Pulmonary Gas Exchange Efficiency Research Articles

Fourteen Days Of Hypoxia And Apnea Training Does Not Modify Pulmonary Gas Exchange Efficiency

Fourteen Days Of Hypoxia And Apnea Training Does Not Modify Pulmonary Gas Exchange Efficiency

272 A SUDDENLY RIGHT-TO-LEFT SHUNT: THE IMPORTANCE OF EVALUATING PATENT FORAMEN OVALE DURING CARDIOPULMONARY EXERCISE TESTING

Abstract A 55-years-old male affected by heart failure with reduced ejection fraction (HFrEF) was accepted into the Cardiology Department for increasing dyspnea during the last few months. He previously underwent implantation of a biventricular implantable cardioverter defibrillator (ICD) in primary prevention. Medical history included healthy coronary vessels at invasive coronary angiography and an episode of transient ischemic attack (TIA). The patient was referred to our center to evaluate the dyspnea components and to establish an etiology for the novel onset of left ventricular impairment. He underwent a left-right catheterization that did confirm the absence of obstructive coronary disease and signs of pulmonary hypertension (PH) at rest. The transthoracic echocardiogram showed a dilated left ventricle and global hypokinesia (LVEF of 35%). During the stay, the therapy was further optimized according to the latest European guidelines. Before discharge, in order to better assess the dyspnea and the limited tolerance to exercise, a cardiopulmonary exercise testing (CPET) was performed. CPET showed that the VO2 peak was severely reduced compared to the predicted value (16.8 ml/kg/min, corresponding to 51% of the predicted). After 6 minutes of exercise, at around 60 WR, a considerable increase in PETO2 and RER with a concomitant decrease in PETCO2 and a slight oxygen desaturation were observed. Also, a deep increase in VE/VCO2 slope was seen, underlying an exercise-induced pulmonary hypertension. In the suspicion of an inter-atrial shunt, a subsequent rest transthoracic echocardiogram with a bubble test was performed, demonstrating the presence of a patent foramen ovale (PFO). Discussion The foramen ovale is a vestigial communication between the atria that works as a bypass of the pulmonary circulation during fetal life and then seals at birth after the start of breathing in most people. In around 25% of adults, patency of foramen ovale persists and, in some cases, can lead to a source of a right-to-left shunt, particularly in patients with heart failure that can experience PH at rest or during exercise. This may allow a mixture of oxygenated and non-oxygenated blood that affects pulmonary gas exchange efficiency and may allow blood clots formed in the right circulation to embolize into the left circulation. From a pathophysiological point of view, a right-to-left passage of deoxygenated blood induces the activation of chemoreceptors which induce hyperventilation to adequately compensate for the high amount of CO2 in blood from the right sections of the heart. In people not experiencing pulmonary pressure increase during exercise, right-to-left shunt via a PFO is very unlikely since left atrial pressure is higher than right atrial pressure. However, in the presence of PH, right atrial pressure can overcome left atrial pressure and force venous blood through the defect directly into the systemic circulation. The concomitant increase in VE/VCO2 slope underlines exercise-induced PH, which is frequently associated with heart failure and further contributes to exercise intolerance. Conclusions In the presented case, CPET helped diagnose a misunderstood PFO with a right-to-left shunt induced by effort in a patient with a previous TIA. This observation demonstrates that it could be helpful to identify this eventuality during exercise, to discern patients with higher risk of cardiovascular events who would benefit from a percutaneous closure.

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.

Non-invasive Measurement of Pulmonary Gas Exchange Efficiency: The Oxygen Deficit.

