Adipose tissue alleviates the stress response by releasing adiponectin during laparoscopic surgery in patients with colorectal cancer.

BACKGROUND AND OBJECTIVES: Laparoscopic colorectal surgery causes a lower stress response than open surgery. Adiponectin is mainly derived from adipocytes and has antidiabetic, antioxidative, and anti-inflammatory capabilities. The objective of the present study was to investigate the protein expression of adiponectin in adipose tissue, and the serum levels of adiponectin, oxidative stress markers and proinflammatory factors during laparoscopic colorectal surgery and open surgery periods. METHODS: Forty patients aged 60 to 80, with American Society of Anesthesiologists (ASA) I ~ II who underwent radical resection of colorectal cancer were recruited to the study. Laparoscopic group and open group included 20 patients each. Mesenteric adipose tissue and venous blood before (T1) and at the end (T2) of surgery were collected to examine adiponectin levels, and venous blood was collected to examine serum levels of oxidative stress related markers (superoxide dismutase (SOD), glutathione (GSH), lipid peroxide (LPO), malondialdehyde (MDA)), and inflammation-related factors (interleukin (IL)-1ß, interleukin (IL)-6, tumor necrosis factor-α (TNF-α)). RESULTS: Protein and serum levels of adiponectin were analyzed, and adiponectin levels were significantly increased at T2 than T1 in the laparoscopic surgery, while adiponectin levels were significantly higher in the laparoscopic surgery than in the open surgery at T2. In addition, the serum levels of SOD and GSH were significantly higher in the laparoscopic surgery than in open surgery at T2. However, the serum levels of LPO, TNF-α, IL-1ß, and IL-6 were significantly lower in the laparoscopic group than in open group at T2. CONCLUSION: Laparoscopic surgery induced higher levels of adiponectin in both adipose tissue and the bloodstream. Oxidative stress and the inflammatory response were lower during laparoscopic colorectal surgery than during conventional open surgery. These data suggest that adipose tissue may alleviate the stress response during laparoscopic surgery by releasing adiponectin in patients with colorectal cancer.

Driving Pressure-Guided Individualized Positive End-Expiratory Pressure in Abdominal Surgery: A Randomized Controlled Trial.

BACKGROUND: The optimal positive end-expiratory pressure (PEEP) to prevent postoperative pulmonary complications (PPCs) remains unclear. Recent evidence showed that driving pressure was closely related to PPCs. In this study, we tested the hypothesis that an individualized PEEP guided by minimum driving pressure during abdominal surgery would reduce the incidence of PPCs. METHODS: This single-centered, randomized controlled trial included a total of 148 patients scheduled for open upper abdominal surgery. Patients were randomly assigned to receive an individualized PEEP guided by minimum driving pressure or an empiric fixed PEEP of 6 cm H2O. The primary outcome was the incidence of clinically significant PPCs within the first 7 days after surgery, using a χ2 test. Secondary outcomes were the severity of PPCs, the area of atelectasis, and pleural effusion. Other outcomes, such as the incidence of different types of PPCs (including hypoxemia, atelectasis, pleural effusion, dyspnea, pneumonia, pneumothorax, and acute respiratory distress syndrome), intensive care unit (ICU) admission rate, length of hospital stay, and 30-day mortality were also explored. RESULTS: The median value of PEEP in the individualized group was 10 cm H2O. The incidence of clinically significant PPCs was significantly lower in the individualized PEEP group compared with that in the fixed PEEP group (26 of 67 [38.8%] vs 42 of 67 [62.7%], relative risk = 0.619, 95% confidence intervals, 0.435-0.881; P = .006). The overall severity of PPCs and the area of atelectasis were also significantly diminished in the individualized PEEP group. Higher respiratory compliance during surgery and improved intra- and postoperative oxygenation was observed in the individualized group. No significant differences were found in other outcomes between the 2 groups, such as ICU admission rate or 30-day mortality. CONCLUSIONS: The application of individualized PEEP based on minimum driving pressure may effectively decrease the severity of atelectasis, improve oxygenation, and reduce the incidence of clinically significant PPCs after open upper abdominal surgery.

Dexmedetomidine attenuates H2O2-induced apoptosis of rat cardiomyocytes independently of antioxidant enzyme expression.

