Comparison of preoxygenation efficiency measured by the oxygen reserve index between high-flow nasal oxygenation and facemask ventilation: a randomised controlled trial.

BACKGROUND: High-flow nasal oxygenation and the oxygen reserve index (ORI), which is a non-invasive and innovative modality that reflects the arterial oxygen content, are used in general anaesthesia. This study compares the preoxygenation efficiency (measured by the ORI) of high-flow nasal oxygenation and facemask ventilation during the induction process. METHODS: This single-centre, two-group, randomised controlled trial included 197 patients aged ≥ 20 years who underwent orotracheal intubation for general anaesthesia for elective surgery. The patients were randomly allocated to receive preoxygenation via facemask ventilation or high-flow nasal oxygenation. The ORI was measured and compared between both groups. RESULTS: The ORI increased during preoxygenation in all patients. At 1 min of preoxygenation, the ORI was significantly higher in the high-flow nasal oxygenation group (0.34 ± 0.33) than in the facemask ventilation group (0.21 ± 0.28; P = 0.003). The highest ORI was not significantly different between the two groups (0.68 ± 0.25 in the high-flow nasal oxygenation group vs. 0.70 ± 0.28 in the facemask ventilation group; P = 0.505). CONCLUSIONS: High-flow nasal oxygenation results in an oxygenation status similar to that provided by facemask ventilation during the induction process of general anaesthesia; therefore, high-flow nasal oxygenation is a feasible preoxygenation method. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04291339).

Predictors of difficult intubation when using a videolaryngoscope with an intermediate-angled blade during the first attempt: a prospective observational study.

The curvature of a videolaryngoscope blade has been diversified from the standard macintosh-type to the hyperacute-angle-type, resulting in different performances. We aimed to determine the intubation success rate and identify predictors of difficult intubation when using an intermediate-angled videolaryngoscope in the first attempt of intubation under routine anaesthesia settings. We enrolled 808 patients between 19 and 79 years of age, scheduled for elective surgeries under general anaesthesia with orotracheal intubation from July 2017 to November 2018; patients who were candidates for awake intubation were excluded. We obtained patient demographic data and performed airway evaluation before induction of anaesthesia for elective surgeries. We used the UEScope for tracheal intubation with a hockey stick-shaped malleable stylet. The intubation time was defined as the total duration from the entry of the blade into the oropharynx to the detection of first end-tidal carbon dioxide capnogram; this duration was recorded along with the number of intubation attempts. Difficult intubation was defined as either > 60 s duration for tracheal intubation, or > 1 intubation attempt. The use of the UEScope demonstrated a 99.4% success rate for intubation; however, increased difficulties were observed in patients who were male, obese, had a short thyromental distance, limited mouth opening, and high upper-lip-bite test class. Despite the high intubation success rate using an intermediate-angled videolaryngoscope, we recommend preparing backup plans, considering the increased difficulty in patients with certain preoperative features.Clinical trial number and registry URL: Clinical Trials.gov Identifier: NCT03215823 (Date of registration: 12 July).

Lipid Emulsion Restoration of Myocardial Contractions After Bupivacaine-Induced Asystole In Vitro: A Benefit of Long- and Medium-Chain Triglyceride Over Long-Chain Triglyceride.

