Neuron-targeted caveolin-1 improves neuromuscular function and extends survival in SOD1G93A mice.

Interventions that preserve motor neurons or restore functional motor neuroplasticity may extend longevity in amyotrophic lateral sclerosis (ALS). Delivery of neurotrophins may potentially revive degenerating motor neurons, yet this approach is dependent on the proper subcellular localization of neurotrophin receptor (NTR) to plasmalemmal signaling microdomains, termed membrane/lipid rafts (MLRs). We previously showed that overexpression of synapsin-driven caveolin-1 (Cav-1) (SynCav1) increases MLR localization of NTR [e.g., receptor tyrosine kinase B (TrkB)], promotes hippocampal synaptic and neuroplasticity, and significantly improves learning and memory in aged mice. The present study crossed a SynCav1 transgene-positive (SynCav1+) mouse with the mutant human superoxide dismutase glycine to alanine point mutation at amino acid 93 (hSOD1G93A) mouse model of ALS. When compared with hSOD1G93A, hSOD1G93A/SynCav1+ mice exhibited greater body weight and longer survival as well as better motor function. Microscopic analyses of hSOD1G93A/SynCav1+ spinal cords revealed preserved spinal cord α-motor neurons and preserved mitochondrial morphology. Moreover, hSOD1G93A/SynCav1+ spinal cords contained more MLRs (cholera toxin subunit B positive) and MLR-associated TrkB and Cav-1 protein expression. These findings demonstrate that SynCav1 delays disease progression in a mouse model of ALS, potentially by preserving or restoring NTR expression and localization to MLRs.-Sawada, A., Wang, S., Jian, M., Leem, J., Wackerbarth, J., Egawa, J., Schilling, J. M., Platoshyn, O., Zemljic-Harpf, A., Roth, D. M., Patel, H. H., Patel, P. M., Marsala, M., Head, B. P. Neuron-targeted caveolin-1 improves neuromuscular function and extends survival in SOD1G93A mice.

Neuron-Targeted Caveolin-1 Promotes Ultrastructural and Functional Hippocampal Synaptic Plasticity.

A delicate interneuronal communication between pre- and postsynaptic membranes is critical for synaptic plasticity and the formation of memory. Evidence shows that membrane/lipid rafts (MLRs), plasma membrane microdomains enriched in cholesterol and sphingolipids, organize presynaptic proteins and postsynaptic receptors necessary for synaptic formation and signaling. MLRs establish a cell polarity that facilitates transduction of extracellular cues to the intracellular environment. Here we show that neuron-targeted overexpression of an MLR protein, caveolin-1 (SynCav1), in the adult mouse hippocampus increased the number of presynaptic vesicles per bouton, total excitatory type I glutamatergic synapses, number of same-dendrite multiple-synapse boutons, increased myelination, increased long-term potentiation, and increased MLR-localized N-methyl-d-aspartate receptor subunits (GluN1, GluN2A, and GluN2B). Immunogold electron microscopy revealed that Cav-1 localizes to both the pre- and postsynaptic membrane regions as well as in the synaptic cleft. These findings, which are consistent with a significant increase in ultrastructural and functional synaptic plasticity, provide a fundamental framework that underlies previously demonstrated improvements in learning and memory in adult and aged mice by SynCav1. Such observations suggest that Cav-1 and MLRs alter basic aspects of synapse biology that could serve as potential therapeutic targets to promote neuroplasticity and combat neurodegeneration in a number of neurological disorders.

Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampus-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

Caveolin-1 regulation of disrupted-in-schizophrenia-1 as a potential therapeutic target for schizophrenia.

