Development of optic disc edema during 30 days of hypercapnic head-down tilt bed rest is associated with short sleep duration and blunted temperature amplitude.

Sleep and circadian temperature disturbances occur with spaceflight and may, in part, result from the chronically elevated carbon dioxide (CO2) levels on the international space station. Impaired sleep may contribute to decreased glymphatic clearance and, when combined with the chronic headward fluid shift during actual spaceflight or the spaceflight analog head-down tilt bed rest (HDTBR), may contribute to the development of optic disc edema. We determined if strict HDTBR combined with mildly elevated CO2 levels influenced sleep and core temperature and was associated with the development of optic disc edema. Healthy participants (5 females) aged 25-50 yr, underwent 30 days of strict 6° HDTBR with ambient Pco2 = 4 mmHg. Measures of sleep, 24-h core temperature, overnight transcutaneous CO2, and Frisén grade edema were made pre-HDTBR, on HDTBR days 4, 17, 28, and post-HDTBR days 4 and 10. During all HDTBR time points, sleep, core temperature, and overnight transcutaneous CO2 were not different than the pre-HDTBR measurements. However, independent of the HDTBR intervention, the odds ratios {mean [95% confidence interval (CI)]} for developing Frisén grade optic disc edema were statistically significant for each hour below the mean total sleep time (2.2 [1.1-4.4]) and stage 2 nonrapid eye movement (NREM) sleep (4.8 [1.3-18.6]), and above the mean for wake after sleep onset (3.6 [1.2-10.6]) and for each 0.1°C decrease in core temperature amplitude below the mean (4.0 [1.4-11.7]). These data suggest that optic disc edema occurring during HDTBR was more likely to occur in those with short sleep duration and/or blunted temperature amplitude.NEW & NOTEWORTHY We determined that sleep and 24-h core body temperature were unaltered by 30 days exposure to the spaceflight analog strict 6° head-down tilt bed rest (HDTBR) in a 0.5% CO2 environment. However, shorter sleep duration, greater wake after sleep onset, and lower core temperature amplitude present throughout the study were associated with the development of optic disc edema, a key finding of spaceflight-associated neuro-ocular syndrome.

AltitudeOmics: effects of 16 days acclimatization to hypobaric hypoxia on muscle oxygen extraction during incremental exercise.

Acute altitude exposure lowers arterial oxygen content ([Formula: see text]) and cardiac output ([Formula: see text]) at peak exercise, whereas O2 extraction from blood to working muscles remains similar. Acclimatization normalizes [Formula: see text] but not peak [Formula: see text] nor peak oxygen consumption (V̇o2peak). To what extent acclimatization impacts muscle O2 extraction remains unresolved. Twenty-one sea-level residents performed an incremental cycling exercise to exhaustion near sea level (SL), in acute (ALT1) and chronic (ALT16) hypoxia (5,260 m). Arterial blood gases, gas exchange at the mouth and oxy- (O2Hb) and deoxyhemoglobin (HHb) of the vastus lateralis were recorded to assess arterial O2 content ([Formula: see text]), [Formula: see text], and V̇o2. The HHb-V̇o2 slope was taken as a surrogate for muscle O2 extraction. During moderate-intensity exercise, HHb-V̇o2 slope increased to a comparable extent at ALT1 (2.13 ± 0.94) and ALT16 (2.03 ± 0.88) compared with SL (1.27 ± 0.12), indicating increased O2 extraction. However, the HHb/[Formula: see text] ratio increased from SL to ALT1 and then tended to go back to SL values at ALT16. During high-intensity exercise, HHb-V̇o2 slope reached a break point beyond which it decreased at SL and ALT1, but not at ALT16. Increased muscle O2 extraction during submaximal exercise was associated with decreased [Formula: see text] in acute hypoxia. The significantly greater muscle O2 extraction during maximal exercise in chronic hypoxia is suggestive of an O2 reserve.NEW & NOTEWORTHY During incremental exercise muscle deoxyhemoglobin (HHb) and oxygen consumption (V̇o2) both increase linearly, and the slope of their relationship is an indirect index of local muscle O2 extraction. The latter was assessed at sea level, in acute and during chronic exposure to 5,260 m. The demonstrated presence of a muscle O2 extraction reserve during chronic exposure is coherent with previous studies indicating both limited muscle oxidative capacity and decrease in motor drive.

