Physiological Responses to Acute Hypobaric and Normobaric Hypoxia: Differences in Maximal Exercise and Clinical Impact

Abstract

Ferrarini, Giovanni, Mattia Canevari, Valeria Azzini, Piergiuseppe Agostoni, Beatrice Pezzuto, and Carlo Vignati. Physiological responses to acute hypobaric and normobaric hypoxia: Differences in maximal exercise and clinical impact. High Alt Med Biol. 00:00–00, 2026.—Hypoxia, defined by inspired partial pressure of oxygen (PiO₂) <150 mmHg, has been extensively studied in conditions of both reduced barometric pressure (hypobaric hypoxia, HH) and reduced inspired fraction of oxygen (FiO₂) at sea level (normobaric hypoxia, NH). Traditionally considered interchangeable, mounting evidence indicates that HH and NH elicit distinct cardiovascular, ventilatory, and gas-exchange responses during physical effort, likely due to factors beyond PiO₂, including air density, alveolar gas composition, exercise modality, and the age and sex of the individual performing the effort. A thorough understanding of how different hypoxic modalities affect exercise responses provides fundamental insights into human physiology and pathophysiology under extreme conditions, with practical implications for sports medicine and athletic training, as well as for patients with pathologies potentially influenced by hypoxia dealing with high altitude. This narrative review synthesizes current evidence on the differential effects of HH and NH on exercise responses, with an emphasis on maximal exercise capacity and underlying the physiological mechanisms regarding cardiovascular function, ventilatory adaptation, and gas-exchange responses, also outlining the implications for athletes, clinical populations (heart failure, chronic obstructive pulmonary disease, pulmonary hypertension), and altitude medicine.

Keywords

acute hypoxia cardiopulmonary physiology exercise hypobaric hypoxia normobaric hypoxia

Introduction

Hypoxia, defined as any combination of reduced barometric pressure (Patm) and/or a reduced inspired oxygen fraction (FiO₂), leading to an inspired partial pressure of oxygen (PiO₂) below 150 mmHg (Millet et al., 2012), represents a common environmental condition challenging human physiological homeostasis (Vignati et al., 2021).

Traditionally, hypoxia has been studied in two contexts: hypobaric hypoxia (HH), resulting from reduced Patm at high altitude or in decompression chambers, and normobaric hypoxia (NH), achieved by reducing FiO₂ while maintaining sea level Patm, usually through nitrogen enrichment of inspired gas (Mounier and Brugniaux, 2012; Richard and Koehle, 2012).

For decades, it was assumed that, for a given PiO₂, HH and NH elicited equivalent physiological effects and were thus interchangeable for research and training purpose (Mounier and Brugniaux, 2012), a premise that has underpinned much of altitude physiology and acclimatization research (Mounier and Brugniaux, 2012).

However, increasing evidence suggests that HH and NH do not provoke entirely overlapping physiological responses (Coppel et al., 2015; Mounier and Brugniaux, 2012; Netzer et al., 2017; Raberin et al., 2024b; Tanner et al., 2021). Factors such as differences in air density and gas diffusivity—which, unlike in HH, remains unchanged in NH- as well as potential microbubble formation in HH, may contribute to distinct responses (Coppel et al., 2015; Netzer et al., 2017; Savourey et al., 2003).

Although differences at rest and during submaximal exercise have been suggested (Richard and Koehle, 2012; Treml et al., 2020), attention has recently turned to how these two hypoxic modalities affect peak exercise responses. This topic is of particular interest for mountain medicine, sports medicine, athletic preparation, and the understanding of human limits in hypoxic environments (Coppel et al., 2015; Treml et al., 2020).

This narrative review examines the differential effects of HH versus NH on maximal exercise capacity and related physiological mechanisms, highlighting implications for athletes and patients with heart failure (HF), chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. We identified and included the most relevant and methodologically robust studies in the field, aiming to provide comprehensive coverage of the topic, including experimental, clinical, and applied perspectives. Where appropriate, findings obtained at rest or during submaximal exercise or at low altitude rather than sea level are discussed to provide physiological context and mechanistic interpretation of maximal exercise responses.

HH Versus NH: Physiological Bases

To elucidate potential differences between HH and NH during maximal exercise, it is first essential to consider the underlying physiological mechanisms.

Beside PiO₂, the main stimulus (Netzer et al., 2017), absolute Patm can modulate physiological responses through several mechanisms (Coppel et al., 2015; Millet et al., 2012; Mounier and Brugniaux, 2012; Savourey et al., 2003; Tanner et al., 2021):

Effects on alveolar gas composition and tissue nitrogen washout

In HH, the reduction in Patm induces tissue nitrogen washout, since ambient nitrogen partial pressure (PN₂) is initially lower than body PN₂ (Ånell et al., 2019). N₂ diffuses from tissues into the alveoli, transiently reducing alveolar partial pressures of O₂ (PAO₂) and CO₂ (PACO₂), a phenomenon absent in NH (Ånell et al., 2019; Coppel et al., 2015; Mounier and Brugniaux, 2012; Vinetti et al., 2025). This likely explains findings of faster in vivo blood desaturation in HH versus NH during short, severe hypoxic exposures (Coppel et al., 2015; Ferretti et al., 1997; Mounier and Brugniaux, 2012).

The alveolar gas equation (Conkin, 2016),

{PAO}_{2} (mmHg) = (PB - 47) \times {FiO}_{2} - [{FiO}_{2} + ((1 - {FiO}_{2}) / RER)]

where

FiO₂ is the dry-gas fraction of oxygen,

47 mmHg is water vapor partial pressure at 37°C (body temperature),

RER is the respiratory exchange ratio (carbon dioxide production − V̇CO₂/oxygen uptake − V̇O₂, as ml/min standard temperature and pressure, dry), and

1 – FiO₂ is the dry-gas fraction of nitrogen (FiN₂),

indicates that RER can influence PAO₂ differently between HH and NH at the same PiO₂, particularly when RER deviates from 1 (Millet et al., 2012; Vinetti et al., 2025). When RER is <1.0, PAO₂ tends to be higher in HH, and vice versa when RER is >1.0 (Conkin, 2016).

Inspired gas density and work of breathing

High-altitude air has lower density than normobaric air at the same PiO₂ (Raberin et al., 2024b). This lower density decreases airway resistance and the work of breathing (Richard and Koehle, 2012), with implications for resting and exertional respiratory muscle fatigue (Richard and Koehle, 2012).

