Impeded Alveolar-Capillary Gas Transfer With Saline
Infusion in Heart Failure
Marco Guazzi, Piergiuseppe Agostoni, Maurizio Bussotti, Maurizio D. Guazzi
Downloaded from http://hyper.ahajournals.org/ by guest on July 31, 2017
Abstract—The microvascular pulmonary endothelium barrier is critical in preventing interstitial fluid overflow and
deterioration in gas diffusion. The role of endothelium in transporting small solutes in pathological conditions, such as
congestive heart failure (CHF), has not been studied. Monitoring of pulmonary gas transfer during saline infusion in
CHF was used to probe this issue. Carbon monoxide diffusion (DLCO), its membrane diffusion (DM) and capillary blood
volume (VC) subcomponents, and mean right atrial (rap) and mean pulmonary wedge (wpp) pressures after saline or 5%
D-glucose solution infusions were compared with baseline in 26 moderate CHF patients. Saline was also tested in 13
healthy controls. In patients, 750 mL of saline lowered DLCO (28%, P,0.01 versus baseline), DM (210%, P,0.01
versus baseline), aldosterone (229%, P,0.01 versus baseline), renin (252%, P,0.01 versus baseline), and hematocrit
(26%, P,0.05 versus baseline) and increased VC (20%, P,0.01 versus baseline), without changing rap and wpp. Saline
at 150 mL produced qualitatively similar results regarding DLCO (25%, P,0.01 versus baseline), DM (27%, P,0.01
versus baseline), VC (9%, P,0.01 versus baseline), rap, wpp, aldosterone (29%, P,0.05 versus baseline), and renin
(214%, P,0.05 versus baseline). Glucose solution (750 mL), on the contrary, increased DLCO (5%, P,0.01 versus 750
mL of saline) and DM (11%, P,0.01 versus 750 mL of saline) and decreased VC (29, P,0.01 versus 750 mL of saline);
aldosterone (240%), renin (241%), hematocrit (23%), rap, and wpp behaved as they did after saline infusion. In
controls, responses to both saline amounts were similar to responses in CHF patients regarding aldosterone, renin,
hematocrit, rap, and wpp, whereas DLCO, DM, and VC values tended to rise. Hindrance to gas transfer (reduced DLCO and
DM) with salt infusion in CHF, despite an increase in VC and no variations in pulmonary hydrostatic forces, indicates
an upregulation in sodium transport from blood to interstitium with interstitial edema. Redistribution of blood from the
lungs, facilitating interstitial fluid reabsorption, or sodium uptake from the alveolar lumen by the sodium-glucose
cotransport system might underlie the improved alveolar-capillary conductance with glucose. (Hypertension.
1999;34:1202-1207.)
Key Words: capillaries n epithelium n glucose n heart failure n sodium
F
hydrostatic pressures3 or may be present even if pressures
are normal.4 Whether altered hemodynamics are the exclusive mechanisms for pulmonary edema in CHF and
whether alterations in the capillary endothelium and/or in
the alveolar epithelium barrier contribute to changes in
salt, water, and gas transfer have been the subjects of only
limited research.3 Cardiogenic anatomic injuries of the
alveolar-capillary membrane have been reported in animals and humans.5,6
We examined the hypothesis of an alteration in the microvascular endothelium barrier by infusing saline into CHF
patients and monitoring the pulmonary diffusing capacity for
CO (DLCO) and its subdivisions, ie, alveolar-capillary membrane diffusing capacity (DM) and capillary blood volume
available for gas exchange (VC). We reasoned that an alteration in sodium handling by the alveolar-capillary membrane
would be substantiated if infusions of saline amounts devoid
of hydrostatic effects were proven to impede the membrane
or the lung parenchyma to allow gas exchange between
blood and gas in the alveoli, a continuous clearance is
required of the excess of fluid into the interstitial space and
the alveolar lumen. Excessive water accumulation in these
compartments is called pulmonary and alveolar edema, respectively. The pulmonary microvascular endothelium and
the alveolar epithelium constitute a barrier that is critical for
gas exchange and modulation of fluid and solute passage
between blood, the interstitial compartment, and alveoli.1
Despite the substantial progress that has been made in
understanding the physiology of the endothelial and epithelial
layers in regulating lung fluid balance, further study regarding the local and systemic regulatory factors under pathological conditions is necessary.1
An imbalance in hydrostatic forces is interpreted as the
basic mechanism for volume overload and cardiogenic
pulmonary edema.2 In congestive heart failure (CHF),
pulmonary edema may be absent despite elevation of the
Received May 14, 1999; first decision June 8, 1999; revision accepted July 26, 1999.