The efficiency of pulmonary gas exchange has long been assessed using the alveolar-arterial difference in PO2, the A-aDO2, a construct developed by Richard Riley ~70years ago. However, this measurement is invasive (requiring an arterial blood sample), time consuming, expensive, uncomfortable for the patients, and as such not ideal for serial measurements. Recent advances in the technology now provide for portable and rapidly responding measurement of the PO2 and PCO2 in expired gas, which combined with the well-established measurement of arterial oxygen saturation via pulse oximetry (SpO2) make practical a non-invasive surrogate measurement of the A-aDO2, the oxygen deficit. The oxygen deficit is the difference between the end-tidal PO2 and the calculated arterial PO2 derived from the SpO2 and taking into account the PCO2, also measured from end-tidal gas. The oxygen deficit shares the underlying basis of the measurement of gas exchange efficiency that the A-aDO2 uses, and thus the two measurements are well-correlated (r2~0.72). Studies have shown that the new approach is sensitive and can detect the age-related decline in gas exchange efficiency associated with healthy aging. In patients with lung disease the oxygen deficit is greatly elevated compared to normal subjects. The portable and non-invasive nature of the approach suggests potential uses in first responders, in military applications, and in underserved areas. Further, the completely non-invasive and rapid nature of the measurement makes it ideally suited to serial measurements of acutely ill patients including those with COVID-19, allowing patients to be closely monitored if required.

Wearable Transcutaneous CO2 Monitor Based on Miniaturized Nondispersive Infrared Sensor.

Transcutaneous oxygen and carbon dioxide provide the status of pulmonary gas exchange and are of importance in diagnosis and management of respiratory diseases. Though significant progress has been made in oximetry, not much has been explored in developing wearable technologies for continuous monitoring of transcutaneous carbon dioxide. This research reports the development of a truly wearable sensor for continuous monitoring of transcutaneous carbon dioxide using miniaturized nondispersive infrared sensor augmented by hydrophobic membrane to address the humidity interference. The wearable transcutaneous CO2 monitor shows well-behaved response curve to humid CO2 with linear response to CO2 concentration. The profile of transcutaneous CO2 monitored by the wearable device correlates well with the end-tidal CO2 trend in human test. The feasibility of the wearable device for passive and unobstructed tracking of transcutaneous CO2 in free-living conditions has also been demonstrated in field test. The wearable transcutaneous CO2 monitoring technology developed in this research can be widely used in remote assessment of pulmonary gas exchange efficiency for patients with respiratory diseases, such as COVID-19, sleep apnea, and chronic obstructive pulmonary disease (COPD).

Reduction in Pulmonary Arterial Pressure at Rest and During Exercise and Improvement in Gas Exchange Efficiency Following Percutaneous Closure of Patent Foramen Ovale

PURPOSE The patent foramen ovale (PFO) is a source of intracardiac right-to-left shunt and is present in ~1/3rd of the adult population. Deficits in pulmonary gas exchange efficiency associated with PFO have been well-documented (Lovering et al, J Appl Physiol 2016). However, changes in pulmonary artery pressure and total pulmonary resistance (TPR) following closure have not previously been reported. METHODS Four candidates (3F, 1M) for closure of PFO were identified by local cardiologists and referred to our laboratory as subjects. 3 subjects (3F) received physician clearance to participate in the exercise trials. 1 subject (1M) was not cleared for exercise so only resting measures were taken. Presence and size of PFO was confirmed utilizing transthoracic saline contrast echocardiography (TTSCE). A radial arterial catheter was placed utilizing aseptic technique. Subjects exercised at 4 sub-maximal workloads (25%, 50%, 75% and 90% of pre-closure VO2Max), with arterial blood drawn anaerobically during the last 30 seconds of each workload and immediately analyzed in duplicate for gas content. Transthoracic ultrasound measures of cardiac output (QT) and pulmonary arterial systolic pressure (PASP) were taken prior to exercise and during the final minute of each workload. TPR was calculated as PASP/ QT. Subjects then underwent percutaneous closure of PFO utilizing a commercially available closure device (Amplatzer PFO Occluder, Abbott, Illinois; Cardioform Septal Occluder, GORE, Arizona). All measures were repeated in the laboratory 3-6 months after closure of PFO following confirmation of endothelialization of the closure device with TTSCE. RESULTS Data were analyzed by a 2-way (Closure x Workload) RMANOVA. There was a main effect of closure on PASP F(1, 11) = 21.05, p = 0.0008, and a main effect of closure on TPR F(1, 11) = 9.899, p = 0.0093, with reductions in both following closure. There was a main effect of workload, but not closure, on cardiac output F(4, 11) = 60.18, p < 0.0001. There were main effects of both workload F(4,11) = 73665, p = .0033 and closure F(1,11) = 28.31, p = .0002 on pulmonary gas exchange efficiency. CONCLUSION Improvements in pulmonary gas exchange efficiency are expected with removal of the intracardiac right-to-left shunt. However, our results demonstrating a significantly reduced pulmonary artery pressure, due to a significantly reduced TPR, are intriguing and deserve more attention to better understand the contributing factors of a PFO to exercise-induced pulmonary hypertension.

