Costantino Balestra

Background: Inspired oxygen fraction (FiO₂) may alter the internal physiological cost of supramaximal interval training. This randomized exploratory active-comparator study compared functional adaptations to hyperoxic versus hypoxic Tabata-format high-intensity interval training (HIIT). Methods: Twenty-three physically active men completed 3 weeks of supramaximal Tabata-format HIIT (3 sessions·week⁻¹; 8 × 20 s with 10 s recovery) under hyperoxia (FiO₂ = 0.60, n = 13) or hypoxia (FiO₂ = 0.16, n = 10). Intensity was initially prescribed from baseline CPET-derived Wmax and operationally regulated using heart rate to maintain the intended internal cardiovascular strain. V̇O₂max was the primary outcome; ventilatory thresholds, peak blood lactate, perceived exertion, heart-rate outcomes, and available workload records were secondary or exploratory outcomes. Results: V̇O₂max increased from 37.77 ± 8.67 to 41.46 ± 8.41 mL·kg⁻¹·min⁻¹ in hyperoxia and from 38.30 ± 9.91 to 39.80 ± 9.80 mL·kg⁻¹·min⁻¹ in hypoxia, with a larger baseline-adjusted improvement under hyperoxia. VT1 increased from 175.0 ± 52.0 to 213.5 ± 46.3 W in hyperoxia and from 160.0 ± 47.4 to 170.0 ± 48.3 W in hypoxia. VT2 increased from 232.7 ± 51.4 to 263.5 ± 40.3 W in hyperoxia and from 207.5 ± 55.3 to 222.5 ± 49.2 W in hypoxia. Peak lactate decreased from 9.58 ± 1.37 to 8.81 ± 1.47 mmol·L⁻¹ in hyperoxia but increased from 8.93 ± 0.84 to 9.25 ± 0.75 mmol·L⁻¹ in hypoxia. Wmax increased from 278.8 ± 55.8 to 334.6 ± 45.1 W in hyperoxia and from 247.5 ± 73.1 to 282.5 ± 63.5 W in hypoxia. Conclusions: Hyperoxic and hypoxic Tabata-format HIIT elicited divergent functional response profiles within this internally regulated two-arm protocol. Hyperoxia was associated with broader aerobic functional improvements and lower post-exercise peak lactate, whereas hypoxia produced smaller aerobic gains and a higher post-exercise peak lactate response. These findings should be interpreted as exploratory because of the small sample, absence of a normoxic comparator, and limited session-level external-load and heart-rate recording. Clinical trial number: ClinicalTrials.gov, NCT07551869. Retrospectively registered on 5 April 2026.

Introduction: This paper is a narrative review and theoretical perspective presenting principles, concepts, and perspectives for improving decompression procedures. It distinguishes three levels of evidence: established observations, hypotheses with experimental support, and mechanistic scenarios that remain hypothetical. Methods: We organize decompression around two linked dimensions: bubbles as the primary physical event and microparticles (MPs) as a physiological consequence. We hypothesize that a substantial proportion of decompression-related microbubbles originate from pre-existing gas micronuclei associated with active hydrophobic sites (AHS) at three locations: distal arterial, venous, and extravascular. From these assumptions, five bubble scenarios are considered: growth and detachment from distal arterial AHS; growth and detachment from venous AHS; pulmonary bubble filtration; survival of arterial gas microbubbles and their potential target organs; and intravascular bubble development. Physiological factors may generate MPs, endothelial dysfunction, systemic inflammation, and possibly a secondary generation of microbubbles. Results and discussion: The proposed scenarios align with decompression sickness (DCS) pathophysiology across five target organ systems: skin, brain, inner ear, spinal cord, and musculoskeletal tissue. Inflammatory stress appears important for defining post-dive intervals and multiday diving patterns. Designing decompression procedures therefore requires integrating individual variability and dive history; dive characteristics such as rapid ascents, yo-yo diving, and surface decompression; the bubble scenarios triggered during ascent; and accumulated oxidative stress, oxy-inflammation, and endothelial damage that modify susceptibility to DCS. Conclusion: There is no single ultimate decompression algorithm; rather, different strategies reflect different experience, assumptions, and operational contexts.

