An interpretable machine learning model to predict off-pump coronary artery bypass grafting-associated acute kidney injury.

BACKGROUND: Off-pump coronary artery bypass grafting-associated acute kidney injury (OPCAB-AKI) is related to 30-day perioperative mortality. Existing mathematical models cannot be applied to help clinicians make early diagnosis and intervention decisions. OBJECTIVES: This study used an interpretable machine learning method to establish and screen an optimized OPCAB-AKI prediction model. MATERIAL AND METHODS: Clinical data of 1110 patients who underwent OPCAB in the Department of Cardiac Surgery of General Hospital of Northern Theater Command (Shenyang, China) from January 2018 to December 2020 were collected retrospectively. Four machine learning models were used, including logistic regression (LR), decision tree (DT), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The SHapley Additive exPlanation (SHAP) tool was used for explanatory analysis of the black-box model. The mean absolute value of the characteristic SHAP parameter was defined and sorted. The correlation between the characteristic parameters and OPCAB-AKI was determined based on the SHAP value. A quantitative analysis of a single characteristic and an interaction analysis of multiple characteristics were carried out for the main risk factors. RESULTS: The RF prediction model had the best performance, with an area under the curve (AUC) of 0.90, a precision rate of 0.80, an accuracy rate of 0.83, a recall rate of 0.74, and an F1 score of 0.78 for positive samples. The interpretation analysis of the SHAP model results showed that intraoperative urine volume contributed to the greatest extent to the RF model, and other parameters included intraoperative sufentanil dosage, intraoperative dexmedetomidine dosage, cyclic variation coefficient during the induction period, intraoperative hypotension duration, age, preoperative baseline serum creatinine, body mass index (BMI), and Acute Physiology, Age and Chronic Health Evaluation (APACHE) II score. CONCLUSIONS: The model constructed by the RF ensemble learning algorithm predicted OPCAB-AKI, and indicators such as intraoperative urine volume were closely related to OPCAB-AKI.

[Effect of transcutaneous electrical acupoint stimulation on catheter related bladder discomfort after ureteroscopic lithotripsy].

OBJECTIVE: To verify the efficacy of transcutaneous electrical acupoint stimulation (TEAS) on catheter related bladder discomfort after ureteroscopic lithotripsy. METHODS: Sixty male patients with selective ureteroscopic lithotripsy under general anesthesia were randomly divided into a TEAS group (30 cases, one case dropped off) and a sham TEAS group (30 cases, 2 cases dropped off). Before anesthesia induction, the patients in the TEAS group were treated with TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) for 30 min, with disperse-dense wave, frequency of 2 Hz/ 15 Hz and current intensity of 6 to 10 mA. The patients in the sham TEAS group were treated with the same TEAS device at the same acupoints, but no electrical stimulation was given. After 30 min, anesthesia induction started. The total dosages of propofol and remifentanil in the two groups were recorded, and the time of operation and anesthesia, the time of wake-up and the time of stay in postanesthesia care unit (PACU) were recorded. The postoperative recovery was evaluated 5 min (T1) after wake-up, 1 h (T2), 2 h (T3) and 6 h (T4) after the operation, including the severity of urinary tract irritation and visual analogue scale (VAS) score. The occurrence of adverse reactions was observed, such as nausea and vomiting, dizziness and headache. RESULTS: The dosage of remifentanil in the TEAS group was significantly lower than that in the sham TEAS group (P<0.05); but the dosage of propofol had no significant difference between the two groups (P>0.05). Compared with the sham TEAS group, the incidence of more-than-moderate urinary tract irritation symptoms in the TEAS group was reduced (P<0.05), and the VAS scores 1 and 2 h after operation were reduced (P<0.05). CONCLUSION: The 30-min TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) before anesthesia induction could significantly control the severity of postoperative urinary tract irritation in patients with ureteroscopic lithotripsy, reduce the dosage of anesthetic drugs and relieve postoperative pain.

Hydrogen­rich solution against myocardial injury and aquaporin expression via the PI3K/Akt signaling pathway during cardiopulmonary bypass in rats.

