Maile L. Ceridon

Exercise intensity-dependent contribution of β-adrenergic receptor-mediated vasodilatation in hypoxic humans

We previously reported that hypoxia‐mediated reductions in α‐adrenoceptor sensitivity do not explain the augmented vasodilatation during hypoxic exercise, suggesting an enhanced vasodilator signal. We hypothesized that β‐adrenoceptor activation contributes to augmented hypoxic exercise vasodilatation. Fourteen subjects (age: 29 ± 2 years) breathed hypoxic gas to titrate arterial O2 saturation (pulse oximetry) to 80%, while remaining normocapnic via a rebreath system. Brachial artery and antecubital vein catheters were placed in the exercising arm. Under normoxic and hypoxic conditions, baseline and incremental forearm exercise (10% and 20% of maximum) was performed during control (saline), α‐adrenoceptor inhibition (phentolamine), and combined α‐ and β‐adrenoceptor inhibition (phentolomine/propranolol). Forearm blood flow (FBF), heart rate, blood pressure, minute ventilation, and end‐tidal CO2 were determined. Hypoxia increased heart rate (P < 0.05) and minute ventilation (P < 0.05) at rest and exercise under all drug infusions, whereas mean arterial pressure was unchanged. Arterial adrenaline (P < 0.05) and venous noradrenaline (P < 0.05) were higher with hypoxia during all drug infusions. The change (Δ) in FBF during 10% hypoxic exercise was greater with phentolamine (Δ306 ± 43 ml min−1) vs. saline (Δ169 ± 30 ml min−1) or combined phentolamine/propranolol (Δ213 ± 25 ml min−1; P < 0.05 for both). During 20% hypoxic exercise, ΔFBF was greater with phentalomine (Δ466 ± 57 ml min−1; P < 0.05) vs. saline (Δ346 ± 40 ml min−1) but was similar to combined phentolamine/propranolol (Δ450 ± 43 ml min−1). Thus, in the absence of overlying vasoconstriction, the contribution of β‐adrenergic mechanisms to the augmented hypoxic vasodilatation is dependent on exercise intensity.

Calculating alveolar capillary conductance and pulmonary capillary blood volume: comparing the multiple- and single-inspired oxygen tension methods

Key elements for determining alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) from the lung diffusing capacity (Dl) for carbon monoxide (DlCO) or for nitric oxide (DlNO) are the reaction rate of carbon monoxide with hemoglobin (thetaCO) and the DmCO/DlNO relationship (alpha-ratio). Although a range of values have been reported, currently there is no consensus regarding these parameters. The study purpose was to define optimal parameters (thetaCO, alpha-ratio) that would experimentally substantiate calculations of Dm and Vc from the single-inspired O2 tension [inspired fraction of O2 (FiO2)] method relative to the multiple-FiO2 method. Eight healthy men were studied at rest and during moderate exercise (80-W cycle). Dm and Vc were determined by the multiple-FiO2 and single-FiO2 methods (rebreathe technique) and were tabulated by applying previously reported thetaCO equations (both methods) and by varying the alpha-ratio (single-FiO2 method) from 1.90 to 2.50. Values were then compared between methods throughout the examined alpha-ratios. Dm and Vc were critically dependent on the applied thetaCO equation. For the multiple-FiO2 method, Dm was highly variable between thetaCO equations (rest and exercise); the range of Vc was less widespread. For the single-FiO2 method, the thetaCO equation by Reeves and Park (1992) combined with an alpha-ratio between 2.08 and 2.26 gave values for Dm and Vc that most closely matched those from the multiple-FiO2 method and were also physiologically plausible compared with predicted values. We conclude that the parameters used to calculate Dm and Vc values from the single-FiO2 method (using DlCO and DlNO) can significantly influence results and should be evaluated within individual laboratories to obtain optimal values.

Influence of bronchial blood flow and conductance on pulmonary function in stable systolic heart failure

BACKGROUND The aim of this study was to determine the relationship between airway blood flow (Q(aw)), airway conductance (G(f-aw)) and pulmonary function in patients with stable HF. METHODS 12 controls (CTRL: age=63±9 years, FVC=98±15%pred, LVEF=61±6%) (all data presented as mean±SD), 16 patients with mild HF (HF-A, NYHA I-II: age=64±9 years, FVC=90±17%pred, LVEF=28±6%), and 14 patients with moderate/severe HF (HF-B, NYHA III-IV: age=65±6 years, FVC=84±12%pred, LVEF=26±6%) were studied. Q(aw) was assessed using soluble gas measurements; perfusion pressure across airway bed (ΔP(aw)) was estimated from systemic and pulmonary pressure measurements; G(f-aw) was calculated as Q(aw)/ΔP(aw); PF was assessed by spirometry. RESULTS While Q˙(aw) was not significantly different between CTRL (61.3±17.9 μL min(-1)mL(-1)), HF-A (70.1±26.9 μL min(-1)mL(-1)) and HF-B (56.2±14.9 μL min(-1)mL(-1)) groups, G(f-aw), was elevated in HF-A (1.1±0.4 μL min(-1)mL(-1)mm Hg(-1), p<0.03) and tended to be elevated in HF-B (1.2±0.6 μL min(-1)mL(-1)mm Hg(-1), p=0.07) when compared to CTRL (0.8±0.3 μL min(-1)mL(-1)mm Hg(-1)). Significant positive correlations were found between G(f-aw) and RV/TLC for HF-A (r=0.63, p<0.02) and HF-B (r=0.58, p<0.05). CONCLUSIONS These results support the hypothesis that increased bronchial conductance and bronchial congestion may be related to greater small airway obstruction and as such may play a role in the PF abnormalities and symptoms of congestion commonly observed in HF patients.