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

What is the central question of this study? How does deep breath-hold diving impact cardiopulmonary function, both acutely and over the subsequent 2.5hours 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 2.5hours. These data provide new insight into the behaviour of the lungs and pulmonary vasculature following deep diving. 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±20m (range: 18-117m). 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 9min, compared to dives that did not exceed RV (24±25 vs. 5±8mmHg; 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.

Case Studies in Physiology: Breath-hold diving beyond 100 meters-cardiopulmonary responses in world-champion divers.

In this case study, we evaluate the unique physiological profiles of two world-champion breath-hold divers. At close to current world-record depths, the extreme physiological responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure are profound. As such, these professional athletes must be capable of managing such stress, to maintain performing at the forefront human capacity. In both divers, pulmonary function before and after deep dives to 102 m and 117 m in the open sea was assessed using noninvasive pulmonary gas exchange (indexed via the O2 deficit, which is analogous to the traditional alveolar to arterial oxygen difference), ultrasound B-line scores, airway resistance, and airway reactance. Hydrostatic-induced lung compression was also quantified via spirometry. Both divers successfully performed their dives. Pulmonary gas exchange efficiency was impaired in both divers at 10 min but had mostly restored within a few hours. Mild hemoptysis was transiently evident immediately following the 117-m dive, whereas both divers experienced nitrogen narcosis. Although B-lines were only elevated in one diver postdive, reductions in airway resistance and reactance occurred in both divers, suggesting that the compressive strain on the structural characteristics of the airways can persist for up to 3.5 h. Marked echocardiographic dyssynchrony was evident in one diver after 10 m of descent, which persisted until resolving at ∼77 m during ascent. In summary, despite the enormous hydrostatic and physiological stress to diving beyond 100 m on a single breath, these data provide valuable insight into the extraordinary capacity of those at the pinnacle of apneic performance.NEW & NOTEWORTHY This study shows that world-champion breath-hold divers demonstrate incredible tolerability to extreme levels of hydrostatic-induced lung compression. Immediately following dives to >100 m, there were acute impairments in pulmonary gas exchange efficiency, mild accummulation of extravascular lung fluid, noticable intrathoracic discomfort, and evident nitrogen narcosis, however, within a few hours, these had all mostly resolved.

Functional state of the cardiorespiratory system after orthotopic heart transplantation with prolonged cold ischemia time

Objective: to assess the functional state of the cardiorespiratory system in the long term after orthotopic heart transplantation (HT) with prolonged cold ischemia time. Materials and methods. The results of 60 orthotopic HTs performed at Meshalkin National Medical Research Center were analyzed. A comparison was made of the immediate and long-term outcomes of HTs in the group with cold ischemia time lasting for less than 240 minutes and in those with farther distance between donor and recipient sites with cold ischemia time of 240 minutes or more. In the long-term follow-up after HT, all patients underwent cardiopulmonary exercise testing, body plethysmography, assessment of the diffusing capacity of the lungs, and quality of life assessment. Results. Prolonged cold ischemia showed a negative effect on the early postoperative period – decreased myocardial contractility on postoperative day 1 and longer duration of inotropic support. At the same time, the survival rate and incidence of graft rejection reactions in the early and late post-HT periods in the studied groups did not differ significantly. Peak oxygen consumption in the general group in the long term after HT was 17 (14.7–21.0) mL/kg/min, VE/ VCO2 slope was 30 (29–36) at 100 (90–120) W threshold load power. All the parameters of pulmonary function tests did not differ significantly depending on cold ischemia duration. Quality of life also did not show significant differences depending on the duration of graft ischemia in terms of both physical and psycho-emotional health components of the SF-36 questionnaire. Conclusion. Long-term cold ischemia of the graft did not show any negative impact on the functional state of the cardiorespiratory system and quality of life in the long term after HT. The studied group of recipients was characterized by high efficiency of pulmonary ventilation and gas exchange, as well as high tolerance to physical activity in the long-term post-HT period.

