Seroconversion panels demonstrate anti-SARS-CoV-2 antibody development after administration of the mRNA-1273 vaccine.

Seroconversion panels are an important tool for investigating antibody responses in acute and chronic phases of disease and development of serological assays for viral diseases including COVID-19. Globally it is anticipated that vaccines against SARS-CoV-2 will facilitate control of the current pandemic. The two COVID-19 seroconversion panels analyzed in this study were obtained from healthcare workers with samples collected before vaccination with the mRNA-1273 vaccine (Moderna) and after the first and second doses of the vaccine. Panel samples were tested for antibodies to SARS-CoV-2 (IgG). Individual subjects with a positive response for anti-SARS-CoV2 IgG in their pre-vaccination samples showed a significantly enhanced response to the first vaccination. In older subjects, lower immunological responses to the first injection were observed, which were overcome by the second injection. All subjects in the study were positive for anti-SARS-CoV-2 IgG after the second dose of vaccine.

Intraoperative open lung condition and postoperative pulmonary complications. A secondary analysis of iPROVE and iPROVE-O2 trials.

BACKGROUND: The preventive role of an intraoperative recruitment maneuver plus open lung approach (RM + OLA) ventilation on postoperative pulmonary complications (PPC) remains unclear. We aimed at investigating whether an intraoperative open lung condition reduces the risk of developing a composite of PPCs. METHODS: Post hoc analysis of two randomized controlled trials including patients undergoing abdominal surgery. Patients were classified according to the intraoperative lung condition as "open" (OL) or "non-open" (NOL) if PaO2 /FIO2 ratio was ≥ or <400 mmHg, respectively. We used a multivariable logistic regression model that included potential confounders selected with directed acyclic graphs (DAG) using Dagitty software built with variables that were considered clinically relevant based on biological mechanism or evidence from previously published data. PPCs included severe acute respiratory failure, acute respiratory distress syndrome, and pneumonia. RESULTS: A total of 1480 patients were included in the final analysis, with 718 (49%) classified as OL. The rate of severe PPCs during the first seven postoperative days was 6.0% (7.9% in the NOL and 4.4% in the OL group, p = .007). OL was independently associated with a lower risk for severe PPCs during the first 7 and 30 postoperative days [odds ratio of 0.58 (95% CI 0.34-0.99, p = .04) and 0.56 (95% CI 0.34-0.94, p = .03), respectively]. CONCLUSIONS: An intraoperative open lung condition was associated with a reduced risk of developing severe PPCs in intermediate-to-high risk patients undergoing abdominal surgery. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT02158923 (iPROVE), NCT02776046 (iPROVE-O2).

Available COVID-19 serial seroconversion panel for validation of SARS-CoV-2 antibody assays.

Seroconversion panels are an important tool for investigating antibody responses and developing serological assays. A seroconversion panel was generated from a single SARS-CoV-2 positive plasma donor over 87 days. This seroconversion panel was tested against 6 SARS-CoV-2 antibody tests (IgG, IgM, and total Ig). All test kits utilized recombinant antigens that are specific to SARS-CoV-2. The seroconversion panel showed IgG responses for SARS-CoV-2 after day 50. IgM levels peaked on day 50 (prior to IgG) and declined in subsequent samples. This seroconversion panel is a useful tool for validation of SARS-CoV-2 antibody assays.

High-flow nasal cannula oxygenation reduces postoperative hypoxemia in morbidly obese patients: a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) are common in high-risk surgical patients. Postoperative ventilatory management may improve their outcome. Supplemental oxygen through a high-flow nasal cannula (HFNC) has become an alternative to classical oxygenation techniques, although the results published for postoperative patients are contradictory. We examined the efficacy of HFNC in postoperative morbidly obese patients who were ventilated intraoperatively with an open-lung approach (OLA). METHODS: We performed an open, two-arm, randomized controlled trial in 64 patients undergoing bariatric surgery (N.=32 in each arm) from May to November 2017 at the Hospital Clínico of Valencia. Patients were randomly assigned to receive HFNC oxygen therapy at the time of extubation or to receive conventional oxygen therapy, both applied during the first three postoperative hours. Intraoperatively, a recruitment maneuver and individualized positive end-expiratory pressure was applied in all patients. The primary outcome was postoperative hypoxemia. RESULTS: All patients were included in the final analysis. There were no significant differences between the baseline characteristics. Postoperative hypoxemia was less frequent in the HFNC group compared to those who received standard care (28.6% vs. 80.0%, relative risk [RR]: 0.35; 95%CI: 0.150-0.849, P=0.009). Prevalence of atelectasis was lower in the HFNC group (31% vs. 77%, RR: 0.39; 95%CI: 0.166-0.925, P=0.013). No severe PPCs were reported in any patient. CONCLUSIONS: Early application of HFNC in the operating room before extubation and during the immediate postoperative period decreases postoperative hypoxemia in obese patients after bariatric surgery who were intraoperatively ventilated using an OLA approach.

