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Background Resveratrol may improve organ dysfunction after experimental hemorrhagic or septic shock, and some of these effects appear to be mediated by estrogen receptors. However, the influence of resveratrol on liver function and hepatic microcirculation after hemorrhagic shock is unknown, and a presumed mediation via estrogen receptors has not been investigated in this context. Methods Male Sprague-Dawley rats (200-300g, n = 14/group) underwent hemorrhagic shock for 90 min (MAP 35±5 mmHg) and were resuscitated with shed blood and Ringer’s solution. Animals were treated intravenously with vehicle (1% EtOH), resveratrol (0.2 mg/kg), the unselective estrogen receptor antagonist ICI 182,780 (0.05 mg/kg) or resveratrol + ICI 182,780 prior to retransfusion. Sham-operated animals did not undergo hemorrhage but were treated likewise. After 2 hours of reperfusion, liver function was assessed either by plasma disappearance rate of indocyanine green (PDRICG) or evaluation of hepatic perfusion and hepatic integrity by intravital microscopy, serum enzyme as well as cytokine levels. Results Compared to vehicle controls, administration of resveratrol significantly improved PDRICG, hepatic perfusion index and hepatic integrity after hemorrhagic shock. The co-administration of ICI 182,780 completely abolished the protective effect only with regard to liver function. Conclusions This study shows that resveratrol may improve liver function and hepatocellular integrity after hemorrhagic shock in rats; estrogen receptors mediate these effects at least partially.

Resveratrol may improve organ dysfunction after experimental hemorrhagic or septic shock, and some of these effects appear to be mediated by estrogen receptors. However, the influence of resveratrol on liver function and hepatic microcirculation after hemorrhagic shock is unknown, and a presumed mediation via estrogen receptors has not been investigated in this context. Male Sprague-Dawley rats (200-300g, n = 14/group) underwent hemorrhagic shock for 90 min (MAP 35±5 mmHg) and were resuscitated with shed blood and Ringer's solution. Animals were treated intravenously with vehicle (1% EtOH), resveratrol (0.2 mg/kg), the unselective estrogen receptor antagonist ICI 182,780 (0.05 mg/kg) or resveratrol + ICI 182,780 prior to retransfusion. Sham-operated animals did not undergo hemorrhage but were treated likewise. After 2 hours of reperfusion, liver function was assessed either by plasma disappearance rate of indocyanine green (PDR.sub.ICG) or evaluation of hepatic perfusion and hepatic integrity by intravital microscopy, serum enzyme as well as cytokine levels. Compared to vehicle controls, administration of resveratrol significantly improved PDR.sub.ICG, hepatic perfusion index and hepatic integrity after hemorrhagic shock. The co-administration of ICI 182,780 completely abolished the protective effect only with regard to liver function. This study shows that resveratrol may improve liver function and hepatocellular integrity after hemorrhagic shock in rats; estrogen receptors mediate these effects at least partially.

The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 ± 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 ± 4% (p < 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 ± 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 ± 4% (p < 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p < 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 ± 7%; p < 0.05 vs. HGl Con; HGl Con 59 ± 5%).

Background APRV has been used for ARDS in the past. Little is known about the risk of ventilator- induced lung- injury (VILI) in APRV vs. BIPAP in the management of in COVID19-associated ARDS (CARDS). This study aimed to compare transpulmonary pressures (TPP) in APRV vs. BIPAP in CARDS in regard to lung protective ventilator settings. Methods This retrospective, monocentric cohort study (ethical approval: 21-1553) assessed all adult ICU- patients with CARDS who were ventilated with BIPAP vs. APRV and monitored with TPP from 03/2020 to 10/2021. Ventilator-settings / -pressures, TPP, hemodynamic and arterial blood gas parameters were compared in both modes. Results 20 non- spontaneously breathing patients could be included in the study: Median TPPendexpiratory was lower / negative in APRV (-1.20mbar; IQR − 4.88 / +4.53) vs. positive in BIPAP (+ 3.4mbar; IQR + 1.95 / +8.57; p  < .01). Median TPPendinspiratory did not differ. In APRV, mean tidal- volume per body- weight (7.05 ± 1.28 vs. 5.03 ± 0.77 ml; p  < .01) and mean airway- pressure (27.08 ± 1.67 vs. 22.68 ± 2.62mbar; p  < .01) were higher. There was no difference in PEEP, peak-, plateau- or driving- pressure, compliance, oxygenation and CO 2 - removal between both modes. Conclusion Despite higher tidal- volumes / airway-pressures in APRV vs. BIPAP, TPPendinspirator y was not increased. However, in APRV median TPPendexpiratory was negative indicating an elevated risk of occult atelectasis in APRV- mode in CARDS. Therefore, TPP- monitoring could be a useful tool for monitoring a safe application of APRV- mode in CARDS.

