The resistive and elastic work of breathing during exercise in patients with chronic heart failure.

Patients with heart failure (HF) display numerous derangements in ventilatory function, which together serve to increase the work of breathing (W(b)) during exercise. However, the extent to which the resistive and elastic properties of the respiratory system contribute to the higher W(b) in these patients is unknown. We quantified the resistive and elastic W(b) in patients with stable HF (n = 9; New York Heart Association functional class I-II) and healthy control subjects (n = 9) at standardised levels of minute ventilation (V'(E)) during graded exercise. Dynamic lung compliance was systematically lower for a given level of V'(E) in HF patients than controls (p<0.05). HF patients displayed slightly higher levels of inspiratory elastic W(b) with greater amounts of ventilatory constraint and resistive W(b) than control subjects during exercise (p<0.05). Our data indicates that the higher W(b) in HF patients is primarily due to a greater resistive, rather than elastic, load to breathing. The greater resistive W(b) in these patients probably reflects an increased hysteresivity of the airways and lung tissues. The marginally higher inspiratory elastic W(b) observed in HF patients appears related to a combined decrease in the compliances of the lungs and chest wall. The clinical and physiological implications of our findings are discussed.

Lung-to-lung circulation times during exercise in heart failure.

Circulation time (the transit time for a bolus of blood through the circulatory system) is a potential index of cardiac dysfunction in chronic heart failure (HF). In healthy subjects, circulation time falls as cardiac output (Q) rises during exercise, however little is known about this index in HF. In this study we examined the relationship between lung-to-lung circulation time (LLCT) during exercise in ten HF (53 +/- 14 year, resting ejection fraction = 23 +/- 8%) and control subjects (51 +/- 18 year). We hypothesized that HF patients would have slower LLCT times during exercise when compared to control subjects. Each subject completed two identical incremental exercise tests during which LLCT was measured in one test and Q measured in the other. Q was measured using the open circuit C(2)H(2) washin technique and circulation time measured using an inert gas technique. In HF patients and control subjects, LLCT decreased and Q increased from rest (HF:LLCT = 53.6 +/- 8.2 s, Q = 4.3 +/- 1.1 l min(-1); control: LLCT = 55.3 +/- 10.9 s, Q = 4.5 +/- 0.5 l min(-1)) to peak exercise (HF:LLCT = 20.6 +/- 3.9* s, Q = 8.8 +/- 2.5* l min(-1); control:LLCT = 14.9 +/- 2.4 s, Q = 16.5 +/- 1.2 l min(-1); *P < 0.05 vs control). LLCT was significantly (P < 0.05) slower for the HF group when compared to the control group during submaximal exercise and at peak exercise. However, at a fixed Q the HF subjects had a faster LLCT. We hypothesize that the faster LLCT at a fixed Q for HF patients, may be the result of a more intensive peripheral vasoconstriction of non-active beds and a better redistribution of blood flow.

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.

Effects of acute changes in pulmonary wedge pressure on periodic breathing at rest in heart failure patients.

BACKGROUND: Patients with heart failure (HF) display a number of breathing abnormalities including periodic breathing (PB) at rest. Although the mechanism(s) contributing to PB remain unclear, we examined whether changes in pulmonary wedge pressure (PWP) and pulmonary vascular resistance (PVR) alter PB in patients with established HF. METHODS: We studied 12 male patients with HF (age, 50 +/- 11 years; ejection fraction, 18.3 +/- 3.8 %; New York Heart Association class, 3.2 +/- 0.4), with PB at rest, who are undergoing right heart catheterization with infusion of nitroprusside. RESULTS: At baseline, patients with HF displayed minute ventilation (V(E)) oscillations with amplitude of 5.5 +/- 2.7 L/min (57 +/- 34% of the average V(E)) and cycle length of 61 +/- 18 seconds. Cardiac index (CI), PVR, and mean PWP averaged 2.0 +/- 0.4 L min(-1) m(-2), 281.9 +/- 214.9 dyne/s per cm(-5), and 28.3 +/- 5.4 mm Hg, respectively. During nitroprusside infusion, CI increased to 3.1 +/- 0.6 L min(-1) m(-2), PVR decreased to 163.9 +/- 85.2 dyne/s per cm(-5), and PWP fell to 10.0 +/- 4.2 mm Hg. Nitroprusside reduced the amplitude (2.6 +/- 2.4 L/min, 23 +/- 21% of average V(E); P < .01) and cycle length (41.4 +/- 28.8 seconds; P < .01) of V(E) oscillations while abolishing oscillations in 3 patients. Although average V(E) and PaCO2 remained unchanged, there was a significant increase in the ratio of tidal volume to inspiratory time (V(T)/T(I); P < .01), suggesting an increase in ventilatory drive. The change in the amplitude of V(E) oscillations was positively correlated with the change in PWP (r = 0.75; P < .01), negatively correlated with the change in PVR (r = 0.63; P < .05), and not correlated with the change in CI. CONCLUSIONS: These data suggest that PWP (left atrial pressure) may play a direct role in the PB observed in HF at rest.