Does gallic acid improve cardiac function by attenuation of oxidative stress and inflammation in an elastase-induced lung injury?

Objective(s):Cardiovascular disease has an important role in mortality caused by lung injury. Emphysema is associated with impaired pulmonary gas exchange efficiency and airflow limitation associated with small airway inflammation. The aim was to evaluate the interactions between lung injury, inflammation, and cardiovascular disease. Since gallic acid has antioxidant and anti-inflammatory effects, we hypothesized that gallic acid protects the lung and the related heart dysfunction in elastase-induced lung injury. Materials and Methods:Forty-eight Sprague-Dawley male rats were randomly divided into six groups: Control, Porcine pancreatic elastase (PPE) , PPE+GA, and 3 groups for different doses of gallic acid (GA 7.5, GA 15, GA 30 mg/kg). PPE was injected intra-tracheally on days 1 and 10 of the test. In each group, electrocardiography, hemodynamic parameters, oxidative stress, and bronchoalveolar lavage fluid were examined.Results:PPE administration showed a decrease in HR and QRS voltage of electrocardiogram parameters, as well as in hemodynamic parameters (P<0.05, P<0.01, and P<0.001) and superoxide dismutase (SOD) (P<0.05). Tumor Necrosis Factor α (TNF-α) (P<0.001), interleukin 6 (IL-6) (P<0.001), interleukin 6 (MDA) (P<0.001), and the total number of white blood cells (P<0.001) showed an increase in PPE groups. Gallic acid preserved the values of hemodynamic properties, oxidative stress, inflammation, and electrocardiogram parameters in comparison to the PPE group.Conclusion:Briefly, this study showed the valuable effect of gallic acid in cardiac dysfunction related to elastase-induced lung injury. These findings suggested that gallic acid, as a natural antioxidant, has a potential therapeutic effect on preventing oxidative stress, inflammation, and subsequent cardiovascular disease.

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.

What is the central question of this study? Do individuals with a patent foramen ovale (PFO+ ) have a larger alveolar-to-arterial difference in ( ) 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 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. 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 ( ) 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 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 30min after breathing four levels of hypoxia (16%, 14%, 12%, 10% O2 , randomized and balanced order) at rest. The was significantly greater in PFO+ compared to PFO- while breathing air (2.1±0.7vs. 0.4±0.3Torr), 16% O2 (1.8±1.2vs. 0.7±0.8Torr) and 14% O2 (2.3±1.2vs. 0.7±0.6Torr), 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.

Measuring the efficiency of pulmonary gas exchange using expired gas instead of arterial blood: comparing the "ideal" Po2 of Riley with end-tidal Po2.

When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar Po2 and the calculated arterial Po2. The end-tidal Po2 is measured using a rapid gas analyzer, and the arterial Po2 is derived from pulse oximetry after allowing for the effect of the Pco2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal Po2 and Pco2 are highly reproducible, providing a solid foundation for the measurement of the oxygen deficit. We compare the oxygen deficit with the classical ideal alveolar-arterial Po2 difference (A-aDO2) as originally proposed by Riley, and now extensively used in clinical practice. This assumes Riley's criteria for ideal alveolar gas, namely no ventilation-perfusion inequality, the same Pco2 as arterial blood, and the same respiratory exchange ratio as the whole lung. It transpires that, in normal subjects, the end-tidal Po2 is essentially the same as the ideal value. This conclusion is consistent with the very small oxygen deficit that we have reported in young normal subjects, the significantly higher values seen in older normal subjects, and the much larger values in patients with lung disease. We conclude that this noninvasive measurement of the efficiency of pulmonary exchange is identical in many respects to that based on the ideal alveolar Po2, but that it is easier to obtain.

