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J Appl Physiol 92: 1409-1416, 2002. First published November 23, 2001; doi:10.1152/japplphysiol.00724.2001
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Vol. 92, Issue 4, 1409-1416, April 2002

Exercise hyperpnea in chronic heart failure: relationships to lung stiffness and expiratory flow limitation

Piergiuseppe Agostoni1, Riccardo Pellegrino2, Cristina Conca1, Joseph R. Rodarte3, and Vito Brusasco4

1 Centro Cardiologico Monzino, IRCCS, Istituto di Cardiologia dell' Università degli Studi di Milano, IRCCS, Centro di Studio per le Ricerche Cardiovascolari del CNR, 20138 Milan, Italy; 2 Fisiopatologia Respiratoria e Cardiologia, Azienda Ospedaliera S. Croce e Carle, 12100 Cuneo, Italy; 3 Pulmonary Section, Baylor College of Medicine, Houston, Texas 77030; and 4 Cattedra di Fisiopatologia Respiratoria, DISM, Università di Genova, 16132 Genova, Italy


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The changes in breathing pattern and lung mechanics in response to incremental exercise were compared in 14 subjects with chronic heart failure and 15 normal subjects. In chronic heart failure subjects, exercise hyperpnea was achieved by increasing breathing frequency more than tidal volume. The rate of increase in breathing frequency with carbon dioxide output was inversely correlated (r = -0.61, P < 0.05) with dynamic lung compliance measured at rest, but not with static lung compliance either at rest or at maximum exercise. Although decrease in expiratory flow reserve near functional residual capacity in chronic heart failure occurred earlier with exercise than in the normal subjects (P < 0.01), it was not correlated with changes in breathing pattern or occurrence of tachypnea. Tachypnea was achieved in chronic heart failure subjects with an increase in duty cycle because of a greater than normal decrease in expiratory time with exercise. We conclude that in chronic heart failure preexisting increase in lung stiffness plays a significant role in causing tachypnea during exercise. The results of the present study do not support the hypothesis that dynamic compression of the airways downstream from the flow-limiting segment occurring during exercise contributes to hyperpnea.

static and dynamic lung compliance; breathing pattern; flow-volume curves; expiratory flow reserve


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

PATIENTS AFFECTED BY chronic heart failure (CHF) often exhibit excessive ventilation for a given workload during exercise (4, 8, 11, 14, 21, 33, 34), mostly sustained by an increase in breathing frequency rather than in tidal volume (VT) (4, 8, 14, 33). Several mechanisms have been proposed to explain the increased ventilatory response to exercise in CHF, including ventilation-perfusion abnormalities, altered control of breathing, impaired central and peripheral hemodynamics, early onset of anaerobic metabolism, and respiratory and skeletal muscle fatigue (6). The reasons and the mechanisms causing exercise hyperpnea to be achieved by increasing breathing frequency more than VT in CHF are unknown and represent the object of this study.

The most prominent pulmonary abnormality in CHF is an increased lung stiffness (9, 14, 21, 24, 26, 34, 35). This may result from a number of mechanisms, including vascular congestion, interstitial edema and fibrosis, increased alveolar surface tension, ventilation inhomogeneities, and activation of contractile elements. An increased lung stiffness may contribute to alter the pattern of breathing during exercise by different mechanisms. First, vascular congestion and interstitial edema, either preexisting or developing during exercise, may trigger rapid and shallow breathing by direct stimulation of irritant or J receptors (8, 25). Second, an increase in breathing frequency may be necessary from the beginning of exercise because the increase in VT is limited by mechanical constraints. These are represented by 1) an excessive elastic work of breathing, which limits the increase of end-inspiratory lung volume, and 2) premature occurrence of expiratory flow limitation (EFL) (15), which prevents the physiological decrease of functional residual capacity (FRC) during exercise.