Ventilatory Expired Gas at Constant-Rate Low-Intensity Exercise Predicts Adverse Events and is Related to Neurohormonal Markers in Patients With Heart Failure

BACKGROUND Ventilatory efficiency (VE/VCO(2) ratio) and the partial pressure of end-tidal carbon dioxide (P(ET)CO(2)), obtained during moderate to high levels of physical exertion demonstrate prognostic value in heart failure (HF). The present investigation assesses the clinical utility of these variables during low-intensity exercise. METHODS AND RESULTS One hundred and thirty subjects diagnosed with HF underwent a 2-minute, constant-rate treadmill session at 2 miles per hour. Both the VE/VCO(2) ratio and P(ET)CO(2) were recorded during exercise (30-second average) and their change (Delta) from rest. B-type and atrial natriuretic peptide (BNP and ANP) were also determined. Only P(ET)CO(2) and DeltaP(ET)CO(2) emerged from the multivariate Cox regression. Receiver operating characteristic curve analysis revealed the prognostic classification schemes were significant with thresholds of < or >or=34 mm Hg (hazard ratio: 4.2, 95% CI: 2.2-8.0, P < .001) and < or >or=1 mm Hg (hazard ratio: 3.5, 95% CI: 1.9-6.6, P < .001) being optimal for P(ET)CO(2) and DeltaP(ET)CO(2), respectively. Moreover, subjects with a P(ET)CO(2)>or=34 mm Hg had a significantly lower BNP (214.1 +/- 431.9 vs. 1110.5 +/- 1854.0 pg/mL, P=.005) and ANP (108.2 +/- 103.6 vs. 246.2 +/- 200.4 pg/mL, P < .001). CONCLUSIONS The results of this pilot study indicate ventilatory expired gas analysis during a short bout of low-intensity exercise may provide insight into prognosis and cardiac stability.

Incidence and symptoms of high altitude illness in South Pole workers: Antarctic study of altitude physiology (ASAP)

Introduction Each year, the US Antarctic Program rapidly transports scientists and support personnel from sea level (SL) to the South Pole (SP, 2835 m) providing a unique natural laboratory to quantify the incidence of acute mountain sickness (AMS), patterns of altitude related symptoms and the field effectiveness of acetazolamide in a highly controlled setting. We hypothesized that the combination of rapid ascent (3 hr), accentuated hypobarism (relative to altitude), cold, and immediate exertion would increase altitude illness risk. Methods Medically screened adults (N = 246, age = 37 ± 11 yr, 30% female, BMI = 26 ± 4 kg/m2) were recruited. All underwent SL and SP physiological evaluation, completed Lake Louise symptom questionnaires (LLSQ, to define AMS), and answered additional symptom related questions (eg, exertional dyspnea, mental status, cough, edema and general health), during the 1st week at altitude. Acetazolamide, while not mandatory, was used by 40% of participants. Results At SP, the barometric pressure resulted in physiological altitudes that approached 3400 m, while T °C averaged -42, humidity 0.03%. Arterial oxygen saturation averaged 89% ± 3%. Overall, 52% developed LLSQ defined AMS. The most common symptoms reported were exertional dyspnea-(87%), sleeping difficulty-(74%), headache-(66%), fatigue-(65%), and dizziness/lightheadedness-(46%). Symptom severity peaked on days 1-2, yet in >20% exertional dyspnea, fatigue and sleep problems persisted through day 7. AMS incidence was similar between those using acetazolamide and those abstaining (51 vs. 52%, P = 0.87). Those who used acetazolamide tended to be older, have less altitude experience, worse symptoms on previous exposures, and less SP experience. Conclusion The incidence of AMS at SP tended to be higher than previously reports in other geographic locations at similar altitudes. Thus, the SP constitutes a more intense altitude exposure than might be expected considering physical altitude alone. Many symptoms persist, possibly due to extremely cold, arid conditions and the benefits of acetazolamide appeared negligible, though it may have prevented more severe symptoms in higher risk subjects.