Hyperoxia-induced stepwise reduction in blood flow through intrapulmonary, but not intracardiac, shunt during exercise.

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) (QIPAVA) increases during exercise breathing air, but it has been proposed that QIPAVA is reduced during exercise while breathing a fraction of inspired oxygen ([Formula: see text]) of 1.00. It has been argued that the reduction in saline contrast bubbles through IPAVA is due to altered in vivo microbubble dynamics with hyperoxia reducing bubble stability, rather than closure of IPAVA. To definitively determine whether breathing hyperoxia decreases saline contrast bubble stability in vivo, the present study included individuals with and without patent foramen ovale (PFO) to determine if hyperoxia also eliminates left heart contrast in people with an intracardiac right-to-left shunt. Thirty-two participants consisted of 16 without a PFO; 8 females, 8 with a PFO; 4 females, and 8 with late-appearing left-sided contrast (4 females) completed five, 4-min bouts of constant-load cycle ergometer exercise (males: 250 W, females: 175 W), breathing an [Formula: see text] = 0.21, 0.40, 0.60, 0.80, and 1.00 in a balanced Latin Squares design. QIPAVA was assessed at rest and 3 min into each exercise bout via transthoracic saline contrast echocardiography and our previously used bubble scoring system. Bubble scores at [Formula: see text]= 0.21, 0.40, and 0.60 were unchanged and significantly greater than at [Formula: see text]= 0.80 and 1.00 in those without a PFO. Participants with a PFO had greater bubble scores at [Formula: see text]= 1.00 than those without a PFO. These data suggest that hyperoxia-induced decreases in QIPAVA during exercise occur when [Formula: see text] ≥ 0.80 and is not a result of altered in vivo microbubble dynamics supporting the idea that hyperoxia closes QIPAVA.

Consequences of Preterm Birth: Knowns, Unknowns, and Barriers to Advancing Cardiopulmonary Health.

Preterm birth occurs in 10% of all live births and creates challenges to neonatal life, which persist into adulthood. Significant previous work has been undertaken to characterize and understand the respiratory and cardiovascular sequelae of preterm birth, which are present in adulthood, i.e., "late" outcomes. However, many gaps in knowledge are still present and there are several challenges that will make filling these gaps difficult. In this perspective we discuss the obstacles of studying adults born preterm, including (1) the need for invasive (direct) measures of physiologic function; (2) the need for multistate, multinational, and diverse cohorts; (3) lack of socialized medicine in the United States; (4) need for detailed and better-organized birth records; and (5) transfer of neonatal and pediatric knowledge to adult care physicians. We conclude with a discussion on the "future" of studying preterm birth in regards to what may happen to these individuals as they approach middle and older age and how the improvements in perinatal and postnatal care may be changing the phenotypes observed in adults born preterm on or after the year 2000.

Quantification of shunt fraction using contrast ultrasound and indicator dilution in an in vitro model.

Transthoracic saline contrast echocardiography is commonly used to assess intrathoracic shunt flow in vivo. Though the technique has many advantages (safe, simple, repeatable), the measurement technique lacks specificity, and the contrast agent has limited stability. This study sought to determine if the indicator dilution modeling technique could be applied to ultrasound contrast data to quantify shunt fraction and to determine if buoyant force has a significant effect on microbubble pathway determination at a "vascular" bifurcation. A model of the pulmonary circuit was perfused with blood at three distinct flow rates (low, medium and high) over shunt fractions ranging from ∼2-10 %. The buoyancy effect on contrast was quantified using a simplified in vitro model of a vascular bifurcation that had an upper and lower outflow tract where saline contrast formed from carbon monoxide (CO) gas passed through the bifurcation, was collected and quantified. The indicator dilution model was found to have a mean bias of - 3.2 % for the low flow stage, - 2.6 % for the medium flow stage and - 1.4 % for the high flow stage compared to volumetric measurements, suggesting agreement increases with increasing flow rate. Investigations of the buoyant effects revealed that at lower flow rates, contrast bubbles that encounter a bifurcation will favor the upper outflow tract over the lower. However, this effect is reduced by increasing the flow rate two-fold. These data identify that application of indicator dilution theory to contrast ultrasound data and the pathway ultrasound contrast travels in a network of tubules is flow dependent.