This study was undertaken to investigate whether differences in ventilation during an incremental exercise test between CHF and normal subjects are related to differences in lung stiffness, EFL, or both. Both static and dynamic lung compliance were measured at rest and during exercise in an attempt to separate the effects of various determinants of increased lung stiffness. The occurrence of EFL was inferred from the reduction of the expiratory flow reserve (EFR), i.e., the difference between tidal and forced expiratory flows in the range of tidal breathing.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Subjects

The study included 14 CHF and 15 normal subjects (Table 1). Inclusion criteria for CHF subjects were to have a history of congestive heart failure and to have been in stable clinical conditions in the 2 mo preceding the study. Exclusion criteria were primary pulmonary disease, peripheral vascular disease, primary pulmonary hypertension, primary valvular disease, artificial pacemaker, exercise-induced arrhythmias, chronic obstructive pulmonary disease, and bronchial asthma. The cause of CHF was ischemic dilated cardiomyopathy in 3 cases and primary dilated cardiomyopathy in 11 cases. All CHF subjects were under pharmacological treatment: 6 with digitalis, 13 with diuretics, 14 with angiotensin-converting enzyme inhibitors, and 4 with beta -blockers. All normal subjects were physically active in recreational activities. The protocol was approved by the local Ethics Committee, and written consent was obtained from each participant before the study.

                              
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  		Table 1.   Main anthropometric data

Lung Function Measurements

Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured in triplicate by a mass flow sensor (Vmax, SensorMedics, Yorba Linda, CA) following the American Thoracic Society recommendation (3). Maximum forced expiratory flows at 50% and 25% of FVC from a full flow-volume curve were calculated after volume had been corrected for the difference between predicted and measured total lung capacity (TLC). TLC, residual volume (RV), and FRC were measured by multibreath nitrogen washout (2200 Pulmonary Function Laboratory, SensorMedics). Diffusion capacity for carbon monoxide was measured by single-breath constant-expiratory flow technique (SensorMedics 2200) (13). Arterial oxygen and carbon dioxide tensions and pH were measured by a gas analyzer (ABL 520, Radiometer, Copenhagen, Denmark).

Lung mechanics before and during exercise were measured by using a Direc/NEP 200A recording system (Raytech, Vancouver, BC). Flow was measured by a screen-type pneumotachograph placed between mouthpiece and mass flow sensor and connected to a differential pressure transducer (±5 cmH2O). Transpulmonary pressure (Ptp) was estimated from the difference between esophageal and mouth pressures. Esophageal pressure was measured by positioning a 10-cm-long thin latex balloon in the esophagus, 38-42 cm from the nostrils. Volume and pressure channels were calibrated before each study according to the recommendations of the manufacturer by using a 3-liter syringe and a water-filled manometer, respectively. The balloon was connected to a pressure transducer (±100 cmH2O) and filled with 0.8 ml of air. Its positioning was considered correct if Ptp remained constant while mouth pressure increased during a gentle effort against a small orifice (20). Mouth pressure was measured by a pressure transducer (±100 cmH2O). Care was taken to avoid thermal drift by zeroing the flow and volume signals immediately before recording tidal breathing necessary to compute dynamic compliance (CLdyn) and before recording quasi-static pressure-volume (PV) curves. The latter were measured by intermittent manual occlusion of the expiratory port of the pneumotachograph with the patient slowly expiring from TLC. Quasi-static lung compliance (CLst) was measured only at rest and within 2 min from the end of maximum exercise, whereas CLdyn was measured at rest and at each step of the incremental exercise test. The frequency responses of flow- and Ptp-measuring systems had been determined to be flat up to 10 Hz. All signals were recorded at a frequency of 100 Hz and digitized by a computer for subsequent analysis.

During exercise, minute ventilation (VE), oxygen consumption (VO2), and carbon dioxide output (VCO2) were measured breath by breath (Vmax, SensorMedics). Sets of simple and very reproducible maneuvers consisting of four to six regular tidal breaths immediately followed by a forced expiration from end-tidal inspiration to near RV (partial forced expiration) and a forced inspiration to TLC were performed in triplicate at rest and once over the last 20 s at the end of each step to estimate the changes in FRC, end-inspiratory lung volume (EILV), EFR, partial forced expiratory flow at 50% of FVC (Vpart50), and maximal inspiratory flow at 50% of FVC. Specifically, changes in FRC and EILV during exercise were defined as the changes in dynamically determined lung volumes at end-tidal expiration and inspiration, respectively. Both FRC and EILV were related to TLC, which was assumed to remain constant during exercise. This assumption was verified by measuring Ptp at TLC. EFR was determined at each step of the test from the difference between partial and tidal expiratory flows near FRC (27). In the case that FRC tended to increase when tidal expiratory flow near FRC impinged on partial flow at some level of ventilation, EFR was computed as the difference between the tidal expiratory flow near the increased lung volume and the partial flow measured at the level of the lowest FRC attained during the test. Thus EFR becomes negative if FRC increases.

