Performing Platform Governance: Facebook and the Stage Management of Data Relations.

Controversies surrounding social media platforms have provided opportunities for institutional reflexivity amongst users and regulators on how to understand and govern platforms. Amidst contestation, platform companies have continued to enact projects that draw upon existing modes of privatized governance. We investigate how social media companies have attempted to achieve closure by continuing to set the terms around platform governance. We investigate two projects implemented by Facebook (Meta)-authenticity regulation and privacy controls-in response to the Russian Interference and Cambridge Analytica controversies surrounding the 2016 U.S. Presidential Election. Drawing on Goffman's metaphor of stage management, we analyze the techniques deployed by Facebook to reinforce a division between what is visible and invisible to the user experience. These platform governance projects propose to act upon front-stage data relations: information that users can see from other users-whether that is content that users can see from "bad actors", or information that other users can see about oneself. At the same time, these projects relegate back-stage data relations-information flows between users constituted by recommendation and targeted advertising systems-to invisibility and inaction. As such, Facebook renders the user experience actionable for governance, while foreclosing governance of back-stage data relations central to the economic value of the platform. As social media companies continue to perform platform governance projects following controversies, our paper invites reflection on the politics of these projects. By destabilizing the boundaries drawn by platform companies, we open space for continuous reflexivity on how platforms should be understood and governed.

Resampling reduces bias amplification in experimental social networks.

Large-scale social networks are thought to contribute to polarization by amplifying people's biases. However, the complexity of these technologies makes it difficult to identify the mechanisms responsible and evaluate mitigation strategies. Here we show under controlled laboratory conditions that transmission through social networks amplifies motivational biases on a simple artificial decision-making task. Participants in a large behavioural experiment showed increased rates of biased decision-making when part of a social network relative to asocial participants in 40 independently evolving populations. Drawing on ideas from Bayesian statistics, we identify a simple adjustment to content-selection algorithms that is predicted to mitigate bias amplification by generating samples of perspectives from within an individual's network that are more representative of the wider population. In two large experiments, this strategy was effective at reducing bias amplification while maintaining the benefits of information sharing. Simulations show that this algorithm can also be effective in more complex networks.

Flexible social inference facilitates targeted social learning when rewards are not observable.

Groups coordinate more effectively when individuals are able to learn from others' successes. But acquiring such knowledge is not always easy, especially in real-world environments where success is hidden from public view. We suggest that social inference capacities may help bridge this gap, allowing individuals to update their beliefs about others' underlying knowledge and success from observable trajectories of behaviour. We compared our social inference model against simpler heuristics in three studies of human behaviour in a collective-sensing task. Experiment 1 demonstrated that average performance improved as a function of group size at a rate greater than predicted by heuristic models. Experiment 2 introduced artificial agents to evaluate how individuals selectively rely on social information. Experiment 3 generalized these findings to a more complex reward landscape. Taken together, our findings provide insight into the relationship between individual social cognition and the flexibility of collective behaviour.

Does big data serve policy? Not without context. An experiment with in silico social science.

The DARPA Ground Truth project sought to evaluate social science by constructing four varied simulated social worlds with hidden causality and unleashed teams of scientists to collect data, discover their causal structure, predict their future, and prescribe policies to create desired outcomes. This large-scale, long-term experiment of in silico social science, about which the ground truth of simulated worlds was known, but not by us, reveals the limits of contemporary quantitative social science methodology. First, problem solving without a shared ontology-in which many world characteristics remain existentially uncertain-poses strong limits to quantitative analysis even when scientists share a common task, and suggests how they could become insurmountable without it. Second, data labels biased the associations our analysts made and assumptions they employed, often away from the simulated causal processes those labels signified, suggesting limits on the degree to which analytic concepts developed in one domain may port to others. Third, the current standard for computational social science publication is a demonstration of novel causes, but this limits the relevance of models to solve problems and propose policies that benefit from the simpler and less surprising answers associated with most important causes, or the combination of all causes. Fourth, most singular quantitative methods applied on their own did not help to solve most analytical challenges, and we explored a range of established and emerging methods, including probabilistic programming, deep neural networks, systems of predictive probabilistic finite state machines, and more to achieve plausible solutions. However, despite these limitations common to the current practice of computational social science, we find on the positive side that even imperfect knowledge can be sufficient to identify robust prediction if a more pluralistic approach is applied. Applying competing approaches by distinct subteams, including at one point the vast TopCoder.com global community of problem solvers, enabled discovery of many aspects of the relevant structure underlying worlds that singular methods could not. Together, these lessons suggest how different a policy-oriented computational social science would be than the computational social science we have inherited. Computational social science that serves policy would need to endure more failure, sustain more diversity, maintain more uncertainty, and allow for more complexity than current institutions support.

