INTRODUCTION

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Orthopnea is common in patients with chronic left ventricular failure (LVF), but the underlying pathophysiology is uncertain. It has been proposed that the increased pulmonary venous and capillary pressures in the supine posture lead to vascular distension and perivascular, peribronchiolar, and perhaps interstitial edema (1), either directly compressing airways or leading to the activation of (lung) receptors, which, in turn, provoke reflex bronchoconstriction and "cardiac asthma." Only a few studies have been made of pulmonary mechanics in patients with orthopnea. Studies using esophageal balloons to measure intrathoracic pressures in the 1950s (2, 3) suggested an increase in airflow resistance and a decrease in dynamic compliance in the supine position, but at that time, potential errors that artefactually increased the recorded change in esophageal pressure in the supine posture in the presence of cardiomegaly and central vascular congestion were not well recognized (4). Furthermore, on adopting the supine posture in normal subjects, the cephalic shift of the diaphragm and an increase in intrathoracic blood volume reduces resting lung volume; this accounts for the observed rise in resistance in the supine posture in normal subjects (5). Clearly, therefore, to interpret changes in pulmonary mechanics in orthopnea, changes in lung volume need to be monitored. To provide further insight into the changes accompanying orthopnea in chronic LVF, we have adapted the forced oscillation technique applied at the mouth during normal tidal breathing to measure total respiratory airflow resistance and lung volumes in both sitting and supine postures in patients with chronic LVF. To examine the underlying mechanisms we have studied the resolution of changes after resuming the sitting position and the effects of treatment with an inhaled anti-muscarinic drug.

	METHODS

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Subjects

In the main investigation we studied 10 patients (nine male; mean [SEM] age, 61.4 [2.0] yr) with chronic LVF and 10 control subjects who were well matched for age, height, weight, and sex. Nine of the patients with LVF were studied as outpatients shortly after hospitalization for an episode of acute LVF; the tenth patient was studied after recovery while still an inpatient. All had persisting orthopnea, and at the time of study the New York Heart Association (NYHA) score for dyspnea was Class II in four and Class III in six patients, chest radiography showed cardiomegaly in nine patients, and prominence of upper zone vessels in all patients. Mean left ventricular fractional shortening was 17.0 (3.6)%. All patients were free of peripheral edema during treatment with diuretics, and eight were also receiving ACE-inhibitor drugs, which were continued on the day of the study. Nine of the patients had FEV₁/FVC ratios > 70%; FEV₁/VC was 52% in the remaining patient. Details are summarized in Table 1, which also shows the causes of LVF in the patients and smoking histories, which differed between patients and control subjects. Written consent was obtained from all subjects, and the protocol was approved by the Research Ethics Committee of Imperial College School of Medicine.

Measurements

Forced oscillation was applied at the mouth during normal tidal breathing to measure respiratory impedance. The subject supported the cheeks and floor of the mouth with the palms of the hands in order to minimize dissipation of the applied flow in the upper airway. The head and neck were kept in a neutral to slightly extended position while the subject maintained tidal breathing via a large bore mouthpiece and with a noseclip in place.

The oscillation apparatus consisted of a loudspeaker, which was attached to a tube leading to a screen pneumotachograph. A complex signal of sinusoidal sound-wave oscillation containing all harmonics of 2 Hz to 26 Hz was applied by the loudspeaker (6). The signal was presented as preprogrammed pseudorandom noise, the sequence being repeated every 0.5 s for a 16-s period. During oscillation, mouth pressure (applied peak-peak signal < 2 cm H₂O) and airflow were recorded by two identical differential transducers (Validyne MP45; Validyne Engineering Corp., Northridge, CA) with carefully matched short tubing giving adequate matching up to 30 Hz. Pressure and flow signals were fed into a Fourier analyzer, ensemble-averaged in the frequency domain over the measurement period of 16 s and calculated to give the values of impedance at 2 Hz intervals from 2 Hz to 26 Hz. The derived values were the time-averaged mean of inspiratory and expiratory impedance over the several breaths of the 16-s period. This impedance was further analyzed as the in-phase component (resistance [Rrs]) and the out-of-phase component (reactance [Xrs]) of pressure and flow (7). The in-phase component of the signal, Rrs, is an index of airflow resistance analogous to resistance derived by other methods such as body plethysmography but comprising total resistance (upper airway, intrathoracic airways, lung tissue, and chest wall). The oscillatory frequency at which reactance is zero is resonant frequency (f_res). We also calculated the frequency dependence of Rrs (f_Rrs) as the slope of change in Rrs between 6 and 26 Hz. The reliability of the derived values was indicated by a coherence function for measurements at each frequency. Results were only accepted when coherence was > 0.95; in some subjects, values at 2 Hz fell below this value, so we report only results at 4 to 26 Hz. Three consecutive sets of measurements over 16 s were made while the subject breathed quietly and continuously via the mouthpiece, and the mean of the three sets was used for analysis.