Schizophrenia is a debilitating psychiatric disorder manifested in early adulthood. Disrupted-in-schizophrenia-1 (DISC1) is a susceptible gene for schizophrenia (Hodgkinson et al. 2004; Millar et al. 2000; St Clair et al. 1990) implicated in neuronal development, brain maturation, and neuroplasticity (Brandon and Sawa 2011; Chubb et al. 2008). Therefore, DISC1 is a promising candidate gene for schizophrenia, but the molecular mechanisms underlying its role in the pathogenesis of the disease are still poorly understood. Interestingly, caveolin-1 (Cav-1), a cholesterol binding and scaffolding protein, regulates neuronal signal transduction and promotes neuroplasticity. In this study we examined the role of Cav-1 in mediating DISC1 expression in neurons in vitro and the hippocampus in vivo. Overexpressing Cav-1 specifically in neurons using a neuron-specific synapsin promoter (SynCav1) increased expression of DISC1 and proteins involved in synaptic plasticity (PSD95, synaptobrevin, synaptophysin, neurexin, and syntaxin 1). Similarly, SynCav1-transfected differentiated human neurons derived from induced pluripotent stem cells (hiPSCs) exhibited increased expression of DISC1 and markers of synaptic plasticity. Conversely, hippocampi from Cav-1 knockout (KO) exhibited decreased expression of DISC1 and proteins involved in synaptic plasticity. Finally, SynCav1 delivery to the hippocampus of Cav-1 KO mice and Cav-1 KO neurons in culture restored expression of DISC1 and markers of synaptic plasticity. Furthermore, we found that Cav-1 coimmunoprecipitated with DISC1 in brain tissue. These findings suggest an important role by which neuron-targeted Cav-1 regulates DISC1 neurobiology with implications for synaptic plasticity. Therefore, SynCav1 might be a potential therapeutic target for restoring neuronal function in schizophrenia. NEW & NOTEWORTHY: The present study is the first to demonstrate that caveolin-1 can regulate DISC1 expression in neuronal models. Furthermore, the findings are consistent across three separate neuronal models that include rodent neurons (in vitro and in vivo) and human differentiated neurons derived from induced pluripotent stem cells. These findings justify further investigation regarding the modulatory role by caveolin on synaptic function and as a potential therapeutic target for the treatment of schizophrenia.

Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics.

Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood-brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and (2) potential therapies that include biologics (stem cells, gene therapy, peptides), pharmacological (anti-inflammatory, antiepileptic, progrowth), and noninvasive (exercise, transcranial magnetic stimulation). In final, the review briefly discusses membrane/lipid rafts (MLR) and the MLR-associated protein caveolin (Cav). Interventions that increase Cav-1, MLR formation, and MLR recruitment of growth-promoting signaling components may augment the efficacy of pharmacologic agents or already existing endogenous neurotransmitters and neurotrophins that converge upon progrowth signaling cascades resulting in improved neuronal function after injury.

Membrane lipid rafts and neurobiology: age-related changes in membrane lipids and loss of neuronal function.

A better understanding of the cellular physiological role that plasma membrane lipids, fatty acids and sterols play in various cellular systems may yield more insight into how cellular and whole organ function is altered during the ageing process. Membrane lipid rafts (MLRs) within the plasma membrane of most cells serve as key organizers of intracellular signalling and tethering points of cytoskeletal components. MLRs are plasmalemmal microdomains enriched in sphingolipids, cholesterol and scaffolding proteins; they serve as a platform for signal transduction, cytoskeletal organization and vesicular trafficking. Within MLRs are the scaffolding and cholesterol binding proteins named caveolin (Cav). Cavs not only organize a multitude of receptors including neurotransmitter receptors (NMDA and AMPA receptors), signalling proteins that regulate the production of cAMP (G protein-coupled receptors, adenylyl cyclases, phosphodiesterases (PDEs)), and receptor tyrosine kinases involved in growth (Trk), but also interact with components that modulate actin and tubulin cytoskeletal dynamics (e.g. RhoGTPases and actin binding proteins). MLRs are essential for the regulation of the physiology of organs such as the brain, and age-related loss of cholesterol from the plasma membrane leads to loss of MLRs, decreased presynaptic vesicle fusion, and changes in neurotransmitter release, all of which contribute to different forms of neurodegeneration. Thus, MLRs provide an active membrane domain that tethers and reorganizes the cytoskeletal machinery necessary for membrane and cellular repair, and genetic interventions that restore MLRs to normal cellular levels may be exploited as potential therapeutic means to reverse the ageing and neurodegenerative processes.