Rationale and study design for an individualised perioperative open-lung ventilatory strategy with a high versus conventional inspiratory oxygen fraction (iPROVE-O2) and its effects on surgical site infection: study protocol for a randomised controlled trial.

INTRODUCTION: Surgical site infection (SSI) is a serious postoperative complication that increases morbidity and healthcare costs. SSIs tend to increase as the partial pressure of tissue oxygen decreases: previous trials have focused on trying to reduce them by comparing high versus conventional inspiratory oxygen fractions (FIO2) in the perioperative period but did not use a protocolised ventilatory strategy. The open-lung ventilatory approach restores functional lung volume and improves gas exchange, and therefore it may increase the partial pressure of tissue oxygen for a given FIO2. The trial presented here aims to compare the efficacy of high versus conventional FIO2 in reducing the overall incidence of SSIs in patients by implementing a protocolised and individualised global approach to perioperative open-lung ventilation. METHODS AND ANALYSIS: This is a comparative, prospective, multicentre, randomised and controlled two-arm trial that will include 756 patients scheduled for abdominal surgery. The patients will be randomised into two groups: (1) a high FIO2 group (80% oxygen; FIO2 of 0.80) and (2) a conventional FIO2 group (30% oxygen; FIO2 of 0.30). Each group will be assessed intra- and postoperatively. The primary outcome is the appearance of postoperative SSI complications. Secondary outcomes are the appearance of systemic and pulmonary complications. ETHICS AND DISSEMINATION: The iPROVE-O2 trial has been approved by the Ethics Review Board at the reference centre (the Hospital Clínico Universitario in Valencia). Informed consent will be obtained from all patients before their participation. If the approach using high FIO2 during individualised open-lung ventilation decreases SSIs, use of this method will become standard practice for patients scheduled for future abdominal surgery. Publication of the results is anticipated in early 2019. TRIAL REGISTRATION NUMBER: NCT02776046; Pre-results.

Remote Ischemic Preconditioning Decreases Oxidative Lung Damage After Pulmonary Lobectomy: A Single-Center Randomized, Double-Blind, Controlled Trial.

BACKGROUND: During lobectomy in patients with lung cancer, the operated lung is often collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when the lung is re-expanded. We hypothesized that remote ischemic preconditioning (RIPC) would decrease oxidative lung damage and improve gas exchange in the postoperative period. METHODS: We conducted a single-center, randomized, double-blind trial in patients with nonsmall cell lung cancer undergoing elective lung lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion induced by an ischemia cuff applied on the thigh) and/or control therapy without RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC) and arterial blood immediately after anesthesia induction and before RIPC and surgery (T0, baseline); during operated lung collapse, immediately before resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2); and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane levels in EBC at T1, T2, and T3. Secondary outcomes included the following: NO2+NO3, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2+NO3) and pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory index). RESULTS: Patients subjected to RIPC had lower EBC 8-isoprostane levels when compared with controls at T1, T2, and T3 (differences between means and 95% confidence intervals): -15.3 (5.8-24.8), P = .002; -20.0 (5.5-34.5), P = .008; and -10.4 (2.5-18.3), P = .011, respectively. In the RIPC group, EBC NO2+NO3 and H2O2 levels were also lower than in controls at T2 and T1-T3, respectively (all P < .05). Blood levels of 8-isoprostane and NO2+NO3 were lower in the RIPC group at T2 (P < .05). The RIPC group had better PaO2/FiO2 compared with controls at 2 hours, 8 hours, and 24 hours after lobectomy in 95% confidence intervals for differences between means: 78 (10-146), 66 (14-118), and 58 (12-104), respectively. CONCLUSIONS: Limb RIPC decreased EBC 8-isoprostane levels and other oxidative lung injury markers during lung lobectomy. RIPC also improved postoperative gas exchange as measured by PaO2/FiO2 ratio.

