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Abstract The compensatory reserve index (CRI), derived from machine learning algorithms from peripherally obtained photoplethysmography signals, provides a non‐invasive assessment of cardiovascular stability, that may be useful clinically. Briefly, the CRI device provides a value between 0 and 1, with 1 reflecting full compensable capabilities and 0 reflecting little to no compensable capabilities. However, the CRI algorithm was developed in younger to middle aged adults, such that it is unknown if older age modulates CRI responses to cardiovascular challenges. In young and older subjects, we compared CRI responses to normothermic and hyperthermic progressive lower body negative pressure (LBNP), and volume loading with saline infusion. Eleven younger (20–36 years) and 10 older (61–75 years) healthy participants underwent (1) graded normothermic LBNP up to 30 mmHg, (2) graded hyperthermic (1.5°C increase in blood temperature) LBNP up to 30 mmHg, and (3) infusion of 15 mL/kg saline (volume loading) with hyperthermia maintained. CRI was obtained throughout each procedure. CRI at 30 mmHg LBNP was 0.18 and 0.24 units greater in the older group during normothermic and hyperthermic LBNP, respectively. However, CRI was not different between age groups at any other LBNP stage, nor did CRI change with volume loading regardless of age. In response to passive hyperthermia alone, regression analyses showed that heart rate was the strongest predictor of CRI. Blood temperature, rate pressure product, and stroke volume were also predictive of CRI but to a lesser extent. In conclusion, age attenuates the reduction in CRI during progressive normothermic and hyperthermic LBNP, but only at 30 mmHg. Second, the CRI was unchanged during volume loading in all subjects. Future studies should determine whether the age differences in CRI reflect age differences in LBNP tolerance.

Background: A cold environment and exercise separately affect the autonomic nervous system (ANS), baroreflex sensitivity (BRS), and blood pressure variability (BPV) but their combined effects on post-exercise recovery are not known. Our cross-over trial examined these responses following upper-body static and dynamic exercise performed in a cold and neutral environment in patients with coronary artery disease (CAD).Methods: 20 patients with stable coronary artery disease performed both graded static (10%–30% of maximal voluntary contraction) and dynamic (light, moderate and high perceived intensity) upper-body exercise at −15°C and +22°C for 30 min. Electrocardiogram and continuous blood pressure were measured to compute post-exercise (10 and 30 min after exercise) spectral powers of heart rate (HR), blood pressure variability and BRS at low (0.04–0.15 Hz) and high (0.15–0.4 Hz) frequencies.Results: Static upper-body exercise performed in a cold environment increased post-exercise high frequency (HF) spectral power of heart rate (HF RR) (p < 0.001) and reduced heart rate (p = 0.001) and low-to-high frequency (LF/HF) ratio (p = 0.006) more than in a neutral environment. In addition, post-exercise mean BRS (p = 0.015) and high frequency BRS (p = 0.041) increased more following static exercise in the cold than in a neutral environment. Dynamic upper-body exercise performed in a cold environment reduced post-exercise HF BRS (p = 0.019) and systolic blood pressure (p = 0.003).Conclusion: Static upper-body exercise in the cold increased post-exercise BRS and overall vagal activity but without reduced systolic blood pressure. Dynamic upper-body exercise in the cold reduced post-exercise vagal BRS but did not affect the other parameters. The influence of cold exposure on post-exercise autonomic and cardiovascular responses following static upper-body exercise require further studies. This information helps understanding why persons with cardiovascular diseases are vulnerable to low environmental temperature. ClinicalTrials.gov: NCT02855905 (04/08/2016).

Profound heat stress can damage the gastrointestinal barrier, leading to microbial translocation from the gut and subsequent systemic inflammation. Despite the greater vulnerability of older people to heat wave-related morbidity and mortality, it is unknown if age modulates gastrointestinal barrier damage and inflammation during heat stress. Therefore, the aim of this study was to determine if aging impacted enterocyte damage and systemic inflammatory responses to a 3-h exposure to very hot and dry (47 °C, 15% humidity) heat with accompanying activities of daily living (intermittent activity at 3 METS). Data from 16 young (age 21 to 39 years) and 16 older (age 65 to 76 years) humans were used to address this aim. In each group, log-transformed plasma concentrations of intestinal fatty acid binding protein (I-FABPlog), interleukin-8 (IL-8log), and tissue factor (TFlog) were assessed as indices of enterocyte damage, systemic inflammation, and blood coagulation, respectively, before and after the 3-h heat exposure. In the younger cohort, I-FABPlog concentration did not increase from pre to post heat exposure (p = 0.264, d = 0.20), although it was elevated in the older group (p = 0.014, d = 0.67). The magnitude of the increase in I-FABPlog was greater in the older participants (p = 0.084, d = 0.55). Across all participants, there was no correlation between the change in core temperature and the change in IFABPlog. There was no change in IL-8log in the younger group (p = 0.193, d = 0.23) following heat exposure, but we observed a decrease in IL-8log in the older group (p = 0.047, d = 0.48). TFlog decreased in the younger group (p = 0.071, d = 0.41), but did not change in the older group (p = 0.193, d = 0.15). Our data indicate that I-FABPlog concentration (an index of enterocyte damage) is increased in older humans during a 3-h extreme heat exposure. Future studies should determine whether this marker reflects increased gastrointestinal barrier permeability in older individuals during heat exposure.