BACKGROUND: The relative efficacies of a long- and medium-chain triglyceride (LCT/MCT) emulsion and an LCT emulsion for treatment of bupivacaine (BPV)-induced cardiac toxicity are poorly defined. METHODS: After inducing asystole by BPV, varied concentrations (1%-12%) of either LCT/MCT (Lipofundin; B. Braun, Melsungen, Germany) or LCT emulsion (Intralipid; Fresenius Kabi, Upsala, Sweden) were applied to observe the recovery of stimulated contractile responses and contractile forces in either a recirculating or washout condition for 60 minutes, using guinea pig papillary muscles. The recirculation condition was used to demonstrate BPV binding by lipid emulsion. The washout condition was used to determine whether the time-dependent recovery of contraction is due to their metabolic enhancement. Oxfenicine, an inhibitor of carnitine palmitoyltransferase I in heart mitochondria, was used to evaluate the effect of each lipid emulsion on mitochondrial metabolic inhibition by BPV. To examine the effect of the lipid emulsion alone on contractility, either lipid emulsion was examined. BPV concentrations in solution and myocardial tissues were measured. RESULTS: In the recirculating condition, LCT/MCT emulsions (2%-12%) restored regular stimulated contractile responses in all muscles. Eight percent and 12% LCT/MCT emulsions led to complete recovery of contractile forces after 30 minutes. Meanwhile, LCT emulsions (4%-12%) did not restore regular stimulated contractile responses in some muscles (6, 3, and 2 in 9 muscles each in 4%, 8%, and 12% emulsions, respectively). Partial recovery, approximately 60%, of contractile forces was observed with 8% and 12% LCT emulsions. In the washout experiments, after asystole, LCT/MCT emulsions (1%-12%) restored contractility to baseline levels earlier and greater than LCT emulsion. Partial recovery, approximately 60%, was observed with a high concentration of LCT emulsion (12%). In the oxfenicine-pretreated group, the contractile recovery was enhanced with LCT/MCT emulsion but showed no change with LCT emulsion. Contractile depression by 40% was observed with high concentrations of LCT emulsion alone (8% and 12%), whereas no depression or enhanced contraction was observed with LCT/MCT emulsion (1%-12%) alone. Both types of lipid emulsions (2%-12%) caused concentration-related reductions of tissue BPV levels; LCT/MCT emulsions reduced tissue BPV levels slightly greater than LCT emulsion in a recirculating condition. CONCLUSIONS: An LCT/MCT emulsion was more beneficial than an LCT emulsion in terms of local anesthetic-binding and metabolic enhancement for treating acute BPV toxicity. The metabolic benefit of MCT, combined with the local anesthetic-binding effect of LCT, in an LCT/MCT emulsion may improve contractile function better than an LCT emulsion in an isolated in vitro animal myocardium model.

Lipid Emulsion Improves Functional Recovery in an Animal Model of Stroke.

Stroke is a life-threatening condition that leads to the death of many people around the world. Reperfusion injury after ischemic stroke is a recurrent problem associated with various surgical procedures that involve the removal of blockages in the brain arteries. Lipid emulsion was recently shown to attenuate ischemic reperfusion injury in the heart and to protect the brain from excitotoxicity. However, investigations on the protective mechanisms of lipid emulsion against ischemia in the brain are still lacking. This study aimed to determine the neuroprotective effects of lipid emulsion in an in vivo rat model of ischemic reperfusion injury through middle cerebral artery occlusion (MCAO). Under sodium pentobarbital anesthesia, rats were subjected to MCAO surgery and were administered with lipid emulsion through intra-arterial injection during reperfusion. The experimental animals were assessed for neurological deficit wherein the brains were extracted at 24 h after reperfusion for triphenyltetrazolium chloride staining, immunoblotting and qPCR. Neuroprotection was found to be dosage-dependent and the rats treated with 20% lipid emulsion had significantly decreased infarction volumes and lower Bederson scores. Phosphorylation of Akt and glycogen synthase kinase 3-ß (GSK3-ß) were increased in the 20% lipid-emulsion treated group. The Wnt-associated signals showed a marked increase with a concomitant decrease in signals of inflammatory markers in the group treated with 20% lipid emulsion. The protective effects of lipid emulsion and survival-related expression of genes such as Akt, GSK-3ß, Wnt1 and ß-catenin were reversed by the intra-peritoneal administration of XAV939 through the inhibition of the Wnt/ß-catenin signaling pathway. These results suggest that lipid emulsion has neuroprotective effects against ischemic reperfusion injury in the brain through the modulation of the Wnt signaling pathway and may provide potential insights for the development of therapeutic targets.

Neuroprotection from Excitotoxic Injury by Local Administration of Lipid Emulsion into the Brain of Rats.