Predicted values are from Quanjer et al. (29) for lung function tests and from Jones (16) for the exercise test.

Study Protocol

Screening day. All subjects attended the laboratory for clinical history and physical examination, electrocardiogram, and lung function measurements. CHF subjects also underwent an echocardiography. All subjects were taught how to perform reproducibly the partial forced expiratory maneuvers required for the study and underwent an incremental cardiopulmonary exercise test to have their maximum exercise capacity determined.

Study day. The subjects attended the laboratory in the midafternoon after a light meal. Partial and full forced expiratory flow-volume curves were recorded in triplicate through the mass flow sensor. Blood pressure and heart rate were measured. All CHF and six normal subjects accepted to have an esophageal balloon positioned after topical anesthesia of the nose and throat. Before starting the exercise test, at least three quasi-static PV curves, two sets of CLdyn, and several regular breaths followed by three sets of reproducible tidal, partial, and maximal flow-volume curves were obtained.

A symptom-limited exercise test was performed on an electronically braked cycle ergometer (Ergometrics 800S, SensorMedics), with the subject wearing a nose clip and breathing through a mass flow sensor (dead space 75 ml) connected to a saliva trap. A 12-lead electrocardiogram was continuously recorded (MAX1, SensorMedics). After 3 min of resting and 2 min of warm-up, the exercise load was increased every 2 min by 10 or 15 W for the CHF patients, depending on the previous exercise test, and by 25 W for the normal subjects until exhaustion. The subjects pedaled at ~50-60 revolutions/min. Ptp, flow, and volume were recorded during tidal breathing to compute CLdyn at least twice at rest for ~2 min and once during the first 40 s of the second minute at each step. Tidal and partial flow-volume loops were measured at rest and during the last 20 s of each work level. Special care was taken to maintain the position of the trunk fairly constant during the test. A second set of three quasi-static PV curves was recorded within 2 min from the end of exercise.

Data Analysis

Quasi-static PV curves were constructed by taking the relevant signals at zero flow. CLst was the slope of the best fit of the curves between FRC and 0.5 liters above it. CLdyn was estimated on at least six tidal breaths by playing back the files recorded at each step. Irregular breaths, sighs, swallows, and portions of the files with volume drift were discarded before analysis. With the aid of a cursor, VT and Ptp were measured at end-inspiratory lung volume (PtpEILV) and at FRC (PtpFRC) for each breath. CLdyn was computed by dividing VT by the difference between PtpEILV and PtpFRC (31).

Only representative breaths recorded during the exercise test before the partial forced expiratory maneuver were used for analysis of breathing pattern. VT and inspiratory and expiratory times (TI and TE, respectively) were calculated breath by breath and averaged over several breaths, thus allowing minute ventilation (VE), breathing frequency, and ratio of inspiratory time to total respiratory cycle duration (TI/Ttot) to be computed.

To allow comparison between subjects with different respiratory volumes, VT and VE were normalized to TLC, which is the most representative index of lung volumes in CHF, and were referred to as adjusted VT (VTadj) and adjusted VE (VEadj), respectively. Differences in breathing pattern during exercise between groups were assessed by regressing breathing frequency, TI, TE, TI/Ttot, VTadj, PtpEILV, CLdyn, Vpart50, VO2, and EFR against VCO2, rather than considering their single values at maximum exercise as conventionally done. Such an analysis is expected to give an accurate estimate of the changes in breathing pattern during exercise, because it takes into account all the values recorded during the test and minimizes the high variability of a single value. The reason for regressing the variables against VCO2 rather than the more conventional VE or VEadj relies on the fact that, for a given VCO2, VE is much higher in CHF than in normal subjects. Thus using VE instead of VCO2 would have led to a systematic overestimation of the relationship of the relevant variables with the respiratory stimulus in the normal subjects and possibly blurred the mechanisms causing tachypnea in the CHF.

The regression of EFR against VCO2 was taken as an index of EFL during exercise on the basis of the following reasoning. When ventilation increases, EFR tends to decrease because tidal expiratory flow increases and FRC decreases. When EFR is reduced to zero, flow is limited and greater ventilation can be achieved only by increasing FRC. Thus a lower intercept and/or a greater slope of the regression of EFR vs. VCO2 in CHF compared with normal individuals would suggest occurrence of premature EFL and/or worsening of it with the increase in ventilatory stimulus, or both.