Blunted hypoxic pulmonary vasoconstriction in apnoea divers.

NEW FINDINGS: What is the central question of this study? Does the hyperbaric, hypercapnic, acidotic, hypoxic stress of apnoea diving lead to greater pulmonary vasoreactivity and increased right heart work in apnoea divers? What is the main finding and its importance? Compared with sex- and age-matched control subjects, divers experienced significantly less change in total pulmonary resistance in response to short-duration isocapnic hypoxia. With oral sildenafil (50 mg), there were no differences in total pulmonary resistance between groups, suggesting that divers can maintain normal pulmonary artery tone in hypoxic conditions. Blunted hypoxic pulmonary vasoconstriction might be beneficial during apnoea diving. ABSTRACT: Competitive apnoea divers dive repetitively to depths >50 m. During the final portions of ascent, divers experience significant hypoxaemia. Additionally, hyperbaria during diving increases thoracic blood volume while simultaneously reducing lung volume and increasing pulmonary artery pressure. We hypothesized that divers would have exaggerated hypoxic pulmonary vasoconstriction, leading to increased right heart work owing to their repetitive hypoxaemia and hyperbaria, and that the administration of sildenafil would have a greater effect in reducing pulmonary resistance in divers. We recruited 16 divers (Divers) and 16 age- and sex-matched non-diving control subjects (Controls). Using a double-blinded, placebo-controlled, cross-over design, participants were evaluated for normal cardiac and lung function, then their cardiopulmonary responses to 20-30 min of isocapnic hypoxia (end-tidal partial pressure of O2  = 50 mmHg) were measured 1 h after ingestion of 50 mg sildenafil or placebo. Cardiac structure and cardiopulmonary function were similar at baseline. With placebo, Divers had a significantly smaller increase in total pulmonary resistance than Controls after 20-30 min isocapnic hypoxia (change -3.85 ± 72.85 vs. 73.74 ± 91.06 dyns cm-5 , P = 0.0222). With sildenafil, Divers and Controls had similar blunted increases in total pulmonary resistance after 20-30 min of hypoxia. Divers also had a significantly lower systemic vascular resistance after sildenafil in normoxia. These data indicate that repetitive apnoea diving leads to a blunted hypoxic pulmonary vasoconstriction. We suggest that this is a beneficial adaption allowing for increased cardiac output with reduced right heart work and thus reducing cardiac oxygen utilization in hypoxaemic conditions.

Sex Differences in VO2max and the Impact on Endurance-Exercise Performance.

It was not until 1984 that women were permitted to compete in the Olympic marathon. Today, more women than men participate in road racing in all distances except the marathon where participation is near equal. From the period of 1985 to 2004, the women's marathon record improved at a rate three times greater than men's. This has led many to question whether women are capable of surpassing men despite the fact that there remains a 10-12% performance gap in all distance events. The progressive developments in sports performance research and training, beginning with A.V. Hill's establishment of the concept of VO2max, have allowed endurance athletes to continue performance feats previously thought to be impossible. However, even today women are significantly underrepresented in sports performance research. By focusing more research on the female physiology and sex differences between men and women, we can better define how women differ from men in adapting to training and potentially use this information to improve endurance-exercise performance in women. The male advantage in endurance-exercise performance has commonly been attributed to their higher VO2max, even when expressed as mL/kg/min. It is widely known that oxygen delivery is the primary limiting factor in elite athletes when it comes to improving VO2max, but little research has explored the sex differences in oxygen delivery. Thus, the purpose of this review is to highlight what is known about the sex differences in the physiological factors contributing to VO2max, more specifically oxygen delivery, and the impacts on performance.

High prevalence of patent foramen ovale in recreational to elite breath hold divers.

