Effect of Ultra-Marathon Trail Running at Sea Level and Altitude on Alveolar-Capillary Function and Lung Diffusion.

INTRODUCTION: Endurance exercise at altitude can increase cardiac output and pulmonary vascular pressure to levels that may exceed the stress-tolerability of the alveolar-capillary unit. This study examined the effect of ultra-marathon trail racing at different altitudes (ranging from <1000 m to between 1500 - 2700 m) on alveolar-capillary recruitment and lung diffusion. METHODS: Cardiac and lung function were examined before and after an ultra-marathon in 67 runners (age:41 ± 9y, BMI:23 ± 2 kg/m2, 10 females), and following 12-24 h of recovery in a subset (n = 27). Cardiac biomarkers (cTnI & BNP) were assessed from whole blood, while lung fluid accumulation (comet tails), stroke volume (SV) and cardiac output (Q) were quantified via echocardiography. Lung diffusing capacity for carbon monoxide (DLco) and its components, alveolar membrane conductance (Dm) and capillary blood volume (Vc), were determined via a single-breath method at rest and during three stages of submaximal semi-recumbent cycling (20, 30, & 40 W). RESULTS: Average race time was 25 ± 12 h. From pre- to post-race, there was an increase in cardiac biomarkers (cTnI: 0.04 ± .02 vs 0.13 ± .03 ng/ml; BNP: 20 ± 2 vs 112 ± 21 pg/ml, p < 0.01) and lung comet tails (2 ± 1 vs 7 ± 6, p < 0.01), a decrease in resting and exercise SV (76 ± 2 vs 69 ± 2 ml; 40 W: 93 ± 2 vs 88 ± 2 ml, p < 0.01), and an elevation in Q at rest (4.1 ± 0.1 vs 4.6 ± 0.2 l/min, p < 0.01; 40 W: 7.3 ± 0.2 vs 7.4 ± 0.3 l/min, p = 0.899). Resting DLco and Vc decreased after the race (p < 0.01), while Dm was unchanged (p = 0.465); however, during the three stages of exercise DLco, Vc and Dm were all reduced from pre- to post-race (40 W: 36.3 ± 0.9 vs 33.0 ± 0.8 mL/min/mmHg; 83 ± 3 vs 73 ± 2 mL; 186 ± 6 vs 170 ± 7 mL/min/mmHg, respectively, p < 0.01). When corrected for alveolar volume and Q, DLco decreased from pre- to post-race (p < 0.01), and changes in DLco were similar for all ultra-marathon events (p > 0.05). CONCLUSIONS: Competing in an ultra-marathon leads to a transient increase in cardiac injury biomarkers, mild lung-fluid accumulation, and impairments in lung diffusion. Reductions in DLco are predominantly caused by a reduced Vc and possible pulmonary capillary de-recruitment at rest. However, impairments in alveolar-capillary recruitment and Dm both contribute to a fall in exertional DLco following an ultra-marathon. Perturbations in lung diffusion were evident across a range of event distances and varying environmental exposures.

Metabolic insights at the finish line: deciphering physiological changes in ultramarathon runners through breath VOC analysis.

Exhaustive exercise can induce unique physiological responses in the lungs and other parts of the human body. The volatile organic compounds (VOCs) in exhaled breath are ideal for studying the effects of exhaustive exercise on the lungs due to the proximity of the breath matrix to the respiratory tract. As breath VOCs can originate from the bloodstream, changes in abundance should also indicate broader physiological effects of exhaustive exercise on the body. Currently, there is limited published data on the effects of exhaustive exercise on breath VOCs. Breath has great potential for biomarker analysis as it can be collected non-invasively, and capture real-time metabolic changes to better understand the effects of exhaustive exercise. In this study, we collected breath samples from a small group of elite runners participating in the 2019 Ultra-Trail du Mont Blanc ultra-marathon. The final analysis included matched paired samples collected before and after the race from 24 subjects. All 48 samples were analyzed using the Breath Biopsy Platform with GC-Orbitrap™ via thermal desorption gas chromatography-mass spectrometry. The Wilcoxon signed-rank test was used to determine whether VOC abundances differed between pre- and post-race breath samples (adjustedP-value < .05). We identified a total of 793 VOCs in the breath samples of elite runners. Of these, 63 showed significant differences between pre- and post-race samples after correction for multiple testing (12 decreased, 51 increased). The specific VOCs identified suggest the involvement of fatty acid oxidation, inflammation, and possible altered gut microbiome activity in response to exhaustive exercise. This study demonstrates significant changes in VOC abundance resulting from exhaustive exercise. Further investigation of VOC changes along with other physiological measurements can help improve our understanding of the effect of exhaustive exercise on the body and subsequent differences in VOCs in exhaled breath.