Statistics

Student's paired and unpaired t-tests and chi 2 test with Yates correction were used to analyze resting differences between groups. Correlations were assessed by Pearson's test. P < 0.05 was considered statistically significant. All values are expressed as means ± SD.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Pulmonary Function Tests at Rest

Although within predicted normal limits, lung volumes tended to be slightly less in CHF than in normal subjects (Table 2). The EFR of CHF subjects was on average less than half of that of normal subjects (P < 0.05), but this difference was apparently not due to a decrease in maximal expiratory flows (similar maximum forced expiratory flows at 50% and 25%). Breathing pattern, PtpFRC, CLst, and CLdyn were similar in CHF and normal subjects, although CLdyn tended to be less in the former (P < 0.06). Diffusion capacity for carbon monoxide was slightly but significantly reduced in CHF patients (P < 0.02). FRC as percent of predicted was significantly correlated with CLdyn (r = 0.48, P < 0.05). Arterial PO2, arterial PCO2, and pH were similar in the two groups. According to maximum exercise tests performed before the study, seven patients were in class A of the New York Heart Association (NYHA) classification (peak VO2 > 20 ml · min-1 · kg-1), five in NYHA class B (peak VO2 = 15-20 ml · min-1 · kg-1), and two in NYHA class C (peak VO2 < 10 ml · min-1 · kg-1).

                              
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  		Table 2.   Pulmonary and cardiovascular function data at rest

Maximum Exercise Test

In the CHF group there was a mild to moderate degree of exercise impairment, as evidenced by reduced power output and lower VO2 peak (Table 3). At end exercise, VE was <50% of MVV, estimated as FEV1 · 35, and HR and O2 pulse were also low. CLst decreased significantly from rest to end exercise in CHF but not in normal subjects, although this difference was not significant between groups, likely because of the small number of normal subjects (n = 4) who made reproducible PV curves both at rest and at maximum exercise. In neither group was PtpTLC modified by exercise. No intergroup differences in the slope of the relationships between CLdyn or PtpEILV vs. VCO2 were observed. Compared with rest, FRC tended to increase in CHF and to decrease in normal subjects. These different trends resulted in a significant difference in FRC change between groups (P < 0.01). EILV increased less in CHF than in normal subjects at the end of the test (P < 0.05).

                              
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  		Table 3.   Main respiratory and cardiovascular variables at maximum exercise

Analysis of the most important variables of breathing pattern during exercise (Fig. 1) revealed that exertional hyperpnea was achieved by proportionally more rapid breathing in CHF than in normal subjects, as documented by a significantly greater slope of breathing frequency vs. VCO2 (10.9 ± 5.5 in CHF and 5.7 ± 2.6 in normal subjects, P < 0.01) and a similar slope of VTadj vs. VCO2. In the CHF group, the slope of breathing frequency vs. VCO2 was inversely correlated with resting CLdyn (r = -0.61, P < 0.05) (Fig. 2), FEV1 %predicted (r = -0.58, P < 0.05), FVC %predicted (r = -0.67, P < 0.01), TLC %predicted (r = -0.74, P < 0.01), and FRC %predicted (r = -0.56, P < 0.05). In contrast, the slope of breathing frequency vs. VCO2 did not correlate with baseline CLst, change in CLst at end exercise, slope of CLdyn vs. VCO2, and regression parameters of EFR vs. VCO2. Thus exercise tachypnea mostly occurred in those subjects who had restrictive abnormalities and/or reduced CLdyn at baseline.


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  		Fig. 1.   Mean regression lines of some of the respiratory variables plotted against CO2 production (VCO2) during exercise in chronic heart failure patients (CHF; solid lines) and in the control group (dashed lines). A: tidal volume (VTadj). B: breathing frequency (f). C and D: inspiratory and expiratory times (TI and TE, respectively). E: respiratory duty cycle (TI/Ttot). F: partial forced expiratory flow at 50% of control forced vital capacity (Vpart50). G: expiratory flow reserve (EFR). H: lung dynamic compliance (CLdyn). Significant differences of intercept (Int) and slopes (Sl) are reported.



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  		Fig. 2.   Slope of the linear regression of f vs. VCO2 during exercise plotted against CLdyn at control in the CHF group (r = -0.61, P < 0.05).