Myocardial ischemia, hypoxia and reperfusion injury are induced by aortic occlusion, cardiac arrest and resuscitation during cardiopulmonary bypass (CPB), which can severely affect cardiac function. The aim of the present study was to investigate the effects of hydrogen­rich solution (HRS) and aquaporin (AQP) on cardiopulmonary bypass (CPB)­induced myocardial injury, and determine the mechanism of the phosphatidylinositol 3­kinase (PI3K)/protein kinase B (Akt) signaling pathway. Sprague Dawley rats were divided into a sham operation group, a CPB surgery group and a HRS group. A CPB model was established, and the hemodynamic parameters were determined at the termination of CPB. The myocardial tissues were observed by hematoxylin and eosin, and Masson staining. The levels of myocardial injury markers [adult cardiac troponin I (cTnI), lactate dehydrogenase (LDH), creatine kinase MB (CK­MB) and brain natriuretic peptide (BNP)], inflammatory factors [interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α (TNF­α)] and oxidative stress indicators [superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO)] were determined by ELISA. Furthermore, H9C2 cells were treated with HRS following hypoxia/reoxygenation. Cell viability and cell apoptosis were investigated. The expression of apoptosis regulator Bcl­2 (Bcl­2), apoptosis regulator Bax (Bax), caspase 3, AQP­1, AQP­4, phosphorylated (p)­Akt, heme oxygenase 1 (HO­1) and nuclear factor erythroid 2­related factor 2 (Nrf2) were investigated using western blotting and quantitative­polymerase chain reaction of tissues and cells. Following CPB, myocardial cell arrangement was disordered, myocardial injury markers (cTnI, LDH, CK­MB and BNP), inflammatory cytokines (IL­1ß, IL­6 and TNF­α) and MDA levels were significantly increased compared with the sham group; whereas the SOD levels were significantly downregulated following CPB compared with the sham group. HRS attenuated myocardial injury, reduced the expression levels of cTnI, LDH, CK­MB, BNP, IL­1ß, IL­6, TNF­α, MDA and MPO, and increased SOD release. Levels of Bcl­2, AQP­1, AQP­4, p­Akt, HO­1 and Nrf2 were significantly increased following HRS; whereas Bax and caspase­3 expression levels were significantly reduced following CPB. HRS treatment significantly increased the viability of myocardial cells, reduced the rate of myocardial cell apoptosis and the release of MDA and LDH compared with the CPB group. A PI3K inhibitor (LY294002) was revealed to reverse the protective effect of HRS treatment. HRS was demonstrated to attenuate CPB­induced myocardial injury, suppress AQP­1 and AQP­4 expression following CPB treatment and protect myocardial cells via the PI3K/Akt signaling pathway.

Hydrogen-rich solution attenuates myocardial injury caused by cardiopulmonary bypass in rats via the Janus-activated kinase 2/signal transducer and activator of transcription 3 signaling pathway.

The incidence of complications and mortality following open-heart surgery with cardiopulmonary bypass (CPB) is associated with the severity of the myocardial injury that occurs during surgery. Hydrogen-rich solution (HRS) may prevent antioxidant stress and inhibit apoptosis and inflammation. The present study was designed to investigate the effects of HRS on CPB-induced myocardial injury, and to investigate its potential regulation of the Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. The HRS treatment resulted in the significant upregulation of malonyl dialdehyde (MDA) and myeloperoxidase (MPO), whilesuperoxide dismutase (SOD) levels were significantly downregulated, compared with the Sham group (P<0.05). Additionally, HRS treatment improved myocardial injury, and decreased the expression levels of cardiac troponins, heart-type fatty acid binding protein, interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, MDA and MPO, and increased SOD release in CPB rats (P<0.05). Additionally, in the CPB group without the HRS treatment, the expression levels of B-cell lymphoma (Bcl)-2, JAK2, phospho-JAK2 (p-JAK2), STAT3 and phospho-STAT3 (p-STAT3) were significantly decreased, and Bax was significantly increased, compared with the Sham group (P<0.05). By contrast, compared with the CPB group, the expression levels of B-cell lymphoma 2 (Bcl-2), JAK2, phosphorylated (p)-JAK2, STAT3 and p-STAT3 in the HRS group were significantly increased, and Bcl-2-associated X protein expression was significantly decreased (P<0.05). In JAK2 knockdown experiments using siRNA, HRS treatment following hypoxia/reoxygenation also significantly increased the viability of myocardial cells, decreased the rate of myocardial cell apoptosis, elevated the levels of SOD and suppressed the release of MDA and lactate dehydrogenase in the control siRNA and CPB groups (P<0.05). Furthermore, JAK2 siRNA attenuated these protective effects of HRS (P<0.05 vs. control siRNA, HRS and CPB groups). Additionally, the results demonstrated that the HRS treatment significantly increased the expression levels of p-JAK2, p-STAT3 and Bcl-2 in myocardial cells following hypoxia and decreased Bax expression in the control siRNA and CPB groups (P<0.05). In addition, JAK2 siRNA was determined to attenuate these effects of HRS (P<0.05 vs. control siRNA, HRS and CPB groups). Taken together, these results indicated that HRS may alleviate CPB-induced myocardial injury, inhibit myocardial cell apoptosis and protect myocardial cells through regulation of the JAK2/STAT3 signaling pathway.