Effects of anesthetics on early postoperative cognitive outcome and intraoperative cerebral oxygen balance in patients undergoing lung surgery: a randomized clinical trial.

PURPOSE: One-lung ventilation (OLV) may impair cerebral oxygen balance and induce postoperative cognitive dysfunction (POCD). It is unclear whether the type of anesthetic influences the incidence of POCD in patients undergoing OLV. This prospective study compared the incidence of POCD and intraoperative cerebral oxygen desaturation in OLV patients anesthetized with propofol vs sevoflurane during lung surgery. METHODS: There were 148 participants enrolled in this study and randomized equally to either the propofol or the sevoflurane group. Anesthesia was maintained with either propofol or sevoflurane combined in both groups with fentanyl and epidural anesthesia. Regional cerebral oxygen saturation (rSO2), jugular bulb venous oxygen saturation (SjO2), and the incidence of cerebral oxygen desaturation (rSO2 or SjO2 < 50% or rSO2 < 80% of baseline) were measured during anesthesia. Cognitive function was assessed using seven neurocognitive tests two days preoperatively, five days postoperatively (primary outcome), and three months postoperatively. Bivariable and multivariable regression analyses were conducted to identify factors associated with POCD. RESULTS: Rates of POCD did not differ statistically between groups five days postoperatively (propofol, 16/72 patients; sevoflurane, 24/72 patients; RR, 0.67; 95% CI, 0.39 to 1.15; P = 0.14) or three months postoperatively (propofol, 9/60 patients; sevoflurane, 12/58 patients; RR, 0.73; 95% CI, 0.33 to 1.59; P = 0.42). Only three subjects per group showed intraoperative cerebral oxygen desaturation. Multivariable regression analysis revealed older age as an independent predictor of POCD. CONCLUSIONS: No statistically significant difference in the incidence of POCD could be detected between the sevoflurane and propofol anesthesia groups. Postoperative cognitive dysfunction was relatively frequent following OLV in both groups. ( REGISTRATION NUMBER: UMIN 000002826).

RéSUMé: OBJECTIF: La ventilation unipulmonaire (VUP) pourrait avoir un impact négatif sur l'équilibre d'oxygène cérébral et induire une dysfonction cognitive postopératoire (DCPO). Nous ne savons pas si le type d'agent anesthésique influence l'incidence de DCPO chez les patients recevant une VUP. Cette étude prospective a comparé l'incidence de DCPO et de désaturation peropératoire en oxygène cérébral chez les patients sous VUP anesthésiés avec du propofol vs du sévoflurane pendant une chirurgie pulmonaire. MéTHODE: Au total, 148 patients ont participé à cette étude et ont été randomisés en deux groupes égaux à recevoir du propofol ou du sévoflurane. L'anesthésie a été maintenue à l'aide de propofol ou de sévoflurane, et l'agent de choix a été combiné à du fentanyl et à une anesthésie péridurale dans les deux groupes. La saturation en oxygène cérébral régional (rSO2), la saturation en oxygène veineux au bulbe de la veine jugulaire (SjO2) et l'incidence de désaturation en oxygène cérébral (rSO2 ou SjO2 < 50 % ou rSO2 < 80 % par rapport aux valeurs de base) ont été mesurées pendant l'anesthésie. La fonction cognitive a été évaluée à l'aide de sept tests neurocognitifs deux jours avant l'opération, cinq jours après l'opération (critère d'évaluation principal) et trois mois après l'opération. Des analyses de régression bivariée et multivariée ont été réalisées afin d'identifier les facteurs associés à une DCPO. RéSULTATS: D'un point de vue statistique, les taux de DCPO n'étaient pas différents entre les groupes à cinq jours postopératoires (propofol, 16/72 patients; sévoflurane, 24/72 patients; RR, 0,67; IC 95 %, 0,39 à 1,15; P = 0,14) ou à trois mois postopératoires (propofol, 9/60 patients; sévoflurane, 12/58 patients; RR, 0,73, IC 95 %, 0,33 à 1,59; P = 0,42). Seuls trois patients par groupe ont manifesté une désaturation peropératoire en oxygène cérébral. L'analyse de régression multivariée a révélé qu'un âge avancé était un prédicteur indépendant de DCPO. CONCLUSION: Aucune différence significative d'un point de vue statistique n'a été observée en ce qui a trait à l'incidence de DCPO entre les groupes anesthésiés au sévoflurane ou au propofol. La dysfonction cognitive postopératoire était relativement fréquente après une VUP dans les deux groupes. (Numéro d'enregistrement: UMIN 000002826).

