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1.
JAMA Netw Open ; 2(11): e1915011, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31722025

RESUMO

Importance: Exposure to a weightless environment during spaceflight results in a chronic headward blood and tissue fluid shift compared with the upright posture on Earth, with unknown consequences to cerebral venous outflow. Objectives: To assess internal jugular vein (IJV) flow and morphology during spaceflight and to investigate if lower body negative pressure is associated with reversing the headward fluid shift experienced during spaceflight. Design, Setting, and Participants: This prospective cohort study included 11 International Space Station crew members participating in long-duration spaceflight missions . Internal jugular vein measurements from before launch and approximately 40 days after landing were acquired in 3 positions: seated, supine, and 15° head-down tilt. In-flight IJV measurements were acquired at approximately 50 days and 150 days into spaceflight during normal spaceflight conditions as well as during use of lower body negative pressure. Data were analyzed in June 2019. Exposures: Posture changes on Earth, spaceflight, and lower body negative pressure. Main Outcomes and Measures: Ultrasonographic assessments of IJV cross-sectional area, pressure, blood flow, and thrombus formation. Results: The 11 healthy crew members included in the study (mean [SD] age, 46.9 [6.3] years, 9 [82%] men) spent a mean (SD) of 210 (76) days in space. Mean IJV area increased from 9.8 (95% CI, -1.2 to 20.7) mm2 in the preflight seated position to 70.3 (95% CI, 59.3-81.2) mm2 during spaceflight (P < .001). Mean IJV pressure increased from the preflight seated position measurement of 5.1 (95% CI, 2.5-7.8) mm Hg to 21.1 (95% CI, 18.5-23.7) mm Hg during spaceflight (P < .001). Furthermore, stagnant or reverse flow in the IJV was observed in 6 crew members (55%) on approximate flight day 50. Notably, 1 crew member was found to have an occlusive IJV thrombus, and a potential partial IJV thrombus was identified in another crew member retrospectively. Lower body negative pressure was associated with improved blood flow in 10 of 17 sessions (59%) during spaceflight. Conclusions and Relevance: This cohort study found stagnant and retrograde blood flow associated with spaceflight in the IJVs of astronauts and IJV thrombosis in at least 1 astronaut, a newly discovered risk associated with spaceflight. Lower body negative pressure may be a promising countermeasure to enhance venous blood flow in the upper body during spaceflight.

3.
JAMA Ophthalmol ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415055

RESUMO

Importance: Optic disc edema among astronauts after long-duration spaceflight is associated with 1-carbon pathway single-nucleotide polymorphisms and B vitamin status. A recent strict 6° head-down tilt bed rest (HDTBR) study documented development of optic disc edema and increased total retinal thickness in participants exposed to carbon dioxide, 0.5%, for 30 days, but genetic risk factors have not been explored in the cohort. Objective: To examine whether peripapillary retinal thickness measures obtained from optical coherence tomography images during HDTBR and carbon dioxide, 0.5%, exposure are associated with B vitamin status and single-nucleotide polymorphisms involved in folate-dependent and vitamin B12-dependent 1-carbon metabolism pathways. Design, Setting, and Participants: This study was conducted with a cohort of healthy volunteers at the Institute of Aerospace Medicine at the German Aerospace Center in Cologne, Germany. Data collection occurred from October 2017 to November 2017. After a 14-day ambulatory phase without carbon dioxide, participants maintained strict HDTBR with carbon dioxide, 0.5%, for 30 days, followed by a 13-day ambulatory phase without carbon dioxide. Main Outcomes and Measures: Blood samples were collected before HDTBR to assess vitamin levels and single-nucleotide polymorphism status. Optical coherence tomographic images were collected before HDTBR; at days 1, 15, and 30 of the resting period; and 6 and 13 days after the period ended. Total retinal thickness was measured from a radial-24 B-scan centered over the optic disc, and global retinal nerve fiber layer thickness was measured from a circle scan. The changes in total retinal thickness and retinal nerve fiber layer thickness were evaluated against the number of risk alleles (defined as 5-methyltetrahydrofolate-homocysteine methyltransferase reductase [MTRR] 66 G and serine hydroxymethyltransferase 1 [SHMT1] 1420C alleles), along with folate, vitamin B6 (pyridoxine), and vitamin B12 (cobalamin) status. Results: Eleven heathy volunteers (6 men and 5 women) had a mean (SD) age of 33.4 (8.0) years and a mean (SD) body mass index of 23.4 (2.2). After statistical adjustment for B vitamin status, total retinal thickness at the end of HDTBR in participants with 3 or 4 risk alleles was 40 um (SE, 19 µm) greater than in participants with 0 to 2 risk alleles. In addition, the baseline retinal nerve fiber layer thickness was 14 um (SE, 2 µm) greater in those with 3 or 4 risk alleles compared with those with 0 to 2 risk alleles. Conclusions and Relevance: The magnitude of optic disc edema in individuals experiencing HDTBR and exposed to a chronic headward fluid shift in a mild hypercapnic environment was higher in participants with more MTRR 66 G and SHMT1 1420C alleles, even when this finding was statistically adjusted for B vitamin status. These findings may help explain the variability in magnitude of optic disc edema observed during bed rest and spaceflight and thereby improve efforts to counteract this phenomenon.