Lipid emulsion was recently shown to attenuate cell death caused by excitotoxic conditions in the heart. There are key similarities between neurons and cardiomyocytes, such as excitability and conductibility, which yield vulnerability to excitotoxic conditions. However, systematic investigations on the protective effects of lipid emulsion in the central nervous system are still lacking. This study aimed to determine the neuroprotective effects of lipid emulsion in an in vivo rat model of kainic acid-induced excitotoxicity through intrahippocampal microinjections. Kainic acid and/or lipid emulsion-injected rats were subjected to the passive avoidance test and elevated plus maze for behavioral assessment. Rats were sacrificed at 24 h and 72 h after kainic acid injections for molecular study, including immunoblotting and qPCR. Brains were also cryosectioned for morphological analysis through cresyl violet staining and Fluorojade-C staining. Anxiety and memory functions were significantly preserved in 1% lipid emulsion-treated rats. Lipid emulsion was dose-dependent on the protein expression of ß-catenin and the phosphorylation of GSK3-ß and Akt. Wnt1 mRNA expression was elevated in lipid emulsion-treated rats compared to the vehicle. Neurodegeneration was significantly reduced mainly in the CA1 region with increased cell survival. Our results suggest that lipid emulsion has neuroprotective effects against excitotoxic conditions in the brain and may provide new insight into its potential therapeutic utility.

Intralipid Restoration of Myocardial Contractions Following Bupivacaine-Induced Asystole: Concentration- and Time-Dependence In Vitro.

BACKGROUND: The concentration- and time-response relationships of lipid emulsion (LE; Intralipid) on the recovery of myocardial contractility following bupivacaine (BPV)-induced asystole are poorly defined. METHODS: After achieving asystole by 500-µM BPV, varied concentrations of LE were applied to determine the recovery of stimulated contractile responses and contractions in the cardiac tissues of guinea pigs at a 1.2-Hz stimulation rate. These experiments were performed with LE in either a recirculating (2%-16%) or washout (nonrecirculating) condition (0.05%-12%) for 60 minutes. The effect of LE itself (0.05%-12%) was examined. Oxfenicine was used to evaluate the metabolic action of LE to reverse asystole. BPV concentrations in solution and myocardial tissues were measured. RESULTS: In the recirculation condition, partial recovery of contractile forces was observed for 60 minutes at 4%, 8%, and 12% LE. A contracture followed after exposure to 16% LE in some asystolic muscles. In the washout experiments, following asystole, LE (0.05%-12%) had no effect on the recovery time of the first and regular contractile responses. LE (0.1%-8%) restored contractility to baseline levels after 45 minutes; partial recovery was shown with lower (0.05%) and higher (12%) concentrations. Oxfenicine did not alter the recovery of contractile forces. Contractile depression was observed with 12% LE alone. Concentration-related reduction of tissue BPV concentration by LE was observed in both circulating conditions. CONCLUSIONS: LE induced time- and concentration-dependent recovery of stimulated myocardial contractions from BPV-induced asystole. The lipid uptake effect, along with other undefined mechanisms of LE, seems to contribute to the recovery of contractile function; however, the LE effect on myocardial metabolism is less likely involved at this concentration (500 µM) of BPV.

Determination of the appropriate oropharyngeal airway size in adults: Assessment using ventilation and an endoscopic view.

INTRODUCTION: Size 9 and 8 airways for men and women, respectively, have been proposed as most appropriate based on endoscopy. However, a limitation of this guideline is that ventilation was not assessed. METHODS: In this retrospective review of prospectively collected data, 149 patients requiring tracheal intubation for general anesthesia were included. The adequacy for manual and pressure-controlled mechanical ventilation and views at the distal end of each airway was assessed using a fiber-optic bronchoscope with various airway sizes (7, 8, 9, 10, and 11). RESULTS: For men, size 9, 10, and 11 airways permitted clear manual and adequate mechanical ventilation; size 7 and 8 airways caused partially obstructed manual and inadequate mechanical ventilation. On endoscopy, size 7 and 8 airways caused complete obstruction by the tongue; size 10 and 11 airways either touched or passed beyond the tip of the epiglottis. For women, the size 7 airway caused partially obstructed manual and inadequate mechanical ventilation; size 9 and 10 airways provided clear manual and adequate mechanical ventilation. The size 8 airway permitted clear manual ventilation, though mechanical ventilation was inadequate in one patient. On endoscopy, the size 7 airway caused complete obstruction in >50% of women; size 9, 10, and 11 airways either touched or passed beyond the tip of the epiglottis. CONCLUSIONS: With respect to adequate ventilation in conjunction with an acceptable endoscopic view, size 9 and size 8 oropharyngeal airways appear to be the most appropriate sizes for clinical use in men and women, respectively.

Determination of the appropriate sizes of oropharyngeal airways in adults: correlation with external facial measurements: A randomised crossover study.

