Age and sex differences in vascular responsiveness in healthy and trauma patients: contribution of estrogen receptor-mediated Rho kinase and PKC pathways.

Several medical conditions exhibit age- and sex-based differences. Whether or not traumatic shock exhibits such differences with regard to vascular responsiveness is not clear. In a cohort of 177 healthy subjects and 842 trauma patients (21-82 years) as well as different ages (4, 8, 10, 14, 18, and 24 wk; 1 and 1.5 years) and sexes of Sprague-Dawley normal and traumatic shock rats, the age- and sex-based differences of vascular responsiveness and the underlying mechanisms were investigated. Middle-aged and young women as well as female rats of reproductive age had higher vascular responsiveness in the normal condition and a lower decrease in vascular responsiveness after traumatic shock than older men and male rats of identical age. Exogenous supplementation of 17ß-estrdiol increased vascular reactivity in both male and femal rats of 8-24 wk and preserved vascular responsiveness in rats following traumatic shock. No effect was observed in rats 1 to 1.5 years. These protective effects of estrogen were closely related to G protein-coupled receptor (GPR)30, estrogen receptor-mediated Rho kinase, and PKC pathway activation. Vascular responsiveness exhibits age- and sex-based differences in healthy subjects and trauma patients. Estrogen and its receptor (GPR30) mediated activation of Rho kinase and PKC using genomic and nongenomic mechanisms to elicit protective effects in vascular responsiveness. This finding is important for the personalized treatment for several age- and sex-related diseases involving estrogen.

CO2 artificial pneumothorax on coagulation and fibrinolysis during thoracoscopic esophagectomy.

BACKGROUND: CO2 artificial pneumothorax creates a sufficient operative field for thoracoscopic esophagectomy. However, it has potential complications and continuous CO2 insufflation may impede coagulation and fibrinolysis. We sought to compare the effects of CO2 artificial pneumothorax on perioperative coagulation and fibrinolysis during thoracoscopic esophagectomy. METHODS: We investigated patients who underwent thoracoscopic esophagectomy with (group P, n = 24) or without CO2 artificial pneumothorax (group N, n = 24). The following parameters of coagulation-fibrinolysis function: intraoperative bleeding volume; serum levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), thromboelastogram (TEG), D-Dimer; and arterial blood gas levels were compared with two groups. RESULTS: Group P showed higher levels of PaCO2, reaction time (R) value and kinetics (K) value, but significantly lower pH value, alpha (α) angle and Maximum Amplitude (MA) value at 60 minutes after the initiation of CO2 artificial pneumothorax than group N ((P < .05, all). The t-PA level after CO2 insufflation for 60 minutes was significantly higher in group P than in group N (P < .05), but preoperative levels were gradually restored on cessation of CO2 insufflation for 30 min (P > .05). There was no significant difference in D-dimer. CONCLUSION: CO2 artificial pneumothorax during thoracoscopic esophagectomy had a substantial impact on coagulation and fibrinolysis, inducing significant derangements in pH and PaCO2. TRIAL REGISTRATION: The study was registered at the Chinese clinical trial registry (ChiCTR1800019004).

Seawater Immersion Aggravates Burn Injury Causing Severe Blood Coagulation Dysfunction.

This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group), or burn injury combined with seawater immersion (BI group), or only immersion in seawater (I group), or control animals with no injury or immersion (C group). The circulating endothelial cell (CEC) count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P < 0.05). The von Willebrand factor (vWF) activity, plasminogen activator inhibitor (PAI-1), and the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1α (6-K-PGF1α ) in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA) in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis.

Comparative study on effects of burn-blast combined injury and burn-firearm combined injury complicated with seawater immersion on vascular endothelial cells.

OBJECTIVE: To comparatively study the effects and mechanisms of burn-blast combined injury and burn-firearm combined injury complicated with seawater immersion on vascular endothelial cells. METHODS: A total of 40 healthy adult hybrid dogs of both sexes, weighing 12-15 kg, were used in this study. Randomly-selected 20 dogs were established as models of burn-blast combined injury (the burn-blast injury group) and the other 20 dogs as models of burn-firearm combined injury (the burn-firearm injury group). Then the wounds of all the dogs were immediately immersed in seawater for 4 hours, and then they were taken out from the seawater. Blood samples were withdrawn from the central vein of the dogs before injury, and at 4, 7, 10, 20, and 28 hours after injury to measure the circulating endothelial cells and the von Willebrand factor. RESULTS: Circulating endothelial cells increased significantly at 4 hours after injury in all the dogs. But they reached peak at 7 hours after injury in the burn-blast injury group and at 28 hours after injury in the burn-firearm injury group. The changes of circulating endothelial cells in the burn-blast injury group were significantly different from those in the burn-firearm injury group at 4, 7, 20, and 28 hours after injury (P < 0.01). The von Willebrand factor reached peak at 4 hours after injury in the burn-blast injury group and at 28 hours in the burn-firearm injury group. The changes of von Willebrand factor in the burn-blast injury group were significantly different from those in the burn-firearm injury group at 4, 20, and 28 hours after injury (P < 0.01). CONCLUSIONS: In burn-blast injury combined with seawater immersion, the vascular endothelial cells changed most significantly at 4 hours or 7 hours after injury, while burn-firearm injury combined with seawater immersion have the same at 20 hours or 28 hours after injury.