[The Implication of Dietary Supplements and Herbal Medicines in Perioperative Period].

Total sales of dietary supplements and herbal medi- cines exceed two trillion yen in Japan. Approximately 60% of Japanese use dietary supplements or herbal medicines. In general, many people believe that dietary supple- ments and herbal medicines are safe natural prod- ucts; however, they could induce serious adverse events (bleeding, myocardial infarction stroke and glucose intolerance) in perioperative period. Coagulation and cardiovascular system can be nega- tively affected by those products. Thus careful preop- erative assessment is required for the patients who need regional anesthesia (e.g. epidural anesthesia and spinal anesthesia) and have cardiovascular complica- tions. Unfortunately there is no concise guideline regarding the use of supplements and herbal medicines during perioperative period. Anesthesiologists should be familiar with the adverse effects of dietary supplements and herbal medicines and pay more attention to non-prescribed medicines in preoperative assessment.

Two cases in which the effectiveness of "laryngospasm notch" pressure against laryngospasm was confirmed by imaging examinations.

We report two cases in which development of laryngospasm and release of the spasm immediately after applying pressure in the "laryngospasm notch" was confirmed by ultrasonographic and fiberoptic examinations. A bronchoscopy was planned under propofol sedation using a laryngeal mask airway for a 61-year-old man after subtotal esophagotomy. When a bronchoscope was advanced into the trachea, the vocal cords suddenly closed. Immediately after pressure with the fingertips was applied to the "laryngospasm notch," the vocal cords opened, which was observed through the bronchoscope in real time. A 22-year-old woman presented for emergency caesarean section under general anesthesia. After the completion of the procedures, the patient was not yet following commands but her breathing was steady. Thus, extubation was performed; however, she began to display signs of respiratory stridor. An ultrasonographic examination revealed that the vocal cords were noted to close, which suggested that she was developing laryngospasm. With this diagnosis, pressure at the "laryngospasm notch" was applied. Immediately after this maneuver, the vocal cords opened. We reconfirmed that applying pressure in the "laryngospasm notch" was effective to release laryngospasm. Imaging studies, especially ultrasonographic examination, were useful for making the decision to apply pressure in the "laryngospasm notch."

A case of refractory pneumothorax and contralateral atelectasis after thoracoscopic subtotal esophagectomy treated with independent lung ventilation.

BACKGROUND: Independent lung ventilation (ILV) allows separate positive end-expiratory pressures (PEEP) and inspiratory pressures for each lung. However, only a few articles have reported ILV management for lungs affected by different pathologies. CASE PRESENTATION: A 56-year-old man underwent video-assisted thoracic surgery for esophageal cancer. The right lung was injured during surgery, causing a bronchopleural fistula and necessitating chest drainage. On the third day in the intensive care unit, the patient's oxygenation worsened during pressure support with continuous positive airway pressure ventilation. ILV was initiated for right-sided severe pneumothorax and left-sided atelectasis and pneumonia. ILV was continued for 2 days, and the patient's trachea was successfully extubated the following day. CONCLUSION: Applying high-level PEEP to the one lung and minimizing the airway pressure on the other lung could be achieved using ILV, which might contribute to successful tracheal extubation.