Activated Α7nachr Improves Postoperative Cognitive Dysfunction and Intestinal Injury Induced by Cardiopulmonary Bypass in Rats: Inhibition of the Proinflammatory Response Through the Th17 Immune Response.

Backgrund/Aims: To investigate the effects of activated α7 nicotinic acetylcholine receptor (α7nAChR) on postoperative cognitive dysfunction (POCD) and intestinal injury induced by cardiopulmonary bypass (CPB) and its relationship with the Th17 response in order to provide a theoretical basis for organ protection and targeted drug therapy during the perioperative period. METHODS: Sprague-Dawley rat models of CPB were established. Rat intestinal and brain injuries were observed after CPB using hematoxylin and eosin staining. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. Inflammatory factors and markers of brain injury in rat serum were measured using enzyme-linked immunosorbent assay. The expression levels of Bcl-2, Bax, caspase-3, ZO-1, occludin, AQP4, RORγT, and α7nAchR were examined using western blotting. Transcription factor RORγT expression was determined using real-time fluorescent quantitative polymerase chain reaction. Th17 cells in the peripheral blood and spleen were determined using flow cytometry. α7nAchR knockout rats were established. The Th17 response in the peripheral blood and spleen of α7nAchR knockout rats was further verified using flow cytometry. RESULTS: CPB can induce POCD and intestinal injury in rats. α7nAchR activation markedly reduced intestinal injury, POCD, neuronal apoptosis, proinflammatory factor expression, and number of CD4+IL-17+ cells. α7nAchR knockout significantly increased serum D-lactic acid, FABP2, S-100ß, NSE, TNF-α, IL-6, and IL-17 secretion. The number of CD4+IL-17+ cells was also significantly increased. CONCLUSION: α7nAchR activation markedly ameliorates the intestinal injury and POCD induced by CPB. Inhibition of the Th17 immune response can reduce the proinflammatory response, which could provide a new method for clinical perioperative organ protection and targeted drug therapy.

Patient-controlled Intravenous Analgesia With Combination of Dexmedetomidine and Sufentanil on Patients After Abdominal Operation: A Prospective, Randomized, Controlled, Blinded, Multicenter Clinical Study.

OBJECTIVE: To investigate the effect of combination of dexmedetomidine and sufentanil on patient-controlled intravenous analgesia (PCIA) in patients after abdominal operation and to assess the safety and validity of this treatment. METHODS: This is a prospective, randomized controlled, blinded, multicenter clinical study. A total of 210 patients from 9 clinical research centers underwent selective abdominal operation with general anesthesia were enrolled in the study, including laparoscopic-assisted abdominal operation on stomach, intestines or open surgery on stomach, intestines, kidneys and liver, the American Society of Anesthesiologists status I to II. Patients were randomly assigned into 2 groups: control group (group C) sufentanil 100 µg+normal saline 100 mL in total and test group (group D) sufentanil 100 µg+ dexmedetomidine 200 µg+normal saline 100 mL in total. PCIA was set as follow: background infusion of sufentanil 2 µg/h, bolus dose of sufentanil 2 µg, lockout interval 5 minutes. Main measure indices were analgesic consumption, pressing times and effective pressing times of analgesic pump, usage count, and consumption of remedy drug. Validity indices were visual analog scale (VAS) scores and patient satisfaction. Drug safety indices were hemodynamic parameters, drug side effects, and anal exhaust time. RESULTS: In total, 203 cases were analyzed. Seven cases were eliminated for incomplete data record. The total consumption of sufentanil (µg) in 24 hours after operation of group C and group D were 56.9±21.5 and 49.8±15.5, respectively, and the difference was statistically significant (P<0.05). Pressing times of analgesic pump in 24 hours after operation of group C and group D were 9.47±16.07 and 5.02±5.56 times, respectively, and the difference was statistically significant (P<0.05). Effective pressing times of analgesic pump in 24 hours after operation of group C and group D were 7.8±9.7 and 4.57±5.02 times, respectively, and the difference was statistically significant (P<0.05). Resting VAS scores and movement VAS scores at 2, 4, 8, and 24 hours postoperatively were statistically different (P<0.05). Usage times of rescue drug (pethidine) of group C and group D were 9 and 1, mean rank 118.13 and 85.71, respectively, and the difference was statistically significant (P<0.05). Mean rank of general satisfaction of group C and group D were 98.99 and 105.04, respectively, and the difference was statistically significant (P<0.05). Incidence rate of nausea in group C and group D within 24 hours after surgery was 25% and 12.5%, and of vomiting 18.2% and 6.25%, respectively and of vomiting and the difference was statistically significant. CONCLUSIONS: Compared with sufentanil PCIA alone, the combination of dexmedetomidine and sufentanil for PCIA after abdominal operation could reduce sufentanil consumption, decrease VAS scores, lower the rate of nausea and vomiting, and improve patient satisfaction.