Accuracy-Risk Trade-Off Due to Social Learning in Crowd-Sourced Financial Predictions.

A critical question relevant to the increasing importance of crowd-sourced-based finance is how to optimize collective information processing and decision-making. Here, we investigate an often under-studied aspect of the performance of online traders: beyond focusing on just accuracy, what gives rise to the trade-off between risk and accuracy at the collective level? Answers to this question will lead to designing and deploying more effective crowd-sourced financial platforms and to minimizing issues stemming from risk such as implied volatility. To investigate this trade-off, we conducted a large online Wisdom of the Crowd study where 2037 participants predicted the prices of real financial assets (S&P 500, WTI Oil and Gold prices). Using the data collected, we modeled the belief update process of participants using models inspired by Bayesian models of cognition. We show that subsets of predictions chosen based on their belief update strategies lie on a Pareto frontier between accuracy and risk, mediated by social learning. We also observe that social learning led to superior accuracy during one of our rounds that occurred during the high market uncertainty of the Brexit vote.

Bayesian collective learning emerges from heuristic social learning.

Researchers across cognitive science, economics, and evolutionary biology have studied the ubiquitous phenomenon of social learning-the use of information about other people's decisions to make your own. Decision-making with the benefit of the accumulated knowledge of a community can result in superior decisions compared to what people can achieve alone. However, groups of people face two coupled challenges in accumulating knowledge to make good decisions: (1) aggregating information and (2) addressing an informational public goods problem known as the exploration-exploitation dilemma. Here, we show how a Bayesian social sampling model can in principle simultaneously optimally aggregate information and nearly optimally solve the exploration-exploitation dilemma. The key idea we explore is that Bayesian rationality at the level of a population can be implemented through a more simplistic heuristic social learning mechanism at the individual level. This simple individual-level behavioral rule in the context of a group of decision-makers functions as a distributed algorithm that tracks a Bayesian posterior in population-level statistics. We test this model using a large-scale dataset from an online financial trading platform.

Adaptive social networks promote the wisdom of crowds.

Social networks continuously change as new ties are created and existing ones fade. It is widely acknowledged that our social embedding has a substantial impact on what information we receive and how we form beliefs and make decisions. However, most empirical studies on the role of social networks in collective intelligence have overlooked the dynamic nature of social networks and its role in fostering adaptive collective intelligence. Therefore, little is known about how groups of individuals dynamically modify their local connections and, accordingly, the topology of the network of interactions to respond to changing environmental conditions. In this paper, we address this question through a series of behavioral experiments and supporting simulations. Our results reveal that, in the presence of plasticity and feedback, social networks can adapt to biased and changing information environments and produce collective estimates that are more accurate than their best-performing member. To explain these results, we explore two mechanisms: 1) a global-adaptation mechanism where the structural connectivity of the network itself changes such that it amplifies the estimates of high-performing members within the group (i.e., the network "edges" encode the computation); and 2) a local-adaptation mechanism where accurate individuals are more resistant to social influence (i.e., adjustments to the attributes of the "node" in the network); therefore, their initial belief is disproportionately weighted in the collective estimate. Our findings substantiate the role of social-network plasticity and feedback as key adaptive mechanisms for refining individual and collective judgments.

Exposure to anaesthetic trace gases during general anaesthesia: CobraPLA vs. LMA classic.