Pulmonary function changes associated with cardiomegaly in chronic heart failure.

BACKGROUND: This study examined the influence of increased cardiac size on maximal lung volumes, forced expiratory airflows, and the diffusing capacity of the lungs in heart failure (HF) patients compared with controls. METHODS AND RESULTS: Forty-one HF patients of New York Heart Association (NYHA) class: Group A = class I/II (n = 26) and Group B = class III/IV (n = 15) and an equal number matched controls (CTL) were recruited. Participants underwent echocardiography, spirometry, and posteroanterior and lateral chest radiographic evaluation (RAD) for volumetric estimation of the total thoracic cavity (TTC), diaphragm, heart, and lungs. Analysis of variance demonstrated no difference between groups for TTC volume (P = .63). RAD cardiac volumes (% TTC volume) were significantly different among all groups (P < .001). Echocardiograms determined left ventricular mass was elevated in the HF groups compared with the CTL group (P < .001) with no difference between HF groups. Lung volume (% TTC volume) was reduced as a function of disease severity (P < .001). RAD measures of cardiac volume demonstrated the strongest relationship with restrictive lung alterations (t-statistic = -5.627, P < .001 and t-statistic = -4.378, P < .001 for forced vital capacity and forced expiratory volume in 1 second, respectively). CONCLUSIONS: These results suggest cardiac size may pose significant constraints on the lungs and likely plays a major role in the restrictive breathing patterns often reported in HF patients.

The relationship between resting lung-to-lung circulation time and peak exercise capacity in chronic heart failure patients.

BACKGROUND: Peak exercise capacity (VO2peak) is a measure of the severity of chronic heart failure (CHF); however, few indices of resting cardiopulmonary function have been shown to predict VO2peak. A prolonged circulation time has been suggested as an index of increased severity of CHF. The aim of this study was to investigate the relationship between resting lung-to-lung circulation time (LLCT) and VO2peak in CHF. METHODS AND RESULTS: Thirty CHF patients (59 +/- 13 years, New York Heart Association: 1.9 +/- 1.0) undertook the study. Each subject completed resting pulmonary and echocardiography measures and an incremental exercise test. LLCT was measured using the reappearance of end-tidal acetylene (P(ET),C2H2) after a single inhalation. Univariate and multivariate stepwise linear regression was used to determine the predictors of VO2peak. Univariate correlates of VO2peak (group mean 1.53 +/- 0.44 L/min(-1)) included LLCT (r = -0.75), inspiratory capacity (r = 0.41), ejection fraction (r = 0.33), peak early flow velocity (r = -0.39), and the ratio of early to late flow velocity (r = -0.31). LLCT was the only independent predictor where VO(2peak) = 3.923-0.045 (LLCT); r2 = 54%. CONCLUSIONS: These results suggest that resting LLCT determined using the soluble inert gas technique represents a simple, noninvasive method that provides additional information regarding exercise capacity in CHF.

Genetic variation of the beta2-adrenergic receptor is associated with differences in lung fluid accumulation in humans.