Validation of a Noninvasive Assessment of Pulmonary Gas Exchange During Exercise in Hypoxia

Pulmonary gas exchange efficiency, determined by the alveolar-to-arterial Po2 difference (A-aDo2), progressively worsens during exercise at sea-level; this response is further elevated during exercise in hypoxia. Traditionally, pulmonary gas exchange efficiency is assessed through measurements of ventilation and end-tidal gases paired with direct arterial blood gas (ABG) sampling. Because these measures have a number of caveats, particularly invasive blood sampling, the development of new approaches for the noninvasive assessment of pulmonary gas exchange is needed. Is a noninvasive method of assessing pulmonary gas exchange valid during rest and exercise in acute hypoxia? Twenty-five healthy participants (10 female) completed a staged maximal exercise test on a cycle ergometer in a hypoxic chamber (Fio2= 0.11). Simultaneous ABGs via a radial arterial catheter and noninvasive gas-exchange measurements (AGM100) were obtained in 2-minute intervals. Noninvasive gas exchange, termed the O2 deficit, was calculated from the difference between the end-tidal and the calculated Pao2 (via pulse oximetry and corrected for the Bohr effect by using the end-tidal Pco2). Noninvasive O2 deficit was compared with the traditional alveolar to arterial oxygen difference (A-aDo2), using the traditional Riley analysis. Under conditions of rest at room air, hypoxic rest, and hypoxic exercise, strong correlations between the calculated gPao2 and directly measured Pao2 (R2= 0.97; P< .001; mean bias= 1.70mmHg) were observed. At hypoxic rest and exercise, strong relationships between the estimated and directly measured Pao2 (R2= 0.68; P< .001; mean bias= 1.01mmHg) and O2 deficit with the traditional A-aDo2 (R2= 0.70; P< .001; mean bias= 5.24mmHg) remained. Our findings support the use of a noninvasive measure of gas exchange during acute hypoxic exercise in heathy humans. Further studies are required to determine whether this approach can be used clinically as a tool during normoxic exercise in patients with preexisting impairments in gas exchange efficiency.

Oxygen Deficit Is a Sensitive Measure of Mild Gas Exchange Impairment at Inspired O2 between 12.5%–21%

The oxygen deficit (OD) is the difference between the end‐tidal alveolar PO2 and the estimated PO2 of arterial blood derived from the SpO2 that has the potential to be used clinically as a proxy for the alveolar‐arterial PO2 difference. Previous work has shown that a recently developed technology, the Alveolar Gas Meter, is accurate in measuring the efficiency of pulmonary gas exchange, via the OD, in patients with a history of lung disease as well as in normal subjects breathing a hypoxic mixture of 12.5% O2. This study sought to determine how the OD varied as the percent of inspired O2 changed from 21% to 12.5% in 36 healthy subjects split by age (young 22–31, n=23; old 42–90, n=13) to assess the possibility of use in a clinical setting. The PO2 and PCO2 were continually measured as the subject breathed through a mouthpiece using rapidly responding electrochemical cells, and the end‐tidal PO2 and PCO2 were calculated and averaged over 5 steady‐state breaths, while a fingertip pulse oximeter measured the SpO2. After correcting for any change in P50 resulting from the PCO2 differing from 40 mmHg, the arterial PO2 was calculated from the SpO2 by inverting the Hill‐equation. Subjects breathed 12.5, 15, 17.5 and 21% oxygen mixtures (balanced order) and their OD was measured in triplicate. Across all inspired O2 levels, the OD was higher in the older cohort than the young (p &lt;0.0001, repeated measures ANOVA, Table 1). The older cohort had a larger OD at all four oxygen levels (all p&lt;0.0001), with that difference and its variance being greater at higher inspired O2 values (age × O2 interaction p=0.002). The OD at an inspired O2 of 12.5% was significantly less than at 21% for both age cohorts. This is consistent with the known increase in ventilation‐perfusion mismatching that occurs in healthy aging. The decrease in OD magnitude as the inspired oxygen was reduced in both cohorts is consistent with the increased accuracy of the estimated arterial PO2 when based on saturation values on the steep part of the O2‐Hb dissociation curve. Further, as arterial saturation decreases there is an expected decrease in the alveolar‐arterial PO2 difference. The persisting higher OD seen in older subjects, irrespective of inspired O2, suggests that the measurement of oxygen deficit remains sensitive to mild gas exchange impairment, even when breathing air (21% O2).Support or Funding InformationFinancial support from UCSD Measured Oxygen Deficit by Age Young Old p‐value All Inspired O2 (mean±SE) −0.4±0.6 10.6±1.0 &lt;0.0001 Inspired O2 by Age Interaction 0.002 12.5% −1.4±0.7 5.7±0.6 ‐ 15% −2.7±1.0 5.2±1.8 15% vs 12.5%: NS 17.5% −2.7±1.0 9.4±1.8 17.5% vs 12.5%: NS 21% 5.1±1.3 21.9±2.1 21% vs 12.5%: &lt;0.0001

The mechanics of air breathing in gray tree frog tadpoles, Hyla versicolor (Anura: Hylidae).