BACKGROUND: To prospectively investigate the performance, sealing capacity and operating room (OR) staff exposure to waste anaesthetic gases during the use of the Cobra perilaryngeal airway (CobraPLA) compared with the laryngeal mask airway classic (LMA). METHODS: Sixty patients were randomly assigned to the CobraPLA or the LMA group. Insertion time, number of insertion attempts and airway leak pressures were assessed after induction of anaesthesia. Occupational exposure to nitrous oxide (N(2)O) and Sevoflurane (SEV) was measured at the anaesthetists' breathing zone and the patients' mouth using a photoacoustic infrared spectrometer. RESULTS: N(2)O waste gas concentrations differed significantly in the anaesthetist's breathing zone (11.7+/-7.2 p.p.m. in CobraPLA vs. 4.1+/-4.3 p.p.m. in LMA, P=0.03), whereas no difference could be shown in SEV concentrations. Correct CobraPLA positioning was possible in 28 out of 30 patients (more than one attempt necessary in five patients). Correct positioning of the LMA classic was possible in all 30 patients (more than one attempt in three patients). Peak airway pressure was higher in the CobraPLA group (16+/-3 vs. 14+/-2 cmH(2)O, P=0.01). The average leak pressure of the CobraPLA was 24+/-4 cmH(2)O, compared with 20+/-4 cmH(2)O of the LMA classic (P<0.001; all values means+/-SD). CONCLUSION: Despite higher airway seal pressures, the CobraPLA caused higher intraoperative N(2)O trace concentrations in the anaesthetists' breathing zone.

Waste gas exposure to sevoflurane and nitrous oxide during anaesthesia using the oesophageal-tracheal Combitube small adult.

Exposure to sevoflurane (SEV) and nitrous oxide during ventilation using a Combitube (37Fr) small adult (SA) was compared with waste gas exposure using conventional endotracheal tubes. Trace concentrations of SEV and nitrous oxide were assessed using a direct reading spectrometer during 40 gynaecological laparoscopic procedures under general anaesthesia. Measurements were made at the patients' mouth and in the anaesthetists' breathing zone. Mean (SD) concentrations of SEV and nitrous oxide measured at the patients' mouth were comparable in the Combitube SA (SEV 0.6 (0.2) p.p.m.; nitrous oxide 9.7 (8.5) p.p.m.) and endotracheal tube group (SEV 1.2 (0.8) p.p.m.; nitrous oxide 17.2 (10.6) p.p.m.). These values caused comparable contamination of the anaesthetists' breathing zone (SEV 0.6 (0.2) p.p.m. and nitrous oxide 4.3 (3.7) p.p.m. for the Combitube SA group, compared with SEV 0.5 (0.2) p.p.m. and nitrous oxide 4.1 (1.8) p.p.m. for the endotracheal tube group). We conclude that the use of the Combitube SA during positive pressure ventilation is not necessarily associated with increased waste gas exposure, especially when air conditioning and scavenging devices are available.

The esophageal tracheal combitube as a non-invasive alternative to endotracheal intubation. A review.

The esophageal tracheal combitube (ETC) is a supraglottic airway device that functions as an effective alternative to ventilation via mask and tracheal intubation and is therefore a valuable tool in difficult and emergency airway management. The Com-bitube has proven to be a valuable tool for securing the airways and providing adequate ventilation. Its advantages are that it is easy to insert quickly, it may be inserted blindly or with the aid of a laryngoscope, and it provides adequate ventilation and oxygenation in both esophageal and tracheal position. The combitube allows application of high ventilatory pressures and it minimises the risk of aspiration. Several guidelines including European Resuscitation Council, Ame-rican Heart Association, American Society of Anesthesiologists have included the combitube as a primary rescue device in cannot ventilate cannot intubate situations. It has been used in elective patients as well as in emergency situations in- and out-of-hospital. The combitube can be inserted with minimal movement of the cervical spine and is therefore indicated whenever cervical spine movement is anatomically restricted (e.g. rheumatoid arthritis) or should be functionally restricted (e.g. trauma). Since the combitube isolates the lungs from the esophagus it is especially useful in patients at risk for aspiration (e.g., caesarean section, morbid obesity). The combitube is available in two sizes: 37 F SA (Small Adult) and 41 F. Unfortunately, a pediatric size is not commercially available. Training in the use of the combitube under controlled conditions is prerequisite to being expert in an emergency situation. The combitube is another non-surgical airway in the armamentarium of the anaesthesiologist or emergency provider in case of foreseen or unforeseen difficult airways in patients who can neither be intubated or mask ventilated.

The oesophageal-tracheal Combitube Small Adult.