Endotracheal intubation in elective cervical surgery: A randomized, controlled, assessor-blinded study.

BACKGROUND: We compared the effectiveness and safety of endotracheal intubation using the GlideScope (GS) video laryngoscope, CTrach laryngeal mask airway (LMA), or Shikani optical stylet rigid laryngoscope (SOS) during elective cervical surgery. METHODS: Forty-five patients undergoing elective cervical surgery were randomly and equally assigned to endotracheal intubation via GS, LMA, or SOS airway management. RESULTS: Endotracheal intubation was successfully completed in all patients. The mean intubation times of the groups differed significantly (P < .01): GS, 17.9 ±â€Š3.1 s; SOS, 40.4 ±â€Š13.7 s; and LMA, 80.5 ±â€Š22.5 s. The groups had similar heart rates and mean arterial pressures throughout the intubation, except that at 2 minutes after intubation the mean arterial pressure of the GS group (106.1 ±â€Š18.5 mm Hg) was significantly higher than that of the LMA (89.7 ±â€Š18.5 mm Hg) or SOS (89.7 ±â€Š18.5 mm Hg; P < .01). The change in C2-5 Cobb angle from baseline was significantly higher in the GS group (GS, 34.2°â€Š±â€Š7.3°) than the LMA (24.4°â€Š±â€Š5.8°) or SOS (25.5°â€Š±â€Š6.4°); P < .01). CONCLUSIONS: The CTrach LMA and SOS rigid laryngoscope are effective, safe alternatives to the GS video laryngoscope for patients undergoing elective cervical surgery.

α7 nicotinic acetylcholine receptor agonist attenuates the cerebral injury in a rat model of cardiopulmonary bypass by activating the Akt/GSK3ß pathway.

α7 nicotinic acetylcholine receptor (α7nAchR) agonist treatment may provide a promising therapeutic effect for cerebral injuries. However, it is unclear whether the activation of α7nAchR agonist may reduce cerebral injuries induced by cardiopulmonary bypass (CPB). A total of 96 male Sprague­Dawley rats were randomly divided into four groups (n=24/group): i) Sham operation group; ii) CPB group; iii) CPB + α7nAchR agonist group; and iv) CPB + α7nAchR agonist + α7nAchR antagonist group. Following treatment, 24 rats from each group were sacrificed and the serum and hippocampal tissues were collected. The serum expression levels of S100ß, interleukin 6 and tumor necrosis factor α were evaluated by ELISA, hippocampal tissues were analyzed by histopathological examination using hematoxylin & eosin and terminal deoxynucleotidyl­transferase­mediated dUTP nick­end labeling (TUNEL) staining and Caspase 3 expression in the hippocampal tissues was evaluated by immunohistochemistry. In addition, Caspase 3, Akt and glycogen synthase kinase 3ß (GSK3ß), as well as phosphorylated (p)­Akt and (p)­GSK3ß were examined by western blot assay. The present study demonstrated that α7nAchR agonist treatment was able to alleviate pathological damage and inhibit hippocampal cell apoptosis and inflammatory response. α7nAchR agonist treatment also increased the expression levels of p­Akt and p­GSK3ß, which indicated an upregulation in Akt/GSK3ß signaling. These data suggested that α7nAchR agonist may provide a promising new therapeutic approach for cerebral injury caused by CPB.

α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF­κB signaling pathway during cardiopulmonary bypass.

