(Circulation. 1995;91:2769-2774.)
© 1995 American Heart Association, Inc.
Articles |
Reduced Alveolar–Capillary Membrane Diffusing Capacity in Chronic Heart Failure
Its Pathophysiological Relevance and Relationship to Exercise Performance
From the Department of Medicine (Clinical Cardiology and Respiratory Medicine), Royal Postgraduate Medical School, Hammersmith Hospital, London.
Correspondence to Dr J.G.F. Cleland, British Heart Foundation Senior Research Fellow, MRC Clinical Research Initiative in Heart Failure, West Medical Building, Glasgow University, Glasgow, Scotland, UK.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure (CHF) and is an independent predictor of peak exercise oxygen uptake. The pathophysiological basis for this remains unknown. The aim of this study was to partition DLCO into its membrane conductance (DM) and capillary blood volume components (Vc) and to assess if alveolar–capillary membrane function correlated with functional status, exercise capacity, and pulmonary vascular resistance.
Methods and Results The classic Roughton and Forster method of measuring single-breath DLCO at varying alveolar oxygen concentrations was used to determine DM and Vc in 15 normal subjects and 50 patients with CHF. All performed symptom-limited maximal bicycle exercise tests with respiratory gas analysis; 15 CHF patients underwent right heart catheterization. DLCO was significantly reduced in CHF patients compared with normal subjects, predominantly because of a reduction in DM (7.0±2.6 versus 12.9±3.8 versus 20.0±6.1 mmol · min-1 · kPa-1 in New York Heart Association class III, class II, and normal subjects, respectively, P<.0001), even when the reduction in lung volumes was accounted for by the division of DM by the effective alveolar volume. The Vc component of DLCO was not impaired. DM significantly correlated with maximal exercise oxygen uptake (r=.72, P<.0001) and inversely correlated with pulmonary vascular resistance (r=.65, P<.01) in CHF.
Conclusions Reduced alveolar–capillary membrane diffusing capacity is the major component of impaired pulmonary gas transfer in CHF, correlating with maximal exercise capacity and functional status. DM may be a useful marker for the alveolar–capillary barrier damage induced by raised pulmonary capillary pressure.
Key Words: circulation • lung • oxygen
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Although impairment of cardiac performance is the primary abnormality in chronic heart failure, symptoms and exercise capacity correlate poorly with hemodynamic indices of left ventricular function.1 2 Recent studies have shown that abnormalities of skeletal muscle3 4 and lung function5 are prominent features of heart failure and that such secondary abnormalities may explain much of the variability of exercise tolerance observed in patients with left ventricular dysfunction.
Reduction in the pulmonary diffusing capacity for carbon monoxide (DLCO) is well documented in chronic heart failure.6 7 8 The functional significance of this reduction remains controversial; DLCO is an independent predictor of peak exercise oxygen uptake in heart failure,5 and increasing the inspired oxygen concentration has been shown to improve both arterial oxygen saturation and exercise performance in patients.9 These reports would suggest that impairment of pulmonary gas exchange may play a role in the limitation of exercise capacity in chronic heart failure. However, as arterial oxygen desaturation is not prominent in the majority of patients with heart failure,10 11 the proportion of patients with heart failure exhibiting oxygen desaturation during exercise and the pathophysiological process leading to desaturation remains controversial.
DLCO may be partitioned into its two subcomponents using
the classic Roughton and Forster method12 13 :
DM, the molecular diffusion of carbon monoxide
across the alveolar–capillary membrane, and 
. Vc, the chemical
reaction () of carbon monoxide with pulmonary capillary blood (Vc).
Recent experiments have highlighted a possible mechanism leading to a
reduction of DLCO and the diffusing capacity of the
alveolar–capillary membrane (DM) in heart failure. In
animal models, raising lung capillary transmural pressures leads to
disruption and fractures of the endothelial and epithelial
layers.14 The response to pressure-induced trauma in the
pulmonary microvasculature is proliferation of alveolar type II cells,
thickening of the alveolar–capillary interstitium, and some fibrotic
change.15 Such changes would increase alveolar–capillary
membrane thickness and reduce DM. Extensive studies of
pulmonary function have been performed in patients with mitral
stenosis,16 17 including measurement of DM
and
pulmonary capillary blood volume.18 The reduction in
DLCO and DM in this patient group with
elevated left atrial pressure correlates with New York Heart
Association (NYHA) functional class18 and the severity of
histological lung damage,19 supporting the hypothesis that
DM may reflect stress failure of the alveolar–capillary
interface induced by pulmonary capillary hypertension.
