Obesity-dependent molecular alterations in fatal COVID-19: A retrospective postmortem study of metabolomic profile of adipose tissue.

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m-2) or obese (OB BMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.

Cardiorespiratory coupling is associated with exercise capacity in athletes: A cross-sectional study.

PURPOSE: To determine the association between exercise capacity based on peak oxygen uptake (VO2peak) and resting cardiorespiratory coupling (CRC) levels in athletes and non-athletes' subjects. METHODS: A cross-sectional study was carried out in 42 apparently healthy male subjects, aged between 20 and 40 years old. The participants were allocated into athletes (n = 21) and non-athletes (n = 21) groups. Resting electrocardiogram and respiratory movement (RESP) were simultaneously acquired during 15 min in supine position and quiet breathing. The beat-to-beat heart period (HP) and RESP series were determined from the recorded signals. Traditional analysis of HP based on frequency domain indexes was performed considering the high-frequency (0.15 - 0.45 Hz) components. To compute the CRC, the linear association between HP and RESP series was determined via squared coherence function and directionality of interaction was investigated through the causal extension of this approach. The exercise capacity was assessed through incremental cardiopulmonary exercise testing in order to determine the VO2peak. RESULTS: Traditional analysis of HP based on high-frequency index was not correlated with exercise capacity in the athletes (r = -0.1, p = 0.5) and non-athletes (r = -0.1, p = 0.3) cohorts. However, resting CRC values was associated with exercise capacity in athletes (r = 0.4, p = 0.03), but not in the non-athletes group (r = -0.2, p = 0.3). CONCLUSION: These results suggest that improved resting values of CRC is associated with higher exercise capacity (VO2peak) in endurance athletes. Moreover, frequency domain of HP was not sensitive to identifying this relationship, probably because effects of training on parasympathetic modulation might be affected by respiratory dynamics, and this influence has a directionality (i.e., from RESP to HP).

Cardiorespiratory coupling as an early marker of cardiac autonomic dysfunction in type 2 diabetes mellitus patients.

The aim of this study was to assess cardiorespiratory coupling (CRC) in type 2 diabetes mellitus patients (T2DM) and apparently healthy individuals, in order to test the hypothesis that this method can provide additional knowledge to the information obtained through the heart rate variability (HRV). A cross-sectional study was conducted in T2DM patients(T2DMG=32) and health controls (CON=32). For CRC analysis, the electrocardiogram, arterial pressure, and thoracic respiratory movement were recorded at rest in supine position and during active standing. Beat-to-beat series of heart period and systolic arterial pressure were analyzed with the respiratory movement signal via a traditional non-causal approach, such as squared coherence function. In this sample of T2DM, no differences in HRV were observed when compared to the CON, but the T2DMG showed a reduction in resting CRC. We conclude that in CRC in T2DM, reflected by the squared coherence may already be compromised even before HRV changes.

Cardiorespiratory coupling strength in athletes and non-athletes.

PURPOSE: Despite the relevant presence of nonlinear components on heart period (HP) likely due to cardiorespiratory coupling (CRC), the HP is frequently analyzed in absence of concomitant recordings of respiratory movements (RESP). This study aims to assess the cardiovascular dynamics and CRC during postural challenge in athletes and non-athletes via joint symbolic analysis (JSA). METHODS: A cross-sectional study was conducted in 50 men, aged between 20 and 40 yrs, divided into athletes (n = 25) and non-athletes (n = 25) groups. The electrocardiogram, blood pressure and RESP signals were recorded during 15 min in both supine position (REST) and after active postural maneuver (STAND). From the beat-to-beat series of HP, systolic arterial pressure (SAP) and RESP, we computed the time and frequency domain indexes and baroreflex sensitivity. The JSA was based on the definition of symbolic HP and RESP patterns and on the evaluation of the rate of their simultaneous occurrence in both HP and RESP series. RESULTS: The JSA analysis was able to identify higher CRC strength at REST in athletes. Moreover, the response of CRC to STAND depended on the time scales of the analysis and was much more evident in athletes than in non-athletes, thus indicating a more reactive autonomic control in athletes. CONCLUSION: Assessing CRC in athletes via JSA provides additional information compared to standard linear time and frequency domain tools likely due to the more relevant presence of nonlinearities in HP-RESP variability relationship.

