Paul Robach’s research while affiliated with Grenoble Alpes University and other places

Ultra-endurance exercise places extreme physiological demands on oxygen transport, yet its impact on red blood cells (RBCs) remains underexplored. We conducted a multi-omics analysis of plasma and RBCs from endurance athletes before and after a 40-km trail race (MCC) and a 171-km ultramarathon (UTMB®). Ultra-running led to oxidative stress, metabolic shifts, and inflammation-driven RBC damage, including increased acylcarnitines, kynurenine accumulation, oxidative lipid and protein modifications, reduced RBC deformability, enhanced microparticle release, and decreased hematocrit – hallmarks of accelerated RBC aging and clearance. Post-race interleukin-6 strongly correlated with kynurenine elevation, mirroring inflammatory responses in severe infections. These findings challenge the assumption that RBC damage in endurance exercise is primarily mechanical, revealing systemic inflammation and metabolic remodeling as key drivers. This study underscores RBCs as both mediators and casualties of extreme exercise stress, with implications for optimizing athlete recovery, endurance training, and understanding inflammation-linked RBC dysfunction in clinical settings. Teaser Marathon running imparts molecular damage to red blood cells, the effects of which are exacerbated by increased distances of ultramarathons.

Carbon monoxide (CO) rebreathing is frequently used to determine hemoglobin mass (Hbmass) during hypoxic or heat training and high-altitude research. Accurate and reliable carboxyhemoglobin (HbCO) determination is crucial for reliable Hbmass measurements. The aim was therefore to explore the stability of HbCO and interchangeability of two Radiometer analyzers in the determination of Hbmass. Twelve subjects performed a CO rebreathing test. Five capillary blood samples were taken before and after the CO rebreathing test and either analyzed immediately on site (three capillary tubes, Day 1, ABL 90) or stored at room temperature and sent to another laboratory for analysis 4-8 days later (two capillary tubes, ABL 825). Intraclass correlation coefficient (ICC) and relative typical error (TE) were calculated to compare both measurements. A paired sample t test was performed to detect potential differences between Day 1 (ABL 90) and Days 4-8 (ABL 825). A trivial mean difference was observed between the two measurements for ΔHbCO (0.05%, p = 0.01, d = -0.12) and Hbmass (7.7 g, p = 0.01, d = 0.10). High reliability (ICC > 0.98) and low TE (< 0.91%) were found for ΔHbCO and Hbmass. Immediate analysis with the same analyzer remains recommended despite trivial differences between measurements. However, when logistical issues (analyzer breakdown, extreme, and/or remote locations) do not allow optimal procedures, delayed analysis, potentially with a different analyzer, might be used as a viable alternative.

Background: Discordant results have been previously reported regarding the impact of high-altitude exposure on the coagulation. We aimed to investigate changes in coagulation parameters in lowlanders exposed to high altitude for 14 days using a combination of dynamic coagulation assays and conventional in vitro tests. Material and Methods: We assessed coagulation in 10 lowlanders using whole-blood rotational thromboelastometry (ROTEM), thrombin generation assay (TGA) on poor-platelet plasma, and conventional coagulation tests. Tests were performed at low altitude (LA, 210 m) and at the end of a 14-day sojourn at high altitude (HA), including passive ascents to 3,800m for 6 days and then to 5,100m for 8 days. Results: Conventional tests revealed significant changes in coagulation factors and inhibitors after HA exposure, although these changes remained within normal ranges. ROTEM assays demonstrated a delayed clot initiation in EXTEM/FIBTEM, without any alteration in clot firmness, in HA vs. LA (p<0.01). TGA changes showed an increase in time to peak (p<0.01), a decrease in endogenous thrombin potential (p<0.05) and a decrease in thrombin peak (p<0.001). Conclusions: We found no evidence of hypercoagulability in lowlanders after a 14-day sojourn at HA. In contrast, dynamic coagulation assays (ROTEM and TGA) revealed a hypocoagulable pattern.