4.
Science ; 364(6436)2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30975860

RESUMO

To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted. These multiomic, molecular, physiological, and behavioral datasets provide a valuable roadmap of the putative health risks for future human spaceflight.


Assuntos
Adaptação Fisiológica , Astronautas , Voo Espacial , Imunidade Adaptativa , Peso Corporal , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Dano ao DNA , Metilação de DNA , Microbioma Gastrointestinal , Instabilidade Genômica , Humanos , Masculino , Homeostase do Telômero , Fatores de Tempo , Estados Unidos , United States National Aeronautics and Space Administration
6.
Med Sci Sports Exerc ; 50(9): 1961-1980, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29620686

RESUMO

INTRODUCTION: Exposure to microgravity causes alterations in multiple physiological systems, potentially impacting the ability of astronauts to perform critical mission tasks. The goal of this study was to determine the effects of spaceflight on functional task performance and to identify the key physiological factors contributing to their deficits. METHODS: A test battery comprised of seven functional tests and 15 physiological measures was used to investigate the sensorimotor, cardiovascular, and neuromuscular adaptations to spaceflight. Astronauts were tested before and after 6-month spaceflights. Subjects were also tested before and after 70 d of 6° head-down bed rest, a spaceflight analog, to examine the role of axial body unloading on the spaceflight results. These subjects included control and exercise groups to examine the effects of exercise during bed rest. RESULTS: Spaceflight subjects showed the greatest decrement in performance during functional tasks that required the greatest demand for dynamic control of postural equilibrium which was paralleled by similar decrements in sensorimotor tests that assessed postural and dynamic gait control. Other changes included reduced lower limb muscle performance and increased HR to maintain blood pressure. Exercise performed during bed rest prevented detrimental change in neuromuscular and cardiovascular function; however, both bed rest groups experienced functional and balance deficits similar to spaceflight subjects. CONCLUSION: Bed rest data indicate that body support unloading experienced during spaceflight contributes to postflight postural control dysfunction. Further, the bed rest results in the exercise group of subjects confirm that resistance and aerobic exercises performed during spaceflight can play an integral role in maintaining neuromuscular and cardiovascular functions, which can help in reducing decrements in functional performance. These results indicate that a countermeasure to mitigate postflight postural control dysfunction is required to maintain functional performance.

