaling pathway.

Myocardial ischemia/reperfusion (MI/RI) syndrome is one of the leading causes of mortality and disability. Propofol postconditioning is known to improve myocardial ischemia/reperfusion injury (MI/RI). The present study aimed to explore the mechanism of propofol postconditioning in diabetic MI/RI. Diabetic MI/RI rat models were established and the rats were treated via propofol postconditioning. Staining with 2,3,5­triphenyl­2H­tetrazolium chloride, H&E staining, TUNEL staining and ELISA were applied to detect infarct size, pathological changes, apoptosis and oxidative stress­related factor and apoptotic factor levels, respectively. Subsequently, the effect of propofol on H9C2 cells was also assessed using the Cell Counting Kit­8 assay. High­glucose hypoxia/reperfusion (H/R) models of H9C2 cardiomyocytes were established. miR­200c­3p overexpression or AdipoR2 silencing combined with propofol postconditioning was performed in H/R­induced H9C2 cells and STAT3 protein expression levels were determined. Propofol postconditioning significantly reduced myocardial infarct size, oxidative stress and apoptosis in diabetic MI/RI models. Furthermore, propofol postconditioning significantly reduced the oxidative stress and apoptosis of H9C2 cells in high­glucose H/R models. Propofol postconditioning also significantly downregulated miR­200c­3p expression levels and promoted AdipoR2 expression levels. miR­200c­3p overexpression or AdipoR2 downregulation significantly reversed the effects of propofol postconditioning on its antioxidation and anti­apoptotic effects in H9C2 cells and on decreasing STAT3 phosphorylation levels. Together, the results of the present study demonstrated that propofol postconditioning inhibited miR­200c­3p, upregulated AdipoR2 and activated the STAT3 signaling pathway, thus alleviating diabetic MI/RI and therefore highlighting its potential as a treatment of diabetic MI/RI.

Sevoflurane protects cardiomyocytes against hypoxia/reperfusion injury via LINC01133/miR-30a-5p axis.

Previous studies failed to elucidate the detailed mechanisms of anesthetic preconditioning as a protective approach against ischemic/reperfusion (I/R) injury in cells. The present study mainly centered on discovering the mechanisms of Sevoflurane (Sev) in preventing cardiomyocytes against I/R injury. Human cardiomyocyte AC16 cell line was used to simulate I/R injury based on a hypoxia/reperfusion (H/R) model. After Sev treatment, cell viability and apoptosis were detected by MTT assay and flow cytometry, respectively. Lactate dehydrogenase (LDH) content was measured using an LDH Detection Kit. Relative mRNA and protein expressions of LINC01133, miR-30a-5p and apoptosis-related proteins were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. Target gene of miR-30a-5p and their potential binding sites were predicted using Starbase and confirmed by dual-luciferase reporter assay. Cell behaviors were assessed again after miR-30a-5p and LINC01133 transfection. Sev could improve cell viability, reduce LDH leakage, and down-regulate the expressions of apoptosis-related proteins (Bax, cleaved caspase-3 and cleaved caspase-9) and LINC01133 as well as up-regulate miR-30a-5p and Bcl-2 expressions in H/R cells. MiR-30a-5p was the target of LINC01133, and up-regulating miR-30a-5p enhanced the effects of Sev in H/R cells, with a suppression on H/R-induced activation of the p53 signaling pathway. However, up-regulating LINC01133 reversed the enhancing effects of miR-30a-5p on Sev pretreatment in H/R cells. Sev could protect cardiomyocytes against H/R injury through the miR-30a-5p/LINC01133 axis, which may provide a possible therapeutic method for curing cardiovascular I/R injury.

Supplement of Lipid Emulsion to Epinephrine Improves Resuscitation Outcomes of Asphyxia-Induced Cardiac Arrest in Aged Rats.

OBJECTIVE: The goal of the study was to investigate the efficacy of lipid supplement to epinephrine-based therapy in resuscitation of asphyxia-induced cardiac arrest in aged rats. METHODS: The study included two parts: in experiment A, rats underwent asphyxial cardiac arrest and cardiopulmonary resuscitation, randomized to receive epinephrine and normal saline (control group, n=22), epinephrine and intralipid 20% (long-chain triglycerides (LCT) group, n=22) or epinephrine and lipovenoes 20% (LCT/medium-chain triglcerides (MCT) group, n=22). Return of spontaneous circulation, recurrence of asystole after resuscitation, hemodynamic metrics, arterial blood gas values, neurological assessment score and indexes of pulmonary transudation were recorded. In experiment B, rats using the same model and resuscitation protocol were randomly divided into 21 groups: Control 0, Control 20, Control 40, Control 60, Control 80, Control 100, Control 120, LCT 0, LCT 20, LCT 40, LCT 60, LCT 80, LCT 100, LCT 120, LCT/MCT 0, LCT/MCT 20, LCT/MCT 40, LCT/MCT 60, LCT/MCT 80, LCT/MCT 100 and LCT 120 (n=10, the subscripts represent respective endpoint of observation in minutes). Myocardial bioenergetics were determined. RESULTS: In experiment A, the LCT and LCT/MCT groups had a shorter time to return of spontaneous circulation (ROSC) (P=0.001and P<0.001, respectively) and higher survival rate (P=0.033 and P=0.014, respectively) compared with the Control group. The LCT/MCT group had higher MAP (P<0.001 and P=0.001, respectively), HR (P<0.001 and P=0.004, respectively) and RPP (P<0.001 and P<0.001, respectively) compared with the Control and LCT groups, respectively. In experiment B, the LCT/MCT group had a higher energy charge compared with the control group at 20 (P<0.001) and 40 (P<0.001) minutes. The LCT group had higher energy charge compared with the Control group at 40 (P<0.001) and 60 (P<0.001) minutes. CONCLUSION: The supplement of lipid emulsion to epinephrine improves resuscitation outcomes of asphyxia-induced cardiac arrest than epinephrine alone in our in vivo model of aged rat. LCT/MCT emulsion may be superior to LCT emulsion in epinephrine-based resuscitation.