BACKGROUND: Two external facial measurements have been recommended as reference criteria for estimating appropriate oropharyngeal airway sizes: the distances between the maxillary incisors to the angle of the mandible, and that from the corner of the mouth to the angle of the mandible. OBJECTIVE: To compare the two guidelines and to determine the optimal external facial measurements for the selection of an appropriately sized airway in adults. DESIGN: Randomised crossover study. SETTING: Operating theatres in a university hospital. PATIENTS: A total of 113 patients requiring tracheal intubation for general anaesthesia. INTERVENTIONS: Two oropharyngeal airway sizes were selected on the basis of two external facial measurements (tip of the upper central maxillary incisors to the angle of the mandible and corner of the mouth to the angle of the mandible). After assessing manual and pressure-controlled ventilation without an airway, the adequacy of ventilation with each oropharyngeal airway was assessed in a similar manner. Before changing the oropharyngeal airway, the view at the distal end of each airway was evaluated using endoscopy via a fibreoptic bronchoscope. MAIN OUTCOME MEASURES: Ventilation parameters and the endoscopic views at the distal ends of the airways were assessed. RESULTS: In the maxillary incisors to the angle of the mandible group, there was clear manual ventilation through the oropharyngeal airway in all patients, whereas partially obstructed ventilation was observed in 6% of patients in the corner of the mouth to the angle of the mandible group. In the maxillary incisors to the angle of the mandible group, mechanical ventilation through the oropharyngeal airway was adequate in all patients but in the corner of the mouth to the angle of the mandible group, inadequate ventilation was observed in 7% patients. In the maxillary incisors to the angle of the mandible group, the endoscopy did not identify any patient with complete obstruction of the airway by the tongue but in the corner of the mouth to the angle of the mandible group, 40% of patients had complete obstruction by the tongue. In the maxillary incisors to the angle of the mandible group, the tip of the airway passed beyond the tip of the epiglottis in 22% of patients, in contrast, none of the airways in the corner of the mouth to the angle of the mandible group passed beyond the tip of the epiglottis. CONCLUSION: With regard to adequate ventilation in conjunction with an acceptable endoscopic view, an oropharyngeal airway whose size is based upon the distance from the maxillary incisors to the angle of the mandible is more advantageous than if based upon the distance from the corner of the mouth to the angle of the mandible. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01945411. The clinical trial was registered before patient enrolment.

Accuracy of pilot balloon palpation for cuff pressure assessment in small versus large sized tubes: a prospective non-randomized observational study.

Pilot balloon palpation is still a commonly used method to evaluate cuff pressure of the endotracheal tube after intubation. This study determined whether the size of the tracheal tube influenced the accuracy of pilot balloon palpation. A prospective observational analysis of 208 patients intubated with an endotracheal tube of internal diameter (ID) 6.0 or 8.0 was conducted. An anesthesiologist judged the cuff pressure by manual pilot balloon palpation, and then measured the cuff pressure with a pressure gauge. Cuff pressure exceeding 20-30 cmH2O was defined as false recognition. The intracuff pressure was significantly higher in ID 6.0 tube than in the ID 8.0 tube (41.9 ± 18.8 cmH2O vs. 30.3 ± 11.9 cmH2O, p < 0.001). The number of patients that were mistakenly perceived to have appropriate cuff pressure by pilot balloon palpation was significantly higher in the ID 6.0 group compared to the ID 8.0 group (85 (81.7%) vs. 64 (61.5%), p = 0.001). Therefore, a smaller tube size may further increase risk of inaccurate measurement by pilot balloon palpation and although pressure gauge is recommended for all sizes to maximize accuracy, groups with increased risk factors should be targeted for standardized use of the pressure gauge.

Ventilation through a straw.