Water vapor pressure

A critical but often overlooked factor in comparing hypoxic conditions is water vapor pressure (PH₂O) (Richard and Koehle, 2012). Accurate calculation of PiO₂ requires accounting for PH₂O, as its omission can lead to overestimation of the inspired oxygen pressure and misinterpretation of the hypoxic dose.

At body temperature (37°C), PH₂O is around 47 mmHg, which must be subtracted from the atmospheric pressure (Patm) when calculating PiO₂:

{PiO}_{2} = ({FiO}_{2} \times (Patm - {PH}_{2} O))

where Patm is the atmospheric pressure.

Neglecting PH₂O in the calculation of PiO₂ may introduce a variable error depending on barometric pressure and FiO₂ (Coppel et al., 2015). This error increases with greater differences between ambient barometric pressure at the testing site and the target altitude and may exceed ∼6 mmHg in PiO₂, corresponding to a simulated altitude mismatch of up to ∼600 m (Conkin, 2011).

Acid–base balance

HH and NH differ also in the magnitude of acute acid–base disturbances. In both conditions, hypoxemia activates the hypoxic ventilatory response, promoting CO₂ washout and respiratory alkalosis; however, at equivalent PiO₂, HH induces a larger reduction in the arterial partial pressure of CO₂ (PaCO₂) due to the combined effects of hypoxia-driven hyperventilation and the lower ambient CO₂ partial pressure, which increases the diffusion gradient for CO₂ elimination, resulting in a more pronounced alkalosis (Cerretelli and Samaja, 2003). In contrast, acute NH is characterized by milder hypocapnia and relatively preserved plasma bicarbonate concentrations, indicating limited metabolic compensation within the first hours of exposure (Limmer et al., 2020). While this contribution is secondary to the primary buffering provided by hemoglobin and plasma proteins (Cerretelli and Samaja, 2003), it remains physiologically relevant. During maximal exercise, the greater the respiratory alkalosis observed in HH, the less bicarbonate buffering capacity, thereby exacerbating exercise-induced perturbations in blood and muscle pH. Moreover, the more pronounced alkalosis shifts the oxyhemoglobin dissociation curve leftward, potentially impairing peripheral O₂ unloading and altering cerebrovascular regulation, which may contribute to distinct peripheral and central physiological responses between HH and NH.

This small yet important difference in the hemoglobin–oxygen dissociation curve therefore represents one of the modifications occurring along the oxygen cascade during acute hypoxia (Samaja and Ottolenghi, 2023). Further alterations and differences between HH and NH, where present and known, are discussed in the following sections.

Nitric oxide metabolism and bioavailability

HH and NH elicit divergent responses in nitric oxide (NO) metabolism (Ribon et al., 2016). Acute HH is characterized by a significant reduction in the partial pressure of exhaled NO, a phenomenon not observed during acute NH at equivalent PiO₂ (Hemmingsson and Linnarsson, 2009; MacInnis et al., 2015). This decrease in HH is primarily attributed to the physical effects of reduced barometric pressure and gas density, which enhance the axial backdiffusion of NO from the conducting airways into the alveoli, thereby increasing its uptake by hemoglobin in the pulmonary capillaries (Hemmingsson and Linnarsson, 2009; Faiss et al., 2013b). In addition, systemic NO bioavailability decreases during acute HH while remaining stable in NH (Faiss et al., 2013b). This impairment may be exacerbated by the higher oxidative stress typical of the HH environment (Ribon et al., 2016; Faiss et al., 2013b). Moreover, hypoxia influences NO release by Hb O₂ dissociation, which induces local venodilatation in the working muscles. These perturbations in NO homeostasis are physiologically relevant, as impaired NO signaling in HH has been proposed to contribute to lower acute ventilatory responses and increased total pulmonary resistance compared with NH (Faiss et al., 2013b).

Effects of Hypoxia on Functional Capacity

Maximal functional capacity, measured as maximal oxygen uptake (V̇O₂max), is a fundamental parameter of aerobic performance. Cardiopulmonary exercise testing is the gold standard for the evaluation of functional capacity, expressed as V̇O₂ at exercise peak, and for identifying the underlying physiological or pathophysiological mechanisms through the analysis of exhaled gases and ventilation (V̇E) to derive key ventilatory and metabolic variables (Schraufnagel and Agostoni, 2017).

It is well-established that acute exposure to hypoxia significantly reduces peak V̇O₂ (Agostoni et al., 2000; Ferretti et al., 1997; Heubert et al., 2005; Koistinen lv and Martikkala, 1995; Lawler et al., 1988; Martin and O’Kroy, 1993; Mollard et al., 2007; Ofner et al., 2014; Valentini et al., 2012) in direct proportion to PiO₂ decrease (Fulco et al., 1988; Millet et al., 2012; Wehrlin and Hallén, 2006). Several factors modulate the magnitude of this reduction:

Training status: highly trained athletes typically exhibit a greater percentage reduction in peak V̇O₂ under acute hypoxia than less trained or sedentary individuals (Ferretti et al., 1997; Heubert et al., 2005; Koistinen lv and Martikkala, 1995; Lawler et al., 1988; Martin and O’Kroy, 1993; Mollard et al., 2007; Ofner et al., 2014). This is often related to a higher propensity for exercise-induced hypoxemia (EIH), as elevated cardiac output and red blood cells’ rapid transit through pulmonary capillaries can limit gas exchange (Benoit et al., 2003; Ferretti et al., 1997; Koistinen lv and Martikkala, 1995; Lawler et al., 1988; Ward et al., 2017). This greater vulnerability is largely related to an increased propensity for EIH. In these athletes, the combination of very high cardiac output and rapid transit time of red blood cells through the pulmonary capillaries can already constrain pulmonary gas exchange (Durand et al., 2020). In addition, hypoxic pulmonary vasoconstriction (HPV) elevates pulmonary artery pressures (PAPs) and increases capillary stress, promoting fluid accumulation in the interstitial space even before overt alveolar edema develops (Swenson, 2020; Richalet et al., 2023). This subclinical interstitial fluid disrupts the alveolar-capillary barrier, impairs oxygen diffusion, and further exacerbates EIH, ultimately contributing to a greater reduction in peak V̇O₂ and maximal heart rate (HRmax) during hypoxic exercise (Swenson, 2020; Richalet et al., 2023; Durand et al., 2020).

