Influence of rapidly oscillating inspired O2 and N2 concentrations on pulmonary vascular function and lung fluid balance in healthy adults.

Introduction: Aircrew may experience rapidly oscillating inspired O2/N2 ratios owing to fluctuations in the on-board oxygen delivery systems (OBOG). Recent investigations suggest these oscillations may contribute to the constellation of physiologic events in aircrew of high-performance aircraft. Therefore, the purpose of this study was to determine whether these "operationally-relevant" environmental challenges may cause decrements in measures of pulmonary vascular physiology. Methods: Thirty healthy participants (Age: 29 ± 5 years) were recruited and assigned to one of the three exposures. Participants were instrumented for physiologic monitoring and underwent baseline cardiopulmonary physiology testing (ground level) consisting of a rebreathe method for quantifying pulmonary blood flow (Qc), pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (Dm). Ultrasound was used to quantify "comet tails" (measure of lung fluid balance). After baseline testing, the participants had two 45 min exposures to an altitude of 8,000 ft where they breathed from gas mixtures alternating between 80/20 and 30/70 O2/N2 ratios at the required frequency (30 s, 60 s, or 120 s), separated by repeat baseline measure. Immediately and 45 min after the second exposure, baseline measures were repeated. Results: We observed no changes in Qc, Dm or Vc during the 60 s exposures. In response to the 30 s oscillation exposure, there was a significantly reduced Qc and Vc at the post-testing period (p = 0.03). Additionally, exposure to the 120 s oscillations resulted in a significant decrease in Vc at the recovery testing period and an increase in the Dm/Vc ratio at both the post and recovery period (p < 0.01). Additionally, we observed no changes in the number of comet tails. Conclusion: These data suggest "operationally-relevant" changes in inspired gas concentrations may cause an acute, albeit mild pulmonary vascular derecruitment, reduced distention and/or mild pulmonary-capillary vasoconstriction, without significant changes in lung fluid balance or respiratory gas exchange. The operational relevance remains less clear, particularly in the setting of additional environmental stressors common during flight (e.g., g forces).

Relation of Intravascular Volume Profiles to Heart Failure Progression and Clinical Outcomes.

Heart failure (HF) commonly progresses over time and identifying differences in volume profiles may help stratify risk and guide therapy. The aim of this study was to assess the pathophysiologic and prognostic roles of volume profiles for HF progression in stable ambulatory and hospitalized patients. HF patients who had undergone quantitative intravascular volume analysis (185 outpatients and 139 inpatients) were retrospectively assessed for the combined end point of HF-related hospital admissions (outpatients), HF-readmissions (inpatients), and overall all-cause mortality. After multivariate Cox regression analysis, greater total blood volume expansion was associated with higher risk of HF-admission in previously stable outpatients (HR: 1.023, CI 1.005 to 1.043; p = 0.013) while in more advanced HF (inpatients) total blood volume expansion was associated with lower risk for HF-readmission and mortality (HR: 0.982, CI 0.967 to 0.997; p = 0.017). Secondary analysis suggests that subclinical plasma volume expansion was a driving factor for the detrimental association in outpatients (HR: 1.018, CI 0.997 to 1.036; p = 0.054), while an increase in red blood cell mass was central to the beneficial association in advanced HF (HR: 0.979, CI 0.968 to 0.991; p <0.001). In conclusion, understanding differences in plasma volume and red blood cell mass profiles can provide insight into the pathophysiology and progression of HF.

Validation of radiofrequency determined lung fluid using thoracic CT: Findings in acute decompensated heart failure patients.

