ECSS Paris 2023: OP-MH33
INTRODUCTION: Peripheral muscle dysfunction is a well-recognised manifestation of cystic fibrosis [1], impacting exercise tolerance and quality of life, but its persistence in the era of highly effective CFTR modulators remains unclear. In particular, adequately powered controlled studies combining comprehensive assessments of peripheral muscle function and muscle size remain scarce. METHODS: Thirty-nine people with cystic fibrosis (age: 31 ± 13 years, BMI: 21 [4.8] kg·m-2; FEV1%: 73 [32] %pred), all receiving CFTR modulator therapy (92% ETI), were compared with 39 healthy controls matched (1:1) for sex and age, using a maximum age difference of two years (mean absolute age difference: 1.1 ± 0.8 years). Muscle function was assessed according to European recommendations [2], through maximal strength and endurance of knee extensors (isometric chair), maximal upper-limb strength (handgrip) and lower-limb explosive performance (squat jump). Quadriceps muscle thickness was measured using ultrasound imaging. Habitual physical activity was assessed over one week using wrist-worn accelerometry. RESULTS: Compared with healthy controls, people with cystic fibrosis exhibited significantly reduced quadriceps strength (-23%, p<0.001, d = 0.82), endurance (-29% p<0.001, rrb = 0.46) and thickness (-10%, p=0.006, rrb = 0.36), as well as reduced squat jump performance (-17%, p = 0.01, rrb = 0.34) and handgrip strength (-18%, p=0.009, d = 0.61). Reduction in quadriceps strength persisted when normalised to quadriceps muscle thickness (p=0.007, rrb = 0.35). Habitual physical activity indicators did not differ between groups. CONCLUSION: Despite treatment with CFTR modulators, people with cystic fibrosis continue to exhibit substantial peripheral muscle dysfunction. This impairment cannot be explained solely by anthropometric differences, reduced muscle thickness or habitual physical activity levels, suggesting intrinsic alterations in muscle function. These findings support the need for comprehensive assessment of peripheral muscle function in clinical practice and reinforce the relevance of maintaining existing resistance training programmes [3] while developing novel interventions targeting peripheral muscle dysfunction, in the era of highly effective CFTR modulators. [1] Gruet et al. J Cyst Fibros 2017 16(5):538-552 [2] Saynor et al. Eur Respir Rev 2023; 32: 230029 [3] Gruet et al. J Cyst Fibros 2022 e83–e98
Read CV Mathieu GruetECSS Paris 2023: OP-MH33
INTRODUCTION: Training and aging cause modifications in skeletal muscle. Their combined effect is still under debate. We estimate oxidative metabolism and microvasculature health by time-domain (TD) near infrared spectroscopy (NIRS). We preliminary measured the absolute values of oxy- (O2Hb), deoxy- (HHb), total- (tHb) hemoglobin concentration, and tissue oxygen saturation (StO2). Then, we studied distinct vascular control mechanisms exploiting spontaneous oscillations of the hemodynamic parameters in peculiar frequency bands: Endothelial (VI: <0.0095 Hz), NO-related Endothelial (V: 0.0095-0.021 Hz), Neurogenic (IV: 0.021-0.052 Hz) and Myogenic (III: 0.052-0.145 Hz). METHODS: We studied 4 different subjects groups: 1) 15 Old Trained (OT), 72±5 y, master athletes competing in running or cycling and following high-intensity weekly training; 2) 6 Old Untrained (OU), 78±5 y, minimal physical activity, assessed by step-counters; 3) 15 Young trained (YT), 24±3 y, competitive sprinters following high-intensity daily training; 4) 15 Young Untrained (YU), 27±4 y, moderate physical activity without structured training. TD-NIRS acquisitions were performed on the vastus lateralis (VL) muscle of the dominant leg during 300 s at rest, exploiting a portable device (PIONIRS s.r.l., Italy) with 2.5 cm source-detector distance. Absolute values for the concentrations of O2Hb, HHb, tHb and StO2 on VL were calculated and the relative power spectral density (rPSD), for all the parameters, inside bands III-VI were found. Statistically significant differences between groups were identified using Mann-Whitney U tests with correction for multiple comparisons. RESULTS: Basal O2Hb was higher for YT = 100±26 μM vs YU = 738±28 μM, p = 0.029, and OU = 64±22, p = 0.004, but not vs OT = 78±27 μM, p = 0.076, suggesting that training improves perfusion during rest, regardless of aging. Similar results were obtained for tHb. HHb had higher values only for YT (49±17 μM) vs YU (32±1 μM, p = 0.025), showing that venous compartment in the VL muscle is less sensitive to aging and training. StO2 is significantly different among all groups except for YT (68±3 %) vs YU (70±35 %, p = 0.073) and OT (66±4 %, p = 0.109). The StO2 values found for all groups and their differences confirm the effect of aging on muscle oxidative basal metabolism. For rPSD we found that: 1) Bands VI and V: most of the parameters have higher values for OT vs OU and YT vs YU (pmax=0.04), underlying the role of endothelial activity as a marker of microvascular health and adaptability; 2) Bands IV and III: opposite pattern observed, in particular for OT vs OU (pmin=0.07). CONCLUSION: TD-NIRS has the potential to be a useful tool for monitoring early signs of aging-related decline and muscular training effect. Training is more impactful than aging on muscle microvasculature health and basal metabolism. The more trained muscles rely less on autonomic or smooth-muscle-mediated components, underlying the role of endothelial activity as a biomarker of trained muscles.