The accuracy of postoperative, non-invasive Air-Test to diagnose atelectasis in healthy patients after surgery: a prospective, diagnostic pilot study.

OBJECTIVE: To assess the diagnostic accuracy of peripheral capillary oxygen saturation (SpO2) while breathing room air for 5 min (the 'Air-Test') in detecting postoperative atelectasis. DESIGN: Prospective cohort study. Diagnostic accuracy was assessed by measuring the agreement between the index test and the reference standard CT scan images. SETTING: Postanaesthetic care unit in a tertiary hospital in Spain. PARTICIPANTS: Three hundred and fifty patients from 12 January to 7 February 2015; 170 patients scheduled for surgery under general anaesthesia who were admitted into the postsurgical unit were included. INTERVENTION: The Air-Test was performed in conscious extubated patients after a 30 min stabilisation period during which they received supplemental oxygen therapy via a venturi mask. The Air-Test was defined as positive when SpO2 was ≤96% and negative when SpO2 was ≥97%. Arterial blood gases were measured in all patients at the end of the Air-Test. In the subsequent 25 min, the presence of atelectasis was evaluated by performing a CT scan in 59 randomly selected patients. MAIN OUTCOME MEASURES: The primary study outcome was assessment of the accuracy of the Air-Test for detecting postoperative atelectasis compared with the reference standard. The secondary outcome was the incidence of positive Air-Test results. RESULTS: The Air-Test diagnosed postoperative atelectasis with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.82 to 0.98) with a sensitivity of 82.6% and a specificity of 87.8%. The presence of atelectasis was confirmed by CT scans in all patients (30/30) with positive and in 5 patients (17%) with negative Air-Test results. Based on the Air-Test, postoperative atelectasis was present in 36% of the patients (62 out of 170). CONCLUSION: The Air-Test may represent an accurate, simple, inexpensive and non-invasive method for diagnosing postoperative atelectasis. TRIAL REGISTRATION: NCT02650037.

Open lung approach versus standard protective strategies: Effects on driving pressure and ventilatory efficiency during anesthesia - A pilot, randomized controlled trial.

BACKGROUND: Low tidal volume (VT) during anesthesia minimizes lung injury but may be associated to a decrease in functional lung volume impairing lung mechanics and efficiency. Lung recruitment (RM) can restore lung volume but this may critically depend on the post-RM selected PEEP. This study was a randomized, two parallel arm, open study whose primary outcome was to compare the effects on driving pressure of adding a RM to low-VT ventilation, with or without an individualized post-RM PEEP in patients without known previous lung disease during anesthesia. METHODS: Consecutive patients scheduled for major abdominal surgery were submitted to low-VT ventilation (6 ml·kg-1) and standard PEEP of 5 cmH2O (pre-RM, n = 36). After 30 min estabilization all patients received a RM and were randomly allocated to either continue with the same PEEP (RM-5 group, n = 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA group, n = 18) defined as the level resulting in maximal Cdyn during a decremental PEEP trial. We compared the effects on driving pressure and lung efficiency measured by volumetric capnography. RESULTS: OL-PEEP was found at 8±2 cmH2O. 36 patients were included in the final analysis. When compared with pre-RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving pressure when compared to pre-RM. These parameters did not improve in the RM-5. The trend of the DP was significantly different between the OLA and RM-5 groups (p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p = 0.035). CONCLUSIONS: Lung recruitment applied during low-VT ventilation improves driving pressure and lung efficiency only when applied as an open-lung strategy with an individualized PEEP in patients without lung diseases undergoing major abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02798133.

Doxorubicin-induced oxidative stress: The protective effect of nicorandil on HL-1 cardiomyocytes.