BACKGROUND: Noninvasive outpatient monitoring for heart failure (HF) has significant opportunity to reduce patient morbidity and the costs associated with recurrent hospitalization. The purpose of this study was to validate the ability of radiofrequency (RF) to assess lung fluid via a wearable patch device compared to thoracic CT in order to characterize volume overload. METHODS: 120 subjects were studied: 66 acute heart failure (AHF) inpatients and 54 subjects without AHF (Control - 44 healthy and 10 stable HF). All underwent supine thoracic CT scans and supine RF readings from the wearable patch device placed on the left mid-axillary line (age = 74 ± 16 vs. 57 ± 15 yrs.; female = 38 vs. 44%; BMI = 33.2 ± 9.0 vs. 27.3 ± 5.1, AHF vs. Control respectively). Reflected RF signals and subject-specific anthropometric data were used to calculate the RF-determined lung fluid content. CT Lung fluid was reported as percentage of lung volume. Classification analyses were used to compare RF and CT performance. RESULTS: AHF presented with higher lung fluid than controls by both CT and RF (CT: 20.1 ± 4.2% vs. 15.4 ± 2.4%; RF: 20.7 ± 5.6% vs. 15.6 ± 3.3%; p < 0.05 for all). The correlation between lung fluid measured by CT vs. RF was r = 0.7 (p < 0.001). RF determined lung fluid performed as well as CT in distinguishing AHF from control subjects: Sensitivity: 70% vs. 86%; Specificity: 82% vs. 83%; Positive Predictive Value: 82% vs. 86%; Negative Predictive Value: 69% vs. 83%, CT vs. RF respectively. CONCLUSIONS: Noninvasive nonionizing RF determined lung fluid provides a potential alternative to other measures for diagnosing and monitoring pulmonary fluid overload.

Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals.

Wheatley, Courtney M., Sarah E. Baker, Bryan J. Taylor, Manda L. Keller-Ross, Steven C. Chase, Alex R. Carlson, Robert J. Wentz, Eric M. Snyder, and Bruce D. Johnson. Influence of inhaled amiloride on lung fluid clearance in response to normobaric hypoxia in healthy individuals. High Alt Med Biol 18:343-354, 2017. AIM: To investigate the role of epithelial sodium channels (ENaC) on lung fluid clearance in response to normobaric hypoxia, 20 healthy subjects were exposed to 15 hours of hypoxia (fraction of inspired oxygen [FiO2] = 12.5%) on two randomized occasions: (1) inhaled amiloride (A) (1.5 mg/5 mL saline); and (2) inhaled saline placebo (P). Changes in lung fluid were assessed through chest computed tomography (CT) for lung tissue volume (TV), and the diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) for pulmonary capillary blood volume (VC). Extravascular lung water (EVLW) was derived as TV-VC and changes in the CT attenuation distribution histograms were reviewed. RESULTS: Normobaric hypoxia caused (1) a reduction in EVLW (change from baseline for A vs. P, -8.5% ± 3.8% vs. -7.9% ± 5.2%, p < 0.05), (2) an increase in VC (53.6% ± 28.9% vs. 53.9% ± 52.3%, p < 0.05), (3) a small increase in DLCO (9.6% ± 29.3% vs. 9.9% ± 23.9%, p > 0.05), and (4) CT attenuation distribution became more negative, leftward skewed, and kurtotic (p < 0.05). CONCLUSION: Acute normobaric hypoxia caused a reduction in lung fluid that was unaffected by ENaC inhibition through inhaled amiloride. Although possible amiloride-sensitive ENaC may not be necessary to maintain lung fluid balance in response to hypoxia, it is more probable that normobaric hypoxia promotes lung fluid clearance rather than accumulation for the majority of healthy individuals. The observed reduction in interstitial lung fluid means alveolar fluid clearance may not have been challenged.

Impact of chronic systolic heart failure on lung structure-function relationships in large airways.

Heart failure (HF) is often associated with pulmonary congestion, reduced lung function, abnormal gas exchange, and dyspnea. We tested whether pulmonary congestion is associated with expanded vascular beds or an actual increase in extravascular lung water (EVLW) and how airway caliber is affected in stable HF Subsequently we assessed the influence of an inhaled short acting beta agonist (SABA). Thirty-one HF (7F; age, 62 ± 11 years; ht. 175 ± 9 cm; wt. 91 ± 17 kg; LVEF, 28 ± 15%) and 29 controls (11F; age; 56 ± 11 years; ht. 174 ± 8 cm; wt. 77 ± 14 kg) completed the study. Subjects performed PFTs and a chest computed tomography (CT) scan before and after SABA CT measures of attenuation, skew, and kurtosis were obtained from areas of lung tissue to assess EVLW Airway luminal areas and wall thicknesses were also measured : CT tissue density suggested increased EVLW in HF without differences in the ratio of airway wall thickness to luminal area or luminal area to TLC (skew: 2.85 ± 1.08 vs. 2.11 ± 0.79, P < 0.01; Kurtosis: 15.5 ± 9.5 vs. 9.3 ± 5.5 P < 0.01; control vs. HF). PFTs were decreased in HF at baseline (% predicted FVC:101 ± 15% vs. 83 ± 18%, P < 0.01;FEV1:103 ± 15% vs. 82 ± 19%, P < 0.01;FEF25-75: 118 ± 36% vs. 86 ± 36%, P < 0.01; control vs. HF). Airway luminal areas, but not CT measures, were correlated with PFTs at baseline. The SABA cleared EVLW and decreased airway wall thickness but did not change luminal area. Patients with HF had evidence of increased EVLW, but not an expanded bronchial circulation. Airway caliber was maintained relative to controls, despite reductions in lung volume and flow rates. SABA improved lung function, primarily by reducing EVLW.