Read CV Rebecca ReECSS Paris 2023: OP-MH33
INTRODUCTION: The brain is primarily supplied by the common carotid arteries (CCAs) and receives up to 20% of the total cardiac output at rest. Hemodynamic changes in the CCAs due to anatomical asymmetries or vascular abnormalities can increase susceptibility to atherosclerotic plaque formation and may become apparent during physiological stress, such as physical exercise. This study aimed to characterize hemodynamics in both carotid arteries before, during, and after in-magnet exercise in healthy subjects using 2D phase-contrast (PC) MRI. METHODS: After resting-state measurements, subjects performed supine exercise using an MR-compatible bicycle ergometer (Lode) inside a 3 Tesla MRI scanner (Philips). The protocol consisted of two 5-minute stages of steady-state moderate (60% of supine maximal heart rate; HRmax) and vigorous (80% of supine HRmax) exercise, and passive recovery (1). During each stage, transversal 2D PC-MRI series of the CCAs were acquired. CCA flow patterns were evaluated using feature points within the cardiac cycle, and pulsatility (PI) and resistance indices (RI) were calculated (2). Bilateral differences and changes from rest were assessed using mixed model analyses. RESULTS: Healthy subjects (n = 12; 6/6, m/f; 25 ± 6 y) completed the in-magnet exercise protocol. Relative timing of peak systole with respect to the cardiac cycle increased progressively with exercise from 5.3 ± 1.7% (HR, 62 ± 9 beats/min) at rest, to 6.6 ± 1.5% (p ≤ 0.001; HR, 101 ± 7 beats/min) with moderate exercise, and 7.0 ± 1.0%, (p ≤ 0.001; HR, 131 ± 7 beats/min) with vigorous exercise. Larger delays were observed for the secondary systolic peak (rest, 20.9 ± 4.3%; moderate, 27.8 ± 5.6%; vigorous, 32.0 ± 6.3%; p ≤ 0.001) and for onset of diastole (rest, 30.7 ± 3.8%; moderate, 44.2 ± 5.1%; vigorous, 48.8 ± 3.2%; p ≤ 0.001). Consequently, the systolic fraction of total CCA flow increased from 55.7 ± 6.2% at rest to 75.8 ± 10.0% (p ≤ 0.001) during moderate and to 88.9 ± 4.9% (p ≤ 0.001) during vigorous exercise, decreasing to 65.2 ± 7.2% during recovery (p ≤ 0.001). PI and RI increased from rest (PI, 2.3 ± 0.7; RI, 0.8 ± 0.1) to moderate (PI, 2.9 ± 0.8; RI, 0.9 ± 0.1; p ≤ 0.001) and vigorous exercise (PI, 4.0 ± 0.8; RI, 0.9 ± 0.04; p ≤ 0.001), decreasing again during recovery (PI, 2.8 ± 0.6; RI, 0.9 ± 0.1; p ≤ 0.01). No differences were observed between the left and right CCA. CONCLUSION: This study provided quantitative MRI measurements of the hemodynamic response in the CCAs during exercise. Elevated pulsatility and resistance indices suggest that arterial stiffness and cerebrovascular resistance increase during exercise. No asymmetries in any of the parameters were observed in these healthy subjects. Our findings provide insight into the blood flow adaptations through the CCAs in response to exercise that may be relevant for investigating atherosclerosis and neurodegenerative diseases. 1. Mast et al. NeuroImage 2022;250:118961 2. Hoi et al. Physiol Meas 2011;31:3
Read CV Isa H. MastECSS Paris 2023: OP-MH33