The aim of the present study was to determine if the reduction in DLCO reported in heart failure was secondary to impairment of alveolar–capillary membrane function and whether alveolar–capillary membrane function correlated significantly with functional status, exercise capacity, and pulmonary vascular resistance.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Subjects
This study was approved by the Hammersmith Hospital Ethics Committee, and all subjects gave informed consent. Subjects who were currently smoking or gave a history of respiratory disease were excluded. None of the subjects had smoked for at least 12 months before being studied. Forty-eight male and 2 female patients with stable symptomatic chronic heart failure of greater than 6 months' duration were studied. Table 1
summarizes the clinical
characteristics of this group. All were receiving treatment with loop
diuretics at a dose equivalent to 46±20 mg of furosemide
(mean±SD,
and assuming that 1 mg bumetanide is equivalent to 40 mg furosemide)
and angiotensin-converting enzyme inhibitors. Three patients were
receiving amiodarone and 4 patients were taking digoxin. Drug
therapy had remained unaltered in the 8 weeks before the study.
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Fifteen healthy volunteers (14 men, 1 woman; mean age, 52 years; range, 34 to 66 years) without a history of cardiorespiratory disease and with a normal physical examination were also studied.
Pulmonary Function Testing
The forced expiratory volume in 1
second (FEV1) and
vital capacity (VC) were measured in a bellows spirometer
(Vitalograph). The best of three measurements made was recorded. Any
subject with evidence of airways obstruction, as defined by an
FEV1 to VC ratio <70% was excluded. DLCO
was measured using a standard modified Krogh single-breath technique
(PK Morgan).13 This maneuver was performed in duplicate
using as a test gas 0.28% carbon monoxide (CO), 14% helium (He), 21%
O2, balance nitrogen, and then repeated (again in
duplicate) using a test gas with a higher oxygen (O2)
concentration (0.3% CO, 10% He, 89.7% O2). All results
were corrected for the subject's hemoglobin concentration. The
alveolar partial pressure of O2
(PAO2) was recorded for all DLCO
measurements, being estimated from the fractional expired
O2 concentration of the same expired gas sample used for
the measurement of DLCO (Servomex O2 analyzer
570A). Alveolar–capillary membrane diffusing capacity (DM)
and the pulmonary capillary volume of blood available for physiological
gas exchange (Vc) were determined using the classic Roughton and
Forster method, which is described in detail
elsewhere.12 13 This method partitions pulmonary
diffusing
capacity into its component resistances: the diffusive resistance of
the alveolar–capillary membrane (1 · DM) and the
reactive resistance due to pulmonary capillary blood
(1-1 · Vc, where =the rate of
reaction of CO
with hemoglobin). The Roughton and Forster equation12
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links
these resistances. As CO and O2 compete
directly for the available hemoglobin binding sites, is inversely
proportional to PAO2. 1/ was determined
using the following equation, which assumes that the red cell membrane
has a negligible resistance to gas exchange13 :
 |
where
Hb=the subject's hemoglobin (g/dL) and
PAO2 is measured in kPa. If
DLCO is measured at different
PAO2 values, a plot of 1/DLCO
against 1/ will yield a straight line with a y-intercept
of 1/DM and a gradient of 1/Vc.
Exercise Testing
All subjects performed upright
symptom-limited maximal exercise
tests on an electronically controlled bicycle ergometer (Siemens
EM840). A progressive exercise protocol was used, 10-W/min increments
being used in heart failure patients and 20-W/min increments in normal
subjects. Subjects who terminated exercise for reasons other than
breathlessness or fatigue were excluded. Carbon dioxide production,
oxygen consumption, and minute ventilation were recorded on a
breath-by-breath analyzer (Amis 2000 Respiratory Mass Spectrometer,
Innovision). Heart rate and ECG were monitored continuously, while
blood pressure was measured at 1-minute intervals.