Sex: recent studies have highlighted sex-related differences in pulmonary limitations influencing V̇O₂max in both normoxia and hypoxia (Raberin et al., 2024b). Female sex, with smaller lung and airway dimensions, shows lower peak ventilatory values. However, findings on the relative V̇O₂max decrease under acute hypoxia are inconsistent: Some reported a greater percentage decline in men in NH (Raberin et al., 2024b), others found similar decreases in both sexes in HH (Wagner et al., 1979), while Shephard et al. observed a slightly greater decline in women in NH (Shephard et al., 1988).

Type of exercise: treadmill exercise in HH elicits a greater depression of peak V̇O₂ than cycle ergometry in the same condition (Treml et al., 2020), likely reflecting differing metabolic and mechanical demands between exercise modalities in a hypobaric environment.

Beyond these factors, recent evidence reveals subtle but significant differences in peak V̇O₂ reduction between HH and NH. Treml et al. reported a more pronounced decline per 1000 m of simulated altitude in NH than in HH (−7.0% ± 1.4% in NH vs. −5.6% ± 0.9% in HH) (Treml et al., 2020).

However, other works have not consistently found statistically significant differences in peak V̇O₂ between acute HH and NH (Vinetti et al., 2025). These discrepancies have been attributed to several factors:

Magnitude and/or duration of hypoxia: brief exposures (≤5 minutes) elicit similar physiological responses in HH and NH, but these similarities often disappear during acute or subacute exposures (>5 minutes and <24 hours) (Richard and Koehle, 2012).

Inspired CO₂ partial pressure, humidity, and temperature: gas density plays a major role. In HH, lower air density may reduce the work of breathing, allowing greater maximal ventilation (V̇Emax) than in NH, where denser air increases respiratory effort (Mounier and Brugniaux, 2012; Raberin et al., 2024b; Treml et al., 2020; Vinetti et al., 2025). Humidity critically affects hypoxic dose calculations; neglecting PH₂O can lead to an overestimate of the hypoxic dose in NH (Coppel et al., 2015; Mounier and Brugniaux, 2012).

Barometric pressure and related factors: beyond the PiO₂, Patm itself influences physiological responses. HH entails an intrinsic Patm reduction, potentially inducing greater hypoxemia, hypocapnia, and alkalosis than NH at the same PiO₂ (Savourey et al., 2003; Tanner et al., 2021). Beyond its effect on inspired oxygen pressure, changes in ambient barometric pressure may also influence cardiovascular function by modifying transmural vascular pressures and venous capacitance. Experimental evidence indicates that alterations in external pressure gradients can significantly redistribute venous blood volumes and central fluid compartments, thereby affecting venous return and central hemodynamics (Arbeille et al., 2021). Mechanisms related to the alveolar gas equation and N₂ dilution, driven by the reduced PB, may further influence physiological responses and consequently exercise performance (Ånell et al., 2019; Mounier and Brugniaux, 2012).

The following sections provide a detailed analysis of cardiovascular and ventilatory adaptation under hypoxic conditions, comparing NH and HH (Table 1).

Table 1.

Main Physiological Differences Between Normobaric Hypoxia and Hypobaric Hypoxia During Maximal Exercise

Parameter	Normobaric hypoxia (NH) compared with normoxia	Hypobaric hypoxia (HH) compared with normoxia	Differences between HH and NH
Peak V̇O₂			HH vs. NH
HRmax			HH NH
Qmax			Few and conflicting data
BP	At the same workload Maximal values	At the same workload Maximal values	No clear difference documented
V̇Emax			HH NH
RR			HH NH
VT	At rest and during submaximal exercise During maximal exercise	At rest and during submaximal exercise During maximal exercise	NH vs. H At rest and during submaximal exercise
PAP	At rest and during exercise	At rest and during exercise	Limited data
SpO₂	During maximal exercise	During maximal exercise	Conflicting evidence; recent controlled studies suggest HH NH

: decline; : increase; : similar to; : higher than; : lower than.

BP, blood pressure; HRmax, maximal heart rate; PAP, pulmonary arterial pressure; peak V̇O₂, maximal oxygen uptake; Qmax, maximal cardiac output; RR, respiratory rate; SpO₂, peripheral oxygen saturation; TV, tidal volume; V̇Emax, maximal ventilation.

Cardiovascular Responses

Cardiovascular responses to maximal exercise in hypoxia are complex and differ depending on the type of hypoxia and the degree of acclimatization (Fig. 1).

FIG. 1.

Physiological response to hypoxia. Reproduced with permission from Parati et al. (2018). HR, heart rate; PaCO₂, arterial partial pressure of carbon dioxide.

Maximal heart rate

A reduction in HRmax is a well-documented phenomenon in subjects chronically exposed and acclimated to high altitude (PUGH, 1964; Reeves et al., 1987; Richalet et al., 1988; Richalet and Hermand, 2022), and this reduction correlates with both severity and duration of hypoxemia (Savard et al., 1995). Since resting HR increases with altitude, the HR response to exercise is blunted due to the combination of elevated resting HR and peak exercise HR reduction.

The main proposed mechanism for peak exercise HR reduction in chronic hypoxia involves an attenuation of sympathetic nervous system activation and a downregulation of cardiac β-adrenergic receptors (Savard et al., 1995). During maximal exercise at altitude, reduced plasma catecholamine levels are observed (Savard et al., 1995), along with a diminished HR response to a given increase in norepinephrine (an indicator of sympathetic activation) (Richalet et al., 1988; Savard et al., 1995). This receptor downregulation is thought to result from persistently elevated sympathetic tone (Richalet et al., 1988; Savard et al., 1995). A rapid recovery of HRmax upon oxygen supplementation suggests that sympathetic attenuation may be a centrally mediated phenomenon (Savard et al., 1995). Although increased parasympathetic activity has also been suggested as a contributing factor, it is more likely that vagal dominance becomes apparent due to the relative reduction in sympathetic activity (Savard et al., 1995).

Other proposed mechanisms for HRmax reduction in chronic hypoxia include increased blood viscosity, decreased cardiac filling pressure, and alterations in the autonomic regulation (Benoit et al., 2003). This self-limitation of HRmax is considered a cardioprotective adaptation, conserving myocardial oxygen consumption in an environment of reduced oxygen availability (Richalet et al., 1988). Some studies show no significant heart rate variability (HRV) variation between HH and NH (Tanner et al., 2021), suggesting similar overall autonomic regulation (reflected by HRV) despite Patm differences in chronic hypoxia.