The present study aimed to investigate the effect of α7 nicotinic acetylcholine receptor (α7nAChR) agonist on the damage of hippocampal neurons and the expression of toll like receptor 4 (TLR4)/myeloid differentiation primary response 88 (Myd88)/nuclear factor (NF)­κB signal pathway­associated factors in cardiopulmonary bypass (CPB). Sprague Dawley rats were randomly divided into five groups: Sham operation (Sham); CPB; CPB + α7nAChR agonist PHA568487 (PHA); CPB + α7nAChR inhibitor MLA (MLA); and CPB + PHA568487 + TLR4 antagonist (CPT). Blood and brain tissue samples were harvested at 12 h following the withdrawal of CPB. Levels of serum inflammatory factors [interleukin (IL)­1ß, IL­6 and tumor necrosis factor (TNF)­α] and brain injury markers [S­100ß and neuron­specific enolase (NSE)] were measured using ELISA. In addition, pathological histology and apoptosis changes were observed using hematoxylin and eosin staining, and Tunnel assays. Quantitative polymerase chain reaction and western blot assays were used to determine the expression of TLR4, Myd88 and NF­κB mRNA, and protein in the hippocampus. The morphology of hippocampal pyramidal cells in the Sham group was observed to be normal. Pyramidal cells in the CPB, MLA and CPT groups were loosely arranged, and the baselines had disappeared, with clear nucleus pyknosis and neuronal apoptosis. Furthermore, the cells in the PHA group were slightly damaged. IL­1ß, IL­6, TNF­α, S­100ß and NSE expression levels in the CPB, MLA, and CPT groups were significantly higher compared with that in the Sham group (P<0.05). Compared with CPB group, the expression of inflammatory cytokines in the PHA group was significantly lower (P<0.05). The expression of TLR4, Myd88 and NF­κB mRNA, and protein in the hippocampus of CPB, MLA and CPT groups were significantly higher compared with that in the Sham group, and the PHA group expression was significantly lower compared with the CPB group (P<0.05). α7nAChRs agonist can inhibit the apoptosis of rat brain neurons induced by CPB, and may protect against brain injury through the TLR4/Myd88/NF­κB signaling pathway.

Aliskiren increases aquaporin-2 expression and attenuates lithium-induced nephrogenic diabetes insipidus.

The direct renin inhibitor aliskiren has been shown to be retained and persist in medullary collecting ducts even after treatment is discontinued, suggesting a new mechanism of action for this drug. The purpose of the present study was to investigate whether aliskiren regulates renal aquaporin expression in the collecting ducts and improves urinary concentrating defect induced by lithium in mice. The mice were fed with either normal chow or LiCl diet (40 mmol·kg dry food-1·day-1 for 4 days and 20 mmol·kg dry food-1·day-1 for the last 3 days) for 7 days. Some mice were intraperitoneally injected with aliskiren (50 mg·kg body wt-1·day-1 in saline). Aliskiren significantly increased protein abundance of aquaporin-2 (AQP2) in the kidney inner medulla in mice. In inner medulla collecting duct cell suspension, aliskiren markedly increased AQP2 and phosphorylated AQP2 at serine 256 (pS256-AQP2) protein abundance, which was significantly inhibited both by adenylyl cyclase inhibitor MDL-12330A and by PKA inhibitor H89, indicating an involvement of the cAMP-PKA signaling pathway in aliskiren-induced increased AQP2 expression. Aliskiren treatment improved urinary concentrating defect in lithium-treated mice and partially prevented the decrease of AQP2 and pS256-AQP2 protein abundance in the inner medulla of the kidney. In conclusion, the direct renin inhibitor aliskiren upregulates AQP2 protein expression in inner medullary collecting duct principal cells and prevents lithium-induced nephrogenic diabetes insipidus likely via cAMP-PKA pathways.

4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress.

Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenylbutyric acid (4-PBA) improves urinary concentrating defect in lithium-treated rats. Wistar rats received lithium (40 mmol/kg food), 4-PBA (320 mg/kg body wt by gavage every day), or no treatment (control) for 2 wk, and they were dehydrated for 24 h before euthanasia. Lithium treatment resulted in increased urine output and decreased urinary osmolality, which was significantly improved by 4-PBA. 4-PBA also prevented reduced protein expression of aquaporin-2 (AQP2), pS256-AQP2, and pS261-AQP2 in the inner medulla of kidneys from lithium-treated rats after 24-h dehydration. Lithium treatment resulted in increased expression of ER stress markers in the inner medulla, which was associated with dilated cisternae and expansion of ER in the inner medullary collecting duct (IMCD) principal cells. Confocal immunofluorescence studies showed colocalization of a molecular chaperone, binding IgG protein (BiP), with AQP2 in principal cells. Immunohistochemistry demonstrated increased intracellular expression of BiP and decreased AQP2 expression in IMCD principal cells of kidneys from lithium-treated rats. 4-PBA attenuated expression of ER stress markers and recovered ER morphology. In IMCD suspensions isolated from lithium-treated rats, 4-PBA incubation was also associated with increased AQP2 expression and ameliorated ER stress. In conclusion, in experimental lithium-induced NDI, 4-PBA improved the urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in IMCD principal cells.

Role of the Toll­like receptor 3 signaling pathway in the neuroprotective effect of sevoflurane pre­conditioning during cardiopulmonary bypass in rats.