Radionuclide Ventriculography
All patients with heart failure
had left ventricular ejection
fraction (EF) measured at rest by multigated radioisotope analysis
in the supine position.
Right Heart Catheterization
Fifteen patients with heart
failure underwent standard
right heart catheterization with a balloon-tipped pulmonary artery
flotation catheter. Cardiac output (using the thermodilution
technique), pulmonary artery pressure (PAP), and pulmonary capillary
wedge pressure (PCWP) were measured. The average of three consecutive
measurements was used for subsequent analysis. Pulmonary vascular
resistance (PVR) in Wood units was calculated by dividing the mean
transpulmonary gradient (mean PAP-mean PCWP) by cardiac output. The
results of resting hemodynamics in these patients are recorded in Table
2.
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Statistical Analysis
Comparison of results between normal
subjects and patients in
NYHA classes II and III was performed by ANOVA (Scheffe's F test).
Correlation coefficients were calculated by univariate linear
regression analysis. All values are expressed as mean±SD unless
otherwise stated. P<.05 was considered statistically
significant.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Pulmonary Function
Table 3
illustrates the
mean results of spirometry,
effective alveolar volume (VA), and anthropometric details for all
subjects studied. Fig 1 plots the individual results of
all subjects with respect to DLCO, DM,
and Vc.
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P<.05,
DLCO and lung volumes (FEV1, VC, and
VA) were reduced in patients compared with normal subjects and were
lower in patients in NYHA class III than those in NYHA class II
(P<.01, Fig 1
and Table 3). The
FEV1/VC
ratio remained within the normal range (Table 3). The reduction
in
DLCO was predominantly due to a reduction in
DM (Fig 1) and persisted even when the reduction in
lung
volumes was taken into account by plotting DM/VA
(Fig 2). In patients with heart failure, the
alveolar–capillary membrane diffusive resistance formed a greater
proportion of the total pulmonary diffusive resistance
(DLCO/DM) than in normal subjects (Fig 2).
Vc
was similar in normal subjects and patients in NYHA class II (61±23
versus 68±15 mL) but was increased in patients in NYHA class III
(84±26 mL, P<.05).
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Patients who were lifelong nonsmokers and those who were ex-smokers had a similar severity of heart failure (EF, 30±14% versus 29±10%; maximal oxygen consumption on exercise [MVO2 ], 12.1±3.2 versus 13.0±4.2 mL · min-1 · kg-1, respectively), and no significant differences were observed in spirometry, lung volumes (FEV1, VC, VA), or pulmonary diffusion tests (DLCO, DM). This would imply, therefore, that smoking history did not have a major effect on the differences in pulmonary function test results observed between the groups that were studied.
Exercise Testing
Table 4 shows the
pressure-rate product achieved
and MVO2 attained in all subjects. As
expected, the patients with heart failure performed significantly worse
than normal subjects.
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MVO2 in heart failure
patients correlated
significantly with DLCO (r=.6,
P=.001), but an even stronger correlation was observed with
the DM component of DLCO (Fig 3,
r=.72, P<.001). No such
correlations were present in our normal subjects (r=.35,
P=NS). In subjects who underwent right heart catheterization
(Table 2), significant correlation of DM with
MVO2 was again observed (r=.7,
P<.005). In addition, DM inversely correlated
with PVR (Fig 4). No significant correlations were
observed between any of the other resting hemodynamic indices measured
(Table 2) and MVO2 or DM.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Our results confirm the presence of impaired pulmonary gas transfer at rest in chronic heart failure. The reduction in DLCO and lung volumes (FEV1, VC, VA) in this study was in keeping with previous reports.6 7 8 Pulmonary capillary blood volume was similar in control subjects and patients with heart failure, implying that reduced alveolar–capillary membrane diffusing capacity (DM) was the major determinant of impaired pulmonary diffusing capacity. In normal subjects, 50% of the total pulmonary diffusive resistance relates to the alveolar–capillary membrane, irrespective of age.20 The results in our control group were similar to this value. In heart failure patients, however, a larger proportion of the total pulmonary diffusive resistance was caused by a reduction in DM. Abnormalities in alveolar–capillary membrane diffusing capacity were greatest in those subjects with the greatest reduction in MVO2 and the most severe symptoms, although there was clearly a degree of overlap between normal subjects and patients with milder symptoms. Theoretically, a reduction in the alveolar–capillary membrane surface area available for gas exchange, or an alteration in the physical properties of the membrane itself, may be responsible for the reduction in DM.