OBJECTIVES: During apnea diving, a patent foramen ovale may function as a pressure relief valve under conditions of high pulmonary pressure, preserving left-ventricular output. Patent foramen ovale prevalence in apneic divers has not been previously reported. We aimed to determine the prevalence of patent foramen ovale in apneic divers compared to non-divers. DESIGN: Cross sectional. METHODS: Apnea divers were recruited from a training camp in Cavtat, Croatia and the diving community of Split, Croatia. Controls were recruited from the population of Split, Croatia and Eugene, Oregon, USA. Participants were instrumented with an intravenous catheter and underwent patent foramen ovale screening utilizing transthoracic saline contrast echocardiography. Appearance of microbubbles in the left heart within 3 cardiac cycles indicated the presence of patent foramen ovale. Lung function was measured with spirometry. Comparison of patent foramen ovale prevalence was conducted using chi-square analysis, p < .05. RESULTS: Apnea divers had a significantly higher prevalence of patent foramen ovale (19 of 36, 53%) compared to controls (9 of 36, 25%) (X2 (1, N = 72) = 5.844, p = .0156). CONCLUSIONS: Why patent foramen ovale prevalence is greater in apnea divers remains unknown, though hyperbaria during an apnea dive results in a translocation of blood volume centrally with a concomitant reduction in lung volume and alveolar hypoxia during ascent results in hypoxic pulmonary vasoconstriction. These conditions increase pulmonary arterial pressure, increasing right-atrial pressure allowing for right-to-left blood flow through a patent foramen ovale which may be beneficial for preserving cardiac output and reducing capillary hydrostatic forces.

Implications of a patent foramen ovale for environmental physiology and pathophysiology: do we know the 'hole' story?

The foramen ovale is an essential component of the fetal circulation contributing to oxygenation and carbon dioxide elimination that remains patent under certain circumstances in ∼30% of the healthy adult population, without major negative sequelae in most. Adults with a patent foramen ovale (PFO) have a greater tendency to develop symptoms of acute mountain sickness and high-altitude pulmonary oedema upon ascent to high altitude, and PFO presence is associated with worse cardiopulmonary function in chronic mountain sickness. This increase in altitude illness prevalence may be related to dysregulated cerebral blood flow associated with altered respiratory chemoreflex sensitivity; however, the mechanisms remain to be elucidated. Interestingly, men with a PFO appear to have a shift in thermoregulatory control to higher internal temperatures, both at rest and during exercise, and they have blunted thermal hyperpnoea. The teleological 'reason' for this thermoregulatory shift is unclear, but the shift of ∼0.5°C in core body temperature does not appear to be sufficient to have any significant negative consequences in terms of risk of heat illness. Further work in this area is needed, particularly in women, to evaluate mechanisms of heat storage and dissipation in these individuals compared to people without a PFO. Consequences of a PFO in SCUBA divers include a greater incidence of unprovoked decompression sickness, but whether PFO is beneficial or detrimental to breath hold diving remains unexplored. Whether PFO presence will explain interindividual variability in responses to, and consequences from, other environmental stressors such as spaceflight remain entirely unknown.

Lower transfer factor of the lung for carbon monoxide in women with a patent foramen ovale.

NEW FINDINGS: What is the central question of this study? Do individuals with a patent foramen ovale (PFO+ ) have a lower lung transfer factor for carbon monoxide than those without (PFO- )? What is the main finding and its importance? We found a lower rate constant for carbon monoxide uptake in PFO+ compared with PFO- women, which was physiologically relevant (≥0.5 z-score difference), but not for PFO+ versus PFO- men. This suggests that factors independent of the PFO are responsible for our findings, possibly inherent structural differences in the lung. ABSTRACT: The transfer factor of the lung for carbon monoxide (TLCO ) measure assumes that all cardiac output flows through the pulmonary circuit. However, right-to-left blood flow through a shunt can result in a lower transfer factor than predicted. A patent foramen ovale (PFO) is a potential source of right-to-left shunt that is present in ∼35% of the population, but the effect of PFO on TLCO is unknown. We sought to determine the effect of PFO on the TLCO . We conducted a retrospective analysis of TLCO data from 239 (101 women) participants. Anthropometrics and lung function, including spirometry, plethysmography and TLCO , were compiled from our previously published work. Women, but not men, with a PFO had a significantly lower TLCO and rate constant for carbon monoxide uptake (KCO ) (percentage of predicted and z-score) than women without a PFO. Women and men with a PFO had normal alveolar volumes that did not differ from those without a PFO. Correcting the data for haemoglobin in a subset of subjects did not change the results (n = 58; 25 women). The lower KCO in women with versus without a PFO was physiologically relevant (≥0.5 z-score difference). There was no effect of PFO in men. This suggests that factors independent of the PFO are responsible for our findings, possibly inherent structural differences in the lung.

