Ceridon, Maile L.

The classic method for determining alveolar‐capillary membrane conductance (D M ) and pulmonary capillary blood volume (V C ) involves measurement of lung diffusing capacity for carbon monoxide (D LCO ) at multiple inspired O 2 tensions (F I O 2 ). Recently, the technique has been simplified by simultaneously measuring D LNO (nitric oxide) to determine values at a single F I O 2 . Controversy exists over equations for calculation of θ CO (reaction rate of CO with Hgb) and the correct diffusion ratio for NO and CO (α) in the calculation of D MCO . The purpose of this study was to investigate how various published equations and ratios influence D M & V C using both the multiple and single F I O 2 methods. Eight healthy males were studied. D LCO & D LNO were measured using the rebreathe method (inspired vol. ~75% of inspiratory capacity, F I O 2 18, 35, & 55%). D M & V C were first calculated using five reported equations for θ CO . Once D M & V C were optimized based on reported predicted values, the D LNO method was compared using a range of α values. Using the multiple F I O 2 method, depending on the equation for θ CO , D M ranged from 47 to 103 ml/min/mmHg, and V C from 74 to 102 ml. For the calculation of D M & V C using the D LNO method, α ranged from 1.5 to 4.0 in order to optimize D M & V C values to the classic method. The determination of D M & V C is critically dependent on the equations used for θ CO which in turn affects the optimal ratio used to correct the D LNO method. NIH HL71478

Reduced partial pressures of inspired O 2 may influence the bronchial circulation through a number of mechanisms (e.g. altered pulmonary and systemic vascular pressures, lung fluid regulation, airway cooling & drying from increased ventilation). The present study examined the impact of acute, graded hypoxia on bronchial blood flow (Q aw ) in eight healthy adults (28 ± 9 years). Subjects were exposed to inspired O 2 levels resulting in arterial O 2 saturation (SaO 2 ) values of 90% and 80% for 15 min each. To control for the mild hyperventilation that accompanies hypoxia, subjects then mimicked the 80% SaO 2 ventilation (V E ) rate with 21% FIO 2 and again with CO 2 added to the inspirate to maintain normocapnia. Q aw and cardiac output (CO) were measured using soluble gas techniques. Also measured were alveolar‐capillary conductance (D m , index of lung fluid balance), pulmonary capillary blood volume (V c ), and systemic mean (MAP) and pulmonary arterial pressures (PAP). Hypoxia resulted in minimal change in MAP, a small rise in PAP, minimal change in CO and V c , and a rise in D m . There was also a non significant decrease in Q aw with hypoxia. Mild hyperventilation resulted in a significant fall in Q aw , but when normocapnia was maintained, Q aw returned to baseline values. These data suggest that acute, graded hypoxic exposure does not significantly impact Q aw , however, the hypocapnia associated with mild hyperventilation reduces Q aw .

We previously demonstrated a bimodal distribution of vasodilator responsiveness to adenosine (ADO) infusion in human subjects: one subgroup demonstrated robust vasodilator responses to ADO (ADO responders) and the other showed blunted responses (non‐responders). Furthermore, ADO receptor antagonism blunted ADO vasodilator responses only in ADO responders and blunted exercise vasodilation only at high workloads in both groups. To test the hypothesis that ADO transporter antagonism would augment vasodilator responsiveness to ADO and exercise only in ADO responders, we compared forearm vasodilation to intra‐arterial infusion of three doses of ADO to vasodilation during three workloads of forearm handgrip exercise before and after ADO transporter antagonism with dipyridamole (DYP) in 10 subjects. In ADO responders (n=5), the change in forearm vascular conductance above baseline (ml min −1 100mmHg −1 ) for the low, medium, and high doses of ADO, respectively, was 61 ± 15, 117 ± 35, 164 ± 47 before DYP and 160 ± 50, 171 ± 59, and 216 ± 87 after DYP. For non‐responders (n=5), these values were 20 ± 2, 36 ± 6, 57 ± 14 before DYP ( P < 0.05 vs. responders) and were 159 ± 40, 293 ± 53, and 377 ± 82 after DYP ( P > 0.05 vs. responders). ADO transporter blockade had no effect on exercise hyperemia in either group ( P > 0.05 for pre vs. post‐DYP). We conclude that there may be increased ADO transporter activity in non‐responders resulting in increased clearance of ADO from the interstitium and that, in both subgroups, ADO is not obligatory for exercise hyperemia.

The causes of reduced pulmonary function (PF) in heart failure (HF) patients remain unclear, but may be due to increased pulmonary congestion. Rapid fluid loading (RFL) in healthy adults has been used to simulate intra‐thoracic fluid overload common in HF. This study examined PF using plethysmography, and airway lumen cross sectional area (A lumen ), airway wall thickness (t aw ), and vascular volume using non‐contrast CT imaging before and after RFL in 22 healthy adults. Average infusion volume was 2190 ± 412 ml over 20 ± 3 min. Vascular volume, heart rate, and cardiac output increased (p<0.001). O 2 saturation and mean arterial pressure were unchanged. Forced vital capacity (FVC) and expiratory flow measures decreased post RFL (ΔFVC=−13±9%, ΔFEV1=−15±10%, ΔFEF25‐75=−17±19%, p<0.001). A lumen was unchanged from the trachea through airway generation 3; t aw decreased in the trachea (p<0.05) but remained unchanged in airway generations 1–3. Both measures increased at airway generation 4 (p<0.01). Changes in t aw and A lumen were unrelated and were also independent of any changes in vascular volume or PF. This data suggests that RFL in healthy adults results in decreases in PF, however these decreases are not due to changes in A lumen , t aw , or pulmonary blood volume of the larger airways and vessels that can be easily imaged without contrast. Further studies will be needed to assess bronchial changes in the mid to smaller airways.