DM and Lung Volume
Reduced lung volumes are a
feature of chronic heart
failure6 7 and would decrease the surface area
available
for gas exchange. A reduction in lung volumes was observed in this
study in heart failure patients (Table 3), but the reduction in
DM that was also noted persisted even when this reduction
was accounted for (Fig 2), implying that an intrinsic
abnormality of
the alveolar–capillary membrane, such as thickening, also exists.
Further support for this hypothesis comes from failure of
DLCO to improve after cardiac
transplantation21 despite normalization of lung
volumes.22
DM and Inhomogeneity of Lung Function
Maldistribution of ventilation and ventilation-perfusion mismatch
are possible mechanisms that could reduce the effective surface area
for gas exchange. In the absence of significant airflow obstruction, as
in our patients (Table 3), marked inhomogeneity of ventilation
distribution is unlikely. Ventilation-perfusion mismatch would be
expected to cause not only a reduction in effective DLCO
and DM, leaving the proportions of both
(DLCO/DM) relatively unchanged, but to reduce
the volume of pulmonary capillary blood available for gas exchange
(Vc). No reduction in Vc was seen in this study. By contrast, those
patients with the greatest reduction in DM (NYHA class III)
exhibited an increase in Vc. Pulmonary capillary volume is determined
by the radius of the capillary and the surface area of the
alveolar–capillary interface available for physiological gas exchange.
The increase in Vc seen in NYHA class III patients may, therefore,
reflect pulmonary capillary distension secondary to elevation of left
atrial pressure. Alternatively, improved ventilation-perfusion matching
at rest in these patients23 24 may be responsible for
the
increase in Vc.
DM and Pulmonary Oxygen Diffusion Limitation on
Exercise
Pulmonary diffusion limitation has not been thought to be an
important mediator of exercise impairment in heart failure because
exertional arterial oxygen desaturation is not
prominent.10 11 In addition, prolonged pulmonary
capillary
blood transit time may allow greater time for gas transfer, thereby
limiting the importance of any impairment of diffusion that might be
present at the alveolar–capillary membrane.25 Higher
than normal levels of ventilation occur on exercise in chronic heart
failure. This increased level of ventilation should elevate alveolar
oxygen tension and subsequently increase arterial oxygen saturation in
the absence of significant oxygen diffusion limitation or
ventilation-perfusion mismatch. Alveolar-arterial gradients of oxygen
(AaPO2) up to 32 mm Hg, however, occur on
exercise in heart failure,10 implying that either singly
or in combination, some degree of oxygen diffusion limitation or
ventilation-perfusion mismatch exists. A reduced DM may
contribute to the widened AaPO2 gradient in
patients with heart failure. AaPO2 gradients
of 
30 mm Hg, however, would not in themselves cause significant
arterial hypoxemia, and therefore alternative mechanisms may be
responsible for the correlation of DM with
MVO2.
DM as a Marker for Raised Pulmonary Vascular
Resistance
Transient elevation of pulmonary artery pressure has been
shown to cause alveolar epithelial and pulmonary endothelial damage in
experimental models.14 Elevation of pulmonary capillary
pressures may occur at rest in heart failure26 and
increase further on exercise,2 27 28
providing a possible
mechanism for stress failure of the alveolar–capillary
membrane29 and its subsequent dysfunction. In mitral
stenosis, reduced DLCO correlates with the degree of
pulmonary vascular damage.19 The inverse correlation
between pulmonary vascular resistance (PVR) and DM in this
study suggests that these two variables may be different measures of
the same pathological process, namely, pulmonary microvascular
damage.