[Comparison of resuscitation with Parkland formula and with improved protocol on hemodynamics in projectile-burn combined wound in dogs with seawater immersion].

OBJECTIVE: To compare hemodynamic effects of resuscitation with Parkland formula or with the improved protocol on projectile-burn combined wound in dogs with seawater immersion. METHODS: A model of projectile-burn combined wound in dogs with seawater immersion was reproduced, and 20 dogs were randomized into three groups: projectile-burn combined wound with seawater immersion (immersion group, n=8), Parkland formula resuscitation (lactated Ringer's solution 4 ml/kg per 1%total body surface area for 24 hours, standard resuscitation group, n=6), and improved protocol groups (lactated Ringer's solution 2.5 ml/kg per 1% total body surface area colloid solution 6% hetastarch 0.5 ml/kg per 1% total body surface area for 24 hours, improved group, n=6). Changes of hemodynamics and central temperature (CT) before injury, and 4, 7, 10, 20 and 28 hours after injury were observed. The mortality was observed. RESULTS: After resuscitation with Parkland formula, CT as well as hemodynamic indexes and amount of urine were improved, but central venous pressure (CVP) and the amount of urine were higher in early period of resuscitation. CVP was (14.7+/-3.1)cm H2O and the amount of urine was (2.38+/-0.18)ml.h(-1).kg(-1) at 7 hours after injury. Hemodynamics was not stable during later period of experiment. After resuscitation with the improved protocol, the hemodynamics ameliorated better than resuscitation with Parkland formula. No animals died in improved group, but 4 and 1 died respectively in immersion group and standard resuscitation group. CONCLUSION: Fluid resuscitation according to the improved protocol is more suitable for projectile-burn combined wound in dogs with seawater immersion than resuscitation with Parkland formula.

Efficacy and safety of remifentanil and sulfentanyl in painless gastroscopic examination: a prospective study.

We aim to assess efficacy and safety of remifentanil or sulfentanyl combined with propofol during painless gastroscopic examination in patients. In this study, 270 patients were randomly divided into 3 groups: propofol was given only in group P; propofol and remifentanil in group PR; propofol and sulfentanyl in group PS during the gastroscopic examination. Efficiency of group P was significantly higher than that of group PR and PS (P<0.01) [corrected]. Efficiency of group PR was lower than that of group PS (P<0.05). Incidence of chest wall rigidity and oxygen desaturation in group PR were higher than group P and PS (P<0.05), whereas there was no difference between groups P and PS (P>0.05). Propofol combined with remifentanil could provide satisfying anesthesia and more respiratory depression, whereas sulfentanyl at equivalent dose combined with propofol could also provide with satisfying anesthesia and less respiratory depression. Combined sufentanyl with propofol would be an effective anesthesia technique in the daytime procedure.

Identification of synthetic peptides that inhibit lipopolysaccharide (LPS) binding to myeloid differentiation protein-2 (MD-2).

Many studies have suggested that the synergic effect of myeloid differential protein-2 (MD-2) on bacterial lipopolysaccharide (LPS) stimulation of toll-like receptor 4 (TLR4) may be a critical step during the LPS-TLR4 response signaling pathway. We performed a bioinformatic analysis on the MD-2 protein and identified the amino acid sequence NH2-FSKGKYKCV-COOH (K128-132) as a possible key sequence involved in the binding between MD-2 and LPS. We then screened a random phage display peptide library using this sequence as bait in order to identify antagonistic peptides. After 3 rounds of selection, 3 positive clones were identified. All 3 peptides were shown to inhibit, in a dose-dependent manner the production of tumor necrosis factor-α and interleukin-6 in human U937 and THP-1 cell lines as well as human peripheral blood monocytes stimulated by LPS. Only 2 of the 3 peptides were able to bind MD-2 directly as shown by sulfo-SBED biotin label transfer experiments. BALB/C mice were used to estimate the protection of these peptides from LPS challenge, and 2 of the 3 peptides (Lys-Thr-Val-Pro-Asp-Asn-His and Ile-Gly-Lys-Phe-Leu-Tyr-Arg) reduced mortality of the challenged mice from 100% to 53.8%. This study has demonstrated that interfering with the binding between MD-2 and LPS might be a potential therapeutic strategy for treating LPS-induced sepsis, and in doing so has identified 2 potential peptide candidates.