The aim of the present study was to explore the roles and possible molecular mechanism of the alleviating effect of sevoflurane pre­treatment on the extracorporeal circulation and to investigate the possible involvement of the Toll­like receptor (TLR3) signaling pathway. A total of 64 male Sprague Dawley rats were randomly divided into three groups: The sham operation group (H group; n=8), cardiopulmonary bypass (CPB) group (C group; n=24) and sevoflurane pre­conditioning group (S group; n=32). The C group was subjected to tracheal intubation and mechanical ventilation, vessel puncture and catheter placement in the right femoral artery and right internal jugular vein, while no CPB was performed in the H group. The S group was pre­treated with 2.4% sevoflurane for 1 h prior to establishing the CPB model. The CPB in the C and S groups was performed for 1 h. Blood of the rats was analyzed and clinical parameters were detected prior to, during and at various time­points after CPB. In addition, eight rats from the C and S groups each were sacrificed at these time­points and brain tissue samples were analyzed. The levels of the brain damage­specific protein S100­ß as well as IL­6 and IFN­ß in the serum were detected by ELISA; furthermore, the expression levels of TLR3 and TIR­domain­containing adapter­inducing interferon­ß (TRIF) in the left hippocampus were assessed by ELISA and/or western blot analysis. The right hippocampus was assessed for neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The mean arterial pressure, heart rate and hematocrit were significantly decreased following CPB (P<0.05), while there was no significant changes in any other clinical parameters. The serum levels of S100­ß and IL­6 in the C group were significantly increased compared with those in the H group (P<0.05), which was attenuated by sevoflurane­pre­treatment. Compared with the H group, the serum levels of IFN­ß as well as hippocampal protein levels of TLR3 and TRIF were significantly increased in the C group during and after CPB (P<0.05), which was markedly aggravated in the S group (P<0.05). The number of apoptotic hippocampal neurons, although being generally low, was significantly increased in the C group compared with that in the H group (P<0.05), while apoptosis was significantly attenuated by sevoflurane­pre­treatment (P<0.05). The present study therefore concluded that 2.4% sevoflurane pre­treatment has a protective effect on the rat brain against CPB­induced injury, which may be mediated via the TLR3 signaling pathway through upregulating the expression levels of anti­inflammatory and downregulating pro­inflammatory proteins.

Penehyclidine hydrochloride attenuates the cerebral injury in a rat model of cardiopulmonary bypass.

This study investigated the effect of penehyclidine hydrochloride (PHC) on regulatory mediators during the neuroinflammatory response and cerebral cell apoptosis following cardiopulmonary bypass (CPB). Forty-eight rats were randomly divided among 4 groups as follows: sham-operation, vehicle, low-dose PHC (0.6 mg·(kg body mass)(-1)), and high-dose PHC (2.0 mg·(kg body mass)(-1)). CPB was performed in the latter 3 groups. The plasma levels of neuron specific enolase (NSE) and S-100B were tested with ELISA. Real-time PCR and Western blotting were used to evaluate the expression levels of matrix metalloproteinase-9 (MMP-9), IL-10, caspase-3, Bcl-2, and p38 in brain tissue. The ultrastructure of hippocampus tissue was examined under an electron microscope. PHC attenuated the increase of plasma NSE and S-100B following CPB. MMP-9, cleaved caspase-3, and phosphorylated p38 expression were substantially increased in the vehicle group compared with the sham-operation group and gradually diminished with increasing doses of PHC. IL-10 and Bcl-2 expression were markedly lower in the vehicle group than in the sham-operation group and gradually recovered with increasing doses of PHC. PHC attenuated the histopathological changes of cerebral injury following CPB. PHC favorably regulates the inflammatory response and reduces markers of neuronal injury following CPB, potentially by reducing p38 and caspase-3 activation.