The rate of decrease of TI with VCO2 was not significantly different between groups, whereas the rate of decrease of TE with VCO2 was much faster in CHF than in normal subjects (-0.9 ± 0.3 vs. 0.4 ± 0.2, P < 0.001). Thus the slope of TI/Ttot vs. VCO2 was significantly greater in CHF than in normal subjects (3.3 ± 3.9 vs. 0.1 ± 4.5, P < 0.05). The slope of the regression of Vpart50 vs. VCO2 was significantly less in CHF than in normal subjects (0.2 ± 0.4 vs. 0.6 ± 0.4, P < 0.02) and not significantly different from zero, thus suggesting absence of bronchodilatation with exercise in the former. In the normal subjects, Vpart50 tended to increase by ~50% from rest to end exercise. The intercept, but not the slope, of the regression of EFR vs. VCO2 was significantly less in CHF than in normal subjects (0.74 ± 0.33 vs. 1.70 ± 1.13, P < 0.01), suggesting that EFR zeroed at lower VCO2 in the former. The intercept of the regression of CLdyn vs. VCO2 was less in CHF than in the normal subjects (0.16 ± 0.08 vs. 0.28 ± 0.09, P < 0.02). No significant differences were observed between groups for the relationship of PtpFRC vs. VCO2 .

Although the increase in VT with VCO2 was similar between groups, it was achieved with an earlier increase of FRC in CHF (Table 3). In this group, after a transient initial decrease FRC tended to reach the resting value at the end of the test. Without the increase in FRC, impingement of tidal expiratory flow on partial forced flow would have been remarkable (Fig. 3, left). In three subjects, however, FRC decreased from the beginning of exercise and then remained low through the end of the test. EFR never zeroed. In contrast, in the normal group FRC decreased from the beginning of exercise and then remained significantly less than the resting value (Fig. 3, right). Because of an initial high EFR in normal subjects, tidal expiratory flow never impinged on forced expiratory flow, except in two overweight individuals and two former smokers, in whom FRC tended to increase progressively from the beginning of exercise because of a small resting EFR.


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  		Fig. 3.   Composite tidal flow-volume and transpulmonary pressure (Ptp)-volume loops at rest (dashed lines), at ~40% of maximal ventilation (thin solid lines), and at maximum exercise (thick solid lines) in typical CHF (left) and normal (right) subjects. The 2 oblique lines on flow-volume loops are partial forced expiratory flows recorded at rest (dotted line) and at maximum exercise (dashed line). Total lung capacity is at the interception of x- and y-axes on the flow-volume loops. CHF subject: at rest, EFR, i.e., the difference in flow between near end tidal expiration and forced flow at the same absolute volume, is much less than in the normal individual because of the lower functional residual capacity (FRC). At the beginning of exercise, FRC decreases and Ptp (PtpFRC) becomes slightly negative. Tidal expiratory flow near FRC encroaches on forced expiratory flow, thus suggesting initial occurrence of expiratory flow limitation (EFL). Then, FRC tends to increase above resting value at the end of exercise whereas PtpFRC becomes more negative. The increase in PtpFRC is not associated with increase in flow, thus suggesting further EFL. Forced expiratory flow at maximum exercise (dashed oblique line) is similar to resting conditions (dotted oblique line), which is consistent with lack of bronchodilatation. Normal subject: FRC decreases early during exercise and remains low through the end of exercise. PtpFRC becomes slightly negative over the second half of tidal expiration. EFL would have likely occurred at maximum exercise if forced expiratory flow had not increased.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The major findings of this study are that exercise tachypnea in CHF was 1) inversely correlated with resting dynamic compliance but not with quasi-static compliance, either at rest or at maximum exercise, 2) not correlated with the occurrence of EFL, and 3) characterized by a greater rate of decrease in expiratory time than in the normal subjects.

It is well accepted that lung parenchyma is commonly involved in CHF for a series of reasons. Pulmonary congestion and hypertension, edema, increased perivascular pressure, vascular thrombosis, increased heart size, and neurohumoral mechanisms may increase lung stiffness both at rest and during exercise (9, 14, 21, 24, 26, 34, 35). In addition, regional hypoperfusion may result in pneumoconstriction with local decrease in lung compliance (22). Altogether these mechanisms are deemed to decrease lung compliance, thus causing a restrictive lung abnormality (34). In the present study, lung restriction was present only in two patients, as documented by a TLC <80% of predicted, whereas the average lung function of the other subjects was unexpectedly maintained within the normal range. This finding may be explained by the fact that average CLst in CHF was similar to that of normal subjects and is in line with similar values reported by others for CHF patients with similar NYHA class (2, 8, 34).