9.
J Appl Physiol (1985) ; 123(6): 1592-1598, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28970204

RESUMO

Blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) increases in healthy humans breathing hypoxic gas and is potentially dependent on body position. Previous work in subjects breathing room air has shown an effect of body position when Q̇IPAVA is detected with transthoracic saline contrast echocardiography (TTSCE). However, the potential effect of body position on Q̇IPAVA has not been investigated when subjects are breathing hypoxic gas or with a technique capable of quantifying Q̇IPAVA. Thus the purpose of this study was to quantify the effect of body position on Q̇IPAVA when breathing normoxic and hypoxic gas at rest. We studied Q̇IPAVA with TTSCE and quantified Q̇IPAVA with filtered technetium-99m-labeled macroaggregates of albumin (99mTc-MAA) in seven healthy men breathing normoxic and hypoxic (12% O2) gas at rest while supine and upright. On the basis of previous work using TTSCE, we hypothesized that the quantified Q̇IPAVA would be greatest with hypoxia in the supine position. We found that Q̇IPAVA quantified with 99mTc-MAA significantly increased while subjects breathed hypoxic gas in both supine and upright body positions (ΔQ̇IPAVA = 0.7 ± 0.4 vs. 2.5 ± 1.1% of cardiac output, respectively). Q̇IPAVA detected with TTSCE increased from normoxia in supine hypoxia but not in upright hypoxia (median hypoxia bubble score of 2 vs. 0, respectively). Surprisingly, Q̇IPAVA magnitude was greatest in upright hypoxia, when Q̇IPAVA was undetectable with TTSCE. These findings suggest that the relationship between TTSCE and 99mTc-MAA is more complex than previously appreciated, perhaps because of the different physical properties of bubbles and MAA in solution. NEW & NOTEWORTHY Using saline contrast bubbles and radiolabeled macroaggregrates (MAA), we detected and quantified, respectively, hypoxia-induced blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) in supine and upright body positions in healthy men. Upright hypoxia resulted in the largest magnitude of Q̇IPAVA quantified with MAA but the lowest Q̇IPAVA detected with saline contrast bubbles. These surprising results suggest that the differences in physical properties between saline contrast bubbles and MAA in blood may affect their behavior in vivo.

10.
Physiol Rep ; 5(11)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28611153

RESUMO

Many astronauts experience ocular structural and functional changes during long-duration spaceflight, including choroidal folds, optic disc edema, globe flattening, optic nerve sheath diameter (ONSD) distension, retinal nerve fiber layer thickening, and decreased visual acuity. The leading hypothesis suggests that weightlessness-induced cephalad fluid shifts increase intracranial pressure (ICP), which contributes to the ocular structural changes, but elevated ambient CO2 levels on the International Space Station may also be a factor. We used the spaceflight analog of 6° head-down tilt (HDT) to investigate possible mechanisms for ocular changes in eight male subjects during three 1-h conditions: Seated, HDT, and HDT with 1% inspired CO2 (HDT + CO2). Noninvasive ICP, intraocular pressure (IOP), translaminar pressure difference (TLPD = IOP-ICP), cerebral and ocular ultrasound, and optical coherence tomography (OCT) scans of the macula and the optic disc were obtained. Analysis of one-carbon pathway genetics previously associated with spaceflight-induced ocular changes was conducted. Relative to Seated, IOP and ICP increased and TLPD decreased during HDT During HDT + CO2 IOP increased relative to HDT, but there was no significant difference in TLPD between the HDT conditions. ONSD and subfoveal choroidal thickness increased during HDT relative to Seated, but there was no difference between HDT and HDT + CO2 Visual acuity and ocular structures assessed with OCT imaging did not change across conditions. Genetic polymorphisms were associated with differences in IOP, ICP, and end-tidal PCO2 In conclusion, acute exposure to mild hypercapnia during HDT did not augment cardiovascular outcomes, ICP, or TLPD relative to the HDT condition.


Assuntos
Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , Hipercapnia/fisiopatologia , Pressão Intracraniana/fisiologia , Pressão Intraocular/fisiologia , Adulto , Deslocamentos de Líquidos Corporais/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Voo Espacial , Tomografia de Coerência Óptica , Simulação de Ausência de Peso
11.
Respir Physiol Neurobiol ; 243: 47-54, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28536067

RESUMO

Several methods exist to study intrapulmonary arteriovenous anastomoses (IPAVA) in humans. Transthoracic saline contrast echocardiography (TTSCE), i.e., bubble scores, is minimally-invasive, but cannot be used to quantify the magnitude of blood flow through IPAVA (QIPAVA). Radiolabeled macroaggregates of albumin (99mTc-MAA) have been used to quantify QIPAVA in humans, but this requires injection of radioactive particles. Previous work has shown agreement between 99mTc-MAA and TTSCE, but this has not been tested simultaneously in the same group of subjects. Thus, the purpose of this study was to determine if there was a relationship between QIPAVA quantified with 99mTc-MAA and bubble scores obtained with TTSCE. To test this, we used 99mTc-MAA and TTSCE to quantify and detect QIPAVA at rest and during exercise in humans. QIPAVA significantly increased from rest to exercise using 99mTc-MAA and TTSCE and there was a moderately-strong, but significant relationship between methods. Our data suggest that high bubble scores generally correspond with large QIPAVA quantified with 99mTc-MAA during exercise.