Transtracheal jet ventilation can be used for resuscitation of partial airway obstruction. A prerequisite for jet ventilation is that at least a minimum airway opening for gas escape must be secured. Therefore, another option should be considered in cases of complete airway obstruction. The following methods or devices has been used under cricothyrotomy using an intravenous cannula: 1) Ambu (bag valve mask) bagging, 2) Ventrain® , 3) Rapid-O2 oxygen insufflation device (Rapid-O2), and 4) jet ventilation using a dual lumen catheter. During Ambu bagging, extraordinarily high insufflation pressure is required to force oxygen through the cannula. When using a 12-G cannula, long and slow positive-pressure ventilations (10-12 breaths/min) are required, which makes it extremely difficult to compress the bag. Therefore, a 10-G or larger is recommended. Ventrain® is an expiratory assist device capable of forcibly expelling insufflated oxygen through a transtracheal cannula. It is recommended to adjust the inspiratory and expiratory times while observing the chest wall movements. Rapid-O2 is a rescue oxygenation device with adequate ventilation of less importance; therefore, the resulting hypercarbia is inevitable. A 14-G cannula is used. Lastly, jet ventilation using a dual-lumen catheter with a 16-G inflow lumen and 10-G outflow lumen was used to obtain both oxygenation and ventilation. However, the addition of the outer diameters of 16-G and 10-G results in an outer diameter of 5.1 mm, which is too large to puncture the cricothyroid membrane. In conclusion, Ventrain® is considered the most ideal device for use among the devices developed to date.

A propensity score-adjusted analysis of efficacy of high-flow nasal oxygen during awake tracheal intubation.

Oxygen supplementation is crucial for awake tracheal intubation (ATI) using a flexible bronchoscope in patients with an anticipated difficult airway. However, the modality of optimal oxygen delivery remains unclear. This retrospective study compared high-flow nasal oxygen (HFNO) and conventional low-flow oxygen supply during ATI. We applied inverse probability of treatment weighting (IPTW) to account for biases due to clinical characteristic differences between the groups. The primary endpoint was the lowest oxygen saturation during ATI. The secondary endpoints were incidence of desaturation, multiple attempts, failure rate, and procedural duration. After IPTW adjustment, the lowest oxygen saturation in the HFNO group during ATI was significantly higher than that in the conventional oxygenation group (99.3 ± 0.2 vs. 97.5 ± 0.5, P < 0.001). Moreover, the HFNO group had fewer cases with multiple attempts than the conventional oxygenation group (3% vs. 16%, P = 0.007). There were no significant differences between the two groups in the incidence of desaturation, failure and procedural duration. Our findings suggest that HFNO was associated with improved lowest oxygen saturation and a lower rate of multiple attempts during ATI. Therefore, we recommend using HFNO for safer oxygen delivery and improved quality of procedure during ATI.

Effects of Head and Neck Position on Nasotracheal Tube Intracuff Pressure: A Prospective Observational Study.

To prevent endotracheal tube-related barotrauma or leakage, the intracuff pressure should be adjusted to 20-30 cm H2O. However, changes in the nasotracheal tube intracuff pressure relative to neck posture are unclear. In this study, we investigated the effect of head and neck positioning on nasotracheal tube intracuff pressure. Fifty adult patients with nasotracheal tubes who were scheduled for surgery under general anesthesia were enrolled. Following intubation, intracuff pressure was measured by connecting the pilot balloon to a device that continuously monitors the intracuff pressure. Subsequently, the intracuff pressure was set to 24.48 cm H2O (=18 mmHg) for the neutral position. We recorded the intracuff pressures based on the patients' position during head flexion, extension, and rotation. The initial intracuff pressure was 42.2 cm H2O [29.6-73.1] in the neutral position. After pressure adjustment in the neutral position, the intracuff pressure was significantly different from the neutral to flexed (p < 0.001), extended (p = 0.003), or rotated (p < 0.001) positions. Although the median change in intracuff pressure was <3 cm H2O when each patient's position was changed, overinflation to >30 cm H2O occurred in 12% of patients. Therefore, it is necessary to adjust the intracuff pressure after tracheal intubation and each positional change.

Comparison of the selection of nasotracheal tube diameter based on the patient's sex or size of the nasal airway: A prospective observational study.