If the range of operational lung volume is restricted, VT may not be able to increase sufficiently to meet the ventilatory demands during exercise and the required VE may be achieved mostly by increasing breathing frequency. A given increase in VE attained with increase in frequency rather than in VT would result in an increase in dead space, thus requiring a greater VE for a given power output. Moreover, if we accept that breathing pattern is regulated in a way to minimize the work of breathing (19), then we could speculate that the increase in frequency for a given VE is more advantageous in CHF than an increase in VT.

In the present study, the rate of increase of breathing frequency with VCO2 was inversely correlated with resting CLdyn but not with CLst. Although these findings seem to be discrepant at a first sight, it may be speculated that exercise tachypnea is related to increase in lung parenchyma hysteresis rather than to lung stiffness itself. A decrease in CLdyn is known to reflect an involvement of lung parenchyma as a result of exaggerated growth of inextensible fibrotic tissue, vascular congestion and edema, altered alveolar surface tension, activation of contractile elements, recruitment/derecruitment of alveolar units, and ventilation inhomogeneities (12). Whether tachypnea was prevalently triggered by one or more of the above factors cannot be inferred from the present data, although vascular congestion, alteration in surface tension together with large differences between opening and closing pressures, and parenchymal and airways contractile elements appear to be the most plausible ones. Indeed, exaggerated growth of fibrotic tissue, which is known to decrease CLst in addition to CLdyn, is unlikely to have occurred in the subjects of the present study given that baseline CLst was similar between groups and did not correlate with the increase in breathing frequency vs. VCO2. Also ventilation inhomogeneities, which are known to cause decrease in CLdyn with increase in frequency, were likely of little importance in the present study, because CLdyn increased with VCO2 similarly in CHF and normal subjects. Therefore, these data would substantiate at least in part the accepted notion that exercise tachypnea in CHF may be either the most economic breathing adaptation to the high elastic load due to the primary cardiovascular disease (14) or the consequence of neural reflexes evoked by stimulation of the irritant and/or J receptors because of chronic excess of extravascular fluid in the lungs (25). That perturbed breathing frequency during exercise is linked to involvement of the lungs in CHF is also supported by two additional observations. First, the rate of increase of breathing frequency with VCO2 correlated with most of the lung function parameters measured at rest. Second, the relationship between the rate of increase in breathing frequency and resting CLdyn remained significant when the former was expressed as a function of VE (r = -0.53, P < 0.05).

At variance with a previous study (8), the significant decrement in CLst recorded in CHF at maximum exercise did not correlate with an increase of ventilation and especially of breathing frequency. Presumably, such a decrease was due to pulmonary congestion, likely because of high intravascular hydrostatic pressures developed at high ventilation (30). If this is the case, then one would wonder why exercise-induced increase in lung stiffness did not evoke tachypnea as much as preexisting involvement of lung parenchyma. One possible reason is that the tachypnoic response to exercise occurs with a certain time delay and becomes more visible in the recovery phase (8).

Although EFL occurred fairly soon with exercise in CHF, as suggested by a significantly lower intercept of EFR vs. VCO2 than in the control group, there was no relationship between this and exercise tachypnea. Studies in chronic obstructive pulmonary disease during exercise demonstrate that, when EFR occurs, FRC is accommodated to higher lung volume to allow greater ventilation (18, 23, 27). This adaptation entails a mechanical constraint of VT with exercise, so that for a given ventilation breathing frequency has to increase. The fact that in our CHF patients none of the indexes of EFL were associated with rapid shallow breathing does not rule out that EFL may contribute to tachypnea. Other triggers, such as lung stiffness, could have been more predominant in this respect. Alternatively, comparison of tidal and maximal flow measured at the mouth is not sensitive enough to detect the occurrence of regional EFL, as suggested by a recent study (28).