For measurements in the supine posture, the oscillation apparatus was supported by a gantry over the subject who lay supine on a couch. Care was taken to ensure that a similar, slightly extended, position of the head and neck and support of the cheeks and floor of the mouth was sustained in this position. The two differential pressure transducers were positioned perpendicularly so that their orientation was unaltered during measurements in the supine posture.

We also monitored breathing pattern and absolute lung volumes during impedance measurement by integrating the mouth flow signal to obtain volume change. This was displayed on a strip chart recorder. At the end of each impedance measurement, a full inspiration and expiration were made to place tidal volume in relation to the VC. TLC was determined separately by constant-volume body plethysmography (8) in the sitting position to allow calculation of the absolute midtidal lung volume (MTLV) and functional residual capacity (FRC). In estimating MTLV and FRC in the supine position it was assumed TLC did not change with posture either in controls or patients. To adjust Rrs values for alterations in the absolute lung volumes, specific respiratory resistance (SRrs) was calculated as Rrs.MTLV.

Forced expiratory volume in the first second (FEV₁), forced vital capacity (FVC) and maximum expiratory flow-volume curves were recorded simultaneously using a 10 L dry rolling seal spirometer (Model 842; Ohio Instruments, Madison, WI). The flow-volume curves were displayed on an X-Y storage oscilloscope (Model 613; Tektronix Corp., Beaverton, OR) and permanent copies were obtained on a printer for later analysis of isovolumic maximum expiratory flow (MEF) at 50% and 25% of the remaining VC of the first sitting position (MEF₅₀ and MEF₂₅, respectively). In the supine position, it was assumed TLC fell by 100 ml in both patients and controls (see discussion) so MEF was measured at volumes 100 ml closer to supine TLC than 50% and 75% of the initial sitting FVC. A VAS for dyspnea in each position was recorded. The subjects were asked to indicate a score for how breathless they felt on a line that extended from 0 to 10. They were not allowed to refer to previous scoring during each assessment of VAS. Arterial oxygen saturation (Sa_O2) was recorded with a Biox 3740 Pulse Oximeter (Ohmeda, Swindon, UK) and the electrocardiogram (ECG) was monitored by a Cardiac Monitor (Physio-Control, VSM 3, London, UK) throughout the study. Values for spirometry and subdivisions of lung volume were compared with standard reference values (9).

Two to three weeks after recovery from acute LVF, the change in FEV₁ after doubling concentrations of methacholine (0.25 to 16 mg · ml¹) generated by a Wright nebulizer during 2 min of tidal breathing was measured (10). Results were expressed as provocative concentration of methacholine that caused a fall in FEV₁ of 20% (PC₂₀). With this technique, normal values are > 16 mg · ml¹.

Protocol

The subjects were first familiarized with all the techniques of measurements. TLC was measured in the seated position. ECG and Sa_O2 were monitored throughout. Subjects were studied first in the sitting, then in the supine, and again after returning to the seated position. Their VAS were assessed in the sitting position, and this was followed by three successive reproducible measurements of total respiratory system impedance accompanied by the same number of VC maneuvers. Three FEV₁/FVC and maximum expiratory flow-volume loops were then recorded. The same sequence of measurements were made commencing after 5 min in the supine posture and again 5 min after the subjects had returned to the sitting position. The time spent supine was deliberately limited because of the development of dyspnea and the need to avoid serious deterioration.

Additional Study

The effects of inhaled ipratropium bromide (a muscarinic antagonist) were studied using the same protocol in five of the original 10 patients with LVF (4 male; age, 62.6 [3.8] yr; weight, 76.1 [2.6] kg; height, 1.71 [4.8] m; FEV₁/FVC, 78.1 [1.2]%) and four control subjects (all male; age, 62.3 [1.0] yr; weight, 80.6 [3.0] kg; height, 1.78 [5.4] m and FEV₁/ VC, 79.3 [5.6]%). Measurements were made before and 30 min after treatment with inhaled ipratropium bromide (Boehringer, Ingelheim, Ingelheim am Rhein, Germany) 250 µg in 3 ml of 0.9% sodium chloride via a Mini-Neb nebulizer (Intertech/Inspiron; Medic-Aid, Pagham, UK), driven by 6 L · min¹ of compressed air.

