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).

Myocardial adaptability in young and older-aged sea-level habitants sojourning at Mt Kilimanjaro: are cardiac compensatory limits reached in older trekkers?

INTRODUCTION: High-altitude ascent induces left (LV) and right (RV) ventricular adaptations secondary to hypoxia-related hemodynamic and myocardial alterations. Since cardiopulmonary decrements observed with aging (e.g., decreased LV compliance and increased pulmonary vascular resistance) may limit cardiac plasticity, this study examined myocardial adaptability throughout an 11 day sojourn to 5893 m in young and older-aged trekkers. METHODS AND RESULTS: Echocardiography was performed on 14 young (8 men; 32 ± 5 years) and 13 older-aged (8 men; 59 ± 5 years) subjects on non-trekking days (Day 0: 880 m; Day 3: 3100 m; Day 8: 4800 m; Day 12/post-climb: 880 m). RV systolic pressure (mmHg) was systematically higher in older-aged subjects (p < 0.01) with similar progressive increases observed during ascent for young and older subjects, respectively (Day 0: 18 ± 1 vs 20 ± 2; Day 3: 25 ± 2 vs 29 ± 3; Day 8: 30 ± 2 vs 35 ± 2). Estimates of LV filling pressure (E/E') were systematically higher in older subjects (p < 0.01) with similar progressive decreases observed during ascent for young and older-aged subjects, respectively (Day 0: 5.6 ± 0.3 vs 6.7 ± 0.5; Day 3: 5.1 ± 0.2 vs 6.1 ± 0.3; Day 8: 4.7 ± 0.3 vs 5.4 ± 0.3). Overall, RV end-diastolic and end-systolic area increased at altitude (p < 0.01), while LV end-diastolic and end-systolic volume decreased (p < 0.01). However, all RV and LV morphological measures were similar on Day 3 and Day 8 (p > 0.05), and returned to baseline post-climb (p > 0.05). Excluding mild LV dilatation in some older-aged trekkers on Day 8/Day 12 (p < 0.01), altitude-induced morphological and functional adaptations were similar for all trekkers (p > 0.05). CONCLUSION: Altitude-induced myocardial adaptations are chamber specific, secondary to RV and LV hemodynamic alterations. Despite progressive hemodynamic alterations during ascent, morphological and functional cardiac perturbations plateaued, suggesting rapid myocardial adaptation which was mostly comparable in young and older-aged individuals.

A comparison of finger and forehead pulse oximeters in heart failure patients during maximal exercise.

BACKGROUND: Pulse oximeters, clinically used to measure oxygen saturation (SpO2), rely on adequate perfusion of the tissues over which they are placed. Heart failure (HF) patients can have impaired peripheral perfusion which may compromise the accuracy of a peripherally placed pulse oximeter. This decrease in peripheral perfusion may be especially apparent during exercise. The objective of this study was to determine if pulse oximeter accuracy is dependent on location in heart failure patients during peak exercise. METHODS: 20 participants with HF (7F, age 64.±11 yr) and 9 participants with coronary artery disease as controls (CAD: 3F, age 66±5 yr) performed a maximal exertion treadmill exercise stress test while wearing both finger and forehead pulse oximeters. RESULTS: At peak exercise, the two pulse oximeters measurements of SpO2 differed from each other by 3.8 ±â€¯3.3% in the HF group (p<0.01) and 2.0 ±â€¯1.4% in the CAD group (p = 0.065). The difference between the pulse rate from the pulse oximeters and the heart rate from the 12-lead ECG in the HF group was 12±20 BPM (p<0.01) for the finger pulse oximeter, and 2 ±â€¯3 BPM (p = 0.162) for the forehead pulse oximeter. CONCLUSIONS: Forehead pulse oximeters may be more reliable compared to finger pulse oximeters in obtaining SpO2 measurements in HF patients during a treadmill maximal exercise test.

Effect of age on the presence of comet tails at high altitude.

Extravascular lung water (EVLW) increases in healthy adults upon exposure to high altitude, likely due to increased pulmonary vascular resistance (PVR). Older individuals experience increased PVR during exercise, which may be exacerbated by trekking at high altitude. This study aimed to determine whether EVLW development is greater in older versus younger adults during graded altitude exposure. Fourteen younger (32 ± 6y) and 12 older (58 ± 5y) healthy adults completed an 11-day trek of Mount Kilimanjaro. EVLW was assessed at rest via comet tails prior to the trek in Moshi (950 m), at Shira Camp (3505 m), at Barafu Camp (4837 m), and post-descent. An increase in altitude from Baseline to Barafu tended to increase the proportion of participants with mild EVLW (p = 0.06). A higher proportion of older versus younger individuals tended to show mild EVLW at Barafu (56 vs. 14%, p = 0.06). In conclusion, EVLW formation may be more common in older adults trekking at high altitude. However, the presence of EVLW in older adults was subclinical.