Lung "Comet Tails" in Healthy Individuals: Accumulation or Clearance of Extravascular Lung Water?

Parks, Jordan K, Courtney M. Wheatley-Guy, Glenn M. Stewart, Caitlin C. Fermoyle, Bryan J. Taylor, Jesse Schwartz, Briana Ziegler, Kay Johnson, Alice Gavet, Loïc Chabridon, Paul Robach, and Bruce D. Johnson. Lung "Comet Tails" in healthy individuals: accumulation or clearance of extravascular lung water? High Alt Med Biol. 24:230-233, 2023-Ultrasound lung comet tails (or B-lines) tend to be limited in number (<5) or absent under ultrasound examination, and the appearance of diffuse B-lines with lung sliding has been suggested to identify pulmonary edema. Clinical evaluation of B-lines has been utilized as a bedside test to assess pulmonary congestion in patients with heart failure. Exposure to altitude or prolonged exercise can alter fluid regulation and can lead to pulmonary congestion or edema. As such, B-lines have been utilized in the field to monitor for pathological lung fluid accumulation. However, ultrasound lung comet lines might not be as reliable for identifying extravascular lung water (EVLW) as previously thought in healthy individuals exercising at altitude where an increase in the number of ultrasound lung comets would reflect fluid buildup in the interstitial space of the alveoli and pulmonary capillaries. This report will focus on reviewing the literature and our data from a group of ultraendurance runners that completed the Ultra Trail Mont Blanc race that demonstrates that lung comet tails may not always be evidence of pathological fluid accumulation in healthy individuals and as such should be used to assess EVLW in concert with other diagnostic testing.

Pharmacological modulation of adrenergic tone alters the vasodilatory response to passive leg movement in young but not in old adults.

The age-related increase in α-adrenergic tone may contribute to decreased leg vascular conductance (LVC) both at rest and during exercise in the old. However, the effect on passive leg movement (PLM)-induced LVC, a measure of vascular function, which is markedly attenuated in this population, is unknown. Thus, in eight young (25 ± 5 yr) and seven old (65 ± 7 yr) subjects, this investigation examined the impact of systemic ß-adrenergic blockade (propanalol, PROP) alone, and PROP combined with either α1-adrenergic stimulation (phenylephrine, PE) or α-adrenergic inhibition (phentolamine, PHEN), on PLM-induced vasodilation. LVC, calculated from femoral artery blood flow and pressure, was determined and PLM-induced Δ peak (LVCΔpeak) and total vasodilation (LVCAUC, area under curve) were documented. PROP decreased LVCΔpeak (PROP: 4.8 ± 1.8, Saline: 7.7 ± 2.7 mL·mmHg-1, P < 0.001) and LVCAUC (PROP: 1.1 ± 0.7, Saline: 2.4 ± 1.6 mL·mmHg-1, P = 0.002) in the young, but not in the old (LVCΔpeak, P = 0.931; LVCAUC, P = 0.999). PE reduced baseline LVC (PE: 1.6 ± 0.4, PROP: 2.3 ± 0.4 mL·min-1·mmHg-1, P < 0.01), LVCΔpeak (PE: 3.2 ± 1.3, PROP: 4.8 ± 1.8 mL·min-1·mmHg-1, P = 0.004), and LVCAUC (PE: 0.5 ± 0.4, PROP: 1.1 ± 0.7 mL·mmHg-1, P = 0.011) in the young, but not in the old (baseline LVC, P = 0.199; LVCΔpeak, P = 0.904; LVCAUC, P = 0.823). PHEN increased LVC at rest and throughout PLM in both groups (drug effect: P < 0.05), however LVCΔpeak was only improved in the young (PHEN: 6.4 ± 3.1, PROP: 4.4 ± 1.5 mL·min-1·mmHg-1, P = 0.004), and not in the old (P = 0.904). Furthermore, the magnitude of α-adrenergic modulation (PHEN - PE) of LVCΔpeak was greater in the young compared with the old (Young: 3.35 ± 2.32, Old: 0.40 ± 1.59 mL·min-1·mmHg-1, P = 0.019). Therefore, elevated α-adrenergic tone does not appear to contribute to the attenuated vascular function with age identified by PLM.NEW & NOTEWORTHY Stimulation of α1-adrenergic receptors eliminated age-related differences in passive leg movement (PLM) by decreasing PLM-induced vasodilation in the young. Systemic ß-blockade attenuated the central hemodynamic component of the PLM response in young individuals. Inhibition of α-adrenergic receptors did not improve the PLM response in older individuals, though withdrawal of α-adrenergic modulation augmented baseline and maximal vasodilation in both groups. Accordingly, α-adrenergic signaling plays a role in modulating the PLM vasodilatory response in young but not in old adults, and elevated α-adrenergic tone does not appear to contribute to the attenuated vascular function with age identified by PLM.