HR responses in acute hypoxia are less clearly defined. At rest, acute hypoxia typically induces a marked increase in HR compared with normoxia (Richalet et al., 1988; Tanner et al., 2021; Vinetti et al., 2025), attributed to enhanced sympathetic and reduced vagal activity. A direct effect of hypoxia on cardiac electrophysiology has also been proposed (Benoit et al., 2003), while other mechanisms may include a reduced central drive activity (Martin and O’Kroy, 1993). Notably, sex-specific differences have also been reported during acute NH: following a 7-hour exposure, resting heart rate increases significantly in men, whereas it remains unchanged in women (Camacho-Cardenosa et al., 2022).

During maximal exercise, some studies have reported a decrease in peak HR both in acute NH and HH (Benoit et al., 1995; Ferretti et al., 1997; Lundby et al., 2001; Shephard et al., 1988), while others found no significant changes (Cerretelli and Di Prampero, 1980; Hughes et al., 1968). One explanation of HRmax reduction is a protective central mechanism (Verges et al., 2012): a more rapid development of muscle fatigue in moderate hypoxia may lead to increased inhibitory afferent signals to the central nervous system, dampening central drive and limiting peak HR (Ofner et al., 2014). Some studies have suggested that acute HH may induce a higher HR than acute NH (Richard and Koehle, 2012). Furthermore, Netzer et al. compared a real (HH) with a simulated mountain hike (NH), showing a significantly higher mean HR in HH (121 bpm) compared with NH (103 bpm), with a statistically significant difference (p = 0.029) observed at 66% of the time points measured (Netzer et al., 2017). Similarly, initial findings by Savorey et al. indicate a higher HRmax in HH compared with NH during a 40-minute test at a simulated 4500 m altitude (Savourey et al., 2003).

However, other studies have not supported these findings (Coppel et al., 2015; Tanner et al., 2021). Vinetti et al., in a controlled study, found no significant differences in HRmax, resting HR, or submaximal HR between HH and NH (Vinetti et al., 2025). The results of Savorey et al. in 2007, using a similar protocol to their previous study in 2003 (Savourey et al., 2003), showed no significant differences in HR between HH and NH (Savourey et al., 2007). This inconsistency among their own studies highlights the complexity and variability of findings in this area.

Highly trained athletes show a greater reduction in HRmax than individuals with average or low fitness levels (Benoit et al., 2003). Specifically, subjects experiencing EIH under normoxic conditions tend to show an even more marked reduction in HRmax under hypoxic conditions. Indeed, a lower SaO₂ during maximal exercise is correlated with a greater decrease in HRmax (Benoit et al., 2003). Martin and O’Kroy found that trained subjects exhibit both lower peripheral oxygen saturation (SpO₂) values at maximal tests and greater reductions in peak V̇O₂ than the untrained group (Martin and O’Kroy, 1993). Similarly, Ferretti et al. reported lower SaO₂ and greater peak V̇O₂ reduction at maximal exercise in trained subjects, and these differences were accentuated in hypoxia (Ferretti et al., 1997). In fact, a decrease in HRmax in acute hypoxia can have a significant impact on the overall reduction in peak V̇O₂, particularly at higher altitudes and in subjects with a higher peak V̇O₂ (Benoit et al., 2003). As previously mentioned, these performance alterations likely reflect not only systemic cardiovascular limitations but also HPV, which promotes interstitial fluid accumulation (Richalet et al., 2023; Durand et al., 2020). Evidence also indicates that treadmill exercise in HH causes a more marked decrease in HRmax than cycling in HH (Treml et al., 2020).

In terms of HRV, Vinetti et al. reported a significant difference in a resting HRV parameter: The root mean square of successive R–R interval differences (RMSSD) was lower in HH compared with NH (p < 0.05), with a medium effect size. Although other HRV parameters did not change significantly, the difference in RMSSD indicates that not all HRV measures are similar under acute conditions and that reduced intrathoracic pressure oscillations due to lower air density may explain these differences (Vinetti et al., 2025).

Maximum cardiac output and arterial O₂ content

Acute exposure to either NH or HH leads to an increase in cardiac output (Q̇) at rest. This rise is inversely proportional to the drop in PaO₂ and is primarily driven by an increase in HR, while stroke volume (SV) remains unchanged (Naeije, 2010; Siebenmann and Lundby, 2015).

Following acclimatization to high altitude, usually over a period of approximately 2 weeks, cardiac output at rest generally returns to values similar to those observed at sea level. However, HR remains elevated, and this is accompanied by a reduction in SV (Naeije, 2010).

Data from Operation Everest II suggest that in climbers acclimatized to extreme altitudes, cardiac output for a given V̇O₂ is not lower than at sea level. Cardiac function, including cardiac output and myocardial contractility, was preserved, with the increase in HR compensating for the fall in SV, thereby maintaining cardiac output (Reeves et al., 1987).

In contrast, maximum cardiac output (Q̇max) during exercise in moderate acute hypoxia has been reported inconsistently (Reeves et al., 1987), with some studies reporting unchanged Q̇max (Ferretti et al., 1997; Mollard et al., 2007) and others showing a reduction (Fukuda et al., 2010) (Fig. 2).

FIG. 2.

Time course of physiological adaptations to high altitude. The graph shows percentage changes from low-altitude baseline values in several key parameters over 11 days at altitude. Notable responses include increases in sympathetic activity and pulmonary artery pressure, while stroke volume decreases. Other variables such as heart rate, cerebral blood flow, and cardiac output show moderate increases followed by gradual normalization or decline. Reproduced with permission from Rimoldi et al. (2010).

In parallel to the subacute reduction in SV and Q̇max, an increase in arterial O₂ content (CaO₂) is observed. This rise is mainly attributed due to hemoconcentration and may partially counterbalance the decline in Q̇max and the consequent decrease in exercise capacity. Horstman et al. suggested that hemoconcentration may be a central mechanism regulating SV and Q̇max at altitude. In their study, the removal of 450 ml of blood and replacement with an equal volume of Ringer’s lactate solution after a 3-week stay at 4,500 m above sea level resulted in an increase in maximal SV and Q̇max, even though PAO₂ and O₂ saturation remained unchanged and despite a decrease in CaO₂ and consequently in V̇O₂max (Horstman et al., 1980).