A case of afterload mismatch associated with shivering leading to fetal hypoxia in a COVID-19 patient.

BACKGROUND: Fever and associated shivering are frequent symptoms in patients with coronavirus disease 2019 (COVID-19). High body temperature activates the immune system, which might be beneficial. However, shivering leads to high oxygen demand. CASE PRESENTATION: A 38-year-old man diagnosed with COVID-19 was transferred to our intensive care unit (ICU). His oxygen saturation (SpO2) level was approximately 92-95% and was managed with a high flow nasal cannula. Six hours after admission to the ICU, he started shivering, and his systolic blood pressure rose above 200 mmHg. Concomitantly, his SpO2 levels decreased rapidly. Mechanical ventilation was started, but oxygenation could not be maintained, requiring the establishment of extracorporeal membrane oxygenation (ECMO). CONCLUSIONS: COVID-19 is known to cause thrombosis in the pulmonary microvasculature at the early stage of the disease. Under these circumstances, caution should be paid since shivering may worsen the patient's condition.

Life-threatening airway obstruction caused by angioedema in a morbidly obese postoperative patient: a case report.

BACKGROUND: We report a case of a morbidly obese patient who developed life-threatening airway obstruction due to angioedema. CASE PRESENTATION: A 50-year-old Japanese morbidly obese female was treated with enalapril for 10 years, with no history of angioedema. After 3 h of completion of breast cancer resection under general anesthesia with tracheal intubation, she developed airway obstruction and respiratory arrest. Her oral cavity was occupied with a swollen tongue. It was extremely difficult to determine the airway anatomical orientation although tracheal intubation was attempted using a videolaryngoscope. At this time, she probably started gasping respiration, which generated a faint bubble and revealed a possible airway. Her airway was established using a tracheal tube without confirming the glottis or the vocal cord. CONCLUSIONS: Angioedema induced by angiotensin-converting enzyme (ACE) inhibitors is rare; however, once it occurs, it can be potentially life threatening, especially for patients with possible difficult airway. Considering the risk-benefit ratio, we must be careful in administering ACE inhibitor therapy in morbidly obese patients.

Current Status of Clinical Engineer Anesthesia Assistants and Their Effect on Labor Task Shifting in Japan: A Prospective Observational Study in a Single Institute.

INTRODUCTION: Anesthesiologists are in short supply across the world, resulting in perpetually long working hours. To reduce the burden on anesthesiologists, tasks that can be performed by non-physicians must be shifted to other medical staff. In hospitals, clinical engineers can work as anesthesia assistants and perform some of the duties of anesthesiologists. This study aimed to evaluate the effect of task shift performed by clinical engineer anesthesia assistants (CEAAs). METHODS: This was a 1-month prospective observational study that included 33 anesthesiologists (11 fellows and 22 certified anesthesiologists) and 11 CEAAs. The total activity and anesthesia times were extracted from the attendance record as indices of the anesthesiologists' work status. The CEAAs recorded the duration of work performed on behalf of the anesthesiologists as task shift time. The task shift rate was evaluated as follows: task shift time/(task shift time + total activity time) and task shift time/(task shift time) + (total anesthesia time). RESULTS: The study period consisted of 19 weekdays. The average daily activity time of the anesthesiologists was 10.1 h, and the average anesthesia time was 8.5 h. The CEAAs performed a total of 546.8 h of task shift. The defined task shift rate was 20.1% when the total activity time was the denominator and 23.1% when the anesthesia time was the denominator. CONCLUSIONS: CEAAs might be effective in reducing the working hours of anesthesiologists through task shift. Their taking over a portion of the anesthesiologists' duties may allow the anesthesiologists to work more efficiently.

[Preoperative evaluation and prognosis of patients with cerebrovascular disease].