Activating P2Y1 receptors improves function in arteries with repressed autophagy.

AIM: The importance of endothelial cell (EC) autophagy to vascular homeostasis in the context of health and disease is evolving. Earlier, we reported that intact EC autophagy is requisite to maintain shear-stress-induced nitric oxide (NO) generation via glycolysis-dependent purinergic signalling to endothelial NO synthase (eNOS). Here, we illustrate the translational and functional significance of these findings. METHODS AND RESULTS: First, we assessed translational relevance using older male humans and mice that exhibit blunted EC autophagy and impaired arterial function vs. adult controls. Active hyperaemia evoked by rhythmic handgrip exercise-elevated radial artery shear-rate similarly from baseline in adult and older subjects for 60 min. Compared with baseline, indexes of autophagy initiation, p-eNOSS1177 activation, and NO generation, occurred in radial artery ECs obtained from adult but not older volunteers. Regarding mice, indexes of autophagy and p-eNOSS1177 activation were robust in ECs from adult but not older animals that completed 60-min treadmill-running. Furthermore, 20 dyne • cm2 laminar shear stress × 45-min increased autophagic flux, glycolysis, ATP production, and p-eNOSS1177 in primary arterial ECs obtained from adult but not older mice. Concerning functional relevance, we next questioned whether the inability to initiate EC autophagy, glycolysis, and p-eNOSS1177in vitro precipitates arterial dysfunction ex vivo. Compromised intraluminal flow-mediated vasodilation displayed by arteries from older vs. adult mice was recapitulated in vessels from adult mice by (i) NO synthase inhibition; (ii) acute autophagy impairment using 3-methyladenine (3-MA); (iii) EC Atg3 depletion (iecAtg3KO mice); (iv) purinergic 2Y1-receptor (P2Y1-R) blockade; and (v) germline depletion of P2Y1-Rs. Importantly, P2Y1-R activation using 2-methylthio-ADP (2-Me-ADP) improved vasodilatory capacity in arteries from (i) adult mice treated with 3-MA; (ii) adult iecAtg3KO mice; and (iii) older animals with repressed EC autophagy. CONCLUSIONS: Arterial dysfunction concurrent with pharmacological, genetic, and age-associated EC autophagy compromise is improved by activating P2Y1-Rs.

The impact of air pollution on interstitial lung disease: a systematic review and meta-analysis.

Introduction: There is a growing body of evidence suggesting a causal relationship between interstitial lung disease (ILD) and air pollution, both for the development of the disease, and driving disease progression. We aim to provide a comprehensive literature review of the association between air pollution, and ILD, including idiopathic pulmonary fibrosis (IPF). Methods: We systematically searched from six online database. Two independent authors (DL and CF) selected studies and critically appraised the risk of bias using the Newcastle-Ottawa Scale (NOS). Findings are presented through a narrative synthesis and meta-analysis. Meta-analyses were performed exclusively when there was a minimum of three studies examining identical pollutant-health outcome pairs, all evaluating equivalent increments in pollutant concentration, using a random effects model. Results: 24 observational studies conducted in 13 countries or regions were identified. Pollutants under investigation encompassed ozone (O3), nitrogen dioxide (NO2), Particulate matter with diameters of 10 micrometers or less (PM10) and 2.5 micrometers or less (PM2.5), sulfur dioxide (SO2), carbon monoxide (CO), nitric oxide (NO) and nitrogen oxides (NOx). We conducted meta-analyses to assess the estimated Risk Ratios (RRs) for acute exacerbations (AE)-IPF in relation to exposure to every 10 µg/m3 increment in air pollutant concentrations, including O3, NO2, PM10, and PM2.5. The meta-analysis revealed a significant association between the increased risk of AE-IPF in PM2.5, yielding RR 1.94 (95% CI 1.30-2.90; p = 0.001). Findings across all the included studies suggest that increased exposure to air pollutants may be linked to a range of health issues in individuals with ILDs. Conclusion: A scarcity of available studies on the air pollutants and ILD relationship underscores the imperative for further comprehensive research in this domain. The available data suggest that reducing levels of PM2.5 in the atmosphere could potentially reduce AE frequency and severity in ILD patients.