The beta2-adrenergic receptors (beta2AR) play an important role in lung fluid regulation. Previous research has suggested that subjects homozygous for arginine at amino acid 16 of the beta2AR (Arg16) may have attenuated receptor function relative to subjects homozygous for glycine at the same amino acid (Gly16). We sought to determine if the Arg16Gly polymorphism of the beta2AR influenced lung fluid balance in response to rapid saline infusion. We hypothesized that subjects homozygous for Arg at amino acid 16 (n=14) would have greater lung fluid accumulation compared with those homozygous for Gly (n=15) following a rapid intravenous infusion of isotonic saline (30 ml/kg over 17 min). Changes in lung fluid were determined using measures of lung density and tissue volume (computerized tomography imaging) and measures of pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (DM, determined from the simultaneous assessment of the diffusing capacities of the lungs for carbon monoxide and nitric oxide). The saline infusion resulted in elevated catecholamines in both genotype groups (Arg16 283+/-117% vs. Gly16 252+/-118%, P>0.05). The Arg16 group had a larger decrease in DM and increase in lung tissue volume and lung water after saline infusion relative to the Gly16 group (DM -13+/-14 vs. 0+/-26%, P<0.05; lung tissue volume 13+/-11 vs. 3+/-11% and lung water +90+/-66 vs. +48+/-144 ml, P=0.10, P<0.05, for Arg vs. Gly16, respectively, means+/-SD). These data suggest that subjects homozygous for Arg at amino acid 16 of the beta2AR have a greater susceptibility for lung fluid accumulation relative to subjects homozygous for Gly at this position.

Effect of low-xenon and krypton supplementation on signal/noise of regional CT-based ventilation measurements.

Xenon computed tomography (Xe-CT) is used to estimate regional ventilation by measuring regional attenuation changes over multiple breaths while rebreathing a constant Xe concentration ([Xe]). Xe-CT has potential human applications, although anesthetic properties limit [Xe] to

Children with Burn Injury Have Impaired Cardiac Output during Submaximal Exercise.

INTRODUCTION: Burn trauma damages resting cardiac function; however, it is currently unknown if the cardiovascular response to exercise is likewise impaired. We tested the hypothesis that, in children, burn injury lowers cardiac output (Q˙) and stroke volume (SV) during submaximal exercise. METHODS: Five children with 49% ± 4% total body surface area (BSA) burned (two female, 11.7 ± 1 yr, 40.4 ± 18 kg, 141.1 ± 9 cm) and eight similar nonburned controls (five female, 12.5 ± 2 yr, 58.0 ± 17 kg, 147.3 ± 12 cm) with comparable exercise capacity (peak oxygen consumption [peak V˙O2]: 31.9 ± 11 vs 36.8 ± 8 mL O2·kg·min, P = 0.39) participated. The exercise protocol entailed a preexercise (pre-EX) rest period followed by 3-min exercise stages at 20 W and 50 W. V˙O2, HR, Q˙ (via nonrebreathing), SV (Q˙/HR), and arteriovenous O2 difference ([a-v]O2diff, Q˙/ V˙O2) were the primary outcome variables. RESULTS: Using a 2-way factorial ANOVA (group [G] × exercise [EX]), we found that Q˙ was approximately 27% lower in the burned than the nonburned group at 20 W of exercise (burned 5.7 ± 1.0 vs nonburned: 7.9 ± 1.8 L·min) and 50 W of exercise (burned 6.9 ± 1.6 vs nonburned 9.2 ± 3.2 L·min) (G-EX interaction, P = 0.012). SV did not change from rest to exercise in burned children but increased by approximately 24% in the nonburned group (main effect for EX, P = 0.046). Neither [a-v] O2diff nor V˙O2 differed between groups at rest or exercise, but HR response to exercise was reduced in the burn group (G-EX interaction, P = 0.004). When normalized to BSA, SV (index) was similar between groups; however, Q˙ (index) remained attenuated in the burned group (G-EX interaction, P < 0.008). CONCLUSIONS: Burned children have an attenuated cardiovascular response to submaximal exercise. Further investigation of hemodynamic function during exercise will provide insights important for cardiovascular rehabilitation in burned children.