Stroke remains a major perioperative problem for anesthesiologists. In this article, we have described preoperative evaluation and prognosis of patients with cerebrovascular disease. Cerebral infarction accounts for more than 60% of stroke. In patients with recently developed ischemic stroke, a surgery should be delayed at least for a month. Carotid artery stenosis accounts for 15 to 20% of ischemic stroke. In these patients, since the incidence of cardiovascular disease is common, cardiovascular examinations may be required preoperatively. The efficacy of carotid endarterectomy (CEA) to prevent stroke is well established, whereas carotid artery stenting (CAS) has been increasingly advocated as less invasive treatment. Several studies have indicated that the risks of CAS are higher than those of CEA, suggesting that CAS may not be used in good surgical candidates. In the patients with subarachnoid hemorrhage (SAH), preoperative assessments of cardiac and respiratory condition are required. It is reported that unfavorable outcome after SAH is related to rebleeding and cerebral vasospasm.

A case of subcutaneous emphysema/mediastinal emphysema during the use of humidified high-flow nasal cannula.

BACKGROUND: Heated, humidified, high-flow nasal cannula (HHFNC) oxygen therapy allows optimal humidification of inspired gas at high flows and creates a distending pressure similar to nasal continuous positive airway pressure [1]. It has been safely used in adults with moderate hypoxemia with few complications [2, 3]. Hereby, we report serious complications occurred during HHFNC oxygen therapy. CASE PRESENTATION: A 53-year-old female with hemophagocytic lymphohistiocytosis (HLH) was admitted to the intensive care unit because of respiratory failure. After weaning from mechanical ventilation which lasted for 2 weeks, HHFNC therapy at 40 L/min with an FiO2 of 0.5 was started for hypoxemia. Four days later, dyspnea and hypoxemia occurred and chest X-ray and CT scan revealed localized pneumothorax, subcutaneous emphysema, and massive pneumomediastinum. After cessation of HHFNC, respiratory condition improved. CONCLUSION: Subcutaneous emphysema, pneumothorax, and pneumomediastinum should be notified as a serious complication during HHFNC therapy.

A pediatric case developing critical abdominal distension caused by a combination of humidified high-flow nasal cannula oxygen therapy and nasal airway.

BACKGROUND: We describe a pediatric patient who suffered from critical abdominal distention caused by a combination of humidified, high-flow nasal cannula (HHFNC) oxygen therapy and nasal airway. CASE PRESENTATION: A 21-month-old boy with a history of chronic lung disease was admitted to the intensive care unit (ICU). Immediately after admission, his airway was established using a tracheal tube and mechanical ventilation was started. Five days after the commencement of mechanical ventilation, finally, his trachea was extubated. Immediately after extubation, HHFNC therapy at 20 L/min with an FiO2 of 0.35 was applied. However, severe stridor was observed, then a nasal airway was placed in the left nostril. However, he became restless. Critical abdominal distention was observed. A subsequent chest X-ray revealed that the nasal airway was placed too deeply, and the gastrointestinal air was severely accumulated. Immediately, the nasal airway was removed, and HHFNC flow was reduced to 10 L/min. Frequent suctioning and continuous gastric drainage were required, which achieved gradual improvement of respiratory condition. CONCLUSIONS: We need to recognize that HHFNC therapy is one of the positive pressure ventilation system. Therefore, HHFNC therapy might cause the similar adverse events to noninvasive pressure ventilation.

Risk factors for bradypnea in a historical cohort of surgical patients receiving fentanyl-based intravenous analgesia.