Sex-Specific Physiological Responses to Ultramarathon.

PURPOSE: Despite a growing body of literature on the physiological responses to ultramarathon, there is a paucity of data in females. This study assessed the female physiological response to ultramarathon and compared the frequency of perturbations to a group of race- and time-matched males. METHODS: Data were collected from 53 contestants of an ultramarathon trail race at the Ultra-Trail du Mont-Blanc (UTMB®) in 2018/19. Before and within 2 h of the finish, participants underwent physiological assessments, including blood sampling for biomarkers (creatine kinase-MB isoenzyme [CK-MB], cardiac troponin I [cTnI], brain natriuretic peptide [BNP], and creatinine [Cr]), pulmonary function testing (spirometry, exhaled NO, diffusing capacities, and mouth pressures), and transthoracic ultrasound (lung comet tails, cardiac function). Data from eight female finishers (age = 36.6 ± 6.9 yr; finish time = 30:57 ± 11:36 h:min) were compared with a group of eight time-matched males (age = 40.3 ± 8.3 yr; finish time = 30:46 ± 10:32 h:min). RESULTS: Females exhibited significant pre- to postrace increases in BNP (25.8 ± 14.6 vs 140.9 ± 102.7 pg·mL -1 ; P = 0.007) and CK-MB (3.3 ± 2.4 vs 74.6 ± 49.6 IU·L -1 ; P = 0.005), whereas males exhibited significant pre- to postrace increases in BNP (26.6 ± 17.5 vs 96.4 ± 51.9 pg·mL -1 ; P = 0.002), CK-MB (7.2 ± 3.9 vs 108.8 ± 37.4 IU·L -1 ; P = 0.002), and Cr (1.06 ± 0.19 vs 1.23 ± 0.24 mg·dL -1 ; P = 0.028). Lung function declined in both groups, but males exhibited additional reductions in lung diffusing capacities (DL CO = 34.4 ± 5.7 vs 29.2 ± 6.9 mL⋅min -1 ⋅mm Hg -1 , P = 0.004; DL NO = 179.1 ± 26.2 vs 152.8 ± 33.4 mL⋅min -1 ⋅mm Hg -1 , P = 0.002) and pulmonary capillary blood volumes (77.4 ± 16.7 vs 57.3 ± 16.1 mL; P = 0.002). Males, but not females, exhibited evidence of mild postrace pulmonary edema. Pooled effect sizes for within-group pre- to postrace changes, for all variables, were generally larger in males versus females ( d = 0.86 vs 0.63). CONCLUSIONS: Ultramarathon negatively affects a range of physiological functions but generally evokes more frequent perturbations, with larger effect sizes, in males compared to females with similar race performances.

Persistent vascular dysfunction following an acute nonpharmacological reduction in blood pressure in hypertensive patients.