No effect of patent foramen ovale on acute mountain sickness and pulmonary pressure in normobaric hypoxia.

NEW FINDINGS: What is the central question to this study? Is there a relationship between a patent foramen ovale and the development of acute mountain sickness and an exaggerated increase in pulmonary pressure in response to 7-10 h of normobaric hypoxia? What is the main finding and its importance? Patent foramen ovale presence did not increase susceptibility to acute mountain sickness or result in an exaggerated increase in pulmonary artery systolic pressure with normobaric hypoxia. This suggests hypobaric hypoxia is integral to the increased susceptibility to acute mountain sickness previously reported in those with patent foramen ovale, and patent foramen ovale presence alone does not contribute to the hypoxic pulmonary pressor response. ABSTRACT: Acute mountain sickness (AMS) develops following rapid ascent to altitude, but its exact causes remain unknown. A patent foramen ovale (PFO) is a right-to-left intracardiac shunt present in ∼30% of the population that has been shown to increase AMS susceptibility with high altitude hypoxia. Additionally, high altitude pulmonary oedema (HAPE) is a severe type of altitude illness characterized by an exaggerated pulmonary pressure response, and there is a greater prevalence of PFO in those with a history of HAPE. However, whether hypoxia per se is causing the increased incidence of AMS in those with a PFO and whether a PFO is associated with an exaggerated increase in pulmonary pressure in those without a history of HAPE is unknown. Participants (n = 36) matched for biological sex (18 female) and the presence or absence of a PFO (18 PFO+) were exposed to 7-10 h of normobaric hypoxia equivalent to 4755 m. Presence and severity of AMS was determined using the Lake Louise AMS scoring system. Pulmonary artery systolic pressure, cardiac output and total pulmonary resistance were measured using ultrasound. We found no significant association of PFO with incidence or severity of AMS and no association of PFO with arterial oxygen saturation. Additionally, there was no effect of a PFO on pulmonary pressure, cardiac output or total pulmonary resistance. These data suggest that hypobaric hypoxia is necessary for those with a PFO to have increased incidence of AMS and that presence of PFO is not associated with an exaggerated pulmonary pressor response.

Physiological aspects of cardiopulmonary dysanapsis on exercise in adults born preterm.

Progressive improvements in perinatal care and respiratory management of preterm infants have resulted in increased survival of newborns of extremely low gestational age over the past few decades. However, the incidence of bronchopulmonary dysplasia, the chronic lung disease after preterm birth, has not changed. Studies of the long-term follow-up of adults born preterm have shown persistent abnormalities of respiratory, cardiovascular and cardiopulmonary function, possibly leading to a lower exercise capacity. The underlying causes of these abnormalities are incompletely known, but we hypothesize that dysanapsis, i.e. discordant growth and development, in the respiratory and cardiovascular systems is a central structural feature that leads to a lower exercise capacity in young adults born preterm than those born at term. We discuss how the hypothesized system dysanapsis underscores the observed respiratory, cardiovascular and cardiopulmonary limitations. Specifically, adults born preterm have: (1) normal lung volumes but smaller airways, which causes expiratory airflow limitation and abnormal respiratory mechanics but without impacts on pulmonary gas exchange efficiency; (2) normal total cardiac size but smaller cardiac chambers; and (3) in some cases, evidence of pulmonary hypertension, particularly during exercise, suggesting a reduced pulmonary vascular capacity despite reduced cardiac output. We speculate that these underlying developmental abnormalities may accelerate the normal age-associated decline in exercise capacity, via an accelerated decline in respiratory, cardiovascular and cardiopulmonary function. Finally, we suggest areas of future research, especially the need for longitudinal and interventional studies from infancy into adulthood to better understand how preterm birth alters exercise capacity across the lifespan.