Age-dependent effects of thoracic and capillary blood volume distribution on pulmonary artery pressure and lung diffusing capacity.

Aging is associated with pulmonary vascular remodeling and reduced distensibility. We investigated the influence of aging on changes in cardiac output (Q), mean pulmonary artery pressure (mPAP), and lung diffusing capacity in response to alterations in thoracic blood volume. The role of pulmonary smooth muscle tone was also interrogated via pulmonary vasodilation. Nine younger (27 ± 4 years) and nine older (71 ± 4 years) healthy adults reached steady-state in a Supine (0°), Upright (+20°), or Head-down (-20°) position in order to alter thoracic blood volume. In each position, echocardiography was performed to calculate mPAP and Q, and lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO) was assessed. Next, 100 mg sildenafil was administered to reduce pulmonary smooth muscle tone, after which the protocol was repeated. mPAP (P ≤ 0.029) and Q (P ≤ 0.032) were lower in the Upright versus Supine and Head-down positions, and mPAP was reduced following sildenafil administration (P = 0.019), in older adults only. SV was lower in the Upright versus Supine and Head-down positions in both younger (P ≤ 0.008) and older (P ≤ 0.003) adults. DLCO and DLNO were not greatly altered by position changes or sildenafil administration. However, the DLNO/DLCO ratio was lower in the Supine and/or Head-down positions (P ≤ 0.05), but higher following sildenafil administration (P ≤ 0.007), in both younger and older adults. In conclusion, older adults experience greater cardiopulmonary alterations following thoracic blood volume changes, and pulmonary smooth muscle tone plays a role in resting mPAP in older adults only. Furthermore, mPAP is an important determinant of pulmonary capillary blood volume distribution (DLNO/DLCO), regardless of age.

The influence of pulmonary vascular pressures on lung diffusing capacity during incremental exercise in healthy aging.

Alveolar-capillary surface area for pulmonary gas exchange falls with aging, causing a reduction in lung diffusing capacity for carbon monoxide (DLCO). However, during exercise additional factors may influence DLCO, including pulmonary blood flow and pulmonary vascular pressures. First, we sought to determine the age-dependent effect of incremental exercise on pulmonary vascular pressures and DLCO. We also aimed to investigate the dependence of DLCO on pulmonary vascular pressures during exercise via sildenafil administration to reduce pulmonary smooth muscle tone. Nine younger (27 ± 4 years) and nine older (70 ± 3 years) healthy subjects performed seven 5-min exercise stages at rest, 0 (unloaded), 10, 15, 30, 50, and 70% of peak workload before and after sildenafil. DLCO, cardiac output (Q), and pulmonary artery and wedge pressure (mPAP and mPCWP; subset of participants) were collected at each stage. mPAP was higher (P = 0.029) and DLCO was lower (P = 0.009) throughout exercise in older adults; however, the rate of rise in mPAP and DLCO with increasing Q was not different. A reduction in pulmonary smooth muscle tone via sildenafil administration reduced mPAP, mPCWP, and the transpulmonary gradient (TPG = mPAP-mPCWP) in younger and older subjects (P < 0.001). DLCO was reduced following the reduction in mPAP and TPG, regardless of age (P < 0.001). In conclusion, older adults successfully adapt to age-dependent alterations in mPAP and DLCO. Furthermore, DLCO is dependent on pulmonary vascular pressures, likely to maintain adequate pulmonary capillary recruitment. The rise in pulmonary artery pressure with aging may be required to combat pulmonary vascular remodeling and maintain lung diffusing capacity, particularly during exercise.

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.

The effect of aging and cardiorespiratory fitness on the lung diffusing capacity response to exercise in healthy humans.