Background: Intermittent Hypoxic–Hyperoxic Training (IHHT) induces physiological adaptations. While its efficacy in athletic performance remains debated, IHHT improves health markers in pathological and geriatric populations. This Exploratory Pilot Study aimed to explore the safety and feasibility of two IHHT protocols through preliminary responses. Methods: Twelve healthy volunteers completed a 4-week intervention (two sessions/week, 45 min/session) combining IHHT simultaneously during low-intensity exercise. The study compared a Training Group (TG: 30 min hypoxia, 7.5 min normoxia, 7.5 min hyperoxia) with a Conditioning Group (CG: 15 min hypoxia, 22.5 min normoxia, 7.5 min hyperoxia). Outcomes assessed included cardiorespiratory parameters, Acute Mountain Sickness symptoms, Perceived Exertion, a comprehensive biochemical panel, systemic inflammation, oxidative stress, and renal status. Results: Both protocols were well-tolerated. The TG exhibited significantly greater oxygen desaturation than the CG (p = 0.048). Moreover, the CG demonstrated a significantly attenuated increase in Interleukin-6 (p = 0.021) compared to the TG. Additionally, preliminary variations highlighted an interesting reduction in lipid parameters (TC, LDL, and Apo A1/B ratios) in both groups, although these did not reach statistical significance after FDR correction. Conclusions: While both protocols proved feasible and safe, a more balanced hyperoxic-to-hypoxic exposure (CG) showed better acute physiological tolerability, attenuating cardiovascular strain and mitigating systemic pro-inflammatory responses compared to the unbalanced exposure (TG). Finally, the preliminary variations observed in lipid parameters provide a rationale that warrants further controlled investigations.

Background: Whether inspired oxygen fraction (FiO₂) can modulate the internal meta-bolic cost of supramaximal high-intensity interval training (HIIT) and thereby direct training adaptation remains unclear. We tested whether hyperoxic versus hypoxic ex-posure during Tabata-format HIIT induces distinct adaptive phenotypes. Methods: Twenty-three physically active men completed 3 weeks of supramaximal Tabata HIIT (3 sessions·week⁻¹; 8 × 20 s with 10 s recovery) under hyperoxia (FiO₂ = 0.60, n = 13) or hypoxia (FiO₂ = 0.16, n = 10). Training intensity was regulated to main-tain a comparable internal physiological stimulus rather than an identical external workload. Pre- and post-intervention assessments included maximal oxygen uptake (VO₂max), first and second ventilatory thresholds (VT1, VT2), peak blood lactate, and session rating of perceived exertion (RPE). Post-intervention between-group differences were analysed using ANCOVA adjusted for baseline values; RPE was analysed using a linear mixed-effects model. Results: VO₂max improved in both groups but increased more after hyperoxic training than after hypoxic training (+3.69 vs. +1.50 mL·kg⁻¹·min⁻¹; β = 2.18 mL·kg⁻¹·min⁻¹, 95% CI [1.77–2.59], p < 0.001). Hyperoxia also produced larger gains in VT1 (β = 29.99 W, 95% CI [17.09–42.89], p < 0.001) and VT2 (β = 20.74 W, 95% CI [9.43–32.05], p = 0.001). Peak lactate responses diverged bidirectionally, decreasing in hyperoxia (−0.77 mmol·L⁻¹) and increasing slightly in hypoxia (+0.27 mmol·L⁻¹), with a significant ad-justed between-group effect (β = −1.02 mmol·L⁻¹, 95% CI [−1.47 to −0.57], p < 0.001). RPE declined across sessions in both groups, with a steeper decrease under hyperoxia (Con-dition × Session: β = −0.36, 95% CI [−0.44 to −0.28], p < 0.001). Conclusions: Hyperoxic and hypoxic supramaximal HIIT elicited distinct functional adaptive profiles. Hyperoxia induced greater improvements in aerobic capacity and ventilatory thresholds, reduced peak lactate accumulation, and accelerated the decline in perceived exertion, whereas hypoxia was associated with a more glycolytic response pattern. These findings support the interpretation that FiO₂ acts as a modulator of in-ternal physiological load and shapes the metabolic phenotype of adaptation during su-pramaximal interval training.

As we have been studying oxygen for 250 years

Nitric oxide (NO) plays a crucial role in muscle oxidative capacity, which predicts muscle strength. This study aimed to investigate whether different breathing techniques (nasal or oral breathing) affect muscle performance during acute exhaustive exercise. In our study, 49 healthy individuals (24♀/25♂; age 22.8 ± 3.4 years) performed two Wingate anaerobic tests in a counterbalanced order. Although perceived exertion was significantly higher with oral breathing (Borg Scale: 9.0 ± 1.1 vs. 8.0 ± 1.3, p = 0.04), breathing mode did not impact power output (peak: 749 ± 290 vs. 728 ± 284 W; average: 576 ± 217 vs. 575 ± 216 W, p = 0.2). NIRS data indicated no significant differences in muscle desaturation between the two breathing modes; however, nasal breathing resulted in significantly faster (0.45 ± 0.4 vs. 0.23 ± 0.12%/s, p = 0.02) and greater (75.2 ± 4.0 vs. 73.1 ± 3.6%, p = 0.04) post-exercise muscle recovery. As an indirect marker of NO bioavailability, flow-mediated dilation (FMD) was associated with a significant improvement (Pre: 107.4 ± 3.0% vs. Post: 110.3 ± 3.6%, p < 0.001) via nasal breathing only, with a significant difference between the two breathing modes (p < 0.0001). Therefore, we suggest that the nitrate–nitrite–NO pathway enhances muscle energy and function, which highlights the importance of nasal breathing.