Reduced rate of alveolar-capillary recruitment and fall of pulmonary diffusing capacity during exercise in patients with heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) have reduced pulmonary diffusing capacity for carbon monoxide (DLCO). Acute pulmonary congestion also causes reduction of DLCO, which is reversible. We hypothesized for patients with CHF that the rate of rise of exercise DLCO is reduced compared to healthy controls and falls near end-exercise consistent with progressive interstitial edema. METHODS AND RESULTS: DLCO and pulmonary blood flow (QC)) were measured by a rebreathe technique in CHF subjects (n = 11) and controls (n = 8) at rest, during constant workload exercise, and after exercise. DLCO of CHF subjects was less than controls at rest (16.5 +/- 1 vs. 21.9 +/- 2 mL/min/mm Hg, P < .01). CHF subjects exercised 11 +/- 2 minutes to 90% peak VO2, whereas controls exercised 17 +/- 2 minutes, reaching 88% peak VO2. In CHF subjects, DLCO increased to 19 +/- 2 mL/min/mm Hg and for controls to 38 +/- 3 mL/min/mm Hg. During the final 3 minutes of exercise, DLCO increased 5% in controls while decreasing 5% in CHF subjects (DLCO/Q(C)) was lower in CHF subjects at rest and progressively lower throughout exercise (P < .01). CONCLUSION: In patients with CHF, DLCO has reduced rate of rise with exercise and falls near end-exercise consistent with limitation of alveolar-capillary recruitment and progressive interstitial edema.

Competition for intrathoracic space reduces lung capacity in patients with chronic heart failure: a radiographic study.

BACKGROUND: The purpose of this study was to determine the influence of changes in cardiac size on total lung volume in patients with chronic heart failure compared to control subjects. METHODS: Forty-four patients and age-, gender-, and height-matched control participants were recruited. All participants underwent posteroanterior and lateral chest radiography for volumetric estimations of the total thoracic cavity (TTC), diaphragm, heart, and lungs. To assess the relationship between chronic heart failure severity and cardiac enlargement, patients with chronic heart failure were classified into groups based on New York Heart Association class, as follows: class I and II, n = 26 (group A); class III and IV, n = 18 (group B). RESULTS: There was no difference between the groups for TTC volume (TTCV) [p = 0.56]. Cardiac volumes were significantly different between all groups for both the absolute volumes (p < 0.001) were calculated as a percentage of TTCV (p < 0.001), with the largest cardiac volumes in group B (twice the volume of healthy control subjects). When expressed as a percentage of TTCV, there also was a clear reduction in lung volumes as a function of disease severity (p < 0.001). CONCLUSIONS: The present study demonstrates a close relationship between the severity of heart failure and cardiac size. These changes in cardiac size within a closed thoracic cavity may pose significant constraints on the lungs, resulting in reductions in lung volumes that likely play a major role in the restrictive breathing patterns often reported in patients with chronic heart failure.

Influence of beta2-adrenergic receptor genotype on airway function during exercise in healthy adults.

BACKGROUND: In humans, beta(2)-adrenergic receptors (beta(2)ARs) influence airway tone. There are known functional polymorphisms of the beta(2)AR, such as substitution of glycine for arginine at codon 16. We sought to determine if this variation in genotype differentially influences airway function during exercise. METHODS: Healthy subjects without asthma who were either homozygous for Arg16 (n = 16; mean age, 29 +/- 2 years [+/- SD]; mean maximum oxygen uptake [Vo(2)], 32 +/- 2 mL/kg/min) or the Gly16 allele (n = 26; mean age, 30 +/- 1 years; mean maximum Vo(2), 33 +/- 1 mL/kg/min) participated in the study. Baseline testing included spirometry and maximal symptom-limited exercise. On a separate day, an arterial cannula was placed to measure catecholamine levels. Subjects then performed exercise at two work levels (40% and 75% of peak work) for 9 min each and performed spirometry at 3-min intervals for assessment of airway function. RESULTS: There were no statistically significant differences between groups in maximum Vo(2) or baseline spirometry (p > 0.05). With both light and heavy exercise, the groups had similar increases in the forced expiratory flow at 50% of vital capacity (FEF(50)). FEF(50) increased by 14 +/- 4% and 15 +/- 3% in arginine and glycine groups, respectively, by end exercise (p > 0.05). During recovery (5 min and 10 min after), the Gly16 homozygotes demonstrated persistent bronchodilation (10 min after FEF(50) = + 7 +/- 2% over pre-exercise) while the Arg16 subjects had a rapid return to baseline (10 min after FEF(50) = - 3 +/- 3%, p = 0.007 between groups). No differences were observed in the catecholamine responses between genotypes, although the increase in epinephrine in the arginine group tended to be higher (p = 0.07). CONCLUSIONS: These data suggest that the Arg16Gly polymorphism of the beta(2)AR does not influence airway function during short-duration low- and high-intensity exercise. However, during recovery, the Arg16 genotype is associated with a reduced bronchodilation, possibly due to increased catecholamine desensitization.