Differential Brain and Muscle Tissue Oxygenation Responses to Exercise in Tibetans Compared to Han Chinese.

The Tibetans' better aerobic exercise capacity at altitude remains ill-understood. We tested the hypothesis that Tibetans display better muscle and brain tissue oxygenation during exercise in hypoxia. Using near-infrared spectrometry (NIRS) to provide indices of tissue oxygenation, we measured oxy- and deoxy-hemoglobin ([O2Hb] and [HHb], respectively) responses of the vastus lateralis muscle and the right prefrontal cortex in ten Han Chinese and ten Tibetans during incremental cycling to exhaustion in a pressure-regulated chamber at simulated sea-level (air at 1 atm: normobaric normoxia) and 5,000 m (air at 0.5 atm: hypobaric hypoxia). Hypoxia reduced aerobic capacity by ∼22% in both groups (d = 0.8, p < 0.001 vs. normoxia), while Tibetans consistently outperformed their Han Chinese counterpart by ∼32% in normoxia and hypoxia (d = 1.0, p = 0.008). We found cerebral [O2Hb] was higher in Tibetans at normoxic maximal effort compared Han (p = 0.001), while muscle [O2Hb] was not different (p = 0.240). Hypoxic exercise lowered muscle [O2Hb] in Tibetans by a greater extent than in Han (interaction effect: p < 0.001 vs. normoxic exercise). Muscle [O2Hb] was lower in Tibetans when compared to Han during hypoxic exercise (d = 0.9, p = 0.003), but not during normoxic exercise (d = 0.4, p = 0.240). Muscle [HHb] was not different between the two groups during normoxic and hypoxic exercise (p = 0.778). Compared to Han, our findings revealed a higher brain tissue oxygenation in Tibetans during maximal exercise in normoxia, but lower muscle tissue oxygenation during exercise in hypoxia. This would suggest that the Tibetans privileged oxygenation of the brain at the expense of that of the muscle.

Temporal changes in pulmonary gas exchange efficiency when breath-hold diving below residual volume.

NEW FINDINGS: What is the central question of this study? How does deep breath-hold diving impact cardiopulmonary function, both acutely and over the subsequent 2.5 hours post-dive? What is the main finding and its importance? Breath-hold diving, to depths below residual volume, is associated with acute impairments in pulmonary gas exchange, which typically resolve within 2.5 hours. These data provide new insight into the behaviour of the lungs and pulmonary vasculature following deep diving. ABSTRACT: Breath-hold diving involves highly integrative and extreme physiological responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure. Over two diving training camps (Study 1 and 2), 25 breath-hold divers (recreational to world-champion) performed 66 dives to 57 ± 20 m (range: 18-117 m). Using the deepest dive from each diver, temporal changes in cardiopulmonary function were assessed using non-invasive pulmonary gas exchange (indexed via the O2 deficit), ultrasound B-line scores, lung compliance and pulmonary haemodynamics at baseline and following the dive. Hydrostatically induced lung compression was quantified in Study 2, using spirometry and lung volume measurement, enabling each dive to be categorized by its residual volume (RV)-equivalent depth. From both studies, pulmonary gas exchange inefficiency - defined as an increase in O2 deficit - was related to the depth of the dive (r2  = 0.345; P < 0.001), with dives associated with lung squeeze symptoms exhibiting the greatest deficits. In Study 1, although B-lines doubled from baseline (P = 0.027), cardiac output and pulmonary artery systolic pressure were unchanged post-dive. In Study 2, dives with lung compression to ≤RV had higher O2 deficits at 9 min, compared to dives that did not exceed RV (24 ± 25 vs. 5 ± 8 mmHg; P = 0.021). The physiological significance of a small increase in estimated lung compliance post-dive (via decreased and increased/unaltered airway resistance and reactance, respectively) remains equivocal. Following deep dives, the current study highlights an integrated link between hydrostatically induced lung compression and transient impairments in pulmonary gas exchange efficiency.