Effect of supine posture on airway blood flow and pulmonary function in stable heart failure

BACKGROUND The aim of this study was to determine the relationship between body position, pulmonary function (PF) and bronchial blood flow (Q(aw)) in a group of heart failure (HF) and control subjects. METHODS Thirty-six subjects were studied: 24 stable, ambulatory HF patients (HF: LVEF=27±6%, age=65±9 yr) and 12 age- and sex-matched controls (CTRL: LVEF=60±7%, age=62±8 yr). Measures of Q˙(aw) (soluble gas method) and PF were collected upright and following 30min in the supine position. RESULTS Q˙(aw) was similar between groups and remained unchanged with body position. Declines in forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1) with the supine position were observed in both groups; declines in forced expiratory flow 25-75% (FEF(25-75)) and FEF 75% (FEF75) with the supine position were observed in the HF group only. Changes in Q˙(aw) were related to changes in PF only in the HF patient groups (ΔFVC, % predicted, r = -0.45, p<0.04, ΔFEV1 r = -0.61, p<0.01, ΔFEV1% predicted, r = -0.45, p<0.04). CONCLUSION These data demonstrate that relationships between postural changes in Q˙(aw) and PF exist only in the HF population and that the bronchial circulation may contribute to postural PF decline in HF.

Influence of Rapid Fluid Loading on Airway Structure and Function in Healthy Humans

BACKGROUND The present study examined the influence of rapid intravenous fluid loading (RFL) on airway structure and pulmonary vascular volumes using computed tomography imaging and the subsequent impact on pulmonary function in healthy adults (n = 16). METHODS AND RESULTS Total lung capacity (DeltaTLC = -6%), forced vital capacity (DeltaFVC = -14%), and peak expiratory flow (DeltaPEF = -19%) decreased, and residual volume (DeltaRV = +38%) increased post-RFL (P < .05). Airway luminal cross-sectional area (CSA) decreased at the trachea, and at airway generation 3 (P < .05), wall thickness changed minimally with a tendency for increasing in generation five (P = .13). Baseline pulmonary function was positively associated with airway luminal CSA; however, this relationship deteriorated after RFL. Lung tissue volume and pulmonary vascular volumes increased 28% (P < .001) post-RFL, but did not fully account for the decline in TLC. CONCLUSIONS These data suggest that RFL results in obstructive/restrictive PF changes that are most likely related to structural changes in smaller airways or changes in extrapulmonary vascular beds.

Exercise-related change in airway blood flow in humans: Relationship to changes in cardiac output and ventilation

This study examined the relationship between airway blood flow (Q(aw)), ventilation (V(E)) and cardiac output (Q(tot)) during exercise in healthy humans (n=12, mean age 34+/-11 yr). Q(aw) was estimated from the uptake of the soluble gas dimethyl ether while V(E) and Q(tot) were measured using open circuit spirometry. Measurements were made prior to and during exercise at 34+/-5 W (Load 1) and 68+/-10 W (Load 2) and following the cessation of exercise (recovery). Q(aw) increased in a stepwise fashion (P<0.05) from rest (52.8+/-19.5 microl min(-1) ml(-1)) to exercise at Load 1 (67.0+/-20.3 microl min(-1) ml(-1)) and Load 2 (84.0+/-22.9 microl min(-1) ml(-1)) before returning to pre-exercise levels in recovery (51.7+/-13.2 microl min(-1) ml(-1)). Q(aw) was positively correlated with both Q(tot) (r=0.58, P<0.01) and V(E) (r=0.50, P<0.01). These results demonstrate that the increase in Q(aw) is linked to an exercise related increase in both Q(tot) and V(E) and may be necessary to prevent excessive airway cooling and drying.

Sleep disordered breathing and acute mountain sickness in workers rapidly transported to the South Pole (2835 m)

BACKGROUND Sleep disordered breathing may be a risk factor for high altitude illness. Past Antarctic sleep studies suggest that rapid transport from sea level (SL) to the Amundsen Scott South Pole Station (SP, 2835 m) increases risk of Acute Mountain Sickness (AMS). We analyzed sleep studies in 38 healthy polar workers to explore the association between sleep disordered breathing and AMS after rapid transport to the South Pole. METHODS Subjects completed a baseline questionnaire, performed basic physiology tests, and were evaluated for AMS and medication use using an extended Lake Louise Questionnaire (LLQ) during their first week at the South Pole. Participants were included in this study if they took no medications and underwent polysomnography on their first nights at Sea Level and the South Pole using the Vivometrics LifeShirt(®). Within group changes were assessed with Wilcoxon signed rank tests and between group differences were assessed with Kruskal-Wallis rank sum tests. RESULTS Overall, 21/38 subjects met criteria for AMS at some time on or prior to the third morning at the South Pole. Subjective poor sleep quality was reported by both AMS (65%) and no AMS (41%) groups. The Apnea Hypopnea Index (AHI) increased significantly in both the AMS and no AMS groups, but the difference in the increase between the two groups was not statistically significant. Increased AHI was not associated with increased AMS symptoms. Previous altitude illness (p=0.06) and residence at low altitudes (p = 0.02) were risk factors for AMS. CONCLUSION AMS was not significantly associated with sleep architecture changes or increased AHI. However, AHI sharply increased at South Pole (19/38 participants) primarily due to central apneas. Those developing AMS were more likely to have experienced previous problems at altitude and reported living at lowland altitudes within the 3 months prior to rapid transport to the South Pole than those without AMS.