Assuntos
Anastomose Arteriovenosa/fisiologia , Exercício/fisiologia , Hemodinâmica/fisiologia , Circulação Pulmonar/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Adulto , Anastomose Arteriovenosa/diagnóstico por imagem , Ecocardiografia , Humanos , Masculino , Testes de Função Respiratória , Espirometria , Agregado de Albumina Marcado com Tecnécio Tc 99m/metabolismo , Tomógrafos Computadorizados , Tomografia Computadorizada de Emissão de Fóton Único , Adulto Jovem
13.
J Appl Physiol (1985) ; 118(9): 1100-12, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25678698

RESUMO

A patent foramen ovale (PFO), present in ∼40% of the general population, is a potential source of right-to-left shunt that can impair pulmonary gas exchange efficiency [i.e., increase the alveolar-to-arterial Po2 difference (A-aDO2)]. Prior studies investigating human acclimatization to high-altitude with A-aDO2 as a key parameter have not investigated differences between subjects with (PFO+) or without a PFO (PFO-). We hypothesized that in PFO+ subjects A-aDO2 would not improve (i.e., decrease) after acclimatization to high altitude compared with PFO- subjects. Twenty-one (11 PFO+) healthy sea-level residents were studied at rest and during cycle ergometer exercise at the highest iso-workload achieved at sea level (SL), after acute transport to 5,260 m (ALT1), and again at 5,260 m after 16 days of high-altitude acclimatization (ALT16). In contrast to PFO- subjects, PFO+ subjects had 1) no improvement in A-aDO2 at rest and during exercise at ALT16 compared with ALT1, 2) no significant increase in resting alveolar ventilation, or alveolar Po2, at ALT16 compared with ALT1, and consequently had 3) an increased arterial Pco2 and decreased arterial Po2 and arterial O2 saturation at rest at ALT16. Furthermore, PFO+ subjects had an increased incidence of acute mountain sickness (AMS) at ALT1 concomitant with significantly lower peripheral O2 saturation (SpO2). These data suggest that PFO+ subjects have increased susceptibility to AMS when not taking prophylactic treatments, that right-to-left shunt through a PFO impairs pulmonary gas exchange efficiency even after acclimatization to high altitude, and that PFO+ subjects have blunted ventilatory acclimatization after 16 days at altitude compared with PFO- subjects.


Assuntos
Aclimatação/fisiologia , Forame Oval Patente/fisiopatologia , Troca Gasosa Pulmonar/fisiologia , Adulto , Altitude , Doença da Altitude/fisiopatologia , Gasometria/métodos , Dióxido de Carbono/metabolismo , Exercício/fisiologia , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Descanso/fisiologia , Adulto Jovem
14.
Ann Am Thorac Soc ; 11(10): 1528-37, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25380058

RESUMO

RATIONALE: Adults born very to extremely preterm, with or without bronchopulmonary dysplasia (BPD), have obstructive lung disease, but it is unknown whether this results in respiratory limitations, such as mechanical constraints to Vt expansion during exercise leading to intolerable dyspnea and reduced exercise tolerance, as it does in patients with chronic obstructive pulmonary disease. OBJECTIVES: To test the hypothesis that adult survivors of preterm birth (≤32 wk gestational age) with (n = 20) and without BPD (n = 15) with reduced exercise capacity demonstrate clinically important respiratory limitations at near-maximal exercise compared with full-term control subjects (n = 20). METHODS: Detailed ventilatory and sensory measurements were made before and during exercise on all patients in the three study groups. MEASUREMENTS AND MAIN RESULTS: During exercise at 90% of peak [Formula: see text]o2 ([Formula: see text]o2peak), inspiratory reserve volume decreased to ∼0.5 L in all groups, but this occurred at significantly lower absolute workloads and [Formula: see text]e in ex-preterm subjects with and without BPD compared with full-term control subjects. Severe dyspnea was present and similar at comparable [Formula: see text]e between all groups, but leg discomfort at comparable workloads was greater in ex-preterm subjects with and without BPD compared with control subjects. At 50 to 90% of [Formula: see text]o2peak, exercise-induced expiratory flow limitation was significantly greater in ex-preterm subjects with BPD compared with ex-preterm subjects without BPD and control subjects. The degree of expiratory flow limitation in ex-preterm subjects with and without BPD was significantly related to neonatal O2 therapy duration. CONCLUSIONS: Severe dyspnea and leg discomfort associated with critical constraints on Vt expansion may lead to reduced exercise tolerance in adults born very or extremely preterm, whether or not their birth was complicated by BPD and despite differences in expiratory flow limitation. In this regard, adults born very or extremely preterm have respiratory limitations to exercise similar to patients with chronic obstructive pulmonary disease.