A reduction in SV and Q̇max during exercise has been observed in both HH and NH (Fulco et al., 1988; Naeije, 2010); however, comparative data under maximal exertion remain limited. Petrassi et al. investigated Q̇ at several workloads under HH and NH conditions and found significantly lower values both at rest and at 100 W in HH compared with NH (Petrassi et al., 2018). The authors attributed these changes to variations in pulmonary hemodynamics, specifically increased total pulmonary resistance in HH, possibly due to increased lung volumes and reduced NO availability. Similarly, Levine et al. reported reduced Q̇ in hypobaric normoxia with a parallel increase in pulmonary vascular resistance (PVR), suggesting the vasoconstrictor role of PB reduction (Levine et al., 1988).

However, contradictory results were presented in a more recent study by Rosales et al., which demonstrated significantly higher Q̇ values at rest and during exercise in HH compared with NH (Rosales et al., 2022). These discrepancies highlight the complexity of comparing Q̇max between HH and NH, particularly given that Q̇, whether at rest, during submaximal, or maximal effort, varies with the degree and duration of altitude adaptation.

Systemic blood pressure

The physiological mechanisms involved in controlling systemic blood pressure (SBP) in hypoxia have been the subject of numerous studies (Bilo et al., 2019; Caravita et al., 2015; Parati et al., 2014; Veglio et al., 1999; Wolfel et al., 1994). Data on differences in SBP during maximal exercise in HH compared with NH are not available in the literature, and therefore, only hypotheses can be formulated. However, since more and more people are exposed to hypoxic environments (Mounier and Brugniaux, 2012; Savonitto et al., 1992), and a significant percentage of them are hypertensive (Vignati et al., 2026), it is useful to briefly discuss the temporal trend of SBP during hypoxic exposure.

As described above, in acute exposure, activation of the sympathetic system induces an increase in HR and consequently in Q̇, and parallel peripheral vasodilation. This causes SBP to remain unchanged in the first few minutes. Later, the vasoconstrictive role of sympathetic activation prevails, and there is an increase in both systolic and diastolic values (Bilo et al., 2019; Wolfel et al., 1994). This increase persists for days and months during hypoxic exposure, despite the subsequent decrease in Q̇ (Bilo et al., 2019; Wolfel et al., 1994). Little data are available in the literature, but a study conducted on young soldiers indicated increased SBP values even after 12 months of living at high altitude (Siqués et al., 2009).

Data on chronic exposure are inconclusive, although some evidence suggests a direct correlation between altitude and SBP even in individuals who have lived at high altitude for years (Aryal et al., 2016). In Andean highlanders, hypertension is often underestimated by office measurements because masked hypertension is common. Ambulatory hypertension, frequently associated with excessive erythrocytosis and cardiometabolic risk factors, provides a more accurate estimate of cardiovascular burden (Bilo et al., 2020). Excessive erythrocytosis increases blood viscosity, altering hemorheological properties and affecting both central circulation and peripheral resistance; the resulting impairment of microvascular flow promotes higher peripheral vascular resistance and contributes to the development of arterial hypertension, including masked forms and those detected through ambulatory monitoring in Andean highlanders (Stauffer et al., 2020; Tremblay et al., 2019).

During exercise, SBP tends to be higher in hypoxia than in normoxia (Naeije, 2010). However, since exercise capacity is reduced in hypoxia, the absolute maximum SBP values during exercise do not differ from those obtained in normobaric normoxia (Caravita et al., 2018).

In this context, particular attention should be paid to patients with arterial hypertension, as they more easily reach higher SBP values during exercise than normotensive subjects (Caravita et al., 2015; Savonitto et al., 1992; Winkler et al., 2017). Furthermore, hypertensive patients in normoxia have a higher slope of the SBP/V̇O₂ ratio while performing exercise in hypoxia, indicating that uncontrolled arterial hypertension in normoxia will be even less controlled in hypoxia (Bilo et al., 2019; Caravita et al., 2018).

At rest during acute NH (7-hour exposure simulating ∼3,000 m), no significant sex differences in SBP response have been reported (Camacho-Cardenosa et al., 2022), while during real HH exposure at high altitude (e.g., ∼3,480 m), a more pronounced increase in SBP has been observed predominantly in men (Camacho-Cardenosa et al., 2022). In women, SBP responses to hypoxia may vary across the menstrual cycle, suggesting a modulatory role of hormonal fluctuations on cardiovascular regulation (Raberin et al., 2024a).

Vignati et al. demonstrated that advancing age is associated with a more pronounced increase in SBP during HH exposure. In particular, older individuals, especially those with a history of hypertension or cardiovascular disease, exhibit higher systolic blood pressure values both at rest and during exercise under hypoxic conditions compared with younger subjects (Vignati et al., 2026).

Pulmonary circulation

As a result of acute hypoxia exposure, there is a vasoconstriction response in the pulmonary arterioles and a subsequent rise in the PAP. This is secondary to increased sympathetic activation and hypoxia-induced pulmonary vascular smooth cell activation and aims to optimize the ventilation/perfusion mismatch by redirecting the blood flow to better ventilated regions of the lungs (Dunham-Snary et al., 2017). The HPV develops within seconds of exposure to hypoxia, reaches a maximum intensity within minutes, and persists for months until it becomes irreversible due to the adverse capillary remodeling (Dunham-Snary et al., 2017).

During hypoxic exercise, where both effort and hypoxia contribute to PAP elevation, there is a steeper rise in PAP compared with normoxia, due to the HPV, leading to an increased right ventricular afterload. Some authors have suggested that this result may represent one of the limiting factors of exercise capacity in hypoxia, supported by evidence from studies reporting higher peak V̇O₂ values following the administration of pulmonary vasodilators (Ghofrani et al., 2004; Naeije et al., 2010).

However, these results have not been consistently confirmed across studies, and when present, the improvement has generally been modest, leading other investigators to question this interpretation (Anholm and Foster, 2011; Talbot et al., 2024). Similarly, Toro-Salinas et al. also provide further evidence supporting the hypothesis that reducing PAP through Sildenafil administration does not necessarily improve physical performance in conditions of acute real HH (Toro-Salinas et al., 2016). Limited data are available on the differences between HH and NH. A study conducted in 14 healthy volunteers reported lower systolic PAP values during maximal exercise in NH at sea level compared with HH at the Everest Base Camp, despite equivalent PiO₂. However, this result is confounded by the temporal discrepancy between the two tests, as acknowledged by the authors themselves, since the NH test was performed under acute hypoxia, whereas the HH assessment took place after acclimatization, with concomitant high-altitude-induced dehydration (Ghofrani et al., 2004).