BACKGROUND: Vascular dysfunction, an independent risk factor for cardiovascular disease, often persists in patients with hypertension, despite improvements in blood pressure control induced by antihypertensive medications. METHODS: As some of these medications may directly affect vascular function, this study sought to comprehensively examine the impact of reducing blood pressure, by a nonpharmacological approach (5 days of sodium restriction), on vascular function in 22 hypertensive individuals (14 men/8 women, 50 ±â€Š10 years). Following a 2-week withdrawal of antihypertensive medications, two 5-day dietary phases, liberal sodium (liberal sodium, 200 mmol/day) followed by restricted sodium (restricted sodium, 10 mmol/day), were completed. Resting blood pressure was assessed and vascular function, at both the conduit and microvascular levels, was evaluated by brachial artery flow-mediated dilation (FMD), reactive hyperemia, progressive handgrip exercise, and passive leg movement (PLM). RESULTS: Despite a sodium restriction-induced fall in blood pressure (liberal sodium: 141 ±â€Š14/85 ±â€Š9; restricted sodium 124 ±â€Š12/79 ±â€Š9 mmHg, P < 0.01 for both SBP and DBP), FMD (liberal sodium: 4.6 ±â€Š1.8%; restricted sodium: 5.1 ±â€Š2.1%, P = 0.27), and reactive hyperemia (liberal sodium: 548 ±â€Š201; restricted sodium: 615 ±â€Š206 ml, P = 0.08) were not altered. Similarly, brachial artery vasodilation during handgrip exercise was not different between conditions (liberal sodium: Δ0.36 ±â€Š0.19 mm; restricted sodium: Δ0.42 ±â€Š0.18 mm, P = 0.16). Lastly, PLM-induced changes in peak blood flow (liberal sodium: 5.3 ±â€Š2.5; restricted sodium: 5.8 ±â€Š3.6 ml/min per mmHg, P = 0.30) and the total vasodilatory response [liberal sodium: 2 (0.9-2.5) vs. restricted sodium: 1.7 (1.1-2.6) ml/min per mmHg; P = 0.5] were also not different between conditions. CONCLUSION: Thus vascular dysfunction, at both the conduit and microvascular levels, persists in patients with hypertension even when blood pressure is acutely reduced by a nonpharmacological approach.

Cardiovasomobility: an integrative understanding of how disuse impacts cardiovascular and skeletal muscle health.

Cardiovasomobility is a novel concept that encompasses the integration of cardiovascular and skeletal muscle function in health and disease with critical modification by physical activity, or lack thereof. Compelling evidence indicates that physical activity improves health while a sedentary, or inactive, lifestyle accelerates cardiovascular and skeletal muscle dysfunction and hastens disease progression. Identifying causative factors for vascular and skeletal muscle dysfunction, especially in humans, has proven difficult due to the limitations associated with cross-sectional investigations. Therefore, experimental models of physical inactivity and disuse, which mimic hospitalization, injury, and illness, provide important insight into the mechanisms and consequences of vascular and skeletal muscle dysfunction. This review provides an overview of the experimental models of disuse and inactivity and focuses on the integrated responses of the vasculature and skeletal muscle in response to disuse/inactivity. The time course and magnitude of dysfunction evoked by various models of disuse/inactivity are discussed in detail, and evidence in support of the critical roles of mitochondrial function and oxidative stress are presented. Lastly, strategies aimed at preserving vascular and skeletal muscle dysfunction during disuse/inactivity are reviewed. Within the context of cardiovasomobility, experimental manipulation of physical activity provides valuable insight into the mechanisms responsible for vascular and skeletal muscle dysfunction that limit mobility, degrade quality of life, and hasten the onset of disease.

Simultaneous Measurement of Lung Diffusing Capacity and Pulmonary Hemodynamics Reveals Exertional Alveolar-Capillary Dysfunction in Heart Failure With Preserved Ejection Fraction.

Background Hemodynamic perturbations in heart failure with preserved ejection fraction (HFpEF) may alter the distribution of blood in the lungs, impair gas transfer from the alveoli into the pulmonary capillaries, and reduce lung diffusing capacity. We hypothesized that impairments in lung diffusing capacity for carbon monoxide (DLCO) in HFpEF would be associated with high mean pulmonary capillary wedge pressures during exercise. Methods and Results Rebreathe DLCO and invasive hemodynamics were measured simultaneously during exercise in patients with exertional dyspnea. Pulmonary pressure waveforms and breath-by-breath pulmonary gas exchange were recorded at rest, 20 W, and symptom-limited maximal exercise. Patients with HFpEF (n=20; 15 women, aged 65±11 years, body mass index 36±8 kg/m2) achieved a lower symptom-limited maximal workload (52±27 W versus 106±42 W) compared with controls with noncardiac dyspnea (n=10; 7 women, aged 55±10 years, body mass index 30±5 kg/m2). DLCO was lower in patients with HFpEF compared with controls at rest (DLCO 10.4±2.9 mL/min per mm Hg versus 16.4±6.9 mL/min per mm Hg, P<0.01) and symptom-limited maximal exercise (DLCO 14.6±4.7 mL/min per mm Hg versus 23.8±10.8 mL/min per mm Hg, P<0.01) because of a lower alveolar-capillary membrane conductance in HFpEF (rest 16.8±6.6 mL/min per mm Hg versus 28.4±11.8 mL/min per mm Hg, P<0.01; symptom-limited maximal exercise 25.0±6.7 mL/min per mm Hg versus 45.5±22.2 mL/min per mm Hg, P<0.01). DLCO was lower in HFpEF for a given mean pulmonary artery pressure, mean pulmonary capillary wedge pressure, pulmonary arterial compliance, and transpulmonary gradient. Conclusions Lung diffusing capacity is lower at rest and during exercise in HFpEF due to impaired gas conductance across the alveolar-capillary membrane. DLCO is impaired for a given pulmonary capillary wedge pressure and pulmonary arterial compliance. These data provide new insight into the complex relationships between hemodynamic perturbations and gas exchange abnormalities in HFpEF.