When selecting the nasotracheal tube diameter for nasotracheal intubation, atraumatic introduction of the tube through the nasal passage and a safe location of the tube's cuff and tip should be ensured simultaneously. To maintain safety margin for the tube's cuff and tip from the vocal cords and carina (2 cm and 3 cm, respectively), the maximum allowable proximal-cuff-to-tip distance was calculated as 5 cm less than the measured vocal cords-to-carina distance. The primary aim of this study was to find a single predictive preoperative factor of the nostril size and maximum allowable proximal-cuff-to-tip distance of nasotracheal tubes. The secondary aim was to compare the difference in the safety margin between the maximum allowable proximal-cuff-to-tip distance based on the patient's airway and the actual proximal-cuff-to-tip distance of the selected tube. We used fiberoptic bronchoscope to measure the distance from the vocal cords to the carina for the calculation of the maximum allowable proximal-cuff-to-tip distance. We analyzed the association of preoperative characteristics such as age, sex, height, and weight with the nostril size and maximum allowable proximal-cuff-to-tip distance. The proportion of patients with appropriate locations of both the cuff and tip was evaluated. Sex and height were significant predictive factors of the nostril size and maximum allowable proximal-cuff-to-tip distance, respectively (p = 0.0001 and p = 0.0048). The difference in the safety margin was significantly decreased when the tube diameter was selected based on the nostril size rather than by sex (p<0.0001). The proportion of patients who had the appropriate cuff/tip location was significantly larger (75.2%) when the tube diameter was selected by sex compared to when it was selected by the nostril size (65%) (p<0.0001). It is more suitable to select the nasotracheal tube diameter based on sex rather than by nostril size to ensure the safe location of the tube's cuff and tip simultaneously.

Effect of Timing of Intravenous Fentanyl Administration on the Incidence of Posttonsillectomy Nausea and Vomiting.

OBJECTIVE/HYPOTHESIS: Fentanyl is commonly administered toward the end of tonsillectomy to prevent emergence delirium and reduce postoperative pain. However, it can delay emergence from anesthesia and increase the risk of postoperative nausea and vomiting (PONV). The goal of our study was to compare the risk of PONV based on the timing of fentanyl administration at the end of tonsillectomy in children. STUDY DESIGN: Prospective, double-blind, randomized controlled trial. METHODS: One hundred forty patients aged 3 to 7 years undergoing tonsillectomy were divided into two groups. Fentanyl (1 µg/kg) was administered at the end of surgery in group 1 (n = 70) and at 10 to 15 minutes before the end of surgery in group 2 (n = 70). Time to regular breathing and time to emergence from anesthesia were measured from the end of surgery. PONV and pediatric anesthesia emergence delirium scale scores were assessed every 10 minutes after admission to the postanesthesia care unit. RESULTS: Incidences of PONV (2.9% vs. 2.9%, P > .99) and emergence delirium (11.4% vs. 5.7%, P = .23) were not significantly different between the two groups. Time to regular breathing (mean difference = 2.3 minutes; 95% confidence interval [CI]: 0.9 to 3.7 minutes) and time to emergence (median difference = 6.5 minutes; 95% CI, 2.5 to 10.5 minutes) were significantly longer in group 1 than in group 2. CONCLUSIONS: Although there was no beneficial effect on PONV, recovery of regular breathing and consciousness was quicker with earlier fentanyl administration. Emergence delirium was well-controlled, similar to that with fentanyl administration at the end of surgery. LEVEL OF EVIDENCE: 1b Laryngoscope, 2020.

Insertion depth of nasotracheal tubes sized to fit the nostril: an observational study.

OBJECTIVE: Nasotracheal (NT) intubation is commonly applied during head and neck surgery. However, improper tube size and depth may cause complications. In the current study, we investigated whether NT tubes are being appropriately used in terms of size and depth in adult patients. METHODS: Nares were sized in 40 patients using standard nasopharyngeal airways (6.0-8.0) before elective surgery under general anesthesia. The largest sized airway that passed easily into the nasopharynx without resistance was considered as a proper size. Using a fiberoptic scope, the distances from the nares to the vocal cords and the nares to the carina were measured. Rates of proper NT tube positioning were calculated with regard to the cuff and distal tip. RESULTS: The most frequent sizes of properly fitted NT tubes were 6.5 and 6.0 in male and female patients, respectively. Positioning of the cuff and distal tip was only appropriate when using a properly sized tube in 26% and 47% of male and female patients, respectively. CONCLUSION: Care should be taken to determine the insertion depth after placing an NT tube that has been sized to fit the nostril. Moreover, NT tubes of the same diameter may be required in various lengths. Trial registration: Registered at ClinicalTrial.gov; https://clinicaltrials.gov/ct2/show/NCT02876913 ; Registration number NCT02876913.