Raberin et al. suggested that estrogens, acting as vasodilators, attenuate HPV, thereby limiting the hypoxia-induced increase in PAP. This modulatory effect may contribute to the less pronounced rise in pulmonary pressure observed in premenopausal women compared with men during hypoxic exposure (Raberin et al., 2024a).

Advanced age is associated with a more pronounced increase in PAP during acute hypoxic exposure, whereas in children and young adults, the response appears similar, particularly under prolonged hypoxic conditions (Rieger et al., 2022; Balanos et al., 2015; Turner et al., 2015).

Ventilatory Response

Ventilatory responses represent critical components of the oxygen cascade, and their alterations in hypoxia directly influence maximal exercise capacity. The distinctions between HH and NH become particularly evident when examining the following parameters:

Maximum minute ventilation (V̇Emax)

Exercise maximum minute ventilation (V̇Emax) is slightly augmented in HH and decreases in NH with increasing simulated altitude (Treml et al., 2020). Similar results were also obtained in the recent study by Vinetti and colleagues, who found a significantly higher V̇Emax in HH (164.1 ± 39 l/min at body temperature and PB, saturated with water vapor—BTPS) compared with NH (147.8 ± 34.8 l/min BTPS) (Vinetti et al., 2025). This divergence has been attributed to lower airflow resistance in HH due to lower air density, which facilitates greater ventilation (Raberin et al., 2024b; Treml et al., 2020). Supporting this hypothesis, Ogawa and colleagues found higher V̇Emax in hypobaric normoxia compared with normobaric normoxia in 11 subjects undergoing maximal treadmill exercise testing (Ogawa et al., 2019). Furthermore, the metabolic cost of breathing, which depends on the density of inspired gas, was found to be higher in NH (Mounier and Brugniaux, 2012), suggesting that the body, in a normobaric environment, must expend more energy to ventilate the same volume of air. However, some studies have not found significant differences in V̇Emax between normoxia and acute NH (Thompson et al., 2024), highlighting the variability between studies and experimental conditions.

Even in submaximal exercise, this difference is not always observed. Faulhaber and colleagues, in fact, did not find significant differences in their study (Faulhaber et al., 2020), while some authors suggest that ventilation may be higher in NH than in HH (Mounier and Brugniaux, 2012; Richard and Koehle, 2012). This finding has also been linked to reduced air density, which may allow for a lower V̇E during submaximal efforts and a higher V̇Emax at maximal efforts (Treml et al., 2020).

Respiratory rate

The main ventilatory mechanism underlying the rise in V̇Emax is an increase in respiratory rate (RR). This mechanism has been described for both maximal and submaximal efforts (Faulhaber et al., 2020; Vinetti et al., 2025). While data at rest are often conflicting (Faulhaber et al., 2020; Savourey et al., 2007, 2003), studies by Savorey and colleagues, conducted in 2003 and 2007 on 18 subjects evaluated in HH and NH conditions at rest, found higher RR values in HH than in NH in the first 5 minutes of hypoxic exposure, with similar values being reached after 40 minutes of exposure (Savourey et al., 2007, 2003). Faulhaber and colleagues, similarly, found no differences in RR at rest after 30 minutes (Faulhaber et al., 2020). Interpretation of these findings is complicated by the fact that resting RR is subject to significant intra- and interindividual variability, influenced by conscious control, emotional state, and methodological factors, which can confound baseline measurements and comparisons across individuals or groups, with this variability being further amplified during hypoxic exposure (Zhang and Robbins, 2000). In addition, gender differences in ventilatory response are pronounced: Men typically exhibit a greater increase in minute ventilation and loop gain during acute hypoxia, while women demonstrate a steeper decline in oxygen saturation and less efficient ventilatory compensation (Camacho-Cardenosa et al., 2022). Regarding submaximal exercise, Faulhaber et al. described higher RR in HH compared with NH, with a difference of ∼8% (p = 0.06) for 100 W-efforts (Faulhaber et al., 2020). Vinetti and colleagues found no significant differences in RR during submaximal exercise, while during maximal efforts, the difference was significant in favor of a higher RR in HH (62.6 ± 10.2 minute⁻¹ in HH vs. 56.4 ± 8.9 minute⁻¹ in NH, p < 0.001) (Vinetti et al., 2025).

In acute intermittent NH, older individuals exhibit an attenuated ventilatory response compared with younger subjects, particularly RR, but also in VEmax, likely due to reduced chemoreceptor sensitivity; in contrast, during prolonged exposure in a hypobaric environment, older individuals may develop an increased hyperpneic response, which may contribute to improved tolerance to altitude (Liu et al., 2020). Rieger and colleagues demonstrated that even in real HH (∼3,000 m), children exhibit an early increase in VE driven primarily by a rise in RR, whereas adults show little or no significant ventilatory response at the same altitude. This earlier response in children is likely related to greater peripheral chemoreceptor sensitivity and a lower activation threshold for hyperventilation (Rieger et al., 2022).

Tidal volume

The increase in RR is also accompanied by a change in tidal volume (TV), which is lower in HH than in NH both at rest (Faulhaber et al., 2020; Savourey et al., 2007, 2003) and during submaximal exercise (Faulhaber et al., 2020). Similar values were found for maximal efforts (Vinetti et al., 2025). Studies by Savorey and colleagues demonstrated a higher TV during acute exposures in NH compared with HH at rest (Savourey et al., 2007, 2003). Faulhaber and colleagues also found comparable data during submaximal exercise, with VT values 5% lower in HH compared with NH at 100-W efforts (Faulhaber et al., 2020). These values subsequently became comparable at higher-effort intensities. These data were confirmed by the work of Vinetti, who found a significantly lower VT in HH compared with NH at submaximal workloads (1.50 ± 0.23 l BTPS in HH vs. 1.62 ± 0.25 l BTPS in NH at 60–80 W); however, this difference disappeared at maximal efforts (2.62 ± 0.43 l BTPS in HH vs. 2.62 ± 0.45 l BTPS in NH) (Vinetti et al., 2025).