Statistical Analysis

All results were normally distributed. Analysis of variance was performed and significant relations were further analyzed using the Scheffe test, a multiple comparison test. In almost all comparisons, the second set of sitting results were not different from the first set, and therefore comparisons between sitting and supine postures used the initial sitting measurements.

	RESULTS

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Dyspnea and Oxygen Saturation

In the patients with LVF, mean VAS for dyspnea increased from 2.2 to 3.9 (p < 0.05) on adopting the supine posture; the score had not fully returned to initial levels 5 min after returning to the seated position. There was a small, not statistically significant, fall in Sa_O2 in the supine posture (p = 0.086).

Subdivisions of Lung Volume

In the sitting position, TLC was reduced in the patients with LVF (mean [SEM], 4.99 [0.38] L, 82% of predicted values) compared with the control group (mean [SEM], 6.68 [0.42] L, 102% of predicted values; p < 0.01) (Figure 1). VC was also significantly reduced in the patients with LVF; although absolute values of FRC and MTLV were smaller in patients than in control subjects (Table 2), this was partly due to height differences, FRC being 53.8 (3.35)% of predicted TLC in LVF and 56.8 (3.2)% of predicted TLC in control subjects (NS). FRC/ TLC ratio was larger in the patients with LVF, 65.7 (2.57) % than control subjects 55.7 (1.8) % (p < 0.005).

View larger version (49K): [in this window] [in a new window]   Figure 1.   Total lung capacity (TLC) and subdivisions in patients with chronic left ventricular failure (LVF) and control subjects in the sitting position. Mean values are shown as % of predicted TLC to allow for the smaller height of the patients with LVF. MTLV = midtidal lung volume; FRC = functional residual capacity; RV = residual volume.

On adopting the supine posture, mean falls in MTLV and FRC were smaller in patients with LVF than in control subjects (MTLV, 100 [80] ml in patients with LVF versus 610 [180] ml in control subjects [p < 0.02], and FRC, 180 [90] ml in patients with LVF versus 660 [190] ml in control subjects [p < 0.05]). The reduction in VC was a little larger in patients with LVF than in control subjects (200 [70] ml in patients with LVF versus 90 [70] ml in control subjects, NS) (Table 2).

Total Respiratory Impedance

Baseline sitting Rrs values and f_res in the patients with LVF were higher than in the control subjects (p = 0.05 and p < 0.05, respectively). Rrs fell slightly with increasing frequency in the patients with LVF. When patients with LVF adopted the supine posture, Rrs and its frequency dependence greatly increased (Figure 2) and baseline Xrs became more negative, resulting in a higher f_res (Table 3). Five minutes after returning to the sitting position, these measurements had not quite reverted to the initial sitting values. Changes in Rrs and Xrs on adopting the supine posture in the control subjects were similar in direction, but much smaller than in the patients with LVF (Figure 2 and Table 3). Thus, the supine rise in mean Rrs at 6 Hz was 37.6 (10.1) % in control subjects and 80.5 (12.9) % in patients with LVF (p < 0.05), whereas the increase in f_res was 39.0 (10) % in control subjects and 90.2 (18.5) % in patients with LVF (p < 0.05). All the supine changes in the control subjects returned to baseline values within 5 min of returning to the sitting position.

View larger version (23K): [in this window] [in a new window]   Figure 2.   Change of mean values of total respiratory resistance (Rrs) with posture in 10 patients with chronic LVF (a) and in 10 control subjects (b). Bars indicate SEM.

The larger increase in Rrs in patients with LVF in the supine position occurred despite a smaller fall in MTLV (Table 2), so that SRrs (6 Hz) increased 75.8 (12.2)% in the supine posture in patients with LVF compared with a 16.6 (7.7) % increase in control subjects, p < 0.001 (Figure 3).

View larger version (15K): [in this window] [in a new window]   Figure 3.   Change of mean values of specific respiratory resistance (SRrs) measured at 6 Hz with posture in 10 patients with chronic LVF and 10 control subjects. Bars indicate SEM.