Impact of presymptomatic COVID-19 on vascular and skeletal muscle function: a case study.

The impact of COVID-19 has been largely described after symptom development. Although the SARS-CoV-2 virus elevates heart rate (HR) prior to symptom onset, whether this virus evokes other presymptomatic alterations is unknown. This case study details the presymptomatic impact of COVID-19 on vascular and skeletal muscle function in a young woman [24 yr, 173.5 cm, 89 kg, body mass index (BMI): 29.6 kg·m-2]. Vascular and skeletal muscle function were assessed as part of a separate study with the first and second visits separated by 2 wk. On the evening following the second visit, the participant developed a fever and a rapid antigen test confirmed a positive COVID-19 diagnosis. Compared with the first visit, the participant presented with a markedly elevated HR (∼30 beats/min) and a lower mean blood pressure (∼8 mmHg) at the second visit. Vascular function measured by brachial artery flow-mediated dilation, reactive hyperemia, and passive leg movement were all noticeably attenuated (25%-65%) as was leg blood flow during knee extension exercise. Muscle strength was diminished as was ADP-stimulated respiration (30%), assessed in vitro, whereas there was a 25% increase in the apparent Km. Lastly, an elevation in IL-10 was observed prior to symptom onset. Notably, 2.5 mo after diagnosis symptoms of fatigue and cough were still present. Together, these findings provide unique insight into the physiological responses immediately prior to onset of COVID-19 symptoms; they suggest that SARS-CoV-2 negatively impacts vascular and skeletal muscle function prior to the onset of common symptoms and may set the stage for the widespread sequelae observed following COVID-19 diagnosis.NEW & NOTEWORTHY This unique case study details the impact of SARS-CoV-2 infection on vascular and skeletal muscle function in a young predominantly presymptomatic woman. Prior to COVID-19 diagnosis, substantial reductions in vascular, skeletal muscle, and mitochondrial function were observed along with an elevation in IL-10. This integrative case study indicates that the presymptomatic impact of COVID-19 is widespread and may help elucidate the acute and long-term sequelae of this disease.

Effects of exercise on thoracic blood volumes, lung fluid accumulation, and pulmonary diffusing capacity in heart failure with preserved ejection fraction.

Patients with heart failure with preserved ejection fraction (HFpEF) experience symptoms of exertional dyspnea that may be related to lung fluid accumulation during exercise. A computed tomography (CT)-based method was used to measure exercise-induced changes in extravascular lung fluid content and thoracic blood volumes and to determine the effect of lung fluid on lung diffusing capacity for carbon monoxide (DLCO) in stable subjects with HFpEF and healthy controls. Nine subjects with HFpEF (age = 68 ± 8 yr; body mass index = 32.1 ± 2.6 kg/m2) and eight healthy controls (62 ± 9 yr, 23.8 ± 2.4 kg/m2) performed triplicate rebreathe DLCO/DLNO (lung diffusing capacity for nitric oxide) tests in a supine position at rest and duplicate measurements during two 5-min submaximal exercise stages (15W and 35W) and recovery. Subjects subsequently performed a 5-min exercise bout (35W) inside a CT scanner, and extravascular lung fluid content and thoracic blood volumes were quantified at rest and immediately following exercise from thoracic and contrast perfusion scans, respectively. Subjects with HFpEF had a higher lung fluid content at rest compared with controls (means ± SD, HFpEF: 14.4 ± 1.7%, control: 12.8 ± 1.7%, P = 0.043) and a higher lung fluid content following exercise (15.2 ± 2.0% vs. 12.6 ± 1.5%, P = 0.009). Higher lung fluid content was associated with a lower DLCO and alveolar-capillary membrane conductance (Dm) in subjects with HFpEF (DLCO: R = -0.57, P = 0.022, Dm: R = -0.61, P = 0.012) but not in controls. Pulmonary blood volume was not altered by exercise and was similar between groups. Submaximal exercise elicited a greater accumulation of lung fluid in subjects with HFpEF compared with in controls, and lung fluid content was negatively correlated with lung diffusing capacity and alveolar-capillary membrane conductance in subjects with HFpEF.