The primary cardiotoxic action of doxorubicin when used as antitumor drug is attributed to the generation of reactive oxygen species (ROS) therefore effective cardioprotection therapies are needed. In this sense, the antianginal drug nicorandil has been shown to be effective in cardioprotection from ischemic conditions but the underlying molecular mechanism to cope with doxorubicin-induced ROS is unclear. Our in vitro study using the HL-1 cardiomyocyte cell line derived from mouse atria reveals that the endogenous nitric oxide (NO) production was stimulated by nicorandil and arrested by NO synthase inhibition. Moreover, while the NO synthase activity was inhibited by doxorubicin-induced ROS, the NO synthase inhibition did not affect doxorubicin-induced ROS. The inhibition of NO synthase activity by doxorubicin was totally prevented by preincubation with nicorandil. Nicorandil also concentration-dependently (10 to 100 µM) decreased doxorubicin-induced ROS and the effect was antagonized by 5-hydroxydecanoate. The inhibition profile of doxorubicin-induced ROS by nicorandil was unaltered when an L-arginine derivative or a protein kinase G inhibitor was present. Preincubation with pinacidil mimicked the effect of nicorandil and the protection was eliminated by glibenclamide. Quantitative colocalization of fluorescence indicated that the mitochondrion was the target organelle of nicorandil and the observed response was a decrease in the mitochondrial inner membrane potential. Interference with H+ movement across the mitochondrial inner membrane, leading to depolarization, also protected from doxorubicin-induced ROS. The data indicate that activation of the mitochondrial ATP-sensitive K+ channel by nicorandil causing mitochondrial depolarization, without participation of the NO donor activity, was responsible for inhibition of the mitochondrial NADPH oxidase that is the main contributor to ROS production in cardiomyocytes. Impairment of the cytosolic Ca2+ signal induced by caffeine and the increase in lipid peroxidation, both of which are indicators of doxorubicin-induced oxidative stress, were also prevented by nicorandil.

Expression of aquaporins 1 and 5 in a model of ventilator-induced lung injury and its relation to tidal volume.

NEW FINDINGS: What is the central question of this study? Although different studies have attempted to find factors that influence the expression of aquaporins (AQPs) in the lung in different situations, to date no research group has explored the expression of AQP1 and AQP5 jointly in rats mechanically ventilated with different tidal volumes in a model of ventilator-induced lung injury. What is the main finding? Mechanical ventilation with a high tidal volume causes lung injury and oedema, increasing lung permeability. In rats ventilated with a high tidal volume, the pulmonary expression of AQP1 decreases. We analysed the expression of aquaporins 1 and 5 and its relation with tidal volume in a model of ventilator-induced lung injury. Forty-two rats were used. Six non-ventilated animals were killed (control group). The remaining rats were ventilated for 2 h with different tidal volumes (group 7ML with 7 ml kg-1 and group 20ML with 20 ml kg-1 ) and a respiratory rate of 90 breaths min-1 . Lung oedema was measured, and the expression of AQP1 and AQP5 was determined by Western immunoblotting and measurement of mRNA. Lung oedema and alveolar-capillary membrane permeability were significantly increased in the animals of group 20ML compared with the control group. Expression of AQP1 was decreased in groups 7ML and 20ML compared with the control group. In conclusion, mechanical ventilation with a high tidal volume causes lung injury and oedema, increasing lung permeability. In rats ventilated with a high tidal volume, the pulmonary expression of AQP1 decreases.

Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes.

In atrial-derived HL-1 cells, ryanodine receptor and Na(+)/Ca(2+)-exchanger were altered early by 5 µM doxorubicin. The observed effects were an increase of cytosolic Ca(2+) at rest, ensuing ryanodine receptor phosphorylation, and the slowing of Ca(2+) transient decay after caffeine addition. Doxorubicin triggered a linear rise of reactive oxygen species (ROS) with no early effect on mitochondrial inner membrane potential. Doxorubicin and ROS were both detected in mitochondria by colocalization with fluorescence probes and doxorubicin-induced ROS was totally blocked by mitoTEMPO. The NADPH oxidase activity in the mitochondrial fraction was sensitive to inhibition by GKT137831, and doxorubicin-induced ROS decreased gradually as the GKT137831 concentration added in preincubation was increased. When doxorubicin-induced ROS was prevented by GKT137831, the kinetic response revealed a permanent degree of protection that was consistent with mitochondrial NADPH oxidase inhibition. In contrast, the ROS induction by doxorubicin after melatonin preincubation was totally eliminated at first but the effect was completely reversed with time. Limiting the source of ROS production is a better alternative for dealing with oxidative damage than using ROS scavengers. The short-term effect of doxorubicin on Ca(2+) transporters involved in myocardiac contractility was dependent on oxidative damage, and so the impairment was subsequent to ROS production.

The effects of advanced monitoring on hemodynamic management in critically ill patients: a pre and post questionnaire study.