Respiratory and cardiopulmonary limitations to aerobic exercise capacity in adults born preterm.

Adults born preterm, regardless of whether they develop bronchopulmonary dysplasia, have underdeveloped respiratory and cardiopulmonary systems. The resulting impaired respiratory and cardiopulmonary systems are inadequate for the challenges imposed by aerobic exercise, which is exacerbated by the presence of bronchopulmonary dysplasia. Thus the respiratory and cardiopulmonary systems of these preterm individuals may be the most influential contributors to the significantly lower aerobic exercise capacity compared with their term born counterparts. The precise underlying cause(s) of the lower aerobic exercise capacity in adults born preterm is not entirely known but could be a number of interrelated parameters including mechanical ventilatory constraints, impaired pulmonary gas exchange efficiency, and excessive cardiopulmonary pressures. Likewise, additional aspects, such as impaired cardiovascular function and altered muscle bioenergetics, may play additional roles in limiting aerobic exercise capacity. Whether or not all or some of these aspects are present in adults born preterm and precisely how they may contribute to the lower aerobic exercise capacity are only beginning to be systematically explored. The purpose of this mini-review is to outline what is currently known about the respiratory and cardiopulmonary limitations during exercise in this population and to identify key areas where additional knowledge will help to advance this area. Additionally, where possible, we highlight the similarities and differences between obstructive lung disease resulting from preterm birth and chronic obstructive pulmonary disease (COPD) as the physiology and pathophysiology of these two forms of obstructive lung disease may not be identical.

Impaired pulmonary gas exchange efficiency, but normal pulmonary artery pressure increases, with hypoxia in men and women with a patent foramen ovale.

NEW FINDINGS: What is the central question of this study? Do individuals with a patent foramen ovale (PFO+ ) have a larger alveolar-to-arterial difference in PO2 ( A-aDO2 ) than those without (PFO- ) and/or an exaggerated increase in pulmonary artery systolic pressure (PASP) in response to hypoxia? What is the main finding and its importance? PFO+ had a greater A-aDO2 while breathing air, 16% and 14% O2 , but not 12% or 10% O2 . PASP increased equally in hypoxia between PFO+ and PFO- . These data suggest that PFO+ may not have an exaggerated acute increase in PASP in response to hypoxia. ABSTRACT: Patent foramen ovale (PFO) is present in 30-40% of the population and is a potential source of right-to-left shunt. Accordingly, those with a PFO (PFO+ ) may have a larger alveolar-to-arterial difference in PO2 ( A-aDO2 ) than those without (PFO- ) in normoxia and with mild hypoxia. Likewise, PFO is associated with high-altitude pulmonary oedema, a condition known to have an exaggerated pulmonary pressure response to hypoxia. Thus, PFO+ may also have exaggerated pulmonary pressure increases in response to hypoxia. Therefore, the purposes of the present study were to systematically determine whether or not: (1) the A-aDO2 was greater in PFO+ than in PFO- in normoxia and mild to severe hypoxia and (2) the increase in pulmonary artery systolic pressure (PASP) in response to hypoxia was greater in PFO+ than in PFO- . We measured arterial blood gases and PASP via ultrasound in healthy PFO+ (n = 15) and PFO- (n = 15) humans breathing air and 30 min after breathing four levels of hypoxia (16%, 14%, 12%, 10% O2 , randomized and balanced order) at rest. The A-aDO2 was significantly greater in PFO+ compared to PFO- while breathing air (2.1 ± 0.7 vs. 0.4 ± 0.3 Torr), 16% O2 (1.8 ± 1.2 vs. 0.7 ± 0.8 Torr) and 14% O2 (2.3 ± 1.2 vs. 0.7 ± 0.6 Torr), but not 12% or 10% O2 . We found no effect of PFO on PASP at any level of hypoxia. We conclude that PFO influences pulmonary gas exchange efficiency with mild hypoxia, but not the acute increase in PASP in response to hypoxia.