Purpose To investigate the effects of a repeated-sprint training in hypoxia induced by voluntary hypoventilation at low lung volume (RSH-VHL) including end-expiratory breath holding (EEBH) of maximal duration. Methods Over a 4-week period, twenty elite judo athletes (10 women and 10 men) were randomly split into two groups to perform 8 sessions of rowing repeated-sprint exercise either with RSH-VHL (each sprint with maximal EEBH) or with unrestricted breathing (RSN, 10-s sprints). Before (Pre-), 5 days after (Post-1) and 12 days after (Post-2) the last training session, participants completed a repeated-sprint ability (RSA) test on a rowing ergometer (8 × 25-s “all-out” repetitions interspersed with 25 s of passive recovery). Power output (PO), oxygen uptake, perceptual-motor capacity (turning off a traffic light with a predetermined code), cerebral (Δ[Hbdiff]) and muscle (Δ[Hb/Mb]diff) oxygenation, cerebral total haemoglobin concentration (Δ[THb]) and muscle total haemoglobin/myoglobin concentration (Δ[THb/Mb]) were measured during each RSA repetition and/or recovery period. Results From Pre-to Post-1 and Post-2, maximal PO, mean PO (MPO) of the first half of the test (repetitions 1–4), oxygen uptake, end-repetition cerebral Δ[Hbdiff] and Δ[THb], end-repetition muscle Δ[Hb/Mb]diff and Δ[THb/Mb] and perceptual-motor capacity remained unchanged in both groups. Conversely, MPO of the second half of the test (repetitions 5–8) was higher at Post-1 than at Pre-in RSH-VHL only (p < 0.01), resulting in a lower percentage decrement score over the entire RSA test (20.4% ± 6.5% vs. 23.9% ± 7.0%, p = 0.01). Furthermore, MPO (5–8) was greater in RSH-VHL than in RSN at Post-1 (p = 0.04). These performance results were accompanied by an increase in muscle Δ[THb/Mb] (p < 0.01) and a concomitant decrease in cerebral Δ[THb] (p < 0.01) during the recovery periods of the RSA test at Post-1 in RSH-VHL. Conclusion Four weeks of RSH-VHL including maximal EEBH improved the ability of elite judo athletes to repeat high-intensity efforts. The performance improvement, observed 5 days but not 12 days after training, may be due to enhanced muscle perfusion. The unchanged oxygen uptake and the decrease in cerebral regional blood volume observed at the same time suggest that a blood volume redistribution occurred after the RSH-VHL intervention to meet the increase in muscle perfusion.

Background. Since vascular responses to hypoxia in both healthy high-altitude natives and chronic mountain sickness (a maladaptive high-altitude pathology characterised by excessive erythrocytosis and the presence of symptoms – CMS) remain unclear, the role of inflammation and oxidative/nitrosative stress on the endothelium-dependent and -independent responses in both the micro- and macrocirculation, in healthy Andeans at different altitudes and in CMS patients, was examined. Methods. 94 men were included: 18 lowlanders (LL), 38 healthy highlanders permanently living at 3,800 m (n=21 – HL-3,800) or in La Rinconada, the highest city in the world (5,100-5,300 m) (n=17 – HL-5,100/No CMS). Moreover, 14 participants with mild (Mild CMS) and 24 with moderate to severe CMS (Mod/Sev CMS) were recruited. All undertook two reactivity tests: i) local thermal hyperaemia (microcirculation) and ii) flow-mediated dilation (macrocirculation). Endothelium-independent function (glyceryl trinitrate) was also assessed only in La Rinconada. Findings. Conductance and skin blood flow velocity during the microcirculation test, as well as macrocirculation progressively decreased with altitude (LL>HL-3,800>HL-5,100/No CMS). CMS also induced a decrease in macrocirculation (HL-5,100/No CMS>Mild CMS=Mod/Sev CMS), while glyceryl trinitrate restored vascular function. Both oxidative stress and nitric oxide metabolites increased with altitude only. Principal component analysis revealed that increasing inflammation with altitude was associated with a progressive decline in both micro- and macrovascular function in healthy highlanders. Interpretation. Both micro and macrovascular function are affected by chronic exposure to hypoxia, the latter being further compounded by CMS.

We investigated highlanders, permanently living at an altitude of 5100 m and compared Chronic Mountain Sickness (CMS) patients with control volunteers. While we found differences in systemic parameters such as blood oxygen content, hematocrit, hemoglobin concentration, and blood viscosity, the mechanical and rheological properties of single red blood cells did not differ between the two investigated groups. image