Effects of sevoflurane before cardiopulmonary bypass on cerebral oxygen balance and early postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is associated with cardiopulmonary bypass (CPB). We investigated the effect of different doses of inhaled sevoflurane administered prior to CPB on cerebral oxygen supply and demand, and the incidence of associated early POCD. One hundred and twenty patients were randomly allocated into four treatment groups (n = 30, each) and administered a high- [1.5 minimum alveolar concentration (MAC)], moderate- (1.0 MAC), low- (0.5 MAC), or no- sevoflurane dose prior to CPB. Standard blood gas parameters, serum S-100 protein, and neuron-specific enolase (NSE) were measured at different time points. The mini-mental state examination (MMSE) was administered 1 day before and 24 and 72 h after surgery. The jugular bulb venous oxygen saturation (SjvO2) in the moderate- and high-dose groups at a nasopharyngeal temperature of 25-28 °C was significantly higher compared with the control group, while the arteriovenous oxygen content difference (AVDO2) and cerebral extraction of oxygen (CEO2) were significantly reduced. The serum S-100 protein and NSE concentrations of the moderate- and high-dose groups at 1 and 6 h after the cessation of CPB were significantly lower than that of the control group. The 24 h postoperative MMSE scores of the moderate- and high-dose groups were significantly higher than those of the low-dose and control groups. An inhaled optimal concentration of sevoflurane may be beneficial for cerebral oxygen balance during CPB, and may ameliorate cognitive damage. However, the effect is dose-dependent.

Injection of ropivacaine into the subarachnoid changes the ultrastructure and proteome of the rat spinal cord.

1. In the present study, we investigated the impact of 1.0% ropivacaine on the ultrastructure and proteome of the rat spinal cord. 2. Rats received three injections (90-min intervals, 0.2 mL/kg) of 0.9% NaCl, 0.5% ropivacaine or 1.0% ropivacaine via an implanted intrathecal catheter. Transmission electron microscopy was performed to exam the ultrastructure of the spinal cord. Two-dimensional electrophoresis followed by mass spectrometry identification were carried out to investigate the proteome. 3. In the rats administered 1.0% ropivacaine, deformed organelles, detached myelinated nerve fiber layer, and incomplete inner and outer shaft membranes were observed in the spinal cord and posterior root shrunken nuclei. Furthermore, in the rat spinal cord 1.0% ropivacaine induced the down-regulation of voltage-dependent anion channel 2 (VDAC2) and mitochondrial pyruvate dehydrogenase subunit alpha (ODPA), the upregulation of myelin basic protein (MBP), the disappearance of myelin transcription factor 1 (MYT1) and the appearance of heat shock protein 25 (HSP25). Little change was observed in the 0.5% ropivacaine or control groups. 4. Our results suggest that 1.0% ropivacaine treatment led to neurotoxicity, as shown by ultrastructural and proteomic changes in the rat spinal cord. Specific proteins were identified that are implicated in 1.0% ropivacaine-induced neurotoxicity.

Penehyclidine hydrochloride preserves the intestinal barrier function in patients undergoing cardiopulmonary bypass.

OBJECTIVE: The study objective was to investigate the protective effect of penehyclidine hydrochloride on intestinal barrier function integrity and its therapeutic potential on endotoxemia and systemic inflammatory response in patients undergoing cardiopulmonary bypass. METHODS: Forty patients undergoing cardiac valve replacement with cardiopulmonary bypass were enrolled in the study. All patients were randomly divided into the penehyclidine hydrochloride or control group (20 patients in each group). Patients in the penehyclidine hydrochloride group received an intravenous injection of 0.05 mg/kg penehyclidine hydrochloride 10 minutes before cardiopulmonary bypass, and those in the control group were given the same volume of saline. Blood samples for blood glucose, lactic acid, intestinal fatty acid binding protein, D-lactate, serum endotoxin (lipopolysaccharide), interleukin-6, and interleukin-10 measurements were collected during the following time points: immediately after anesthesia induction (T0), 10 minutes after the release of aortic-clamping (T1), immediately after weaning from cardiopulmonary bypass (T2), 2 hours postoperatively (T3), 6 hours postoperatively (T4), and 18 hours postoperatively (T5). RESULTS: Blood glucose, lactic acid, intestinal fatty acid binding protein, D-lactate, lipopolysaccharide, interleukin-6, and interleukin-10 were significantly increased at all postoperative time points. At specific postoperative time points, blood glucose, lactic acid, intestinal fatty acid binding protein, D-lactate, lipopolysaccharide, and interleukin-6 were statistically lower in the penehyclidine hydrochloride group than in the control group. Postoperatively, interleukin-10 did not differ between the penehyclidine hydrochloride and control groups. CONCLUSIONS: Penehyclidine hydrochloride preserves intestinal barrier function integrity, attenuates endotoxemia, and inhibits systemic inflammatory response in patients undergoing cardiopulmonary bypass, possibly by improving intestinal microcirculation and depressing stress response.

Probiotics can alleviate cardiopulmonary bypass-induced intestinal mucosa damage in rats.