Effect of propofol on calcium homeostasis in hypoxia-reoxygenated neonatal rat cardiomyocytes.

Intracellular Ca2+ overload induced by hypoxia-reoxygenation alters Ca2+ homeostasis, which plays an important role in myocardial cell injury. Even though propofol is known as a radical scavenger with Ca2+ channel blocking properties, little is known about cardioprotective effect associated with Ca2+ homeostasis in cardiomyocytes. In the present study, we showed that propofol protects cardiomyocytes against hypoxia-reoxygenation injury. In propofol-treated cardiomyocytes, we observed a decrease in the expression of pro-apoptotic protein Bax, cytochrome c, caspase-3 activation and intracellular Ca2+ content. We also found that propofol treatment enhanced expression of anti-apoptotic protein Bcl-2 and activation of ERK concerned with survival. Propofol attenuated alterations of genes involving Ca2+-regulatory mechanism and significantly modulated abnormal changes of SERCA2a genes in hypoxia-reoxygenated neonatal cardiomyocytes. These results suggest that propofol modulates the expression of genes involved in Ca2+ homeostasis, thereby producing cardioprotective effects through a reduction in apoptotic cell death.

Artemin activates axonal growth via SFK and ERK-dependent signalling pathways in mature dorsal root ganglia neurons.

Artemin, one of the glial cell line-derived neurotrophic factor (GDNF) family, enhances the generation and survival of early sympathetic neurons and superior cervical ganglion (SCG) neurons. Src-family kinases (SFK) are involved in the growth and differentiation of cells, which are composed of unique Src homology 2 (SH2), Src homology 3 (SH3) and kinase domains. Various extra-cellular molecules containing growth factors and G-protein coupled receptors stimulate SFK. In this report, artemin is shown to have a significant effect on the neurite growth of dorsal root ganglia (DRG) neurons. Also, artemin triggers Src-family kinase activation and the phosphorylation of extra-cellular signal-regulated kinases (ERK) mitogen-activated protein kinase (MAPK). Artemin also regulated actin polymerization. There are several indications that another SH3-containing protein, Hck, and an SH3-containing adaptor protein, Nck1, play an important role in the organization of the actin cytoskeleton by cellular signalling. These findings suggest that the exploration of binding partners for the SH3 domain could provide an insight into regulation between the microtubule and actin networks. The binding partners for the SH3 domains of Nck, Src and Hck that we identified were Smc chromosome segregation ATPases, FOG Zn-finger protein and the FYVE zinc-binding domain, respectively.

Phosphoproteome Profiling of SH-SY5y Neuroblastoma Cells Treated with Anesthetics: Sevoflurane and Isoflurane Affect the Phosphorylation of Proteins Involved in Cytoskeletal Regulation.

Inhalation anesthetics are used to decrease the spinal cord transmission of painful stimuli. However, the molecular or biochemical processes within cells that regulate anesthetic-induced responses at the cellular level are largely unknown. Here, we report the phosphoproteome profile of SH-SY5y human neuroblastoma cells treated with sevoflurane, a clinically used anesthetic. Phosphoproteins were isolated from cell lysates and analyzed using two-dimensional gel electrophoresis. The phosphorylation of putative anesthetic-responsive marker proteins was validated using western blot analysis in cells treated with both sevoflurane and isoflurane. A total of 25 phosphoproteins were identified as differentially phosphorylated proteins. These included key regulators that signal cytoskeletal remodeling steps in pathways related to vesicle trafficking, axonal growth, and cell migration. These proteins included the Rho GTPase, Ras-GAP SH3 binding protein, Rho GTPase activating protein, actin-related protein, and actin. Sevoflurane and isoflurane also resulted in the dissolution of F-actin fibers in SH-SY5y cells. Our results show that anesthetics affect the phosphorylation of proteins involved in cytoskeletal remodeling pathways.

Radial nerve paralysis due to Kent retractor during upper abdominal operation.

After general anesthesia, peripheral nerve paralysis is a rare complication. The frequently damaged nerves including: branches of the brachial plexus, the ulnar, radial and common peroneal nerves, and sometimes the facial nerve. The radial nerve is the most infrequently damaged one, accounting for only 3% of nerve damage. We report a case of radial nerve paralysis due to self retractor during abdominal operation, its clinical findings, and review of the literature on peripheral nerve paralysis.