Airway management during gynaecological laparoscopy is complicated by intraperitoneal carbon dioxide inflation, Trendelenburg tilt, increasing airway pressures and pulmonary aspiration risk. We investigated whether the oesophageal-tracheal Combitube 37 Fr SA is a suitable airway during laparoscopy. One hundred patients were randomly allocated to receive either the Combitube SA (n = 49) or tracheal intubation (n = 51). Oesophageal placement of the Combitube was successful at the first attempt [16 (3) s]. Peak airway pressures were 25 (5) cmH2O. An airtight seal was obtained using air volumes of 55 (13) ml (oropharyngeal balloon) and 10 (1) ml (oesophageal cuff). Significant correlations were observed between patient's height and weight and the balloon volumes necessary to produce a seal. Similar findings were recorded for the control group, with tracheal intubation being difficult in three patients. The Combitube SA provided a patent airway during laparoscopy. Non-traumatic insertion was possible and an airtight seal was provided at airway pressures of up to 30 cmH2O.

Effects of positive end-expiratory pressure on hemodynamics and indocyanine green kinetics in patients after orthotopic liver transplantation.

OBJECTIVE: To determine the impact of positive end-expiratory pressure (PEEP) ventilation on hemodynamics and a clinical test for assessment of dynamic liver performance in patients undergoing orthotopic liver transplantation (OLT). DESIGN: Prospective, descriptive patient study. SETTING: University hospital intensive care unit. PATIENTS: A total of 25 patients after OLT. INTERVENTIONS: All patients were intubated and mechanically ventilated with biphasic positive airway pressure. The effects of three different randomly chosen levels of PEEP (0 cm H2O, 5 cm H2O, and 10 cm H2O) were studied in the immediate postoperative period. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, arterial and venous blood gas analyses, and plasma disappearance rate of indocyanine green (ICG(PDR)), using the transpulmonary indicator dilution technique, were obtained simultaneously. For data evaluation, patients were grouped retrospectively according to their hemodynamic response to PEEP (Group A and Group B). In Group A (n = 13), PEEP did not alter cardiac index. In Group B (n = 11), PEEP levels of 5 cm H2O and 10 cm H2O significantly reduced cardiac index and oxygen delivery. ICG(PDR) remained statistically unchanged in both groups. CONCLUSIONS: Short-term pressure-controlled ventilation with PEEP levels of up to 10 cm H2O does not exert detrimental effects on systemic hemodynamics in OLT patients and does not interfere with ICG(PDR). However, it remains to be determined whether these findings could be confirmed under the application of higher PEEP levels over a longer period of time and whether they could be of clinical relevance for the use of indocyanine green as a dynamic liver function test.

Mild and moderate hypothermia (alpha-stat) do not impair the coupling between local cerebral blood flow and metabolism in rats.

BACKGROUND AND PURPOSE: The effects of hypothermia on global cerebral blood flow (CBF) and glucose utilization (CGU) have been extensively studied, but less information exists on a local cerebral level. We investigated the effects of normothermic and hypothermic anesthesia on local CBF (LCBF) and local CGU (LCGU). METHODS: Thirty-six rats were anesthetized with isoflurane (1 MAC) and artificially ventilated to maintain normal PaCO(2) (alpha-stat). Pericranial temperature was maintained normothermic (37.5 degrees C, n=12) or was reduced to 35 degrees C (n=12) or 32 degrees C (n=12). Pericranial temperature was maintained constant for 60 min until LCBF and LCGU were measured with autoradiography. Twelve conscious rats served as normothermic control animals. RESULTS: Normothermic anesthesia significantly increased mean CBF compared with conscious control animals (29%, P<0.05). Mean CBF was reduced to control values with mild hypothermia and to 30% below control animals with moderate hypothermia (P<0.05). Normothermic anesthesia reduced mean CGU by 44%. No additional effects were observed during mild hypothermia. Moderate hypothermia resulted in a further reduction in mean CGU (41%, P<0.05). Local analysis showed linear relationships between LCBF and LCGU in normothermic conscious (r=0.93), anesthetized (r=0.92), and both hypothermic groups (35 degrees C r=0. 96, 32 degrees C r=0.96, P<0.05). The LCBF-to-LCGU ratio increased from 1.5 to 2.5 mL/micromol during anesthesia (P<0.05), remained at 2.4 mL/micromol during mild hypothermia, and decreased during moderate hypothermia (2.1 mL/micromol, P<0.05). CONCLUSIONS: Anesthesia and hypothermia induce divergent changes in mean CBF and CGU. However, local analysis demonstrates a well-maintained linear relationship between LCBF and LCGU during normothermic and hypothermic anesthesia.