INTRODUCTION AND OBJECTIVES: Dexmedetomidine is a highly selective alpha-2 adrenoceptor agonist that has sedative and analgesic properties and myocardial protective effects. However, the mechanism underlying the protective effect of dexmedetomidine on cardiomyocytes remains unknown. This study mainly aimed to investigate the effects of dexmedetomidine on the generation of reactive oxygen species (ROS) in cardiomyocytes and whether it inhibits the apoptosis of cardiomyocytes by affecting antioxidant enzyme expression. METHODS: Neonatal rat cardiomyocytes were pretreated with dexmedetomidine (100 nM) for 24 h. The cardiomyocytes were then incubated with 200 µM hydrogen peroxide solution (H2O2) for 4 h. PCR assay was used to determine the mRNA expression of antioxidant enzymes. Western blot assay was used to determine the protein expression of antioxidant enzymes. Fluorescence microscopy with the MitoSOX probe was used to detect the formation of ROS in cardiomyocytes, and fluorescence-activated cell sorting with annexin V/PI was used to determine the number of apoptotic cardiomyocytes. RESULTS: Dexmedetomidine reduced ROS generation and antioxidant enzymes levels in cardiomyocytes before H2O2 stimulation (p<0.05). However, ROS generation and apoptosis in cardiomyocytes were significantly increased after H2O2 treatment, and dexmedetomidine pretreatment markedly inhibited the changes (p<0.05). CONCLUSION: For the first time, to the best of our knowledge, our study shows that dexmedetomidine has a protective effect on cardiomyocytes through inhibition of ROS-induced apoptosis, and more importantly, this effect is independent of antioxidant enzyme mRNA and protein expression.

An α2-adrenoceptor agonist: Dexmedetomidine induces protective cardiomyocyte hypertrophy through mitochondrial-AMPK pathway.

Aims: Dexmedetomidine (Dex) as a highly selective α2-adrenoceptor agonist, was widely used anesthetic in perioperative settings, whether Dex induces cardiac hypertrophy during perioperative administration is unknown. Methods: The effects of Dex on cardiac hypertrophy were explored using the transverse aortic constriction model and neonatal rat cardiomyocytes. Results: We reported that Dex induces cardiomyocyte hypertrophy with activated ERK, AKT, PKC and inactivated AMPK in both wild-type mice and primary cultured rat cardiomyocytes. Additionally, pre-administration of Dex protects against transverse aortic constriction induced-heart failure in mice. We found that Dex up-regulates the activation of ERK, AKT, and PKC via suppression of AMPK activation in rat cardiomyocytes. However, suppression of mitochondrial coupling efficiency and membrane potential by FCCP blocks Dex induced AMPK inactivation as well as ERK, AKT, and PKC activation. All of these effects are blocked by the α2-adrenoceptor antagonist atipamezole. Conclusion: The present study demonstrates Dex preconditioning induces cardiac hypertrophy that protects against heart failure through mitochondria-AMPK pathway in perioperative settings.

Platelet-derived exosomes promote neutrophil extracellular trap formation during septic shock.

BACKGROUND: Platelets have been demonstrated to be potent activators of neutrophil extracellular trap (NET) formation during sepsis. However, the mediators and molecular pathways involved in human platelet-mediated NET generation remain poorly defined. Circulating plasma exosomes mostly originating from platelets may induce vascular apoptosis and myocardial dysfunction during sepsis; however, their role in NET formation remains unclear. This study aimed to detect whether platelet-derived exosomes could promote NET formation during septic shock and determine the potential mechanisms involved. METHODS: Polymorphonuclear neutrophils (PMNs) were cocultured with exosomes isolated from the plasma of healthy controls and septic shock patients or the supernatant of human platelets stimulated ex vivo with phosphate buffer saline (PBS) or lipopolysaccharide (LPS). A lethal cecal ligation and puncture (CLP) mouse model was used to mimic sepsis in vivo; then, NET formation and molecular pathways were detected. RESULTS: NET components (dsDNA and MPO-DNA complexes) were significantly increased in response to treatment with septic shock patient-derived exosomes and correlated positively with disease severity and outcome. In the animal CLP model, platelet depletion reduced plasma exosome concentration, NET formation, and lung injury. Mechanistic studies demonstrated that exosomal high-mobility group protein 1 (HMGB1) and/or miR-15b-5p and miR-378a-3p induced NET formation through the Akt/mTOR autophagy pathway. Furthermore, the results suggested that IκB kinase (IKK) controls platelet-derived exosome secretion in septic shock. CONCLUSIONS: Platelet-derived exosomes promote excessive NET formation in sepsis and subsequent organ injury. This finding suggests a previously unidentified role of platelet-derived exosomes in sepsis and may lead to new therapeutic approaches.