Association of Cognitive Performance with Time at Altitude, Sleep Quality, and Acute Mountain Sickness Symptoms.

OBJECTIVE: It is well documented that cognitive performance may be altered with ascent to altitude, but the association of various cognitive performance tests with symptoms of acute mountain sickness (AMS) is not well understood. Our objective was to assess and compare cognitive performance during a high-altitude expedition using several tests and to report the association of each test with AMS, headache, and quality of sleep. METHODS: During an expedition to Mount Everest, 3 cognitive tests (Stroop, Trail Making, and the real-time cognitive assessment tool, an in-house developed motor accuracy test) were used along with a questionnaire to assess health and AMS. Eight team members were assessed pre-expedition, postexpedition, and at several time points during the expedition. RESULTS: There were no significant differences (P >.05) found among scores taken at 3 time points at base camp and the postexpedition scores for all 3 tests. Changes in the Stroop test scores were significantly associated with the odds of AMS (P <.05). The logistic regression results show that the percent change from baseline for Stroop score (ß = -5.637; P = .032) and Stroop attempts (ß = -5.269; P = .049) are significantly associated with the odds of meeting the criteria for AMS. CONCLUSIONS: No significant changes were found in overall cognitive performance at altitude, but a significant relationship was found between symptoms of AMS and performance in certain cognitive tests. This research shows the need for more investigation of objective physiologic assessments to associate with self-perceived metrics of AMS to gauge effect on cognitive performance.

Optimizing the calculation of DM,CO and VC via the single breath single oxygen tension DLCO/NO method.

Alveolar-capillary membrane conductance (D(M,CO)) and pulmonary-capillary blood volume (V(C)) are calculated via lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) using the single breath, single oxygen tension (single-FiO2) method. However, two calculation parameters, the reaction rate of carbon monoxide with blood (θ(CO)) and the D(M,NO)/D(M,CO) ratio (α-ratio), are controversial. This study systematically determined optimal θ(CO) and α-ratio values to be used in the single-FiO2 method that yielded the most similar D(M,CO) and V(C) values compared to the 'gold-standard' multiple-FiO2 method. Eleven healthy subjects performed single breath DL(CO)/DL(NO) maneuvers at rest and during exercise. D(M,CO) and V(C) were calculated via the single-FiO2 and multiple-FiO2 methods by implementing seven θ(CO) equations and a range of previously reported α-ratios. The RP θ(CO) equation (Reeves, R.B., Park, H.K., 1992. Respiration Physiology 88 1-21) and an α-ratio of 4.0-4.4 yielded DM,CO and VC values that were most similar between methods. The RP θ(CO) equation and an experimental α-ratio should be used in future studies.

Changes in CT angiographic opacification of porcine coronary artery wall with patchy altered flow in vasa vasorum.

To evaluate the potential of whole-body CT to detect localized areas of decreased or increased vascularity in coronary arterial walls. We used both microsphere embolization of coronary artery vasa vasorum to generate small areas of hypoperfusion and surrounding hyperperfusion of the arterial wall and diet-induced hypercholesterolemia. As a stimulus for localized angiogenesis, such as occurs in early plaque formation in the coronary arterial wall, microspheres were injected selectively into the LAD coronary artery lumens of anesthetized pigs. Fourteen pigs (acute) then had a segment of their LAD harvested during injection of contrast medium and snap-frozen for subsequent cryo-static micro-CT. An additional thirteen pigs (chronic) were allowed to recover, fed a high cholesterol diet and 3 months later were again anesthetized and a segment of the LAD artery harvested and scanned. The spatial distribution of the contrast agent within the arterial wall was measured in contiguous micro-CT images at right angles to the lumen axis with the area of wall in each cross-sectional image being approximately (0.1 mm)(3) in size. In the acute animals there were no localized areas of increased contrast around the hypoperfused embolized perfusion territories in the arterial wall, but in the chronic animals the hypoperfused areas were surrounded by increased contrast. These results suggest that CT might be able to detect localized regions of increased vascularity in the arterial wall as an indicator of early atherosclerotic stimulation of vasa vasorum proliferation.