Peripheral oxygen saturation

Evidence on changes in SpO₂ at maximal exercise between NH and HH is conflicting. A recent study by Vinetti measured significantly higher SpO₂ values in HH compared with NH for all exercise intensities (Vinetti et al., 2025). They hypothesized that this difference was due to the different V̇E and other factors typical of HH, such as increased O₂ diffusion (although other studies have shown a reduction in diffusing capacity of the lungs for carbon monoxide (DLCO) after acute high-altitude exposure, which normalizes and increases after ∼2 weeks of acclimatization) (Agostoni et al., 2013, 2011), increased O₂ delivery to the locomotor muscles secondary to the decreased work of breathing and therefore the corresponding reduced blood supply to the respiratory muscles, and decreased venous return and Q̇ with consequent increased blood transition time in the pulmonary capillaries secondary to the reduced intrathoracic pressure swings in HH (Vinetti et al., 2025).

However, the data from the review by Treml and colleagues contradict these findings; they found no differences in SpO₂ reduction between HH and NH in the studies they analyzed, despite the significant difference in V̇Emax (Treml et al., 2020).

Furthermore, previous studies also described SpO₂ levels that were not different or even lower in HH compared with NH (Coppel et al., 2015; Netzer et al., 2017; Savourey et al., 2003). These studies, however, were conducted in subjects at rest or during submaximal effort, situations in which the cardiorespiratory response is also different. Moreover, some of these studies were conducted in uncontrolled situations, such as those of an unsimulated HH at high altitude, and therefore did not consider other factors such as temperature or humidity (Netzer et al., 2017; Vinetti et al., 2025).

Marked gender differences in SpO₂ during acute NH exposure at rest have also been reported. Camacho-Cardenosa et al. showed that women generally experience a steeper and more rapid decline in SpO₂ during the initial hours of hypoxic exposure, reflecting less effective ventilatory compensation compared with men, who typically maintain higher SpO₂ levels under similar hypoxic conditions. (Camacho-Cardenosa et al., 2022).

Ricart and colleagues described an atypical statistical pattern whereby, following acute exposure to HH at rest, greater increases in ventilation were not systematically associated with larger improvements in SpO₂. Instead, a nonsignificant tendency toward an inverse relationship was observed, which the authors suggested might reflect reduced gas-exchange efficiency or increased respiratory muscle strain (Ricart et al., 2000).

Applications of NH and HH in Specific Contexts

The study of hypoxia is fundamental to understanding human physiological responses and developing clinical and performance strategies. Laboratory research with simulated hypoxia and high-altitude studies have provided valuable insights into the body’s adaptive capabilities, both in healthy subjects and in patients with various cardiorespiratory diseases (Parati et al., 2018).

Athletes/Healthy individuals

Exposure to high altitude induces a series of physiological adjustments aimed at maintaining homeostasis despite reduced oxygen availability (Heistad and Abboud, 1980). Studies such as “Operation Everest II” (Reeves et al., 1987) and “Operation Everest III (Comex ‘97)” (Boussuges et al., 2000) have extensively documented cardiovascular responses at extreme altitudes. The applications of these studies mainly concern performance enhancement and prevention of acute mountain sickness. •

Training strategies: hypoxic training, both normobaric and hypobaric, is widely used to induce adaptations that can improve performance at sea level and altitude (Bonetti and Hopkins, 2012; Faiss et al., 2013a; Millet et al., 2013).

Several methodologies have been developed with specific goals: ◦

Live high–train high: living and training at altitude. Improved endurance power has been demonstrated in subelite and elite athletes, particularly with appropriate management of altitude and training-recovery cycles (Bonetti and Hopkins, 2012; Faiss et al., 2013a); an increase in peak V̇O₂ is likely in subelite athletes (Bonetti and Hopkins, 2012).

◦

Live high–train low: living at altitude but training at low altitude. This approach is considered the most effective for improving endurance performance in both elite and subelite athletes (Bonetti and Hopkins, 2012; Faiss et al., 2013a).

◦

Intermittent hypoxic training: intermittent exposure to hypoxia during training. Despite potential molecular adaptations, benefits for sea level performance are often minimal or inconclusive in trained athletes (Faiss et al., 2013a; Millet et al., 2013), although some improvements in endurance power have been reported in subelite athletes (Bonetti and Hopkins, 2012).

◦

Repeated sprint training in hypoxia: repetition of short-duration “all-out” sprints under hypoxic conditions. This emerging method shows promise for improving sprint performance, with significant molecular and systemic adaptations (Faiss et al., 2013a; Millet et al., 2013), likely involving selective vasodilatory effects on muscle fibers (Millet et al., 2013).

HF patients

Exposure to altitude requires careful evaluation (Rimoldi et al., 2010), although in the absence of significant comorbidities, simulated altitudes up to 3000 m or real exposures around 3400 m have been considered relatively safe. Schmid et al. (Schmid et al., 2015) showed that patients with stable chronic HF and preserved exercise capacity tolerate short-term exposure to 3,454 m, though their peak V̇O₂ decreases by about 22% compared with low altitude.

In HF patients, exercise capacity decreases proportionally to disease severity and altitude (Agostoni, 2013; Agostoni et al., 2000; Parati et al., 2018; Schmid et al., 2015; Vignati et al., 2023). The reduction in peak V̇O₂ can range from about 4% in mild/moderate HF to about 11% in severe HF per 1000 m increase in altitude, compared with 2% in healthy individuals (Agostoni, 2013; Schmid et al., 2015).

DLCO is a key factor in exercise tolerance in hypoxia: HF patients able to increase diffusion during exercise show a lower reduction in capacity at high altitude (Agostoni et al., 2013; Parati et al., 2018; Vignati et al., 2023). In such patients, beta-blocker selection is crucial: Selective β1 beta-blockers are preferable to nonselective agents (Vignati et al., 2023), which inhibit β2 receptors, blunt the hypoxic ventilatory response, and may compromise alveolar-capillary diffusion, regulated by β2 activity (Vignati et al., 2023). Acetazolamide may help prevent pulmonary fluid accumulation, counteract altitude-induced reduction in pulmonary diffusion, and reduce periodic breathing during exercise in HF (Parati et al., 2018). Conversely, angiotensin II receptor antagonists, such as Telmisartan, may be less effective at very high altitudes (above 5400 m) due to suppression of the renin–angiotensin–aldosterone system (Caravita et al., 2018).