BACKGROUND: Cardiopulmonary bypass (CPB) is commonly applied to support circulation during heart surgery but frequently causes adverse effects. AIMS: The purpose of this study was to examine the potential of probiotics to improve small intestinal mucosa barrier function after CPB. METHODS: Twenty-four adult male SD rats were randomly divided into sham-operated (S), CPB-operated (CPB), and probiotic-fed (Y) groups. Diamine oxidase (DAO) activity and concentrations of D-lactic acid, endotoxin, TNFα, and IL-6 were measured in portal vein blood. IgA concentrations were determined in plasma and the small intestine. Vena cava blood and tissue samples were used to monitor bacterial growth. Intestinal epithelial ultrastructure was analyzed by transmission electron microscopy (TEM). Occludin and ZO-1 expression levels in the intestinal epithelium were detected by western blotting and immunohistochemistry, respectively. RESULTS: D-lactic acid, endotoxin, TNFα and IL-6 levels, DAO activity, and bacterial translocation rate were increased (P < 0.05) in CPB and Y compared to the S group. The above indices were relatively lower (P < 0.05) in Y than in CPB. Plasma and small intestinal IgA levels were significantly lower (P < 0.05) in CPB, while in Y they were significantly increased (P < 0.05) but lower than in S (P < 0.05). These results were confirmed by TEM. Consistently, occludin and ZO-1 expression levels were significantly higher in Y than in CPB (P < 0.05) but still lower compared to S (P < 0.05). CONCLUSION: Pre-administration of probiotics can improve, to some extent, intestinal barrier function after CPB in rats, and this effect is likely related to inhibition of the CPB-induced inflammatory response, improvement in local intestinal immune function, and increased expression of intestinal epithelial tight junction proteins.

Protective effects of recombinant human bone morphogenetic protein-7 on focal cerebral ischemia-reperfusion injury.

This study was to investigate the protective effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) on focal cerebral ischemia-reperfusion (IR) injuries and their underlying mechanisms. An intraluminal suture method was used to generate a middle cerebral artery occlusion model in rats, which was followed by reperfusion. A sham operation (SO) group underwent the procedure without occlusion, whereas an IR group and rhBMP-7 treated group (RT) underwent occlusion in the absence and presence of rhBMP-7 (250 µg/kg) administered via a femoral vein injection 30 minutes prior to reperfusion. Twenty-four hours after reperfusion, neurological function, brain water content and morphological alterations were examined. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assays, and immunohistochemical staining and Western blot assays were used to detect nuclear nuclear factor-kappa B (NF-κB) p65 expression. Compared with the SO group, IR rats showed a decrease in neurological function, an increase in brain water content, and pathological and morphological damage (p < 0.05). Higher levels of apoptosis were also detected in the infarct region area. In contrast, RT rats had reduced injury after IR. In addition, while immunohistochemical staining and western blot assays consistently detected increased expression of nuclear NF-κB after IR, these levels were reduced in the RT group. Administration of rhBMP-7 prior to reperfusion effectively inhibited the extent of IR injury by attenuating cerebral edema and ameliorating ultrastructural damage. The underlying mechanisms responsible for these observations potentially involve the inhibition of apoptosis induced by IR by rhBMP-7 via an NF-κB-related signaling cascade.

[Causes of vocal cord dyscinesia and its original factors after endotracheal intubation].

OBJECTIVE: To research the causes of postintubation vocal cord dyskinesia and its contributing factors. METHOD: The causes of vocal cord dyskinesia were confirmed by laryngoscope, three-dimensional spiral CT, stroboscope, and the analysis of therapy. The factors relevant to the causes of vocal cord dyskinesia were analysed based on the following elements: (1) the anatomic or pathological condition of patients or the technical skills of anesthetists. (2) emaciated or obese body and neck. (3) the age of patients. (4) the duration of endotracheal tube retention. (5) the types of operations. (6) anesthesia procedure. RESULT: Among 135 patients, 128 cases (94.81%) manifested arytenoid dislocation, 7 cases (5.19%) vocal cord paralysis. The study showed that the vocal cord dyskinesia associated with anatomic or pathological condition of patients and technical skills of anesthetists (with intubation difficulty) accounted for 76.30%. The patients with relative emaciated body or neck accounted for 90.62% in cases without intubation difficulty. Age had no significant analytical relationship with vocal cord dyskinesia. Prolonged intubation (endotracheal tube retention over 12 hours) was accounted for only 17.64%. The incidence of vocal cord dyskinesia was nearly 0.5% in patients underwent cardio-thoracic surgery, accounting for 59.26% of all the patients. CONCLUSION: There are two major causes of vocal cord dyskinesia: arytenoid dislocation and vocal cord paralysis, and the rate of vocal cord dyskinesia could be reduced by the improvement of technical skill of anesthetists and/or sufficient attention to the intubation condition of patients.