Aging is associated with deterioration in the structure and function of the pulmonary circulation. We characterized the lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary-capillary blood volume (Vc) response to discontinuous incremental exercise at 25, 50, 75, and 90% of peak work (Wpeak) in four groups: 1) Young [27 ± 3 yr, maximal oxygen consumption (V̇o2max): 110 ± 18% age predicted]; 2) Young Highly Fit (27 ± 3 yr, V̇o2max: 147 ± 8% age predicted); 3) Old (69 ± 5 yr, V̇o2max: 116 ± 13% age predicted); and 4) Old Highly Fit (65 ± 5 yr, V̇o2max: 162 ± 18% age predicted). At rest and at 90% Wpeak, DLCO, DmCO, and Vc were decreased with age. At 90% Wpeak, DLCO, DmCO, and Vc were greater in Old Highly Fit vs. Old adults. The slope of the DLCO-cardiac output (Q̇) relationship from rest to end exercise at 90% Wpeak was not different between Young, Young Highly Fit, Old, and Old Highly Fit (1.35 vs. 1.44 vs. 1.10 vs. 1.35 mlCO·mmHg-1·liter blood-1, P = 0.388), with no evidence of a plateau in this relationship during exercise; this was also true for DmCO-Q̇ and Vc-Q̇. V̇o2max was positively correlated with 1) DLCO, DmCO, and Vc at rest; and 2) the rest to end exercise change in DLCO, DmCO, and Vc. In conclusion, these data suggest that despite the age-associated deterioration in the structure and function of the pulmonary circulation, expansion of the pulmonary capillary network does not become limited during exercise in healthy individuals regardless of age or cardiorespiratory fitness level.NEW & NOTEWORTHY Healthy aging is a crucial area of research. This article details how differences in age and cardiorespiratory fitness level affect lung diffusing capacity, particularly during high-intensity exercise. We conclude that highly fit older adults do not experience a limit in lung diffusing capacity during high-intensity exercise. Interestingly, however, we found that highly fit older individuals demonstrate greater values of lung diffusing capacity during high-intensity exercise than their less fit age-matched counterparts.

Noninvasive assessment of cardiac output by brachial occlusion-cuff technique: comparison with the open-circuit acetylene washin method.

Cardiac output (CO) assessment as a basic hemodynamic parameter has been of interest in exercise physiology, cardiology, and anesthesiology. Noninvasive techniques available are technically challenging, and thus difficult to use outside of a clinical or laboratory setting. We propose a novel method of noninvasive CO assessment using a single, upper-arm cuff. The method uses the arterial pressure pulse wave signal acquired from the brachial artery during 20-s intervals of suprasystolic occlusion. This method was evaluated in a cohort of 12 healthy individuals (age, 27.7 ± 5.4 yr, 50% men) and compared with an established method for noninvasive CO assessment, the open-circuit acetylene method (OpCirc) at rest, and during low- to moderate-intensity exercise. CO increased from rest to exercise (rest, 7.4 ± 0.8 vs. 7.2 ± 0.8; low, 9.8 ± 1.8 vs. 9.9 ± 2.0; moderate, 14.1 ± 2.8 vs. 14.8 ± 3.2 l/min) as assessed by the cuff-occlusion and OpCirc techniques, respectively. The average error of experimental technique compared with OpCirc was -0.25 ± 1.02 l/min, Pearson's correlation coefficient of 0.96 (rest + exercise), and 0.21 ± 0.42 l/min with Pearson's correlation coefficient of 0.87 (rest only). Bland-Altman analysis demonstrated good agreement between methods (within 95% boundaries); the reproducibility coefficient (RPC) = 0.84 l/min with R2 = 0.75 at rest and RPC = 2 l/min with R2 = 0.92 at rest and during exercise, respectively. In comparison with an established method to quantify CO, the cuff-occlusion method provides similar measures at rest and with light to moderate exercise. Thus, we believe this method has the potential to be used as a new, noninvasive method for assessing CO during exercise.

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.

Exercise-induced interstitial pulmonary edema at sea-level in young and old healthy humans.

We asked whether aged adults are more susceptible to exercise-induced pulmonary edema relative to younger individuals. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (Dm) and pulmonary-capillary blood volume (Vc) were measured before and after exhaustive discontinuous incremental exercise in 10 young (YNG; 27±3 years) and 10 old (OLD; 69±5 years) males. In YNG subjects, Dm increased (11±7%, P=0.031), Vc decreased (-10±9%, P=0.01) and DLCO was unchanged (30.5±4.1 vs. 29.7±2.9mL/min/mmHg, P=0.44) pre- to post-exercise. In OLD subjects, DLCO and Dm increased (11±14%, P=0.042; 16±14%, P=0.025) but Vc was unchanged (58±23 vs. 56±23mL, P=0.570) pre- to post-exercise. Group-mean Dm/Vc was greater after vs. before exercise in the YNG and OLD subjects. However, Dm/Vc was lower post-exercise in 2 of the 10 YNG (-7±4%) and 2 of the 10 OLD subjects (-10±5%). These data suggest that exercise decreases interstitial lung fluid in most YNG and OLD subjects, with a small number exhibiting evidence for exercise-induced pulmonary edema.