Forced Expiratory Maneuvers

FEV₁ fell by 14.0 (4.5) % in the LVF group and by 6.0 (1.2) % in the control group (p < 0.05) in the supine position. There was a small fall in FEV₁/FVC ratio in patients with LVF, but this remained higher than in control subjects. Decrease in mean MEF₅₀ was 31.2 (10.1) % in patients with LVF as compared with 4.1 (1.5) % in the control subjects (p < 0.01). There was also a greater reduction in MEF₂₅ in patients with LVF, 53.5 (11.6) % compared with 6.4 (3.4) % in the control subjects (p < 0.001) (Table 4).

Response to Inhaled Methacholine

Nine of the 10 patients with LVF had PC₂₀ > 16 mg · ml¹.

Effect of Ipratropium Bromide

In the four control subjects, seated values of Rrs and SRrs were somewhat lower and values of FEV₁ slightly higher than in the main study, reflecting their greater height. As expected, ipratropium modestly reduced Rrs at all frequencies in both postures; this was accompanied by some reduction in Xrs and f_res, although changes were not statistically significant. But the absolute rise in Rrs and SRrs at 6 Hz on adopting the supine posture was very similar before and after ipratropium (mean supine rise in SRrs, 24% before and 26% after).

In the patients with LVF, there were also small reductions in Rrs and SRrs, frequency dependence of Rrs, and f_res in both postures, but the absolute and proportionate supine increase in Rrs and SRrs at 6 Hz was only slightly reduced after ipratropium, the mean rise in SRrs decreasing from 65% before to 59% after treatment (NS) (Figure 4). The supine fall in FEV₁ was similar before and after treatment (mean FEV₁ before sitting 2.25 (0.29), supine 2.04 (0.32) L, after ipratropium sitting 2.40 (0.31), supine 2.21 (0.31) L, (NS); reductions in mean Sa_O2 on adopting the supine position were slightly attenuated (before sitting 97.2%, supine 95.4%; after sitting 97.4%, supine 96.6%). As in the main study, Rrs, SRrs, and FEV₁ had not quite returned to the initial sitting values 5 min after resuming the sitting position.

View larger version (15K): [in this window] [in a new window]   Figure 4.   Change of mean values of SRrs measured at 6 Hz with posture in five patients with chronic LVF and four control subjects before (open symbols) and after (closed symbols) inhalation of ipratropium bromide. Bars indicate SEM.

	DISCUSSION

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The main findings of this study were: (1) in the seated position, although patients with LVF had considerable reduction in TLC, FEV₁, and VC, Rrs and SRrs during tidal breathing were only slightly higher than in control subjects; (2) on adopting the supine position, patients with LVF showed a larger increase in Rrs and a smaller fall in FRC than in control subjects; as a result, SRrs (6 Hz) increased 75.8% in patients with LVF compared with 16.6% in control subjects. The patients with LVF also had larger % falls in FEV₁, MEF₅₀, and MEF₂₅ when supine than did the control subjects; (3) inhaled ipratropium bromide resulted in modest bronchodilatation but only slightly attenuated the supine increase in SRrs in patients with LVF; (4) 5 min after resuming the sitting position, values in control subjects had completely returned to initial sitting values; small residual changes were present in the patients with LVF.

Methodologic Factors

The patients with LVF were studied at the earliest opportunity after recovery from an acute episode when orthopnea persisted but was not so severe as to preclude lying supine for about 7 min. Two subjects restudied several weeks later showed smaller rises in Rrs when supine, but formal sequential studies were not practical in these severely disabled patients. Although the patients with LVF had a greater smoking history than did the control subjects, their mean FEV₁/VC was normal and greater than in the control group, whereas a sensitive test for small airways abnormalities, frequency dependence of Rrs, was only slightly more abnormal than in control subjects in the seated position (Table 3 and Figure 2).

There have been few studies of postural changes in lung mechanics. Linderholm (5) measured airway resistance in normal subjects using a conventional upright and a horizontal body plethysmograph and showed that supine reductions in FRC fully accounted for the increase in airway resistance. This is consistent with earlier studies using forced oscillation (11) and our present finding that expressing our results as SRrs removed most of the observed sitting-supine differences in normal subjects. Early measurements of supine pulmonary mechanics in heart disease or acute central vascular congestion used esophageal-balloon catheters to measure changes in intrathoracic pressure. Increases in pulmonary resistance and falls in dynamic compliance in the supine position were found and attributed to pulmonary congestion (2, 3), although alterations in lung volume were not taken into account. Subsequently, it was shown that changes in esophageal pressure may be exaggerated by cardiomegaly and acute vascular congestion, particularly in the supine position (4). These errors can be avoided with the forced oscillation technique, which can be adapted relatively easily to study respiratory mechanics during tidal breathing in different postures.