Ropivacaine Prevents the Activation of the NLRP3 Inflammasome Caused by High Glucose in HUVECs.

Endothelial dysfunction caused by high glucose is recognized as an important event in the pathogenesis of diabetes-related vascular complications. Ropivacaine is considered to have the best safety profile among the commonly used amide local anesthetics, but the extent of its actions remains incompletely understood. Here, we used human umbilical vein endothelial cells exposed to high glucose to explore the effects of ropivacaine on oxidative stress and markers of inflammation. Ropivacaine treatment exerted significant beneficial effects by rescuing oxidative stress and downregulating interleukin (IL)-1ß and IL-18. We also found that ropivacaine could inhibit the secretion of the high-mobility group box 1 protein and improve cell viability. Importantly, sirtuin-1 (SIRT1) knockdown experiments show that the inhibitory effects of ropivacaine against NLRP3 inflammasome activation are dependent on SIRT1. Taken together, these results demonstrate the potential of ropivacaine as a promising therapy against diabetic endothelial dysfunction.

Comparison of three methods for the confirmation of laryngeal mask airway placement in female patients undergoing gynecologic surgery.

The laryngeal mask airway (LMA) is a supraglottic device that is commonly used to provide lung ventilation during general anesthesia. LMA placement needs to be confirmed to provide adequate lung ventilation. To investigate the feasibility of using ultrasound examination, compared with clinical tests and fiberoptic laryngoscopy, to confirm LMA placement, we performed a clinical study of 64 female patients classified as American Society of Anesthesiologists Physical Status I or II who were scheduled for gynecologic surgery with LMA insertion for airway management. After insertion, placement of the LMA was confirmed by clinical tests, ultrasound examination and fiberoptic laryngoscopy. Of the 64 women, placement was confirmed as acceptable in 89.1% by clinical tests, in 59.4% by fiberoptic laryngoscope assessment and in 67.2% by ultrasound examination. With respect to patients with oropharyngeal leaks classified as high, there were no differences in confirmation of acceptable placement between clinical tests and ultrasound examinations (p = 0.092), but the number of patients determined to have acceptable placement by ultrasound examination was greater than that determined by fiberoptic laryngoscopy (p = 0.034). Thus, ultrasound examination is a superior technique for confirming the seal on the LMA.

MicroRNA-155 is a novel suppressor of ovarian cancer-initiating cells that targets CLDN1.

Previous cDNA microarrays indicated that CLDN1 (claudin-1) is an important gene for ovarian cancer-initiating cell (OCIC) invasion and adhesion. Here, we show that the downregulation of miR-155 in OCICs correlates with CLDN1 overexpression and the suppression of OCIC invasion. Luciferase assays indicate that miR-155 targets CLDN1 mRNA on the 3' UTR. CLDN1 mRNA and claudin-1 protein expression were significantly decreased in miR-155-OCICs. Proliferation assays and Transwell migration assays show that miR-155 significantly suppresses the proliferative and invasive capacity of OCICs. Furthermore, miR-155 suppresses the growth of OCIC xenograft tumors. Thus, overexpression of miR-155 may prevent tumorigenesis in human ovarian cancer through downregulation of CLDN1.

[Effect of transcutaneous acupoint electrical stimulation on lipid peroxidation and cognitive function in patients experiencing craniotomy].

OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) on serum superoxide dismutase (SOD) activity, malondialdehyde (MDA) and S100beta contents in craniotomy patients for studying its cerebral protection mechanism. METHODS: Fifty patients scheduled for neurosurgery were randomly divided into TAES group (n = 25) and control group (n=25) with randomized block method. For patients of TAES group, TAES was applied to bilateral Hegu (LI 4) and Quchi (LI 11), Zusanli (ST 36) and Sanyinjiao (SP 6) from 30 minutes on before anesthesia to the end of operation. Patients of control group were anesthetized with sevoflurane inhalation and intermittent (i.v.) of sulfenany and vecurnium bromide. Blood samples were taken for assaying serum SOD activity, MDA and S100beta contents with purinase oxydasis, biochemiluminescence and enzyme linked immunosorbent assay separately. Scores of cognitive ability were given by using Mini Mental State Examination (MMSE). RESULTS: In comparison with pre-anesthesia, serum SOD activity decreased significantly 1 h after craniotomy in control group, at the end of operation in both control and TAES groups (P<0.05, P<0.01), and increased markedly 48 h after operation in control group (P<0.05). Serum MDA in control group increased significantly 48 h after operation, while that in TAES group reduced apparently 24 h after operation (P<0.01). Serum S100beta content in TAES group decreased remarkably 48 h after operation (P<0.01). Serum SOD activity of TAES group was significantly higher than that of control group 24 h after operation (P<0.05). Compared with control group, serum MDA contents of 24 h and 48 h after operation and serum S100beta levels at 1 h after craniotomy and 48 h after operation were markedly lower in TAES group (P<0.01, P<0.05). No significant differences were found between two groups in the cognitive function scores (P>0.05). CONCLUSION: TAES can increase serum SOD activity and reduce MDA and S100beta levels in patients undergoing craniotomy, which may contribute to its effect in reducing lipid peroxidation induced cerebral injury. But its impact on the patient's cognitive function needs study further.

[Effect of transcutaneous acupoint electrical stimulation on brain oxygen and glucose metabolism in the perioperative period of the craniocerebral operation].

OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) on brain tissue oxygen and glucose metabolism of the brain tissue in peri-operative period of the craniocerebral operation. METHODS: Fifty patients scheduled for neuro-surgery were randomly assigned to the treatment group and the control group equally. Anesthesia applied after induction on all patients was continuous sevoflurane inhalation and intermittent intravenous injection of sulfenany and vecurnium bromide, but to the treatment group TASE was applied additionally from 30 min before anesthesia to the end of operation. Blood samples were taken from artery and jugular venous bulb at different time points, i. e. before induction (T0) , before skin incision (T1) , at the end of operation (T2) , and 10 min after extubation (T3) , for blood-gas analysis. The difference of oxygen, glucose and lactate contents between blood samples of arterial and jugular bulb (Da-jvO2, Da-jvGlu and Da-jvLac) at respective time point were determined and calculated. RESULTS: Da-jvO2 decreased in both group at T1, T2 and T3, and all lower than that at T0 (P < 0.05 or P < 0.01), but significant difference was shown in comparison of the index at T2 and T3 with the same time points in the control group in the treatment group (P < 0.05 or P < 0.01) , and that between groups at T2 and T3 (P < 0.01). Da-jvGlu in the treatment group decreased at T2 and T3 (P < 0.05), but keep unchanged relatively in the control group before and after anesthesia, inter-group comparison showed it was lower at T2 and T3 in the treatment group than that in the control group respectively (P < 0.05). Da-jvGlu in the treatment group at T1, T2, and T3 were all lower than that at the same time points (P < 0. 01). CONCLUSION: TAES can significantly decrease the oxygen and glucose metabolism of the brain tissue in the perioperative period of the craniocerebral operation.

[Effect of transcutaneous acupoint electrical stimulation on blood bioactive compounds involving cerebral injury during craniotomy].

OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) on plasma ET, CGRP and serum IL-6, S100beta during craniotomy. METHODS: Fifty patients scheduled for neurosurgery were randomly divided into TAES group (n=25) and control group (n=25). TAES (2/100 Hz, 8-12 mA) of bilateral Hegu (LI 4)-Quchi (LI 11), Zusanli (ST 36)-Sanyinjiao (SP 6) was administrated for patients of TAES group starting 30 min before anesthesia till the end of the operation. Anesthesia of the patients was maintained with sevoflurane inhalation and intermittent intravenous injection of boluses of sulfenany and vecurnium bromide. Jugular venous blood samples were taken at preanesthesia (T0), 1 hour after craniotomy (T1), closure complete (T2), 24 hours (T3) and 48 hours (T4) after operation respectively for detecting contents of plasma endothelin (ET), calcitonin gene-related peptide (CGRP) and serum interleukin (IL)-6, S100beta with radioimmunoassay and enzyme linked immunosorbent assay separately. RESULTS: Compared with control group, plasma ET at T2, serum IL-6 at T1 S100beta at T1 and T4 in TAES group all decreased significantly (P < 0.01, 0.05), while serum IL-6 at T3 increased remarkably (P < 0.05). It suggests that after TAES, CGRP/ET was improved, favoring cerebral microcirculation to reduce surgery-induced cerebral injury. There were no significant differences between two groups at different time courses in plasma CGRP concentrations (P > 0.05). CONCLUSION: TAES can regulate plasma CGRP/ET and serum IL-6, lower serum S100beta level, which may contribute to its effect in relieving craniotomy-induced brain injury.