INTRODUCTION: The use of both pulse oximetry (SpO2) and respiration rate (RR) monitoring is recommended to prevent the development of respiratory deterioration, particularly after extubation and narcotic analgesic use for pain management. In this study, we investigated the factors contributing to the development of bradypnea in surgical patients receiving fentanyl-based intravenous analgesia after general anesthesia. METHODS: This study involved a historical chart review of postoperative patients outside an intensive care unit setting. We divided the patients according to the data collected during the first hour postoperatively, into those developing bradypnea (RR < 8 breaths per min for > 2 min) and those with normal RR under oxygen administration. We defined oxygen desaturation as SpO2 < 90% for > 10 s. We calculated the effect-site concentrations for fentanyl at the end of surgery and 1 h postoperatively using custom-made software based on chart records. A multivariable analysis was used to determine bradypnea-associated explanatory factors. RESULTS: For the final analysis, we included 258 patients. We detected bradypnea in 125 patients (48%) and oxygen desaturation in 46 patients (18%). We found no difference in the effect-site fentanyl concentrations between patients with and without bradypnea. The logistic regression model revealed that liver dysfunction [odds ratio (OR), 2.918; 95% confidence interval (CI), 1.329-6.405], renal dysfunction (OR, 0.349; 95% CI, 0.128-0.955), and smoking history (OR, 0.236; 95% CI, 0.075-0.735) were independently associated with bradypnea. We found similar incidences of oxygen desaturation between the groups. CONCLUSIONS: Bradypnea was observed in 48% of postoperative patients receiving fentanyl-based intravenous analgesia under oxygen therapy. According to our results, impaired liver function associated positively, whereas smoking history associated negatively with its development. Renal dysfunction was paradoxically associated with less incidence of bradypnea.

Incidence of life-threatening respiratory events after laparoscopic colon surgery with or without continuous respiratory rate monitoring.

BACKGROUND: Respiratory depression (RD) is a critical complication of general anesthesia. The present study investigated the incidence of postoperative life-threatening respiratory events after laparoscopic colon surgery in patients observed using continuous respiratory rate monitoring [RM; with oxygen saturation by pulse oximetry (SpO2)] and traditional respiratory monitoring (TM; SpO2 monitoring only). In addition, postoperative incidence rates of RD and desaturation in the RM group were determined. FINDINGS: In this retrospective observational study, medical records of 214 patients who underwent laparoscopic colon surgery were analyzed. A total of 88 patients with RM were observed and compared with 126 patients with TM. Nineteen patients in the RM group were excluded from the final analyses because of incomplete data. No life-threatening respiratory events were observed in the RM group (0/69), whereas two such events (2/126) occurred in the TM group. Incidence rates of postoperative RD and desaturation within 8 h after surgery were 17.1% (12/69) and 24.3% (17/69), respectively, in the RM group. CONCLUSIONS: No postoperative life-threatening respiratory events were observed in the RM group. Furthermore, the incidence rates of RD and desaturation were noted to be relatively high.

Neuron-Targeted Caveolin-1 Improves Molecular Signaling, Plasticity, and Behavior Dependent on the Hippocampus in Adult and Aged Mice.

BACKGROUND: Studies in vitro demonstrate that neuronal membrane/lipid rafts (MLRs) establish cell polarity by clustering progrowth receptors and tethering cytoskeletal machinery necessary for neuronal sprouting. However, the effect of MLR and MLR-associated proteins on neuronal aging is unknown. METHODS: Here, we assessed the impact of neuron-targeted overexpression of an MLR scaffold protein, caveolin-1 (Cav-1) (via a synapsin promoter, SynCav1), in the hippocampus in vivo in adult (6-month-old) and aged (20-month-old) mice on biochemical, morphologic, and behavioral changes. RESULTS: SynCav1 resulted in increased expression of Cav-1, MLRs, and MLR-localization of Cav-1 and tropomyosin-related kinase B receptor independent of age and time post gene transfer. Cav-1 overexpression in adult mice enhanced dendritic arborization within the apical dendrites of hippocampal cornu ammonis 1 and granule cell neurons, effects that were also observed in aged mice, albeit to a lesser extent, indicating preserved impact of Cav-1 on structural plasticity of hippocampal neurons with age. Cav-1 overexpression enhanced contextual fear memory in adult and aged mice demonstrating improved hippocampal function. CONCLUSIONS: Neuron-targeted overexpression of Cav-1 in the adult and aged hippocampus enhances functional MLRs with corresponding roles in cell signaling and protein trafficking. The resultant structural alterations in hippocampal neurons in vivo are associated with improvements in hippocampal-dependent learning and memory. Our findings suggest Cav-1 as a novel therapeutic strategy in disorders involving impaired hippocampal function.