Interventions that improve pulmonary hemodynamics also improve exercise capacity.30 31 32 In addition, failure to decrease PVR on exercise has been implicated in impaired exercise performance.33 Conventional pulmonary hemodynamics, as measured by right heart catheterization, can only provide an instantaneous assessment of the pulmonary circulation under laboratory conditions. Measurement of DM may reflect long-term cumulative pulmonary microvascular damage, providing a more sensitive and noninvasive marker than hemodynamics measured in the cardiac catheterization laboratory.
Conclusions
We have identified reduced
alveolar–capillary membrane diffusing
capacity as the major component of impaired pulmonary gas transfer in
chronic heart failure. DM significantly correlates with
functional status as measured by NYHA class and maximal exercise
capacity in such patients. Whether this impairment is simply a marker
for the severity of the disease process or plays a pathophysiological
role remains uncertain. Prospective studies are required to assess if
modulation of alveolar–capillary membrane function is possible and has
any effects on exercise performance in heart failure.
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Acknowledgments |
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Dr Puri is supported by a Junior Research Fellowship and Dr Cleland by a Senior Research Fellowship from the British Heart Foundation.
Received October 4, 1994; revision received December 6, 1994; accepted December 18, 1994.
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 M. Guazzi, G. Tumminello, F. Di Marco, C. Fiorentini, and M. D. Guazzi The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2339 - 2348. [Abstract] [Full Text] [PDF]
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M. Bonay, C. Bancal, D. de Zuttere, F. Arnoult, G. Saumon, and F. Camus Normal Pulmonary Capillary Blood Volume in Patients With Chronic Infiltrative Lung Disease and High Pulmonary Artery Pressure Chest, November 1, 2004; 126(5): 1460 - 1466. [Abstract] [Full Text] [PDF]
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 M. Guazzi, G. Reina, G. Tumminello, and M. D. Guazzi Improvement of alveolar-capillary membrane diffusing capacity with exercise training in chronic heart failure J Appl Physiol, November 1, 2004; 97(5): 1866 - 1873. [Abstract] [Full Text] [PDF]
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 Mechanisms and Limits of Induced Postnatal Lung Growth Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 319 - 343. [Full Text] [PDF]
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M. Bussotti, D. Andreini, and P. Agostoni Exercise-induced changes in exhaled nitric oxide in heart failure Eur J Heart Fail, August 1, 2004; 6(5): 551 - 554. [Abstract] [Full Text] [PDF]
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B. K. Gehlbach and E. Geppert The Pulmonary Manifestations of Left Heart Failure Chest, February 1, 2004; 125(2): 669 - 682. [Abstract] [Full Text] [PDF]
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 P. Agostoni, G. Cattadori, M. Bianchi, and K. Wasserman Exercise-Induced Pulmonary Edema in Heart Failure Circulation, November 25, 2003; 108(21): 2666 - 2671. [Abstract] [Full Text] [PDF]
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M. Quantz, S. Wilson, C. Smith, L. Stitt, R. Novick, and D. Ahmad Advantages of the Intrabreath Technique as a Measure of Lung Function Before and After Heart Transplantation Chest, November 1, 2003; 124(5): 1658 - 1662. [Abstract] [Full Text] [PDF]
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M. Guazzi, G. Tumminello, M. Matturri, and M. D. Guazzi Insulin ameliorates exercise ventilatory efficiency and oxygen uptake in patients with heart failure-type 2 diabetes comorbidity J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1044 - 1050. [Abstract] [Full Text] [PDF]
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W. C. Levy and I. B. Hirsch Diabetes and heart failure: is insulin therapy the answer? J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1051 - 1053. [Full Text] [PDF]
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M. Guazzi Alveolar-Capillary Membrane Dysfunction in Heart Failure: Evidence of a Pathophysiologic Role Chest, September 1, 2003; 124(3): 1090 - 1102. [Abstract] [Full Text] [PDF]