We describe air-breathing mechanics in gray tree frog tadpoles (Hyla versicolor). We found that H. versicolor tadpoles breathe by 'bubble-sucking', a breathing mode typically employed by tadpoles too small to break the water's surface tension, in which a bubble is drawn into the buccal cavity and compressed into the lungs. In most tadpoles, bubble-sucking is replaced by breach breathing (breaking the surface to access air) at larger body sizes. In contrast, H. versicolor tadpoles bubble-suck throughout the larval period, despite reaching body sizes at which breaching is possible. Hyla versicolor tadpoles exhibit two bubble-sucking behaviors: 'single bubble-sucking', previously described in other tadpole species, is characterized by a single suction event followed by a compression phase to fill the lungs; 'double bubble-sucking' is a novel, apparently derived form of bubble-sucking that adds a second suction event. Hyla versicolor tadpoles transition from single bubble-sucking to double bubble-sucking at approximately 5.7 mm snout-vent length (SVL), which corresponds to a period of rapid lung maturation when they transition from low to high vascularization (6.0 mm SVL). Functional, behavioral and morphological evidence suggests that double bubble-sucking increases the efficiency of pulmonary gas exchange by separating expired, deoxygenated air from freshly inspired air to prevent mixing. Hyla versicolor, and possibly other hylid tadpoles, may have specialized for bubble-sucking in order to take advantage of this increased efficiency. Single and double bubble-sucking represent two- and four-stroke ventilation systems, which we discuss in the context of other anamniote air-breathing mechanisms.

Deriving the arterial Po2 and oxygen deficit from expired gas and pulse oximetry.

The efficiency of pulmonary gas exchange is often assessed by the ideal alveolar-arterial partial pressure difference (A-aDO2). Through a combination of pulse oximetry and rapidly responding gas analyzers to measure the partial pressures of O2 and CO2 in expired gas, one can measure the oxygen deficit. Defined as the difference between the measured alveolar Po2 and the arterial Po2 calculated from , the oxygen deficit is a substitute for the alveolar-arterial Po2 difference. The oxygen deficit is physiologically reasonable in that it increases with age in healthy subjects and is well correlated with the A-aDO2. To calculate arterial Po2 from saturation, the saturation should be below the very flat upper part of the O2-Hb dissociation curve; good estimates can be made provided the arterial O2 saturation is below ~95%. Since saturations at or above 95% imply reasonably well-maintained gas exchange efficiency, this limitation is of only minor concern. Calculations show that it is necessary to take into account the change in Po2 at a saturation of 50% of the O2-Hb dissociation curve based on the measured alveolar Pco2. As the measurement is designed to be noninvasive, determination of any base excess is not practical, but calculations show that the effect of assuming a zero base excess is modest, with a similar small effect from an abnormal body temperature. Taken together, these results show that a noninvasive assessment of pulmonary gas exchange efficiency can be obtained from subjects with below-normal arterial O2 saturations through a combination of expired O2 and CO2 measurements and made during quiet breathing.NEW & NOTEWORTHY The details and limitations of a noninvasive measurement of pulmonary gas exchange efficiency, the oxygen deficit, are described. The oxygen deficit, calculated from expired gas measurements made during quiet breathing coupled with pulse oximetry, is a good surrogate measurement of the ideal alveolar-arterial Po2 difference and does not require arterial blood gas sampling.