We observed that the rate of increase of TI/Ttot with VCO2 in the CHF was abnormally higher than in the normal subjects. TI decreased with VCO2 similarly in CHF and normal group, but TE decreased as twice as fast in the former. Thus the increase in TI/Ttot was mostly due to excessive shortening of TE with constant decrease in TI. Although we do not have a clear explanation for this finding, we speculate that the greater decrease in TE with exercise may reflect a complex respiratory adaptation tending to limit or contrast functional events specifically arising late on expiration, such as dynamic compression of the airways, which occurred in most of the CHF patients. Under these conditions, increased TI/Ttot could have limited the dangerous effects on the cardiovascular system (10), even though such a strategy may burden the inspiratory muscles. Certainly, any decrease in TE should increase breathing frequency, unless compensated by a change in TI. Thus it is not unreasonable to suspect that what caused the rate of TI/Ttot with VCO2 to increase more in CHF than in the control group also contributed to tachypnea, had TI not blurred the effect.

Dynamic lung hyperinflation is almost mandatory when EFL occurs but has several side effects. Increasing FRC would necessarily decrease VT, unless EILV mutually increased by the same magnitude. In the present study, EILV at maximum load was significantly less in CHF than in normal subjects, thus preventing VTadj from further increase. One reason for this could be that the decrement in CLst recorded at end exercise in CHF, possibly due to regional hypoperfusion and consequent pneumoconstriction (22, 35) or engorged pulmonary vascular bed (1), was such as to impose an extra end-inspiratory load intolerable to the inspiratory muscles, thus prematurely terminating inspiration. Dynamic lung hyperinflation could put the inspiratory muscles in an unfavorable condition to generate force (32); edema formation as a result of increased pulmonary vascular pressure could stimulate lung parenchyma receptors, thus prematurely interrupting ventilation; and, finally, respiratory muscle deoxygenation (17) could lead to inability to sustain lung expansion over an adequate period of time. Alternatively, external factors such as leg fatigue could have contributed to interrupt exercise prematurely and prevented EILV in CHF from increasing as much as in normal subjects.

Although most of the differences in lung function at rest between CHF and normal subjects were quantitatively trivial, EFR was <50% compared with the control group. Its decrement was not likely due to airway narrowing, because forced expiratory flows were similar between groups. More likely, it was the small increase in lung stiffness that caused FRC to accommodate at a lower lung volume at which EFR is necessarily low, as suggested by a significant relationship between FRC as percent of predicted and CLdyn. A still-positive EFR at rest in the CHF patients would explain why VT increased similarly to that of the normal subjects at the beginning of exercise, because it was not such to prevent EILV and FRC from expanding adequately. However, with EFR becoming zero at lower VCO2 than in the normal subjects, breathing pattern had to adapt with a gradual increase in FRC to achieve greater expiratory flow and with a decrease in VT and increase in breathing frequency.

Normal individuals tend to increase maximal flows during exercise (15, 27), likely because of an increase in airway caliber. Catecholamines, decreased vagal tone with exercise, and tidal stretching of airway smooth muscle could be responsible for the phenomenon. If catecholamines in exercising CHF subjects are assumed to increase at least as much as in healthy subjects (1, 7), a lack of increment in forced expiratory flow in CHF would suggest that vagal tone persists in CHF (5) and/or that tidal stretching is ineffective to distend the airways, or that airway walls are inextensible with lung expansion. Whatever the underlying mechanisms, the inability to increase flow during exercise heavily weighted on the choice of breathing adaptation.

In conclusion, the present data are consistent with the notion that lung stiffness may lead to a mainly tachypnoic response to exercise in CHF. This pattern of response seems to be attributable to longstanding decrease in CLdyn, reflecting chronic perivascular and alveolar edema, surface phenomena, and recruitment/derecruitment. According to the present data, dynamic compression of the airways during expiration is not directly involved in tachypnea, although it may contribute to alter breathing pattern.


    ACKNOWLEDGEMENTS

We thank F. Borst and R. Perissin from SensorMedics Italia and T. Cinquanta and M. L. Scapin from the laboratory for invaluable technical assistance.


    FOOTNOTES

Address for reprint requests and other correspondence: V. Brusasco, Dipartimento di Medicina Interna, Università di Genova, Largo R. Benzi, 10, 16132 Genova, Italy (E-mail: brusasco{at}dism.unige.it).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

10.1152/japplphysiol.00724.2001

Received 11 July 2001; accepted in final form 17 November 2001.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

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J APPL PHYSIOL 92(4):1409-1416
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