Abstract Sub‐acute (e.g., inhalation injury) and/or acute insults sustained during a severe burn injury impairs pulmonary function. However, previous work has not fully characterized pulmonary function in adults with well‐healed burn injuries decades after an injury. Therefore, we tested the hypothesis that adults with well‐healed burn injuries have lower pulmonary function years after recovery. Our cohort of adults with well‐healed burn‐injuries (n = 41) had a lower forced expiratory volume in one second (Burn: 93 ± 16 vs. Control: 103 ± 10%predicted, mean ± SD; d = 0.60, p = 0.04), lower maximal voluntary ventilation (Burn: 84 [71–97] vs. Control: 105 [94–122] %predicted, median [IQR]; d = 0.84, p

Background Supine hypertension affects a majority of patients with autonomic failure; it is associated with end‐organ damage and can worsen daytime orthostatic hypotension by inducing pressure diuresis and volume loss during the night. Because sympathetic activation prevents blood pressure (BP) from falling in healthy subjects exposed to heat, we hypothesized that passive heat had a BP‐lowering effect in patients with autonomic failure and could be used to treat their supine hypertension. Methods and Results In Protocol 1 (n=22), the acute effects of local heat (40–42°C applied with a heating pad placed over the abdomen for 2 hours) versus sham control were assessed in a randomized crossover fashion. Heat acutely decreased systolic BP by −19±4 mm Hg (versus 3±4 with sham, P

New Findings What is the central question of this study? The venoarteriolar response (VAR) contributes substantially to the maintenance of orthostatic tolerance in humans. Despite its importance in haemodynamic homeostasis, the impact of ageing on the VAR remains understudied. What is the main finding and its importance? Older adults exhibit an augmented VAR in response to leg dependency. The age‐related augmentation of the VAR might be linked with progressive increases of peripheral vascular resistance with ageing. We found a modest but significant correlation between the leg VAR and the morning blood pressure surge in older adults. Augmented leg VAR might contribute to the blood pressure elevation in the early morning. Abstract The venoarteriolar response (VAR) is a non‐adrenergic, non‐baroreflex‐mediated mechanism of vasoconstriction, which has been proposed to contribute ∼45% of the increase in total peripheral resistance during orthostasis. Despite its importance in human cardiovascular control during orthostatic stress, there is no information available regarding the impact of age and sex on the VAR or its role in diurnal blood pressure (BP) variation. We studied 33 (15 women) young (mean ± SD; 28 ± 4 years old) and 26 (12 women) older (71 ± 3 years old) healthy individuals. Brachial and femoral blood flow were measured using Doppler ultrasound. The percentage reduction in vascular conductance (blood flow/mean BP) during 4 min of limb dependency (35–40 cm below the heart level) was used to assess the VAR. The morning surge in BP was assessed using 24 h ambulatory BP monitoring. Peak VAR in the lower limb, but not in the upper limb, was significantly higher in the older than the younger adults (33 ± 4 versus 26 ± 6%, older versus young; P < 0.05). There was no sex difference in the VAR in either the young or the older group. A greater leg VAR was related to a greater morning surge in BP in older adults (r = −0.4, P = 0.02) but not in the young adults (r = −0.26, P = 0.1). Thus, advancing age enhances the VAR in the lower limb and is associated with the morning blood pressure surge in older adults. Sex does not affect this local axonal reflex in healthy humans.

Central Pulse Pressure (CPP) and Aortic Pulse Wave Velocity (aPWV) share a positive relationship with cerebral pulsatility and are associated with cerebrovascular disorders including stroke. Our aim was to examine the influence of Augmentation Index (AIx) upon this relationship, first by using a cross sectional design across a wide range of CPP and aPWV in healthy individuals and second, following administration of Glyceryl Trinitrate (GTN) to acutely change AIx. We measured CPP, aPWV, AIx and Middle Cerebral Artery Pulsatility Index (MCAPI) in 99 healthy individuals (54 females). In all individuals, after accounting for the effect of age and gender, MCAPI shared an independent inverse relationship with AIx (β = −0.515, R2 = 0.109; p = 0.001), and a positive relationship with CPP (β = 0.570, R2 = 0.093; p = 0.003) but not aPWV (p > 0.05). GTN was administered to 25 of these participants (14 females). Following GTN, AIx75 decreased in all participants relative to baseline (12 ± 19 to 5 ± 16%; p = 0.0001). In the 20 min following GTN administration, CPP shared a positive relationship with MCAPI (β = 0.305, R2 = 0.042; p = 0.002) while AIx, adjusted for heart rate (AIx75), shared an inverse relationship with MCAPI (β = −0.320, R2 = 0.019; p = 0.031). These findings indicate that the positive relationship between CPP and MCAPI may be somewhat modified by AIx. This suggests that an increased AIx may weakly attenuate increases in MCAPI that are associated with aortic stiffening in a healthy population at rest, but also following acute reductions in AIx75 after administration of GTN.