Dynamic of end-tidal carbon dioxide pressure during cardiopulmonary exercise testing before and after heart transplantation

Aim: to assess the dynamic and prognostic significance of the end-tidal carbon dioxide pressure (PetCO 2 ) during cardiopulmonary exercise testing in recipients before and after heart transplantation (HT). Materials and methods. The study included 55 patients with severe chronic heart failure (CHF) from the HT waiting list. All patients underwent cardiopulmonary exercise testing before and in the long-term follow-up after TS, including determination of PetCO 2 at rest and during exercise. Results. Physical capacity, the efficiency of pulmonary ventilation and gas exchange in the long-term after the HT significantly improved compared with the preoperative data. Peak oxygen consumption before and after HT was 10.8 (9.4-11.7) ml/min/kg and 18.9 (18.2-21.0) ml/in/kg (p = 0.020), respectively, the value of the VE/VCO 2 slope decreased from 38 (34-45) to 32 (30-36), p = 0.017. PetCO 2 at rest before the HT was below the norm, amounted to 30 (28-32) mm Hg, increased to the anaerobic threshold by an average of 3.6 (0.2-5.2)%. After the HT, the level of PetCO 2 at rest did not change significantly, but the increase during exercise was 7.6 (3.2-9.4)% (p = 0.001). It was shown that a low baseline PetCO2 value and the absence of its increase during cardiopulmonary exercise test significantly increase the risk of adverse outcome in patients with severe CHF before and after HT (OR 0.62 (0.35-0.87), p = 0.035 and, 16 (0.10-0.24), p = 0.002, respectively). Conclusion. Heart transplantation in patients with severe CHF leads to a significant improvement in the efficiency of pulmonary ventilation and gas exchange in the long-term follow-up. Estimation of the PetCO 2 level at rest and during exercise is a promising predictor of adverse outcomes risk stratification in patients with severe CHF before and after HT.

Pathophysiological mechanisms of exertional breathlessness in chronic obstructive pulmonary disease and interstitial lung disease.

Breathlessness is a common and distressing symptom in patients with chronic obstructive pulmonary disease (COPD) and fibrotic interstitial lung disease (ILD), particularly during exercise. Effective medical management of exertional breathlessness in people living with COPD and fibrotic ILD is challenging for healthcare providers and requires an understanding of its mechanisms. Thus, in this brief review we summarize recent advances in our understanding of the pathophysiological mechanisms of exertional breathlessness in COPD and fibrotic ILD. The collective results of recent physiological and clinical trials suggest that higher intensity ratings of exertional breathlessness in both COPD and fibrotic ILD compared to healthy control individuals is mechanistically linked to the awareness of greater neural respiratory drive (quantified using inspiratory muscle electromyography) needed to compensate for pathophysiological abnormalities in respiratory mechanics and pulmonary gas exchange efficiency. Any therapeutic intervention capable of decreasing intrinsic mechanical loading of the respiratory system and/or increasing pulmonary gas exchange efficiency has the potential to decrease the prevalence and severity of activity-related breathlessness and improve related clinical and patient-reported outcomes (e.g., exercise tolerance and health-related quality of life) by decreasing neural respiratory drive in people with COPD and fibrotic ILD.

Measurements of pulmonary gas exchange efficiency using expired gas and oximetry: results in normal subjects.

We are developing a novel, noninvasive method for measuring the efficiency of pulmonary gas exchange in patients with lung disease. The patient wears an oximeter, and we measure the partial pressures of oxygen and carbon dioxide in inspired and expired gas using miniature analyzers. The arterial Po2 is then calculated from the oximeter reading and the oxygen dissociation curve, using the end-tidal Pco2 to allow for the Bohr effect. This calculation is only accurate when the oxygen saturation is <94%, and therefore, these normal subjects breathed 12.5% oxygen. When the procedure is used in patients with hypoxemia, they breathe air. The Po2 difference between the end-tidal and arterial values is called the "oxygen deficit." Preliminary data show that this index increases substantially in patients with lung disease. Here we report measurements of the oxygen deficit in 20 young normal subjects (age 19 to 31 yr) and 11 older normal subjects (47 to 88 yr). The mean value of the oxygen deficit in the young subjects was 2.02 ± 3.56 mmHg (means ± SD). This mean is remarkably small. The corresponding value in the older group was 7.53 ± 5.16 mmHg (means ± SD). The results are consistent with the age-related trend of the traditional alveolar-arterial difference, which is calculated from the calculated ideal alveolar Po2 minus the measured arterial Po2. That measurement requires an arterial blood sample. The present study suggests that this noninvasive procedure will be valuable in assessing the degree of impaired gas exchange in patients with lung disease.