In critically ill patients, many decisions depend on accurate assessment of the hemodynamic status. We evaluated the accuracy of physicians' conventional hemodynamic assessment and the impact that additional advanced monitoring had on therapeutic decisions. Physicians from seven European countries filled in a questionnaire in patients in whom advanced hemodynamic monitoring using transpulmonary thermodilution (PiCCO system; Pulsion Medical Systems SE, Feldkirchen, Germany) was going to be initialized as part of routine care. The collected information included the currently proposed therapeutic intervention(s) and a prediction of the expected transpulmonary thermodilution-derived variables. After transpulmonary thermodilution measurements, physicians recorded any changes that were eventually made in the original therapeutic plan. A total of 315 questionnaires pertaining to 206 patients were completed. The mean difference (±standard deviation; 95 % limits of agreement) between estimated and measured hemodynamic variables was -1.54 (±2.16; -5.77 to 2.69) L/min for the cardiac output (CO), -74 (±235; -536 to 387) mL/m(2) for the global end-diastolic volume index (GEDVI), and -0.5 (±5.2; -10.6 to 9.7) mL/kg for the extravascular lung water index (EVLWI). The percentage error for the CO, GEDVI, and EVLWI was 66, 64, and 95 %, respectively. In 54 % of cases physicians underestimated the actual CO by more than 20 %. The information provided by the additional advanced monitoring led 33, 22, 22, and 13 % of physicians to change their decisions about fluids, inotropes, vasoconstrictors, and diuretics, respectively. The limited clinical ability of physicians to correctly assess the hemodynamic status, and the significant impact that more physiological information has on major therapeutic decisions, support the use of advanced hemodynamic monitoring in critically ill patients.

La elevación del índice de agua pulmonar extravascular como factor predictivo del fracaso de la presión continua en la vía aérea con casco (CPAP-Helmet) en pacientes con insuficiencia respiratoria aguda tras intervención quirúrgica mayor / Elevated Extravascular Lung Water Index (ELWI) as a Predictor of Failure of Continuous Positive Airway Pressure Via Helmet (Helmet-CPAP) in Patients With Acute Respiratory Failure After Major Surgery

Introducción: La ventilación no invasiva (VNI) se utiliza cada vez más para la prevención y el tratamiento de las complicaciones y la insuficiencia respiratorias. Algunos pacientes ingresan en las unidades de reanimación postanestésica portando monitores hemodinámicos avanzados que permiten cuantificar el agua pulmonar extravascular (EVLW) mediante la técnica de termodilución transpulmonar y la permeabilidad vascular pulmonar (PVP), parámetros que permiten obtener información sobre el edema pulmonar. Objetivo: El objetivo de este estudio fue determinar si el índice de EVLW y el índice de la PVP pueden pronosticar el fracaso (intubación) o el éxito (no intubación) en pacientes que desarrollan insuficiencia respiratoria aguda (IRA) durante el período postoperatorio de una intervención quirúrgica mayor abdominal y cuyo tratamiento de primera línea es la presión positiva continua en la vía aérea (CPAP) administrada mediante casco (CPAP-Helmet). Métodos: Se monitorizaron las variables hemodinámicas, el índice de agua pulmonar extravascular (EVLWI) y el índice de permeabilidad vascular pulmonar (PVPI) mediante un dispositivo de monitorización hemodinámica de termodilución transpulmonar (PiCCO(TM)), antes y después de la aplicación de la CPAP. Resultados: En un 66% de los pacientes con CPAP-Helmet se evitó la intubación. En dichos pacientes, el cociente PaO2/FiO2 aumentó de forma significativa (303,33 ± 65,2 vs. 141,6 ± 14,6, p < 0,01) tras la primera hora de aplicación de la CPAP. Antes de iniciar la CPAP-Helmet los valores de EVLWI y PVPI eran significativamente inferiores en los pacientes no intubados (EVLWI 8,6 ± 1,08 vs. 11,8 ± 0,99 ml/kg de peso corporal ideal (PCI), p < 0,01 y PVPI 1,7 ± 0,56 vs. 3,0 ± 0,88, p < 0,01). Se establecieron unos valores de corte óptimos de 9,5 para el EVLWI y de 2,45 para el PVPI (sensibilidad de 0,7; especificidad de 0,9, p < 0,01). Conclusión: En este tipo de pacientes, los parámetros fisiológicos que pronosticaron el fracaso de la CPAP-Helmet con mayor precisión fueron el EVLWI y el PVPI previos al inicio de la CPAP-Helmet, el cociente PaO2/FiO2 y la frecuencia respiratoria tras una hora de CPAP