In the next few years, the number of long-term space missions will significantly increase. Providing safe concepts for emergencies including airway management will be a highly challenging task. The aim of the present trial is to compare different airway management devices in simulated microgravity using a free-floating underwater scenario. Five different devices for airway management [laryngeal mask (LM), laryngeal tube (LT), I-GEL, direct laryngoscopy (DL), and video laryngoscopy (VL)] were compared by n = 20 paramedics holding a diving certificate in a randomized cross-over setting both under free-floating conditions in a submerged setting (pool, microgravity) and on ground (normogravity). The primary endpoint was the successful placement of the airway device. The secondary endpoints were the number of attempts and the time to ventilation. A total of 20 paramedics (3 female, 17 male) participated in this study. Success rate was highest for LM and LT and was 100% both during simulated microgravity and normogravity followed by the I-GEL (90% during microgravity and 95% during normogravity). However, the success rate was less for both DL (60% vs. 95%) and VL (20% vs. 60%). Fastest ventilation was performed with the LT both in normogravity (13.7 ± 5.3 s; n = 20) and microgravity (19.5 ± 6.1 s; n = 20). For the comparison of normogravity and microgravity, time to ventilation was shorter for all devices on the ground (normogravity) as compared underwater (microgravity). In the present study, airway management with supraglottic airways and laryngoscopy was shown to be feasible. Concerning the success rate and time to ventilation, the optimum were supraglottic airways (LT, LM, I-GEL) as their placement was faster and associated with a higher success rate. For future space missions, the use of supraglottic airways for airway management seems to be more promising as compared to tracheal intubation by DL or VL.

Hydroxyethyl starch (HES) may compromise renal function in critically ill patients. As an alternative, gelatin (GEL) was suggested. This study investigated whether GEL (4%) may have advantages over HES (6%, 130/0.4) with respect to acute renal failure (ARF), length of intensive care unit /hospital stay, and 30-day mortality and evaluated dose-dependent effects. We performed a retrospective cohort analysis of 1522 surgical intensive care patients in a single university hospital where HES was changed to GEL in June 2006. The year before, 515 patients received HES; the year after, 540 patients received GEL. Within both years, 497 patients received crystalloids (CRY) only. Fluid therapy was performed upon clinical judgment and did not follow a study protocol. There was no difference in ARF between HES and GEL (P=.292), but ARF was more frequent in both colloid cohorts compared with CRY (HES/GEL vs CRY, P<.05). Mortality and maximum daily dose of both HES (r=0.93) and GEL (r=0.93) were significantly correlated, but mortality and total amount of CRY or total fluid intake were not significantly correlated. Cumulative amounts of fluids given were significantly higher in both colloid groups compared with CRY only, and GEL was given in higher doses than HES. In both colloid cohorts, the need for renal replacement therapy and 30-day mortality were significantly higher, and intensive care unit and hospital stay was longer, compared with CRY. A change of colloid from HES to GEL did not reduce the rate of ARF or mortality in surgical critical care patients. Both colloids appear to have dose-dependent effects on renal function.

Melatonin receptors are highly relevant for the hepatoprotective effects of the pineal hormone melatonin after experimental hemorrhagic shock in rats. In this study, we sought to determine the spatial expression pattern and a putative regulation of two melatonin receptors, membrane bound type 1 and 2 (MT1 and MT2), in the liver of rats. In a male rat model (Sprague Dawley) of hemorrhage and resuscitation, we investigated the gene expression and protein of MT1 and MT2 in rat liver by utilizing real-time quantitative polymerase chain reaction, a western blot analysis, and immunohistochemistry. Plasma melatonin content was measured by an enzyme-linked immunosorbent assay. Male rats underwent hemorrhage and were resuscitated with shed blood and a Ringer’s solution (n = 8 per group). After 90 min of hemorrhage, animals were given vehicle, melatonin, or ramelteon (each 1.0 mg/kg intravenously). Sham-operated controls did not undergo hemorrhage but were treated likewise. Plasma melatonin was significantly increased in all groups treated with melatonin and also after hemorrhagic shock. Only MT1, but not the MT2 messenger ribonucleic acid (mRNA) and protein, was detected in the rat liver. The MT1 protein was located in pericentral fields of liver lobules in sham-operated animals. After hemorrhagic shock and treatment with melatonin or ramelteon, the hepatic MT1 protein amount was significantly attenuated in all groups compared to sham controls (50% reduction; p < 0.001). With respect to MT1 mRNA, no significant changes were observed between groups (p = 0.264). Our results indicate that both endogenous melatonin exposure from hemorrhagic shock, as well as exogenous melatonin and ramelteon exposure, may attenuate melatonin receptors in rat hepatocytes, possibly by means of desensitization.