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M. A. Konstam Colloid osmotic pressure: An under-recognized factor in the clinical syndrome of heart failure J. Am. Coll. Cardiol., August 20, 2003; 42(4): 717 - 718. [Full Text] [PDF]
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 C. G. De Pasquale, A. D. Bersten, I. R. Doyle, P. E. Aylward, and L. F. Arnolda Infarct-induced chronic heart failure increases bidirectional protein movement across the alveolocapillary barrier Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2136 - H2145. [Abstract] [Full Text] [PDF]
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S. Nanas, J. Nanas, O. Papazachou, C. Kassiotis, A. Papamichalopoulos, J. Milic-Emili, and C. Roussos Resting Lung Function and Hemodynamic Parameters as Predictors of Exercise Capacity in Patients With Chronic Heart Failure Chest, May 1, 2003; 123(5): 1386 - 1393. [Abstract] [Full Text] [PDF]
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H. R. Gosker, N. H. M. K. Lencer, F. M. E. Franssen, G. J. van der Vusse, E. F. M. Wouters, and A. M. W. J. Schols Striking Similarities in Systemic Factors Contributing to Decreased Exercise Capacity in Patients With Severe Chronic Heart Failure or COPD Chest, May 1, 2003; 123(5): 1416 - 1424. [Abstract] [Full Text] [PDF]
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T Tomita, H Takaki, Y Hara, F Sakamaki, T Satoh, S Takagi, Y Yasumura, N Aihara, Y Goto, and K Sunagawa Attenuation of hypercapnic carbon dioxide chemosensitivity after postinfarction exercise training: possible contribution to the improvement in exercise hyperventilation Heart, April 1, 2003; 89(4): 404 - 410. [Abstract] [Full Text] [PDF]
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P G Agostoni, M Bussotti, P Palermo, and M Guazzi Does lung diffusion impairment affect exercise capacity in patients with heart failure? Heart, December 1, 2002; 88(5): 453 - 459. [Abstract] [Full Text] [PDF]
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C. C. W. Hsia Recruitment of Lung Diffusing Capacity: Update of Concept and Application Chest, November 1, 2002; 122(5): 1774 - 1783. [Abstract] [Full Text] [PDF]
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M.R. Abraham, L. J. Olson, M. J. Joyner, S. T. Turner, K. C. Beck, and B. D. Johnson Angiotensin-Converting Enzyme Genotype Modulates Pulmonary Function and Exercise Capacity in Treated Patients With Congestive Stable Heart Failure Circulation, October 1, 2002; 106(14): 1794 - 1799. [Abstract] [Full Text] [PDF]
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M. Schaufelberger Pulmonary diffusion capacity as prognostic marker in chronic heart failure Eur. Heart J., March 2, 2002; 23(6): 429 - 431. [Full Text] [PDF]
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M Guazzi, G Pontone, R Brambilla, P Agostoni, and G Reina Alveolar-capillary membrane gas conductance: a novel prognostic indicator in chronic heart failure Eur. Heart J., March 2, 2002; 23(6): 467 - 476. [Abstract] [Full Text] [PDF]
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M. Guazzi, P. Agostoni, and M. D. Guazzi Modulation of alveolar-capillary sodium handling as a mechanism of protection of gas transfer by enalapril, and not by losartan, in chronic heart failure J. Am. Coll. Cardiol., February 1, 2001; 37(2): 398 - 406. [Abstract] [Full Text] [PDF]
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P Faggiano, A D'Aloia, A Gualeni, and A Giordano Relative contribution of resting haemodynamic profile and lung function to exercise tolerance in male patients with chronic heart failure Heart, February 1, 2001; 85(2): 179 - 184. [Abstract] [Full Text]
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Recommendations for exercise testing in chronic heart faliure patients Eur. Heart J., January 1, 2001; 22(1): 37 - 45. [PDF]
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O. A. Al-Rawas, R. Carter, R. D. Stevenson, S. K. Naik, and D. J. Wheatley Exercise Intolerance Following Heart Transplantation : The Role of Pulmonary Diffusing Capacity Impairment Chest, December 1, 2000; 118(6): 1661 - 1670. [Abstract] [Full Text] [PDF]