Developmental neurotoxicity in the context of multiple sevoflurane exposures: Potential role of histone deacetylase 6.

Animal studies have demonstrated that multiple exposures to sevoflurane during the postnatal period lead to impaired synaptogenesis and cognitive deficits in adulthood. However, the underlying mechanisms remain unclear. Histone deacetylase 6 (HDAC6), a unique isoform of class II histone deacetylases (HDACs), mediates diverse cellular processes such as cell survival, inflammation, intracellular trafficking and protein degradation. Varieties of literature suggest the importance of HDAC6 in memory formation and abnormal neurodegenerative diseases. The aim of this study was to investigate potential roles of HDAC6 in sevoflurane-induced developmental neurotoxicity. Postnatal day 7 (P7) rat pups were randomly assigned to control group and sevoflurane group (n = 6 for each group). They were exposed to 60% oxygen and 40% nitrogen with or without 3% sevoflurane for 2 h daily for three consecutive days (P7, P8 and P9). Immediately after the last exposure, both hippocampi were harvested for detection of HDAC6 expression and activity. Next, P7 rat pups were divided into control group, sevoflurane group, sevoflurane + Tubastatin A, and Tubastatin A groups (n = 6 for each group in molecular experiments; n = 16 for each group in behavioral testing). A dose of 25 mg/kg body weight of Tubastatin A (a selective HDAC6 inhibitor) were administrated intraperitoneally 30 min prior to each sevoflurane exposure. After treatments, expression levels of synaptophysin and postsynaptic density 95 protein (PSD95) were quantified using Western blot, and synaptic ultrastructure was evaluated by transmission electron microscopy. Additional pups were raised until P49 to measure cognitive performance using the Morris water maze test. Our results demonstrated that multiple sevoflurane exposures enhanced HDAC6 expression and activity in hippocampi of the developing brain. Tubastatin A ameliorated sevoflurane-induced decreases in synaptophysin and PSD95 expression during development, as well as synaptic ultrastructural damage and cognitive deficits in adulthood. In conclusion, HDAC6 is involved in the developmental neurotoxicity caused by multiple sevoflurane exposures and its inhibition may prevent related damage.

Effects of colloid pre-loading on thromboelastography during elective intracranial tumor surgery in pediatric patients: hydroxyethyl starch 130/0.4 versus 5% human albumin.

BACKGROUND: Volume replacement therapy with colloid is still worth studying in major pediatric surgery with potential risk of bleeding. This study assessed the effects of 6% hydroxyethyl starch (HES) 130/0.4 and 5% Human Albumin (HA) on coagulation tested by thromboelastography (TEG) during elective intracranial tumor surgery in pediatric patients. METHODS: In this randomized controlled trial, 60 patients undergoing intracranial tumor resection under general anesthesia were assigned to HES and HA groups (n = 30), and administered preloads of 20 mL · kg-1 HES 130/0.4 and 5% HA, respectively, prior to dura opening. Primary outcomes were perioperative thromboelastography findings, and hemodynamic and hematological parameters. Blood transfusion, perioperative fluid balance, intracranial pressure, mortality, intensive care unit stay, and hospital stay were also assessed. RESULTS: TEG parameters did not differ after preloading compared to baseline values in either group, except for a decrease in maximum amplitude immediately after infusion (HES group, 57.6 ± 6.0 mm vs. 50.9 ± 9.2 mm; HA group, 60.1 ± 7.9 mm vs. 56.6 ± 7.1 mm; p < 0.01), which was restored to preoperative levels 1 h after fluid infusion. Total perioperative fluid balance, blood loss or transfusion, intracranial pressure, and hematological and hemodynamic variables were similar between both groups (p > 0.05). Mortality, length of hospital stay, and clinical complications were similar between both groups. CONCLUSION: These findings suggest that HES and HA might have no significant differences regarding coagulation as assessed by TEG during pediatric intracranial tumor surgery with 20 ml/kg volume pre-loading, which can maintain stable hemodynamics and may represent a new avenue for volume therapy during brain tumor resection in pediatrics. TRIAL REGISTRATION: ChiCTR-IPR- 16009333 , retrospectively registered October 8, 2016.