Regional pulmonary blood flow in dogs by 4D-X-ray CT.

ECG-triggered computed tomography (CT) was used during passage of iodinated contrast to determine regional pulmonary blood flow (PBF) in anesthetized prone/supine dogs. PBF was evaluated as a function of height within the lung (supine and prone) as a function of various normalization methods: raw unit volume data (PBFraw) or PBF normalized to regional fraction air (PBFair), fractional non-air (PBFgm), or relative number of alveoli (PBFalv). The coefficient of variation of PBFraw, PBFair, PBFalv, and PBFgm ranged between 30 and 50% in both lungs and both body postures. The position of maximal flow along the height of the lung (MFP) was calculated for PBFraw, PBFair, PBFalv, and PBFgm. Only PBFgm showed a significantly different MFP height supine vs. prone (whole lung: 2.60 +/- 1.08 cm supine vs. 5.08 +/- 1.61 cm prone, P < 0.01). Mean slopes (ml/min/gm water content/cm) of PBFgm were steeper supine vs. prone in the right (RL) but not left lung (LL) (RL: -0.65 +/- 0.29 supine vs. -0.26 +/- 0.25 prone, P < 0.02; LL: -0.47 +/- 0.21 supine vs. -0.32 +/- 0.26 prone, P > 0.10). Mean slopes of PBFgm vs. vertical lung height were not different prone vs. supine above this vertical height of MFP (VMFP), but PBFgm slopes were steeper in the supine position below the VMFP in the RL. We conclude that PBFgm distribution was posture dependent in RL but not LL. Support of the heart may play a role. We demonstrate that normalization factors can lead to differing attributions of gravitational effects on PBF heterogeneity.

Relationship between cardiac output and oxygen consumption during upright cycle exercise in healthy humans.

The relationship between cardiac output (CardOut) and oxygen consumption (VO2) during exercise has generally been assumed to be linear. To test this assumption, we studied 72 healthy subjects using a graded, 2-min cycle-ergometry exercise test to maximum while measuring gas exchange continuously and CardOut at the end of each stage, the latter using an open-circuit gas technique. Data for VO2 and CardOut at each stage were fit to a quadratic expression y = a + (b.VO2) + (c.VO2(2)), and statistical significance of the quadratic c term was determined in each subject. Subjects were then divided into two groups: those with statistically significant negative quadratic term ("negative curvature group," n = 25) and those with either nonsignificant quadratic term or c significantly > 0 ("non-negative curvature group," n = 47, 2 with c significantly > 0). We found the negative curvature group had significantly higher maximal VO2/kg (median 37.9 vs. 32.4 ml x min(-1) x kg(-1); P = 0.03) higher resting stroke volume (SV; median 77 vs. 60 ml; P = 0.04), lower resting heart rate (HR; median 72 vs. 82 beats/min, P = 0.04), and higher tissue oxygen extraction at maximal exercise (17.1 +/- 2.2 vs 15.5 +/- 2.1 ml/100 ml; P < 0.01), with tendencies for higher maximal CardOut and SV. We also found the HR vs. VO2 relationship to be negatively curved, with negative curvature in HR associated with the negative curvature in CardOut (P < 0.05), suggesting the curvature in the CardOut vs. VO2 relationship was secondary to curvature in HR vs. VO2. We conclude that the CardOut vs. VO2 relationship is not always linear, and negative curvature in the relationship is associated with higher fitness levels in normal, non-elite-athletic subjects.

Short-term hypoxic exposure at rest and during exercise reduces lung water in healthy humans.