The measurement of the liver function via the plasma disappearance rate of indocyanine green (PDRICG) is a sensitive bed-side tool in critical care. Yet, recent evidence has questioned the value of this method for hyperdynamic conditions. To evaluate this technique in different hemodynamic settings, we analyzed the PDRICG and corresponding pharmacokinetic models after endotoxemia or hemorrhagic shock in rats. Male anesthetized Sprague-Dawley rats underwent hemorrhage (mean arterial pressure 35 ± 5 mmHg, 90 min) and 2 h of reperfusion, or lipopolysaccharide (LPS) induced moderate or severe (1.0 vs. 10 mg/kg) endotoxemia for 6 h (each n = 6). Afterwards, PDRICG was measured, and pharmacokinetic models were analyzed using nonlinear mixed effects modeling (NONMEM®). Hemorrhagic shock resulted in a significant decrease of PDRICG, compared with sham controls, and a corresponding attenuation of the calculated ICG clearance in 1- and 2-compartment models, with the same log-likelihood. The induction of severe, but not moderate endotoxemia, led to a significant reduction of PDRICG. The calculated ICG blood clearance was reduced in 1-compartment models for both septic conditions. 2-compartment models performed with a significantly better log likelihood, and the calculated clearance of ICG did not correspond well with PDRICG in both LPS groups. 3-compartment models did not improve the log likelihood in any experiment. These results demonstrate that PDRICG correlates well with ICG clearance in 1- and 2-compartment models after hemorrhage. In endotoxemia, best described by a 2-compartment model, PDRICG may not truly reflect the ICG clearance.

Air passes through the surrounding space at the side of the drain tube. [...]it is impossible to use this device as a conduit for endotracheal intubation, as recommended in the ASA guidelines for management of the difficult airway [1]. [...]the fiberoptic-guided endotracheal intubation may be performed via the LMA Supreme using an NGT as a guide.

For perioperative mechanical ventilation under general anesthesia, modern respirators aim at combining the benefits of pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV) in modes typically named “volume-guaranteed” or “volume-targeted” pressure-controlled ventilation (PCV-VG). This systematic review and meta-analysis tested the hypothesis that PCV-VG modes of ventilation could be beneficial in terms of improved airway pressures (Ppeak, Pplateau, Pmean), dynamic compliance (Cdyn), or arterial blood gases (PaO2, PaCO2) in adults undergoing elective surgery under general anesthesia. Three major medical electronic databases were searched with predefined search strategies and publications were systematically evaluated according to the Cochrane Review Methods. Continuous variables were tested for mean differences using the inverse variance method and 95% confidence intervals (CI) were calculated. Based on the assumption that intervention effects across studies were not identical, a random effects model was chosen. Assessment for heterogeneity was performed with the χ2 test and the I2 statistic. As primary endpoints, Ppeak, Pplateau, Pmean, Cdyn, PaO2, and PaCO2 were evaluated. Of the 725 publications identified, 17 finally met eligibility criteria, with a total of 929 patients recruited. Under supine two-lung ventilation, PCV-VG resulted in significantly reduced Ppeak (15 studies) and Pplateau (9 studies) as well as higher Cdyn (9 studies), compared with VCV [random effects models; Ppeak: CI −3.26 to −1.47; p < 0.001; I2 = 82%; Pplateau: −3.12 to −0.12; p = 0.03; I2 = 90%; Cdyn: CI 3.42 to 8.65; p < 0.001; I2 = 90%]. For one-lung ventilation (8 studies), PCV-VG allowed for significantly lower Ppeak and higher PaO2 compared with VCV. In Trendelenburg position (5 studies), this effect was significant for Ppeak only. This systematic review and meta-analysis demonstrates that volume-targeting, pressure-controlled ventilation modes may provide benefits with respect to the improved airway dynamics in two- and one-lung ventilation, and improved oxygenation in one-lung ventilation in adults undergoing elective surgery.