[The difficult airway]. / Der schwierige Atemweg.

Management of the difficult airway has gained increasing interest, because hypoxia is one of the leading causes of death and of severe neurological sequelae related to anesthesia or resuscitation. The difficult airway algorithm of the American Society of Anesthesiologists as well as the guidelines of the European Resuscitation Council provide recommendations for the prevention of difficulties in tracheal intubation and/or mask ventilation. Especially preoperative patient evaluation is of major importance. Patients history, oral and maxillofacial anatomy, pharyngeal and laryngeal structures as well as cervical spine mobility have to be assessed and awake fiberoptic intubation has to be performed in all cooperative patients with indices pointing towards difficult airways. If problems in intubating the trachea are encountered after induction of anesthesia and mask ventilation is adequate, one must call for help and decide rapidly whether to awaken the patient or to proceed with alternative intubation techniques (e.g. different laryngoscope blades, flexible fiberoptic scope or other fiberoptic techniques, lighted wand, retrograde intubation or surgical airway). In the potentially life-threatening "cannot intubate--cannot ventilate" situation either transtracheal jet ventilation, laryngeal mask airway, the esophageal-tracheal Combitube or a surgical airway have to be performed or have to be inserted immediately. These alternative methods have to be appropriately taught and--as far as possible--to be trained under routine conditions in order to master emergency situations.

Intermittent capnography during high-frequency jet ventilation for prolonged rigid bronchoscopy.

BACKGROUND: Gas exchange during high-frequency jet ventilation (HFJV) for prolonged rigid bronchoscopy (RBS) is usually monitored by arterial blood gas analysis. Capnography of expired gases during brief HFJV discontinuation may be a reliable and noninvasive supplemental method. Capnography can be performed either for single breaths or with respiratory rate (RR) reduced to 10 x min(-1). The aim of this study was to demonstrate that capnography during short periods of HFJV discontinuation represents a reliable measure of PaCO2 during prolonged RBS. METHODS: We prospectively investigated 100 consecutive patients (75 male and 25 female) undergoing HFJV for RBS. HFJV was delivered through the rigid bronchoscope at the following settings: working pressure 1.2 bar, rate 100 x min(-1), FIO2 0.99, t(i)/t(tot)0.6. The light guiding channel ending at the distal tip of the rigid bronchoscope was used for gas sampling. Capnograms were assessed at 5 min intervals and compared to PaCO2 from arterial blood samples drawn simultaneously. The accuracy of single breath CO2 sampling was compared with sampling at RR=10 x min(-1). RESULTS: Mean duration of RBS was 30+/-21 min. A significant correlation between capnography (PetCO2) and arterial blood gas analysis (PaCO2) was observed, being r=0.90 for the RR= 10 x min(-1) method and r=0.91 for the single breath method. Mean difference between PaCO2 and PetCO2 was 0.37+/-0.2 kPa throughout the entire study period. No significant differences between single breath sampling or sampling at RR=10 x min(-1) were observed. CONCLUSION: Capnography performed during short periods of HFJV discontinuation reliably and noninvasively reflects PaCO2 during prolonged endoscopic procedures. Capnography during HFJV for RBS may reduce the frequency of arterial blood gas sampling, the duration of unmonitored intervals and costs.

Relationship between local cerebral blood flow and metabolism during mild and moderate hypothermia in rats.