Assuntos
Displasia Broncopulmonar/fisiopatologia , Tolerância ao Exercício/fisiologia , Volume Expiratório Forçado/fisiologia , Nascimento Prematuro/fisiopatologia , Sobreviventes/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Retrospectivos , Adulto Jovem
15.
J Appl Physiol (1985) ; 117(5): 473-81, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24970854

RESUMO

Adults with a history of very preterm birth (<32 wk gestational age; PRET) have reduced lung function and significantly lower lung diffusion capacity for carbon monoxide (DLCO) relative to individuals born at term (CONT). Low DLCO may predispose PRET to diffusion limitation during exercise, particularly while breathing hypoxic gas because of a reduced O2 driving gradient and pulmonary capillary transit time. We hypothesized that PRET would have significantly worse pulmonary gas exchange efficiency [i.e., increased alveolar-to-arterial Po2 difference (AaDO2)] during exercise breathing room air or hypoxic gas (FiO2 = 0.12) compared with CONT. To test this hypothesis, we compared the AaDO2 in PRET (n = 13) with a clinically mild reduction in DLCO (72 ± 7% of predicted) and CONT (n = 14) with normal DLCO (105 ± 10% of predicted) pre- and during exercise breathing room air and hypoxic gas. Measurements of temperature-corrected arterial blood gases, and direct measure of O2 saturation (SaO2), were made prior to and during exercise at 25, 50, and 75% of peak oxygen consumption (V̇o2peak) while breathing room air and hypoxic gas. In addition to DLCO, pulmonary function and exercise capacity were significantly less in PRET. Despite PRET having low DLCO, no differences were observed in the AaDO2 or SaO2 pre- or during exercise breathing room air or hypoxic gas compared with CONT. Although our findings were unexpected, we conclude that reduced pulmonary function and low DLCO resulting from very preterm birth does not cause a measureable reduction in pulmonary gas exchange efficiency.


Assuntos
Exercício/fisiologia , Hipóxia/metabolismo , Lactente Extremamente Prematuro/fisiologia , Capacidade de Difusão Pulmonar/fisiologia , Troca Gasosa Pulmonar/fisiologia , Adolescente , Adulto , Limiar Anaeróbio/fisiologia , Feminino , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Adulto Jovem
16.
PLoS One ; 9(3): e92191, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24658407

RESUMO

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.


Assuntos
Aclimatação/fisiologia , Doença da Altitude/fisiopatologia , Altitude , Gasometria , Cognição/fisiologia , Teste de Esforço , Feminino , Hemoglobinas/metabolismo , Humanos , Hipóxia/fisiopatologia , Masculino , Oxigênio/sangue , Adulto Jovem
17.
J Appl Physiol (1985) ; 116(7): 867-74, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24336881

RESUMO

In the lung, acute reductions in oxygen lead to hypoxic pulmonary vasoconstriction, whereas prolonged exposures to hypoxia result in sustained vasoconstriction, pulmonary vascular remodeling, and the development of pulmonary hypertension. Data from both human subjects and animal models implicate a role for hypoxia-inducible factors (HIFs), oxygen-sensitive transcription factors, in pulmonary vascular responses to both acute and chronic hypoxia. In this review, we discuss work from our laboratory and others supporting a role for HIF in modulating hypoxic pulmonary vasoconstriction and mediating hypoxia-induced pulmonary hypertension, identify some of the downstream targets of HIF, and assess the potential to pharmacologically target the HIF system.


