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Importance: Emergency medical services (EMS) providers transiently ascend to high altitude for primary missions and secondary transports in mountainous areas in helicopters that are unpressurised and do not have facilities for oxygen supplementation. The decrease in cerebral oxygen saturation can lead to impairment in attention and reaction time as well as in quality of care during acute exposure to altitude. Objective: The primary aim of the current study was to investigate the effect of oxygen supplementation on cognitive performance in Helicopter EMS (HEMS) providers during acute exposure to altitude. Design, setting, and participants: This interventional, randomized, controlled, double-blind, cross-over clinical trial was conducted in October 2021. Each trial used a simulated altitude scenario equivalent to 4000 m, in which volunteers were exposed to hypobaric hypoxia with a constant rate of ascent of 4 m/s in an environmental chamber under controlled, replicable, and safe conditions. Trials could be voluntarily terminated at any time. Inclusion criteria were being members of emergency medical services and search and rescue services with an age between 18 and 60 years and an American Society of Anesthesiologists physical status class I. Exposures: Each participant conducted 2 trials, one in which they were exposed to altitude with oxygen supplementation (intervention trial) and the other in which they were exposed to altitude with ambient air supplementation (control trial). Main outcomes and measures: Measurements included peripheral oxygen saturation (SpO2), cerebral oxygenation (ScO2), breathing and heart rates, Psychomotor Vigilance Test (PVT), Digit-Symbol Substitution Test (DSST), n-Back test (2-BACK), the Grooved Pegboard test, and questionnaires on subjective performance, stress, workload, and positive and negative affect. Paired t-tests were used to compare conditions (intervention vs. control). Data were further analyzed using generalized estimating equations (GEE). Results: A total of 36 volunteers (30 men; mean [SD] age, 36 [9] years; mean [SD] education, 17 [4] years) were exposed to the intervention and control trials. The intervention trials, compared with the control trials, had higher values of SpO2 (mean [SD], 97.9 [1.6] % vs. 86 [2.3] %, t-test, p = 0.004) and ScO2 (mean [SD], 69.9 [5.8] % vs. 62.1 [5.2] %, paired t-test, p = 0.004). The intervention trials compared with the control trials had a shorter reaction time (RT) on the PVT after 5 min (mean [SD], 277.8 [16.7] ms vs. 282.5 [15.3] ms, paired t-test, p = 0.006) and after 30 min (mean [SD], 276.9 [17.7] ms vs. 280.7 [15.0] ms, paired t-test, p = 0.054) at altitude. While controlling for other variables, there was a RT increase of 0.37 ms for each % of SpO2 decrease. The intervention trials showed significantly higher values for DSST number of correct responses (with a difference of mean [SD], 1.2 [3.2], paired t-test, p = 0.035). Variables in the intervention trials were otherwise similar to those in the control trials for DSST number of incorrect responses, 2-BACK, and the Grooved Pegboard test. Conclusions and relevance: This randomized clinical trial found that oxygen supplementation improves cognitive performance among HEMS providers during acute exposure to 4000 m altitude. The use of oxygen supplementation may allow to maintain attention and timely reaction in HEMS providers. The impact of repeated altitude ascents on the same day, sleep-deprivation, and additional stressors should be investigated. Trial registration NCT05073406, ClinicalTrials.gov trial registration. [ABSTRACT FROM AUTHOR]

Despite the key role of fibrosis in atrial fibrillation (AF), the effects of different spatial distributions and textures of fibrosis on wave propagation mechanisms in AF are not fully understood. To clarify these aspects, we performed a systematic computational study to assess fibrosis effects on the characteristics and stability of re-entrant waves in electrically-remodelled atrial tissues. A stochastic algorithm, which generated fibrotic distributions with controlled overall amount, average size, and orientation of fibrosis elements, was implemented on a monolayer spheric atrial model. 245 simulations were run at changing fibrosis parameters. The emerging propagation patterns were quantified in terms of rate, regularity, and coupling by frequency-domain analysis of correspondent synthetic bipolar electrograms. At the increase of fibrosis amount, the rate of reentrant waves significantly decreased and higher levels of regularity and coupling were observed (p < 0.0001). Higher spatial variability and pattern stochasticity over repetitions was observed for larger amount of fibrosis, especially in the presence of patchy and compact fibrosis. Overall, propagation slowing and organization led to higher stability of re-entrant waves. These results strengthen the evidence that the amount and spatial distribution of fibrosis concur in dictating re-entry dynamics in remodeled tissue and represent key factors in AF maintenance. [ABSTRACT FROM AUTHOR]

Aims: Intramural fibrosis represents a crucial factor in the formation of a three-dimensional (3D) substrate for atrial fibrillation (AF). However, the transmural distribution of fibrosis and its relationship with atrial overload remain largely unknown. The aim of this study is to quantify the transmural profile of atrial fibrosis in patients with different degrees of atrial dilatation and arrhythmic profiles by a high-resolution 3D histology method.Methods and Results: Serial microtome-cut tissue slices, sampling the entire atrial wall thickness at 5 µm spatial resolution, were obtained from right atrial appendage specimens in 23 cardiac surgery patients. Atrial slices were picrosirius red stained, imaged by polarized light microscopy, and analysed by a custom-made segmentation algorithm. In all patients, the intramural fibrosis content displayed a progressive decrease alongside tissue depth, passing from 68.6 ± 11.6% in the subepicardium to 10-13% in the subendocardium. Distinct transmural fibrotic profiles were observed in patients with atrial dilatation with respect to control patients, where the first showed a slower decrease of fibrosis along tissue depth (exponential decay constant: 171.2 ± 54.5 vs. 80.9 ± 24.4 µm, P < 0.005). Similar slow fibrotic profiles were observed in patients with AF (142.8 ± 41.7 µm). Subepicardial and midwall levels of fibrosis correlated with the degree of atrial dilatation (ρ = 0.72, P < 0.001), while no correlation was found in subendocardial layers.Conclusions: Quantification of fibrosis transmural profile at high resolution is feasible by slice-to-slice histology. Deeper penetration of fibrosis in subepicardial and midwall layers in dilated atria may concur to the formation of a 3D arrhythmic substrate. [ABSTRACT FROM AUTHOR]