Introduction: NIV is increasingly used for prevention and treatment of respiratory complications and failure. Some of them are admitted to the PACU with advanced hemodynamic monitors which allow quantification of Extravascular Lung Water (EVLW) by transpulmonary thermodilution technique (TPTD) and Pulmonary Vascular Permeability (PVP) providing information on lung edema. Aim: The objective of this study was to ascertain if EVLW Index and PVP Index may predict failure (intubation) or success (non-intubation) in patients developing acute respiratory failure (ARF) in the postoperative period following major abdominal surgery, where the first line of treatment was non-invasive continuous positive airway pressure via a helmet. Methods: Hemodynamic variables, EVLWI and PVPI were monitored with a transpulmonary thermodilution hemodynamic monitor device (PiCCO(TM)) before and after the application of CPAP. Results: Avoidance of intubation was observed in 66% of patients with Helmet-CPAP. In these patients after the first hour of application of CPAP, PaO2/FiO2 ratio significantly increased (303.33 ± 65.2 vs. 141.6 ± 14.6, P < .01). Before starting Helmet-CPAP values of EVLWI and PVPI were significantly lower in non-intubated patients (EVLWI 8.6 ± 1.08 vs. 11.8 ± 0.99 ml/kg IBW, P < .01 and PVPI 1.7 ± 0.56 vs. 3.0 ± 0.88, P < .01). An optimal cut-off value for EVLWI was established at 9.5, and at 2.45 for PVPI (sensitivity of 0.7; specificity of 0.9, P < .01). Conclusion: In this type of patient the physiological parameters that predict the failure of Helmet-CPAP with the greatest accuracy were the value of the EVLWI and PVPI before Helmet-CPAP institution and the PaO2/FiO2 ratio and the respiratory rate after one hour of CPAP

Single inhibition of either PDE3 or PDE4 unmasks ß2-adrenoceptor-mediated inotropic and lusitropic effects in the left but not right ventricular myocardium of rat.

Cyclic nucleotide phosphodiesterase (PDE)3 and PDE4 provide the major PDE activity in cardiac myocytes and shape ß1-adrenoceptor-dependent cardiac cAMP signaling but their role in regulating ß2-adrenoceptor-mediated responses is less well known. We investigated potential differences in PDE3 and PDE4 activities between right (RV) and left (LV) ventricular myocardium, and their role in regulating ß2-adrenoceptor effects. PDE3 activity in the microsomal fraction was lower in RV than in LV but was the same in the cytosolic fraction. However, no significant difference between RV and LV was found when the PDE4 activity was studied. ß2-adrenoceptor activation increased inotropism and lusitropism in LV when measured in the presence of either the PDE3 inhibitor cilostamide, the PDE4 inhibitor rolipram or a non-selective PDE inhibitor IBMX. However, the joint inhibition of both PDE3 and PDE4 was necessary in RV to uncover ß2-adrenoceptor-induced inotropic and lusitropic effects. Our results indicate different regulation of ß2-adrenoceptor-mediated contractility by PDE3 and PDE4 in RV and LV of the rat heart. In the case of PDE3 due to a different contribution of the enzyme in the microsomal fraction whereas in the case of PDE4 it can be attributed to differences in the intracellular distribution and coupling to ß2-adrenoceptors.

Neurosurgery planning in rodents using a magnetic resonance imaging assisted framework to target experimentally defined networks.

BACKGROUND AND OBJECTIVE: Meaningful targeting of brain structures is required in a number of experimental designs in neuroscience. Current technological developments as high density electrode arrays for parallel electrophysiological recordings and optogenetic tools that allow fine control of activity in specific cell populations provide powerful tools to investigate brain physio-pathology. However, to extract the maximum yield from these fine developments, increased precision, reproducibility and cost-efficiency in experimental procedures is also required. METHODS: We introduce here a framework based on magnetic resonance imaging (MRI) and digitized brain atlases to produce customizable 3D-environments for brain navigation. It allows the use of individualized anatomical and/or functional information from multiple MRI modalities to assist experimental neurosurgery planning and in vivo tissue processing. RESULTS: As a proof of concept we show three examples of experimental designs facilitated by the presented framework, with extraordinary applicability in neuroscience. CONCLUSIONS: The obtained results illustrate its feasibility for identifying and selecting functionally and/or anatomically connected neuronal population in vivo and directing electrode implantations to targeted nodes in the intricate system of brain networks.

Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery. METHODS: This is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra- and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra- and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications. DISCUSSION: The Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications. TRIAL REGISTRATION: Registered on 5 June 2014 with identification no. NCT02158923 .

Elevated Extravascular Lung Water Index (ELWI) as a Predictor of Failure of Continuous Positive Airway Pressure Via Helmet (Helmet-CPAP) in Patients With Acute Respiratory Failure After Major Surgery.

INTRODUCTION: NIV is increasingly used for prevention and treatment of respiratory complications and failure. Some of them are admitted to the PACU with advanced hemodynamic monitors which allow quantification of Extravascular Lung Water (EVLW) by transpulmonary thermodilution technique (TPTD) and Pulmonary Vascular Permeability (PVP) providing information on lung edema. AIM: The objective of this study was to ascertain if EVLW Index and PVP Index may predict failure (intubation) or success (non-intubation) in patients developing acute respiratory failure (ARF) in the postoperative period following major abdominal surgery, where the first line of treatment was non-invasive continuous positive airway pressure via a helmet. METHODS: Hemodynamic variables, EVLWI and PVPI were monitored with a transpulmonary thermodilution hemodynamic monitor device (PiCCO™) before and after the application of CPAP. RESULTS: Avoidance of intubation was observed in 66% of patients with Helmet-CPAP. In these patients after the first hour of application of CPAP, PaO2/FiO2 ratio significantly increased (303.33±65.2 vs. 141.6±14.6, P<.01). Before starting Helmet-CPAP values of EVLWI and PVPI were significantly lower in non-intubated patients (EVLWI 8.6±1.08 vs. 11.8±0.99ml/kg IBW, P<.01 and PVPI 1.7±0.56 vs. 3.0±0.88, P<.01). An optimal cut-off value for EVLWI was established at 9.5, and at 2.45 for PVPI (sensitivity of 0.7; specificity of 0.9, P<.01). CONCLUSION: In this type of patient the physiological parameters that predict the failure of Helmet-CPAP with the greatest accuracy were the value of the EVLWI and PVPI before Helmet-CPAP institution and the PaO2/FiO2 ratio and the respiratory rate after one hour of CPAP.

Late evaluation of upper limb arterial flow in patients after long radial (PiCCO™) catheter placement.

BACKGROUND: The purpose of the study was to assess blood flow in the upper limb arteries after prolonged catheterization with long radial artery catheters (LRC) which reach the subclavian artery compared to catheterization with standard short radial artery catheters (SRC) and a group of upper limb flow without any catheter placement (NOCATH), with both SRC and NOCATH as control groups. METHODS: Prospective observational study with 20 patients admitted to ICU (40 upper limbs) with LRC and/or SRC inserted >48 h for hemodynamic monitoring. More than 45 days after catheter withdrawal, patients underwent a Doppler ultrasound study of both upper limbs. Arterial flows of arms with LRC (FlowLRC) were compared with arterial flows of arms with SRC (FlowSRC) and those without any catheter (FlowNOCATH). RESULTS: Flow in the ulnar, brachial, and subclavian arteries did not show any significant difference between the two types of catheters. The only significant difference was in the radial arteries, showing a lower mean flow in the arms with LRC than in the arms with SRC (2.2 vs. 8.5 cc/min; p = 0.041). Flow reduction in the radial artery (74%) in the arms with LRC compared to the SRC arms showed a tendency to increase ulnar flow as a compensatory mechanism. None of the patients with LRC included in our study had any ischemic events, in spite of observing complete flow occlusion in three radial arteries (18%) from the Doppler study. CONCLUSIONS: In this sample, the use of PiCCO long radial catheters reaching the subclavian artery did not produce chronic significant changes in brachial or subclavian flows. However, LRC produces a significant reduction in radial flow and a tendency to increase ulnar flow. When comparing these blood flow changes with those produced by SRC use, only the radial flow reduction was significantly lower, whereas the other arterial flow changes did not significantly differ.