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P. Agostoni, M. Guazzi, M. Bussotti, M. Grazi, P. Palermo, and G. Marenzi Lack of improvement of lung diffusing capacity following fluid withdrawal by ultrafiltration in chronic heart failure J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1600 - 1604. [Abstract] [Full Text] [PDF]
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R. L. Johnson Jr Gas Exchange Efficiency in Congestive Heart Failure Circulation, June 20, 2000; 101(24): 2774 - 2776. [Full Text] [PDF]
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F. X. Kleber, G. Vietzke, K. D. Wernecke, U. Bauer, C. Opitz, R. Wensel, A. Sperfeld, and S. Glaser Impairment of Ventilatory Efficiency in Heart Failure : Prognostic Impact Circulation, June 20, 2000; 101(24): 2803 - 2809. [Abstract] [Full Text] [PDF]
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 T. Stys, W. E. Lawson, G. C. Smaldone, and A. Stys Does Aspirin Attenuate the Beneficial Effects of Angiotensin-Converting Enzyme Inhibition in Heart Failure? Arch Intern Med, May 22, 2000; 160(10): 1409 - 1413. [Abstract] [Full Text] [PDF]
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R. Ewert, R. Wensel, L. Bruch, S. Mutze, U. Bauer, M. Plauth, and F.-X. Kleber Relationship Between Impaired Pulmonary Diffusion and Cardiopulmonary Exercise Capacity After Heart Transplantation Chest, April 1, 2000; 117(4): 968 - 975. [Abstract] [Full Text] [PDF]
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J. A. Gomez-Hospital, A. Cequier, P. V. Romero, C. Canete, C. Ugartemendia, J. Mauri, and E. Esplugas Partial Improvement in Pulmonary Function After Successful Percutaneous Balloon Mitral Valvotomy Chest, March 1, 2000; 117(3): 643 - 648. [Abstract] [Full Text] [PDF]
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A. L. Clark, L. C. Davies, D. P. Francis, and A. J.S. Coats Ventilatory capacity and exercise tolerance in patients with chronic stable heart failure Eur J Heart Fail, March 1, 2000; 2(1): 47 - 51. [Abstract] [Full Text] [PDF]
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 M. Guazzi, P. Agostoni, M. Bussotti, and M. D. Guazzi Impeded Alveolar-Capillary Gas Transfer With Saline Infusion in Heart Failure Hypertension, December 1, 1999; 34(6): 1202 - 1207. [Abstract] [Full Text] [PDF]
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A. A. Smith, P. J. Cowburn, M. E. Parker, M. Denvir, S. Puri, K. R. Patel, and J. G. F. Cleland Impaired Pulmonary Diffusion During Exercise in Patients With Chronic Heart Failure Circulation, September 28, 1999; 100(13): 1406 - 1410. [Abstract] [Full Text] [PDF]
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R. Ewert, R. Wensel, M. Bettmann, S. Spiegelsberger, O. Grauhan, M. Hummel, and R. Hetzer Ventilatory and Diffusion Abnormalities in Long-term Survivors After Orthotopic Heart Transplantation Chest, May 1, 1999; 115(5): 1305 - 1311. [Abstract] [Full Text] [PDF]
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S. Puri, D. P. Dutka, B. L. Baker, J. M. B. Hughes, and J. G. F. Cleland Acute Saline Infusion Reduces Alveolar-Capillary Membrane Conductance and Increases Airflow Obstruction in Patients With Left Ventricular Dysfunction Circulation, March 9, 1999; 99(9): 1190 - 1196. [Abstract] [Full Text] [PDF]
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A. L Clark, D. Harrington, T. P. Chua, and A. J S Coats Exercise capacity in chronic heart failure is related to the aetiology of heart disease Heart, December 1, 1997; 78(6): 569 - 571. [Abstract] [Full Text] [PDF]
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M. Guazzi, G. Marenzi, M. Alimento, M. Contini, and P. Agostoni Improvement of Alveolar–Capillary Membrane Diffusing Capacity With Enalapril in Chronic Heart Failure and Counteracting Effect of Aspirin Circulation, April 1, 1997; 95(7): 1930 - 1936. [Abstract] [Full Text]
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 P. Agostoni, G. Marenzi, M. Guazzi, and M. D. Guazzi Influence of ACE Inhibition on Fluid Metabolism in Chronic Heart Failure and Its Pathophysiologic Relevance Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 1996; 1(4): 279 - 286. [Abstract] [PDF]
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