Hypoxia and hypoxic exercise increase pulmonary arterial pressure, cause pulmonary capillary recruitment, and may influence the ability of the lungs to regulate fluid. To examine the influence of hypoxia, alone and combined with exercise, on lung fluid balance, we studied 25 healthy subjects after 17-h exposure to 12.5% inspired oxygen (barometric pressure = 732 mmHg) and sequentially after exercise to exhaustion on a cycle ergometer with 12.5% inspired oxygen. We also studied subjects after a rapid saline infusion (30 ml/kg over 15 min) to demonstrate the sensitivity of our techniques to detect changes in lung water. Pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (D(M)) were determined by measuring the diffusing capacity of the lungs for carbon monoxide and nitric oxide. Lung tissue volume and density were assessed using computed tomography. Lung water was estimated by subtracting measures of Vc from computed tomography lung tissue volume. Pulmonary function [forced vital capacity (FVC), forced expiratory volume after 1 s (FEV(1)), and forced expiratory flow at 50% of vital capacity (FEF(50))] was also assessed. Saline infusion caused an increase in Vc (42%), tissue volume (9%), and lung water (11%), and a decrease in D(M) (11%) and pulmonary function (FVC = -12 +/- 9%, FEV(1) = -17 +/- 10%, FEF(50) = -20 +/- 13%). Hypoxia and hypoxic exercise resulted in increases in Vc (43 +/- 19 and 51 +/- 16%), D(M) (7 +/- 4 and 19 +/- 6%), and pulmonary function (FVC = 9 +/- 6 and 4 +/- 3%, FEV(1) = 5 +/- 2 and 4 +/- 3%, FEF(50) = 4 +/- 2 and 12 +/- 5%) and decreases in lung density and lung water (-84 +/- 24 and -103 +/- 20 ml vs. baseline). These data suggest that 17 h of hypoxic exposure at rest or with exercise resulted in a decrease in lung water in healthy humans.

Comparison of carbon monoxide (CO) single breath pulmonary diffusing capacity with non-rebreathing, open-circuit CO pulmonary diffusing capacity in healthy children.

INTRODUCTION: The standard technique for assessing pulmonary diffusing capacity of the lungs (DL) for carbon monoxide (CO) is the single breath (SB) technique. SB_DLco in children can be problematic because it requires a vital capacity >1.5 L. We have developed an open-circuit technique (OC), which uses the wash-in of CO over a series of 8-10 normal breaths that does not require rebreathing. In this study, we compared the SB_DLco against the OC_DLco. METHODS: Nineteen healthy children between 7 and 18 years performed SB_DLco and OC_DLco tests. The mean SB_DLco was significantly larger than the mean OC_DLco. The mean difference OC_DLco minus SB_ DLco was: -2.92 +/- 4.21 ml/min/mm Hg, though the difference was negatively correlated with the mean of the two (r = 0.73). The lower mean OC_DLco was in part due to lower lung volume (as measured by alveolar volume (VA)) during the maneuver. In both groups there was a positive correlation between VA and DLco, and the mean VA was -2.17 +/- 1.07 L lower using OC compared to SB. The difference was again negatively correlated with the mean (r = 0.82). The mean OC minus SB difference in DLco/VA was: 6.06 +/- 1.98 ml/min/mm Hg/L, though this difference was positively correlated with the mean, r = 0.76. CONCLUSIONS: We found a good correlation between both techniques for DLco, VA, and DLco/VA. The OC offers the advantage of minimal subject cooperation, and may be preferable to use in children.

Correcting the dynamic response of a commercial esophageal balloon-catheter.

It is generally recommended that an esophageal balloon-catheter possess an adequate frequency response up to 15 Hz, such that parameters of respiratory mechanics may be quantified with precision. In our experience, however, we have observed that some commercially available systems do not display an ideal frequency response (<8-10 Hz). We therefore investigated whether the poor frequency response of a commercially available esophageal catheter may be adequately compensated using two numerical techniques: 1) an exponential model correction, and 2) Wiener deconvolution. These two numerical techniques were performed on a commercial balloon-catheter interfaced with 0, 1, and 2 lengths of extension tubing (90 cm each), referred to as configurations L0, L90, and L180, respectively. The frequency response of the balloon-catheter in these configurations was assessed by empirical transfer function analysis, and its "working" range was defined as the frequency beyond which more than 5% amplitude and/or phase distortion was observed. The working frequency range of the uncorrected balloon-catheter extended up to only 10 Hz for L0, and progressively worsened with additional tubing length (L90 = 3 Hz, L180 = 2 Hz). Although both numerical methods of correction adequately enhanced the working frequency range of the balloon-catheter to beyond 25 Hz for all length configurations (L0, L90, and L180), Wiener deconvolution consistently provided more accurate corrections. Our data indicate that Wiener deconvolution provides a superior correction of the balloon-catheter's dynamic response, and is relatively more robust to extensions in catheter tube length compared with the exponential correction method.