Pulmonary Vascular Pressures and Gas Exchange Response to Exercise in Heart Failure With Preserved Ejection Fraction.

Elevated left ventricular filling pressure (measured as mean pulmonary capillary wedge pressure) at rest or with exercise is diagnostic of heart failure with preserved ejection fraction. However, the capacity of the right ventricle to compensate for a high mean pulmonary capillary wedge pressure and thus maintain an appropriate transpulmonary gradient (TPG) and perfusion of the pulmonary capillaries is likely an important contributor to gas exchange efficiency and exercise capacity. Therefore, this study aimed to determine whether a higher TPG at peak exercise is associated with superior exercise capacity and gas exchange. Gas exchange data from dyspneic patients referred for exercise right heart catheterization were retrospectively analyzed and patients were split into two groups based on TPG. Patients with a higher TPG at peak exercise had a higher peak VO2 (1025 ± 227 vs 823 ± 276, P = .038), end-tidal partial pressure of carbon dioxide (42.2 ± 7.9 vs 38.0 ± 4.7, P = .044), and gas exchange estimates of pulmonary vascular capacitance (408 ± 90 vs 268 ± 108, P = .001). A higher TPG at peak exercise correlated with a higher peak oxygen uptake, O2 pulse, and stroke volume (R = 0.42, 0.44 and 0.42, respectively, all P < 0.05). These findings indicate that a greater TPG with exercise might be important for improving exercise capacity in heart failure with preserved ejection fraction.

The effect of diuresis on extravascular lung water and pulmonary function in acute decompensated heart failure.

AIMS: The effect of extravascular lung water (EVLW) and relationship to functional status as a result of acute decompensated heart failure (ADHF) are not well understood. We sought to quantify changes in clinical variables, EVLW, airway anatomy, spirometry, and diffusing capacity for carbon monoxide before and after treatment for ADHF. METHODS AND RESULTS: Fifteen patients were recruited within 24 h of hospital admission. Spirometry, diffusing capacity for carbon monoxide, and surrogates of EVLW by computed tomography were measured and were then repeated within 24 h of discharge. From the computed tomography (CT) scan, surrogates of EVLW were calculated from the distribution of CT attenuation of the lung tissue. Airways were segmented using the VIDA Apollo software. Patients were hospitalized for 4.6 ± 2.1 days, had 10 ± 4.8 L of fluid removed (7.0 ± 4.2 L between study visits), and lost 7.1 ± 4.9 kg. Patients had significant clearance of fluid from the lungs (per cent change: mean, 4.2 ± 6.1%; skew, 17.5 ± 27.0%; kurtosis, 37.6 ± 56.7%; full-width half-maximum, 10.2 ± 13.5%). Static lung volumes and maximal flows improved significantly (per cent change: forced vital capacity, 14.5 ± 13.6%; forced expiratory volume in 1 s, 15.9 ± 14.0%; forced expiratory flow at 25-75% of forced vital capacity, 27.2 ± 42.9%). The ratio of membrane conductance to capillary blood volume improved significantly (per cent change: alveolar-capillary membrane conductance/capillary blood volume, 23.4 ± 22.8%). Weight loss during hospitalization was significantly correlated with improved spirometry and diffusing capacity. CONCLUSIONS: Extravascular lung water contributes to the pulmonary congestive syndrome in ADHF patients, and its clearance is an important component of the improvement in pulmonary function as a result of inpatient treatment.