Vascularity of myocardium and gastrocnemius muscle in rats selectively bred for endurance running capacity.

We tested the hypothesis that changes in the arteriolar branching architecture contributed to increased running capacity of rats subjected to two-way artificial selection for intrinsic aerobic endurance treadmill running capacity resulting in strains of low-capacity and high-capacity endurance rats. Hearts and gastrocnemius muscles were harvested from each strain, and the microvasculature's branching geometry measured from micro-CT images. The vascular branching geometry of the hearts and skeletal muscle from the high capacity was indistinguishable from low-capacity rats. Our hypothesis was not supported. Neither remodeling nor an increase in arteriolar microvasculature branching appears to play a role in the enhanced performance of the high capacity rats. We are led to speculate that endothelial tolerance for shear stress and/or increased coupling of myocardial muscle fiber metabolic-to-contractile function is increased in the high-capacity runner strain to the effect of allowing either higher flow rate per unit volume of muscle or more efficient use of oxygen and nutrients in the high-capacity endurance rats.

Large-vessel distensibility measurement with electrocardiographically gated multidetector CT: phantom study and initial experience.

The purpose of this study was to prospectively examine vessel distensibility measurements by using electrocardiographically gated multidetector computed tomography (CT) in a phantom compared with measurements by using a digital camera and to examine feasibility in humans. Large-vessel phantoms were constructed, using a pulsatile flow pump, and absolute diameter and percentage diameter changes during pulsation were measured. After institutional review board approval and patient consent were obtained, the abdominal aorta of four patients was scanned with an electrocardiographically gated CT protocol. The mean difference in percentage diameter change between CT and optical measurements for the phantom ranged from -0.47% to 0.14%. The range of area changes in five locations along the abdominal aorta in four patients was 2.97%-37.16%. Findings of this study indicate that electrocardiographically gated CT angiography data reconstructed across cardiac phases permit measurements of large-vessel distensibility in a phantom model and that vessel distensibility measurement in humans may be possible.

Development of a cathartic-free colorectal cancer screening test using virtual colonoscopy: a feasibility study.

OBJECTIVE: The purpose of our study was to develop a method to subtract barium-labeled stool from the colon using a phantom and to evaluate the performance of the technique in a pilot human population. MATERIALS AND METHODS: A phantom containing 6-mm flat polyps and three types of simulated stool (homogeneous, moderately heterogeneous, and severely heterogeneous) mixed with barium was created, scanned, and tested using three stool subtraction algorithms but no cathartic. Thirty patients with suspected colorectal polyps were studied using stool tagging to determine which was the most effective stool subtraction algorithm. Colonoscopy was the reference standard. Examinations were evaluated blindly using the unsubtracted and 6 weeks later both the unsubtracted and subtracted data sets. RESULTS: A threshold of 200 H and expansion and convolution techniques were the most effective tools for subtracting stool and minimizing artifacts. When applied to the human population, sensitivities using the unsubtracted data sets were 90% (18/20) and 68% (26/38) for polyps > or = 1 cm and > or = 5 mm, respectively. Specificities were 100% (4/4) and 75% (3/4) for polyps > or = 1 cm and > or = 5 mm. For the stool-subtracted data sets, sensitivities were 90% (18/20) and 71% (27/38) for polyps > or = 1 cm and > or = 5 mm. Per patient sensitivities were 88% (15/17) and 77% (20/26) for > or = 1 cm and > or = 5 mm polyps. Specificities were 100% (4/4) for large polyps and 25% (1/4) for smaller polyps. CONCLUSION: Image processing tools combining thresholding, expansion, and convolution were the most useful for stool subtraction. Laxative-free colon examinations using barium for stool labeling can be performed at CT colonography with or without stool subtraction with high accuracy. Further study is warranted.