BACKGROUND: Hypothermia may interfere with the relationship between cerebral blood flow (CBF) and metabolism. Because this conclusion was based on the analysis of global values, the question remains whether hypothermic CBF/metabolism uncoupling exists on a local cerebral level. This study investigated the effects of hypothermic anesthesia on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). METHODS: Thirty-six rats were anesthetized with isoflurane (1 minimum alveolar concentration) and artificially ventilated to maintain normal arterial carbon dioxide partial pressure (pH-stat). Pericranial temperature was maintained as normothermic (37.5 degrees C, n = 12) or was reduced to 35 degrees C (n = 12) or 32 degrees C (n = 12). Pericranial temperature was maintained constant for 60 min until LCBF or LCGU were measured by autoradiography. Twelve conscious rats served as normothermic controls. RESULTS: Compared with conscious animals, mean CBF remained unchanged during normothermic anesthesia. Mean CBF significantly increased during mild hypothermia but was unchanged during moderate hypothermia. During normothermic anesthesia, mean CGU was 45% lower than in conscious controls (P < 0.05). No further CGU reduction was found during mild hypothermia, whereas CGU further decreased during moderate hypothermia (48%; P < 0.05). Local analysis showed a linear LCBF/LCGU relationship in conscious (r = 0.94) and anesthetized (r = 0.94) normothermic animals, as well as in both hypothermic groups (35 degrees C: r = 0.92; 32 degrees C: r = 0.95; P < 0.05). The LCBF-to-LCGU ratio increased from 1.4 (conscious controls) to 2.4 (normothermic isoflurane) and 3.6 ml/micromol (mild and moderate hypothermia, P < 0.05). CONCLUSIONS: Decrease of mean CGU at unchanged or increased mean CBF during hypothermic anesthesia may not indicate uncoupling. Local analysis shows a maintained linear relationship that is reset to a higher CBF/CGU ratio.

Interaction of acetylcholine and endothelin-1 in the modulation of pulmonary arterial pressure.

OBJECTIVE: The study was designed to investigate the effects of acetylcholine (ACh) on pulmonary circulation with special regard to mediators that could be involved in the mediation of ACh-induced effects. ACh has been reported to induce either vasodilation or vasoconstriction in the pulmonary circulation of different species. DESIGN: Prospective experimental study in rabbits. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Sixty-six adult rabbits of either sex. INTERVENTIONS: The experiments were performed on 66 isolated and ventilated rabbit lungs that were perfused with a cell- and plasma-free buffer solution. ACh was injected in various concentrations after pulmonary artery preconstriction and in untreated lungs. MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. Perfusate samples were taken intermittently to determine endothelin-1 (ET-1), thromboxane A2 (TXA2), and prostacyclin (PGI2) concentrations. ACh in final dosages from 10(-5) to 10(-2) M (n = 6 each) was injected into the pulmonary artery of lungs treated with U46619 to induce pulmonary arterial hypertension or was injected into untreated lungs. To analyze the potential mechanisms of action, ACh (10(-5) M) was administered in additional experiments after pretreatment with either ETA receptor antagonist BQ123 (10(-6) M; n = 6) or the cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6). In preconstricted pulmonary vessels, ACh (10(-3) and 10(-2) M) initially induced a PAP rise for 10 mins followed by a sustained decrease. In untreated lungs, ACh induced an immediate dose-dependent increase in PAP, requiring as long as 30 mins to return to predrug levels. Simultaneously, significantly elevated TXA2 and PGI2 levels were observed. Furthermore, ET-1 was detected in the perfusate, which was free from ET-1 before ACh administration. Pretreatment with BQ123 reduced substantially the ACh (10(-5) M)-induced PAP increase and the release of TXA2 and PGI2. At 5 mins, the PAP maximum was reduced from 18.5 +/- 3.2 mm Hg to 9.9 +/- 0.65 mm Hg by BQ123 pretreatment (p < .01). An inhibition of PAP increase was also observed after diclofenac pretreatment (11.6 +/- 0.4 mm Hg at 5 mins; p < .05). Inhibitory effects at 5 mins were significantly more pronounced in the BQ123 group compared with the diclofenac group. CONCLUSIONS: The effects of ACh on the pulmonary circulation of isolated rabbit lungs depend on ACh concentration and the basal tone of the arterial vasculature. In lungs with a normal pulmonary vascular resistance, ACh administration causes vasoconstriction via the release of ET-1 and TXA2, whereas vasodilation is induced in preconstricted pulmonary vessels.

Right atrial pressure predicts hemodynamic response to apneic positive airway pressure.