Assuntos
Hipertensão Pulmonar/etiologia , Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/complicações , Artéria Pulmonar/metabolismo , Vasoconstrição , Doença Aguda , Animais , Anti-Hipertensivos/uso terapêutico , Doença Crônica , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Terapia de Alvo Molecular , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Transdução de Sinais , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/uso terapêutico
18.
J Appl Physiol (1985) ; 115(7): 1050-6, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23869070

RESUMO

Cardiopulmonary function is reduced in adults born very preterm, but it is unknown if this results in reduced pulmonary gas exchange efficiency during exercise and, consequently, leads to reduced aerobic capacity in subjects with and without bronchopulmonary dysplasia (BPD). We hypothesized that an excessively large alveolar to arterial oxygen difference (AaDO2) and resulting exercise-induced arterial hypoxemia (EIAH) would contribute to reduced aerobic fitness in adults born very preterm with and without BPD. Measurements of pulmonary function, lung volumes and diffusion capacity for carbon monoxide (DLco) were made at rest. Measurements of maximal oxygen consumption, peak workload, temperature- and tonometry-corrected arterial blood gases, and direct measure of hemoglobin saturation with oxygen (SaO2) were made preexercise and during cycle ergometer exercise in ex-preterm subjects ≤32-wk gestational age, with BPD (n = 12), without BPD (PRE; n = 12), and full term controls (CONT; n = 12) breathing room air. Both BPD and PRE had reduced pulmonary function and reduced DLco compared with CONT. The AaDO2 was not significantly different between groups, and there was no evidence of EIAH (SaO2 < 95% and/or AaDO2 ≥ 40 Torr) in any subject group preexercise or at any workload. Arterial O2 content was not significantly different between the groups preexercise or during exercise. However, peak power output was decreased in BPD and PRE subjects compared with CONT. We conclude that EIAH in adult subjects born very preterm with and without BPD does not likely contribute to the reduction in aerobic exercise capacity observed in these subjects.


Assuntos
Displasia Broncopulmonar/fisiopatologia , Hiperemia/fisiopatologia , Pulmão/fisiopatologia , Troca Gasosa Pulmonar/fisiologia , Adulto , Artérias/metabolismo , Artérias/fisiopatologia , Gasometria/métodos , Displasia Broncopulmonar/metabolismo , Monóxido de Carbono/metabolismo , Exercício/fisiologia , Tolerância ao Exercício/fisiologia , Feminino , Hemoglobinas/metabolismo , Humanos , Hiperemia/metabolismo , Lactente , Pulmão/metabolismo , Masculino , Oxigênio/metabolismo , Consumo de Oxigênio/fisiologia , Respiração , Testes de Função Respiratória/métodos , Volume de Ventilação Pulmonar/fisiologia , Adulto Jovem
19.
Respir Physiol Neurobiol ; 188(1): 71-8, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23648476

RESUMO

Our purpose was to report the prevalence of healthy, young, asymptomatic humans who demonstrate left heart contrast at rest, breathing room air. We evaluated 176 subjects (18-41 years old) using transthoracic saline contrast echocardiography. Left heart contrast appearing ≤3 cardiac cycles, consistent with a patent foramen ovale (PFO), was detected in 67 (38%) subjects. Left heart contrast appearing >3 cardiac cycles, consistent with the transpulmonary passage of contrast, was detected in 49 (28%) subjects. Of these 49 subjects, 31 were re-evaluated after breathing 100% O2 for 10-15min and 6 (19%) continued to demonstrate the transpulmonary passage of contrast. Additionally, 18 of these 49 subjects were re-evaluated in the upright position and 1 (5%) continued to demonstrate the transpulmonary passage of contrast. These data suggest that ~30% of healthy, young, asymptomatic subjects demonstrate the transpulmonary passage of contrast at rest which is reduced by breathing 100% O2 and assuming an upright body position.


Assuntos
Doenças Assintomáticas , Ecocardiografia/métodos , Nível de Saúde , Ventrículos do Coração/diagnóstico por imagem , Mecânica Respiratória/fisiologia , Descanso/fisiologia , Adolescente , Adulto , Ar , Feminino , Humanos , Masculino , Prevalência , Respiração , Estudos Retrospectivos , Adulto Jovem
20.
J Mol Med (Berl) ; 91(3): 297-309, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23334338

RESUMO

Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions, and the appearance of cells expressing smooth muscle-specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular transdifferentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase, and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Endotelina-1/metabolismo , Hipertensão Pulmonar/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Serotonina/metabolismo , Animais , Modelos Animais de Doenças , Endotelina-1/genética , Hipertensão Pulmonar Primária Familiar , Humanos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/fisiopatologia , Camundongos , Artéria Pulmonar/citologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Ratos , Transdução de Sinais , Quinases Associadas a rho/metabolismo
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