In the present study, we only measured TLC in the seated position, but average supine falls in TLC have been found to be small and similar in normal subjects (140 ml) and in patients with cardiac failure (80 ml) (12). We have ignored these small changes in TLC in our calculations of MTLV and FRC in the supine posture. However, to avoid exaggerating supine falls in MEF₅₀ and MEF₂₅, we have assumed TLC was 100 ml smaller in the supine position (in both LVF and control groups) to estimate changes at isovolume.

Changes in Static Lung Volumes

Seated TLC and VC were both reduced by about 20% in patients with LVF, presumably because of a combination of increased volume of heart and central blood vessels, interstitial fluid in the lungs and, in two patients, small pleural effusions. Reductions in VC and TLC with chronic heart failure are largely reversible after successful heart transplantation, the VC increase being mainly explained by the reduction in cardiac volume (13, 14). In contrast, FRC (and MTLV at which impedance was measured) were similar in patients with LVF and control subjects (Figure 1). Preservation of a normal FRC, despite reductions in TLC, has previously been described as functional disability increases in patients with mitral stenosis (15). Because of the associated increase in heart volume and intrathoracic fluid, this implies a somewhat larger thoracic volume at FRC.

On lying supine, the mean fall in VC was small in both patients with LVF and control subjects, but the mean reduction in FRC (180 ml) in patients with LVF was much smaller than in control subjects (760 ml). These results are similar to those found in earlier studies (12, 16). In normal subjects, the supine fall in FRC is due to the fall in relaxation volume caused by combined effects of gravitational forces displacing the diaphragm cranially and increase in intrapulmonary blood volume, and these effects should be present in patients with LVF. Reduction in lung compliance (as suggested by the supine decrease in Xrs at 6 Hz), might reduce the passive change in lung volume in patients with LVF, but probably in the patients supine FRC was sustained above relaxation volume by an adjustment in respiratory muscle or glottal activity. The effect would be to reduce airway narrowing during tidal breathing; the rise in airway resistance induced in dogs by an increase in left atrial pressure is very much greater at small lung volumes (17).

Changes in Airway Function in the Seated Position

Although there were considerable reductions in FEV₁ in the patients with LVF, these reflected the fall in VC and TLC, and the FEV₁/VC ratio was reduced in only one patient. Sa_O2 was also normal in nine of the 10 patients. Furthermore, there were only small increases in Rrs, SRrs, f_res, and frequency dependence of Rrs and small decreases in maximum expiratory flows compared with control subjects. Two previous studies have used the forced oscillation technique in the semi-recumbent position in heart disease. Depeursinge and colleagues (18) found abnormal impedance with frequency dependence of Rrs in 11 patients with acute LVF; the changes did not resolve completely with clinical improvement in their cardiac failure. Interiano and colleagues (19), studying patients sequentially after acute myocardial infarction, showed a modest increase in Rrs with frequency dependence early after infarction, which rapidly resolved. Although patients with "cardiac asthma" and a large bronchodilator response have been described, there is striking disagreement about the prevalence of airway obstruction and increased airway responsiveness in patients with LVF (20). Light and George (23) found that a reduced FEV₁/FVC was common, and Niset and colleagues (14) found that a reduced FEV₁/FVC persisted after heart transplantation. Some of these obstructive changes are likely to be due to associated smoking-related damage to the lungs. In the five patients with LVF we treated with a large inhaled dose of ipratropium, there was only a small improvement in seated SRrs and FEV₁, the fall in SRrs being proportionately similar to that in control subjects. These results are similar to those reported wth the standard clinical dose of inhaled ipratropium (72 µg) in patients with congestive heart failure and in control subjects (24). A larger increase in FEV₁ after ipratropium may occur early in the course of acute LVF (25). Only one of the present patients with LVF had a PC₂₀ < 16 mg · ml¹, contrasting with the study of Cabanes and colleagues (20) who found 21 of 23 patients had airway hyperresponsiveness that was similar in intensity to that in patients with symptomatic asthma (PC₂₀ < 8 mg · ml¹ with the method we used) and persisted over subsequent weeks. In contrast, our patients had little evidence of airway obstruction or a heightened bronchodilator or bronchoconstrictor response when seated.