Objective: To evaluate the effects of different exercise training modalities on maximal and sub-maximal physical fitness in chronic stroke patients and determine the optimal training dosage. Design: Systematic review and meta-analysis of 38 randomized controlled trials. Methods: A comprehensive search was conducted across seven databases (MedLine, Embase, ScienceDirect, Cochrane Library, CINAHL, and SPORTSDiscus) up to March 31, 2024. Maximal fitness was measured by VO2 max/peak, and sub-maximal fitness by the 6- or 12-minute walk test (6MWT) Results: Aerobic and mixed training significantly improved VO2 max/peak (MD = 3.16 [2.83, 3.49], p < 0.00001; I² = 22%). Only aerobic training significantly enhanced 6MWT performance (MD = 34.30 [25.08, 43.53], p < 0.00001; I² = 25%). Sensitivity analysis revealed that VO2 max/peak gains were greater with moderate-to-high intensity, while moderate intensity sufficed for 6MWT improvement. The optimal regimen was 45-minute sessions of moderate-to-high intensity aerobic training, at least three times weekly for a minimum of eight weeks. Conclusion: Moderate-to-vigorous aerobic training enhances physical fitness in chronic stroke. High-intensity and mixed training programs yield greater maximal fitness improvements, while moderate intensity benefits sub-maximal capacity. Targeted, intensity-monitored exercise programs of ≥45 minutes, three times weekly over ≥8 weeks, are recommended for significant fitness gains.

Background and Objectives: This study investigates the effects of a five-week training program on the medial gastrocnemius muscle, comparing two approaches: blood flow restriction (BFR) training and normobaric hyperoxia (oxygen supplementation). It evaluates three strengthening modalities (dynamic, isometric, and the 3/7 method) analyzing their impact on maximal voluntary contraction (MVC), muscle architecture, and perceived exertion. Methods: A total of 36 young healthy participants (21 females, 15 males) were randomized into six subgroups (n = 6 each) based on the type of contraction and oxygen condition. Training sessions (three per week) were conducted for five weeks at 30% of MVC. Measurements of MVC, muscle circumference, pennation angle, fascicle length, and perceived exertion were taken at baseline (T0), mid-protocol (T1), and post-protocol (T2). Results: All groups demonstrated significant increases in MVC after five weeks, with no notable differences between BFR and oxygen conditions. Structural changes were observed in specific subgroups: the BFR-isometric group showed increased calf circumference (p < 0.05), and the 3/7 groups exhibited significant fascicle length gains (p < 0.05). Perceived exertion was consistently higher in BFR groups compared to oxygen supplementation, particularly in dynamic exercises. Conclusions: Both BFR and oxygen supplementation are effective in enhancing strength with light loads, though they elicit different structural and perceptual responses. Oxygen supplementation may be more comfortable and less strenuous, offering a viable alternative for populations unable to tolerate BFR. Future research should focus on optimizing training parameters and exploring applications tailored to specific athletic or clinical contexts.

The goal of this study was to evaluate inflammatory and oxidative stress responses in human subjects (9 females and 15 males) (age [29.6 ± 11.5 years old (mean ± SD)], height [172.0 ± 10.05 cm], and weight [67.8 ± 12.4 kg]) exposed to 1.45 ATA of helium (He) or nitrogen (N₂) without concurrent hyperoxia. We hypothesized that elevated gas pressures would elicit an inflammatory response concurrent with oxidative stress. Consistent with ex vivo studies, both gasses elicited neutrophil activation, small elevations in microparticles (MPs) and increases in intra-MP interleukin (IL)-1β and inflammatory nitric oxide synthase, and an increase in urinary IL-6 concurrent with a marked reduction in plasma gelsolin. Mixed responses indictive of oxidative stress, with some biomarker elevations but little change in others and a decrease in some, were observed. Overall, these results demonstrate that exposure to typical diving gasses at a mildly elevated partial pressure will initiate inflammatory responses, which may play a significant role in decompression sickness (DCS). The complex pattern of oxidative stress responses may be indicative of competing systemic reactions and sampling different body fluids.

Underwater activities are characterized by an imbalance between reactive oxygen/nitrogen species (RONS) and antioxidant mechanisms, which can be associated with an inflammatory response, depending on O₂ availability. This review explores the oxidative stress mechanisms and related inflammation status (Oxy-Inflammation) in underwater activities such as breath-hold (BH) diving, Self-Contained Underwater Breathing Apparatus (SCUBA) and Closed-Circuit Rebreather (CCR) diving, and saturation diving. Divers are exposed to hypoxic and hyperoxic conditions, amplified by environmental conditions, hyperbaric pressure, cold water, different types of breathing gases, and air/non-air mixtures. The “diving response”, including physiological adaptation, cardiovascular stress, increased arterial blood pressure, peripheral vasoconstriction, altered blood gas values, and risk of bubble formation during decompression, are reported.