OBJECTIVE: To evaluate if the preexistant filling state, assessed by right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), and right ventricular end-diastolic volume index (EDVI), would define the subsequent hemodynamic effects of increases in airway pressure (Paw). DESIGN: Prospective open clinical study. SETTING: Postoperative intensive care unit, university hospital. PATIENTS: Twenty-two consecutive ventilator-dependent patients with mild to severe acute lung injury with Murray scores (scoring infiltrates on chest radiograph, oxygenation index, lung compliance, and the level of positive end-expiratory pressure) ranging from 0.5 to 3.0 without history of preexisting cardiopulmonary disease. INTERVENTIONS: Paw varied during apnea from 0 to 10, 20, and 30 cm H2O using inspiratory hold maneuvers of 15 secs. MEASUREMENTS AND MAIN RESULTS: Cardiac index and right ventricular ejection fraction were measured by the thermodilution technique. We made measurements in triplicate using manual injection of iced saline. Right ventricular volumes were calculated. Increasing Paw induced variable changes in cardiac index among subjects (+6% to -43% change from baseline 0 cm H2O Paw values), which correlated with percentage changes in both stroke index (r2 = .89) and right ventricular EDVI (r2 = .75), whereas heart rate and right ventricular ejection fraction did not change. The change in cardiac index from 0 to 30 cm H2O Paw correlated with baseline values for RAP, PAOP, and right ventricular EDVI (r2 = .68, .43, and .34, respectively, p < 0.01). Increases in RAP correlated with lung compliance if baseline RAP was >10 mm Hg but did not if it was < or =10 mm Hg. Similarly, patients with baseline RAP < or =10 mm Hg had a greater decrease in cardiac index than patients with a RAP >10 mm Hg (for 30 cm H2O Paw: -30% +/- 9% vs. -8% +/- 7%, p < .01). CONCLUSIONS: Apneic positive Paw decreased cardiac output mainly by reducing venous return. From the investigated filling variables, RAP was most sensitive in predicting the hemodynamic response, followed by PAOP and right ventricular EDVI. Patients with RAP < or =10 mm Hg, if subjected to aggressive positive pressure ventilation, are at risk of hemodynamic deterioration and organ hypoperfusion.

ET-1-induced pulmonary vasoconstriction shifts from ET(A)- to ET(B)-receptor-mediated reaction after preconstriction.

Endothelin-1 (ET-1) has been reported to induce pulmonary vasoconstriction via either ET(A) or ET(B) receptors, and vasorelaxation after ET-1 injection has been observed. Our study investigated the effects of ET-1 in isolated rabbit lungs, which were studied at basal tone (part I) and after preconstriction (U-46619; part II). Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. In part I, ET-1 (10(-8) M; n = 6; control) was injected after pretreatment with the ET(A)-receptor antagonist BQ-123 (10(-6) M; n = 6) or the ET(B)-receptor antagonist BQ-788 (10(-6) M; n = 6). The same protocol was carried out in part II after elevation of pulmonary vascular tone. ET-1 induced an immediate PAP increase (DeltaPAP 4.3 +/- 0.4 mmHg at 10 min) that was attenuated by pretreatment with BQ-123 (P < 0.05 at 10 min and P < 0.01 thereafter) and that was more pronounced after BQ-788 (P < 0.01 at 10 min and P < 0.001 thereafter). In part II, ET-1 induced an immediate rise in PAP with a maximum after 5 min (DeltaPAP 6.3 +/- 1.4 mmHg), leveling off at DeltaPAP 3.2 +/- 0.2 mmHg after 15 min. Pretreatment with BQ-123 failed to attenuate the increase. BQ-788 significantly reduced the peak pressure at 5 min (0.75 +/- 0.4 mmHg; P < 0.001) as well as the plateau pressure thereafter (P < 0.01). We conclude that ET-1 administration causes pulmonary vasoconstriction independent of basal vascular tone, and, at normal vascular tone, the vasoconstriction seems to be mediated via ET(A) receptors. BQ-788 treatment resulted in even more pronounced vasoconstriction. After pulmonary preconstriction, ET(A) antagonism exerted no effects on PAP, whereas ET(B) antagonism blocked the PAP increase. Therefore, ET-1-induced pulmonary vasoconstriction is shifted from an ET(A)-related to an ET(B)-mediated mechanism after pulmonary vascular preconstriction.