COPD patients

Exposure to hypoxic conditions, either HH or NH, can exacerbate respiratory and cardiovascular stress in patients with COPD due to reduced arterial oxygen saturation, increased work of breathing, and elevated PAP (Gong, 1989; Gong et al., 1984). In patients with both HF and COPD, the latter has resulted the main factor limiting altitude exposure due to a greater PaO₂ reduction compared with non-COPD HF subjects (Agostoni, 2013).

Although acute hypoxia (one- to two-night stay) generally impairs exercise performance in COPD patients (Furian et al., 2018; Gutweniger et al., 2021), some evidence suggests that oxygen administration in those living at high altitude and not receiving oxygen permanently might augment endurance capacity, improve cardiovascular performance, and yield muscle functional benefits (Maldonado et al., 2013). However, oxygen supplementation alone has been insufficient to prevent exercise tolerance reduction in lowland COPD patients acutely exposed to altitude (Gutweniger et al., 2021).

Pulmonary hypertension patients

Systemic hypoxia induces diffuse HPV, increasing PVR and mean PAP and leading to transient pulmonary hypertension (PH) (Bailey et al., 2010; Bärtsch and Gibbs, 2007; Bonetti and Hopkins, 2012; Donegani et al., 2014; Pezzuto et al., 2018). While HPV is a physiological adaptation mechanism facilitating ventilation–perfusion matching in localized hypoxia, it becomes maladaptive under global hypoxic exposure (Bailey et al., 2010; Boussuges et al., 2000; Donegani et al., 2014), contributing to vascular remodeling in high-altitude natives (Penaloza and Arias-Stella, 2007), with notable differences between Andean and Himalayan populations.

In lowlander patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH), short-term exposure to both simulated NH and real HH at 2,500 m elicits similar cardiopulmonary responses, although HH is associated with a reduced tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio (TAPSE/SPAP) ratio, suggesting possible right ventricular–arterial uncoupling or reduced right ventricular function at real altitude compared with normobaric simulation (Schneider et al., 2022). In addition, altitude exposure enhances oxidative stress and inflammation while diminishing NO bioavailability (Bailey et al., 2010), increasing the risk of pulmonary edema and right HF (Bärtsch and Gibbs, 2007; Bonetti and Hopkins, 2012).

Recent findings indicate that in stable PAH/CTEPH patients, short-term exposure to moderate altitude increases resting PAP and impairs right ventricular–arterial coupling but does not significantly alter exercise-induced hemodynamic responses compared with low altitude, as assessed by echocardiography during an incremental exercise test (Müller et al., 2025). Both NH and HH were well tolerated in patients with PAH/CTEPH, despite inducing hypoxemia, but with a reduction in constant work rate cycle time (Schneider et al., 2021, 2020), peak exercise capacity, and ventilatory efficiency in incremental exercise test (Müller et al., 2025) compared with normoxia. Moreover, NH did not alter the mean PAP-cardiac output slope or other invasive pulmonary hemodynamic parameters in mild-to-moderate exercise compared with placebo air, despite reduced oxygenation (Lichtblau et al., 2025).

Current guidelines recommend supplemental oxygen for patients with WHO functional class III–IV PH or PaO₂ <60 mmHg during air travel and at altitudes above 1,500–2,000 m (Humbert et al., 2022).

Conclusions

Current evidence confirms that acute exposure to hypoxia reduces maximal exercise capacity, but differences between HH and NH make the two conditions not entirely interchangeable.

At the same PiO₂, HH is characterized by lower air density, which reduces the work of breathing and may promote more efficient ventilation. Meanwhile, tissue denitrogenation and hemodynamic changes related to reduced Patm can influence arterial oxygen saturation and cardiac output differently compared with NH. Some studies report a greater reduction in V̇O₂max in NH than in HH, while cardiovascular (HRmax and Q̇max) and ventilatory responses vary, reflecting the complexity of the interaction between barometric pressure, gas exchange, and autonomic regulation.

Despite decades of research, it remains unclear whether these differences are significant enough to influence training planning, clinical management, or altitude-related prevention. Addressing this question requires studies directly comparing real high-altitude conditions with laboratory simulations. A relevant limitation of the available literature is that studies conducted at high altitude, whether real or simulated, generally include small samples of healthy participants, predominantly males; in addition, the cardiovascular effects of barometric pressure may vary according to geographic location, since atmospheric pressure at the summit of Denali (Alaska) is lower than at sites at the same altitude in the Karakorum.

In this context, an ongoing study—a collaboration between the IRCCS Centro Cardiologico Monzino and the Italian Air Force Medical Service—is comparing three conditions: real HH (high altitude), simulated HH (hypobaric chamber), and normoxia at sea level (Mapelli et al., 2026). This approach will help determine whether the observed differences are solely due to reduced oxygen pressure or whether the barometric and environmental context plays a determining role. The expected results will contribute to more precise guidelines for safety, athletic performance, and patients’ management at high altitudes.

Authors’ Contributions

Conceptualization: B.P. and C.V.; methodology: B.P. and C.V.; data curation: G.F., M.C., V.A., P.A., B.P., and C.V.; writing—original draft preparation: G.F. and M.C.; writing—review and editing: V.A., P.A., B.P., and C.V.; supervision: P.A., B.P., and C.V.; project administration: B.P. and C.V. All authors have read and agreed to the published version of the article.

Footnotes

Author Disclosure Statement

None of the authors declare any conflict of interest.

Funding Information

This work was supported by the Italian Ministry of Health, Ricerca Corrente to Centro Cardiologico Monzino IRCCS.

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Physiological Responses to Acute Hypobaric and Normobaric Hypoxia: Differences in Maximal Exercise and Clinical Impact

Abstract

Keywords

Introduction

HH Versus NH: Physiological Bases

Effects on alveolar gas composition and tissue nitrogen washout

Inspired gas density and work of breathing

Water vapor pressure

Acid–base balance

Nitric oxide metabolism and bioavailability

Effects of Hypoxia on Functional Capacity

Cardiovascular Responses

Maximal heart rate

Maximum cardiac output and arterial O2 content

Systemic blood pressure

Pulmonary circulation

Ventilatory Response

Maximum minute ventilation (V̇Emax)

Respiratory rate

Tidal volume

Peripheral oxygen saturation

Applications of NH and HH in Specific Contexts

Athletes/Healthy individuals

HF patients

COPD patients

Pulmonary hypertension patients

Conclusions

Authors’ Contributions

Footnotes

Author Disclosure Statement

Funding Information

References

Maximum cardiac output and arterial O₂ content