Background Increased pulmonary capillary pressure and a possible desensitization of lung β 2 adrenergic receptors (β 2 AR) involved in fluid removal mechanisms may increase extravascular lung water (E LW ) in stable heart failure (HF) patients. Whether these patients exhibit increased E LW remains controversial. Purpose To determine if HF patients have elevated E LW versus controls (CTL) and if acute β 2 AR agonist inhalation stimulates fluid removal. Methods/Results 14 stable HF patients and 19 healthy age/gender matched CTL were studied. Lung tissue volume (V tis ) (includes tissue, blood and water) and pulmonary capillary blood volume (Vc) were assessed pre and post nebulized albuterol via CT and rebreathe, respectively. E LW was derived as V tis – Vc. Pre albuterol, E LW was greater in HF vs. CTL (861±241 vs. 739±143 ml, P <0.01), with no difference in V tis (938±246 vs. 830±151 ml, P =0.08). Albuterol decreased V tis (–4±2%, P =0.02) but did not change E LW (739±143 vs. 724±132 ml) ( P >0.05) in CTL. In HF, albuterol decreased both V tis (–5±3%) and E LW (– 4±2%) ( P <0.05). There was a negative relationship between baseline values and the pre to post albuterol change for V tis ( r 2 =0.38) and E LW ( r 2 =0.42) ( P <0.01) in HF. Conclusion Lung fluid is elevated in stable HF patients relative to healthy subjects. Stimulation of β 2 ARs appears to enhance fluid removal in HF, especially in patients with elevated lung water at rest.

Background Physical activity has been proposed as a risk factor for altitude illness however it is unclear whether the total amount or intensity of activity determines illness. Purpose To examine activity patterns relative to the incidence of acute mountain sickness (AMS) in United States Antarctic Program workers rapidly transported to the South Pole (SP, 9303 ft). Methods 53 medically screened subjects (age=37±10yr, BMI=24±3 kg/m 2 ) were transported by a 3 hour flight from McMurdo Station (sea level, SL) to the SP. Physical activity was monitored at SL and for 3 days after ascent using BodyMedia® activity monitors. Symptoms of AMS were assessed using Lake Louise Questionnaires. Results 53% of subjects displayed AMS between SP days 1–3 (23% day 1, 43% day 2, 15% day 3). Energy expenditure at SP was 3414±944, 3458±781, & 3543±869 Calories/day for days 1–3, respectively. Steps/day at SP was 12593±4926, 13124±4392, & 12966±4482 for days 1–3, respectively. Overall, more activity at higher intensity (>3 METS) on SP day 1 was associated with higher AMS incidence the next morning (p<0.05). Also, calorie expenditure with activity at >3 METS and time of activity at >6 METS in the first 24 hours after ascent independently increased the odds of AMS on SP day 2 (p<0.05). Conclusions With rapid transport to altitude, moderate to intense activity within the first 24 hours of ascent contributes to the incidence of AMS. NSF ANT 0540710

Maximal expiratory flows (MEF) are dependent on gas density, lung volume, subject effort and airway characteristics. Variable changes in MEF occur after ascent to altitude which may represent an interaction between gas density changes, catecholamine stimulation and mild interstitial edema. Hypoxia induced catecholamine up‐regulation has also been associated with acute mountain sickness (AMS). This study examined the association between MEF variability and AMS symptoms in United States Antarctic Program personnel (n=198, age 37±1 yrs, 3% asthma) rapidly transported to the South Pole (SP, 9302 ft). Spirometric parameters, epinephrine (Epi), norepinepherine (NE) and SaO2 levels were recorded at sea level (SL, McMurdo Station) and after the 2 nd night at SP. AMS was assessed using Lake Louise questionnaires (score ≥ 3). FVC, FEV 1 , FEF 25 , FEF 75 and FEF 25–75 increased by 0, 3, 17, 10 and 14% from SL to SP, respectively. On day 2, AMS incidence was 31% and Epi and NE increased by 44 and 71%. Changes in MEF ranged from −64 to +93% in FEF 25–75 and −63 to +70% in FEF 75 . Subjects with the greatest increase in MEF had higher incidence of AMS (24 vs 41%) and higher NE levels, while the subjects with the greatest decrease in MEF had lower SaO2 values (88 vs 90%). Subjects with increased MEF had increased AMS and bronchodilation while subjects with decreased MEF displayed values consistent with mild interstitial edema.

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/m 2 ) 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.

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 (θCO) and the DmCO/DlNOrelationship (α-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 (θCO, α-ratio) that would experimentally substantiate calculations of Dm and Vc from the single-inspired O2tension [inspired fraction of O2(FiO2)] method relative to the multiple-FiO2method. Eight healthy men were studied at rest and during moderate exercise (80-W cycle). Dm and Vc were determined by the multiple-FiO2and single-FiO2methods (rebreathe technique) and were tabulated by applying previously reported θCOequations (both methods) and by varying the α-ratio (single-FiO2method) from 1.90 to 2.50. Values were then compared between methods throughout the examined α-ratios. Dm and Vc were critically dependent on the applied θCOequation. For the multiple-FiO2method, Dm was highly variable between θCOequations (rest and exercise); the range of Vc was less widespread. For the single-FiO2method, the θCOequation by Reeves and Park (1992) combined with an α-ratio between 2.08 and 2.26 gave values for Dm and Vc that most closely matched those from the multiple-FiO2method and were also physiologically plausible compared with predicted values. We conclude that the parameters used to calculate Dm and Vc values from the single-FiO2method (using DlCOand DlNO) can significantly influence results and should be evaluated within individual laboratories to obtain optimal values.