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.

Airway narrowing measured by spirometry and impulse oscillometry following room temperature and cold temperature exercise.

STUDY OBJECTIVE: The efficacy of using impulse oscillometry (IOS) as an indirect measure of airflow obstruction compared to spirometry after exercise challenges in the evaluation of exercise-induced bronchoconstriction (EIB) has not been fully appreciated. The objective was to compare airway responses following room temperature and cold temperature exercise challenges, and to compare whether IOS variables relate to spirometry variables. DESIGN: Spirometry and IOS were performed at baseline and for 20 min after challenge at 5-min intervals. SETTING: Two 6-min exercise challenges, inhaling either room temperature (22.0 degrees C) or cold temperature (- 1 degrees C) dry medical-grade bottled air. At least 48 h was observed between these randomly assigned challenges. PARTICIPANTS: Twenty-two physically active individuals (12 women and 10 men) with probable EIB. INTERVENTIONS: Subjects performed 6 min of stationary cycle ergometry while breathing either cold or room temperature medical-grade dry bottled air. Subjects were instructed to exercise at the highest intensity sustainable for the duration of the challenge. Heart rate and kilojoules of work performed were documented to verify exercise intensity. MEASUREMENTS AND RESULTS: Strong correlations were observed within testing modalities for post-room temperature and post-cold temperature exercise spirometry and IOS values. Spirometry revealed no differences in postexercise peak falls in lung function between conditions; however, IOS identified significant differences in respiratory resistance (p < 0.05), with room temperature-inspired air being more potent than cold temperature-inspired air. CONCLUSIONS: Correlations were found between spirometric and IOS measures of change in airway function for both exercise challenges, indicating close equivalency of the methods. The challenges appeared to elicit the EIB response by a similar mechanism of water loss, and cold temperature did not have an additive effect. IOS detected a difference in degree of response between the temperatures, whereas spirometry indicated no difference, suggesting that IOS is a more sensitive measure of change in airway function.

An open-circuit method for determining lung diffusing capacity during exercise: comparison to rebreathe.

To avoid limitations associated with the use of single-breath and rebreathe methods for assessing the lung diffusing capacity for carbon monoxide (D(L)CO) during exercise, we developed an open-circuit technique. This method does not require rebreathing or alterations in breathing pattern and can be performed with little cognition on the part of the patient. To determine how this technique compared with the traditional rebreathe (D(L)CO,RB) method, we performed both the open-circuit (D(L)CO,OC) and the D(L)CO,RB methods at rest and during exercise (25, 50, and 75% of peak work) in 11 healthy subjects [mean age = 34 yr (SD 11)]. Both D(L)CO,OC and D(L)CO,RB increased linearly with cardiac output and external work. There was a good correlation between D(L)CO,OC and D(L)CO,RB for rest and exercise (mean of individual r2 = 0.88, overall r2 = 0.69, slope = 0.97). D(L)CO,OC and D(L)CO,RB were similar at rest and during exercise [e.g., rest = 27.2 (SD 5.8) vs. 29.3 (SD 5.2), and 75% peak work = 44.0 (SD 7.0) vs. 41.2 ml.min(-1).mmHg(-1) (SD 6.7) for D(L)CO,OC vs. D(L)CO,RB]. The coefficient of variation for repeat measurements of D(L)CO,OC was 7.9% at rest and averaged 3.9% during exercise. These data suggest that the D(L)CO,OC method is a reproducible, well-tolerated alternative for determining D(L)CO, particularly during exercise. The method is linearly associated with cardiac output, suggesting increased alveolar-capillary recruitment, and values were similar to the traditional rebreathe method.