A Transfer Entropy Approach for the Assessment of the Impact of Inspiratory Muscle Training on the Cardiorespiratory Coupling of Amateur Cyclists.

The strength of cardiorespiratory interactions diminishes with age. Physical exercise can reduce the rate of this trend. Inspiratory muscle training (IMT) is a technique capable of improving cardiorespiratory interactions. This study evaluates the effect of IMT on cardiorespiratory coupling in amateur cyclists. Thirty male young healthy cyclists underwent a sham IMT of very low intensity (SHAM, n = 9), an IMT of moderate intensity at 60% of the maximal inspiratory pressure (MIP60, n = 10) and an IMT of high intensity at the critical inspiratory pressure (CIP, n = 11). Electrocardiogram, non-invasive arterial pressure, and thoracic respiratory movement (RM) were recorded before (PRE) and after (POST) training at rest in supine position (REST) and during active standing (STAND). The beat-to-beat series of heart period (HP) and systolic arterial pressure (SAP) were analyzed with the RM signal via a traditional non-causal approach, such as squared coherence function, and via a causal model-based transfer entropy (TE) approach. Cardiorespiratory coupling was quantified via the HP-RM squared coherence at the respiratory rate (K 2 HP-R M), the unconditioned TE from RM to HP (TER M → HP) and the TE from RM to HP conditioned on SAP (TER M → HP| SAP). In PRE condition we found that STAND led to a decrease of TER M → HP| SAP. After SHAM and CIP training this tendency was confirmed, while MIP60 inverted it by empowering cardiorespiratory coupling. This behavior was observed in presence of unvaried SAP mean and with usual responses of the baroreflex control and HP mean to STAND. TER M → HP and K 2 HP- RM were not able to detect the post-training increase of cardiorespiratory coupling strength during STAND, thus suggesting that conditioning out SAP is important for the assessment of cardiorespiratory interactions. Since the usual response of HP mean, SAP mean and baroreflex sensitivity to postural stressor were observed after MIP60 training, we conclude that the post-training increase of cardiorespiratory coupling during STAND in MIP60 group might be the genuine effect of some rearrangements at the level of central respiratory network and its interactions with sympathetic drive and vagal activity.

Critical inspiratory pressure - a new methodology for evaluating and training the inspiratory musculature for recreational cyclists: study protocol for a randomized controlled trial.

BACKGROUND: Inspiratory muscle training (IMT) has brought great benefits in terms of improving physical performance in healthy individuals. However, there is no consensus regarding the best training load, as in most cases the maximal inspiratory pressure (MIP) is used, mainly the intensity of 60% of MIP. Therefore, prescribing an IMT protocol that takes into account inspiratory muscle strength and endurance may bring additional benefits to the commonly used protocols, since respiratory muscles differ from other muscles because of their greater muscular resistance. Thus, IMT using critical inspiratory pressure (PThC) can be an alternative, as the calculation of PThC considers these characteristics. Therefore, the aim of this study is to propose a new IMT protocol to determine the best training load for recreational cyclists. METHODS: Thirty recreational cyclists (between 20 and 40 years old) will be randomized into three groups: sham (SG), PThC (CPG) and 60% of MIP, according to age and aerobic functional capacity. All participants will undergo the following evaluations: pulmonary function test (PFT), respiratory muscle strength test (RMS), cardiopulmonary exercise test (CPET), incremental inspiratory muscle endurance test (iIME) (maximal sustained respiratory pressure for 1 min (PThMAX)) and constant load test (CLT) (95%, 100% and 105% of PThMÁX) using a linear load inspiratory resistor (PowerBreathe K5). The PThC will be calculated from the inspiratory muscle endurance time (TLIM) and inspiratory loads of each CLT. The IMT will last 11 weeks (3 times/week and 55 min/session). The session will consist of 5-min warm-up (50% of the training load) and three sets of 15-min breaths (100% of the training load), with a 1-min interval between them. RMS, iIME, CLT and CPET will be performed beforehand, at week 5 and 9 (to adjust the training load) and after training. PFT will be performed before and after training. The data will be analyzed using specific statistical tests (parametric or non-parametric) according to the data distribution and their respective variances. A p value <0.05 will be considered statistically significant. DISCUSSIONS: It is expected that the results of this study will enable the training performed with PThC to be used by health professionals as a new tool to evaluate and prescribe IMT. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02984189 . Registered on 6 December 2016.