Site and Mechanism of Increase in Supine Airflow Resistance

The supine increase in SRrs occurs within a few minutes of lying supine and largely, but not completely, resolves within 5 min of resuming the sitting position. The rapid resolution of the increased SRrs on sitting up has not been documented before, but Pepine and Weiner (26) induced an increase in LV end-diastolic pressure with atrial pacing in 24 subjects with ischemic heart disease that led to a fall in specific airway conductance, which was reversed almost immediately when pacing was terminated. The supine rise in SRrs potentially could be due to increases in the flow resistance of the chest wall or the extrathoracic airways (perhaps because of increased venous blood volume in the pharynx (27) or to glottic braking); but neither change would explain the accompanying change in the maximum expiratory flow-volume curve with larger reductions in maximum flow at small than at large lung volumes, which make it probable that the responsible changes were in the intrathoracic airways.

The supine rises in intrathoracic airway resistance when central vascular pressures are increased have been extensively studied in animals and appear to occur before frank alveolar or airway luminal fluid accumulates (17). Four mechanisms have been suggested: reduction in lung volume, reflex bronchoconstriction mediated by vagal efferents, small airways narrowing induced by competition for space in the bronchovascular bundle, and compression of large airways (28).

The present studies indicate that supine MTLV and FRC are similar in absolute volumes (and larger as % predicted TLC) in patients with LVF and in control subjects. The small reduction in supine VC and FRC and maintenance of supine Sa_O2 in 9 of the 10 patients with chronic LVF also argues against the development of increased gravity-determined small airways closure. The enhanced frequency dependence of Rrs is inconclusive because, although it may be due to increased inequalities of intrapulmonary time constants and airway closure, it may simply reflect an effect of upper airway shunt that develops whenever Rrs is increased and is not completely removed by the external support of the cheeks and floor of the mouth (29).

Reflex bronchoconstriction mediated by vagal nerves could clearly account for the rapid time course of onset and resolution of airway narrowing and has been demonstrated in animal studies (30, 31), but in five of the present patients with LVF, the supine rise in Rrs and SRrs was only slightly attenuated after a large dose of the muscarinic antagonist, ipratropium (Figure 4).

When central vascular pressures are raised acutely in animals there is initially distension of vessels; fluid then accumulates in the perivascular and peribronchial spaces, followed by the development of frank edema in the alveoli and airway lumen (32). Morphologic and CT studies, after inducing interstitial edema in dogs (28) and perivascular and periairway edema in sheep (33, 34), however, have not found reduction in the lumen of the small airways; furthermore, considerable periairway edema, which would be expected to uncouple small airways from their normal support by alveolar attachments to their perimeter, only slightly amplified their constrictor response to inhaled methacholine (33). When frank edema is induced by increased hydrostatic pressure in isolated, perfused sheep lungs with intact lymphatic drainage, the rate of reabsorption of fluid on restoring normal vascular pressure is at best one-third the rate of accumulation (35). If this also applies when periairway and interstitial edema is induced, resolution is likely to have a slower time course than we observed. Measuring Rrs immediately on resuming the sitting position would help to resolve this point.

The increase in supine SRrs might be due to compression of central conducting airways by gravitational effects of the heart and mediastinal structures. Reduced supine ventilation of the left lower lobe has been shown in cardiomegaly (36), but large airway compression would have to be more widespread to account for our results because even complete obstruction of the left lower lobe would only increase Rrs by about 25%. This potential mechanism could be explored by examining respiratory mechanics further in the prone position, whereas central airway dimensions could be assessed by CT.

A further possibility arising from the experiments of Cabanes and colleagues (20) is that swelling of the airway mucosa might develop in the supine posture. We made preliminary experiments in five patients with LVF to see if inhaled treatment nebulizing 10 mg of the -adrenergic agonist, methoxamine, a potent constrictor of bronchial vessels, attenuated the supine elevation of SRrs. Although there were small increases of systolic blood pressure and decreases of heart rate, there was no significant change in SRrs seated or supine. A limitation of these experiments was that they were conducted 2 to 3 wk after recovery from an acute episode when there was less orthopnea and supine rise in SRrs (45%) at baseline than in our other studies.

In conclusion, these studies have shown that patients with chronic left ventricular failure and orthopnea have a considerable increase in airflow resistance on adopting the supine posture. This increase cannot be attributed to reductions in FRC when supine and was only slightly attenuated by treatment with an inhaled muscarinic antagonist. We suggest that the rapid recovery on sitting up and the small rise in supine RV argue against the development of periairway edema and increased airway closure, respectively. An increase in extrathoracic resistance would not explain the accompanying reduction in maximum expiratory flow at smaller volumes. Hence further experiments are required to investigate the mechanism and time course of these changes in humans.