From the Istituto di Cardiologia dell’Università degli Studi, Centro di Studio per le Ricerche Cardiovascolari del Consiglio Nazionale delle Ricerche,
Fondazione “Monzino,” I.R.C.C.S., Milano, Italy.
Correspondence to Marco Guazzi, MD, PhD, Istituto di Cardiologia, Via C. Parea, 4, 20138 Milano, Italy. E-mail [email protected]
© 1999 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
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Guazzi et al
Saline Infusion in CHF
1203
subcomponent of the pulmonary gas transfer in CHF patients
and not in healthy individuals.
Methods
Patients and Controls
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We investigated male patients referred to the Institute of Cardiology,
University of Milan, for evaluation of chronic heart failure. They
presented with either idiopathic cardiomyopathy (cardiac enlargement, reduced ejection fraction [EF], and absence of a specific cause
for cardiac failure) or ischemic heart disease (documented previous
myocardial infarction). Inclusion criteria were (1) cardiac dysfunction, classified as chronic stable NYHA functional class II to III, and
(2) left ventricular EF #40%. Exclusion criteria were (1) present or
past history of smoking (.10 cigarettes per day during 1 of the past
5 years), (2) history of respiratory or renal diseases, (3) evidence of
renal impairment (serum creatinine concentration $0.05 mmol/dL)
or airway obstruction (forced expiratory volume in 1 second [FEV1]
to vital capacity ratio ,70%), (4) DLCO #75% of predicted normal
value on the basis of standard nomograms incorporating age, gender,
height, and weight,7 (5) mitral regurgitation exceeding grade 3 on a
subjective scale from 0 to 5, and (6) angiotensin-converting enzyme
(ACE) inhibitor therapy, acetylsalicylic acid, or other cyclooxygenase inhibitors within the last 2 months. ACE inhibition, in fact,
ameliorates pulmonary diffusion in CHF, and cyclooxygenase blockers counteract this effect.8
Twenty-six patients (10 in NYHA functional class II and 16 in
class III) took part in this investigation; none of them had participated in previous studies in our laboratory. Thirteen healthy men
who were similar in age and physical characteristics to the patients
and who were nonsmokers volunteered to serve as controls. They
had been admitted to the hospital because of atypical chest pain and
had no history of respiratory or renal disease; physical examination,
serum creatinine concentration, ECG, echocardiogram, chest x-ray,
and coronary angiography were all normal for this group.
The protocol was approved by the institution Ethics Committee,
and written informed consent was obtained from each subject. The
procedures followed were in accordance with institutional
guidelines.
Pulmonary Function Testing
Measurements of FEV1, vital capacity, and total lung capacity were
made with the Sensor Medics 2200 Pulmonary Function Test
System. DLCO was determined twice, with washout intervals of at
least 4 minutes (the average was taken as the final result), with a
standard single-breath technique.9 Measured diffusing capacity was
corrected for the subject’s hemoglobin (Hb) concentration. The
single breath alveolar volume (VA) was derived by methane dilution.
DM and VC were determined with the same equipment, according to
the classic Roughton and Forster method.9,10 The high oxygen
concentration in the test gas was 89.7%. Studies of reproducibility
showed a high level of agreement between consecutive measurements of 1/DM, with a correlation coefficient of 0.97 and a coefficient
of variation ,5%. To assess any theoretical effects of CO back
pressure, 4 randomly chosen patients with CHF and 5 normal
subjects underwent a control study using the same study protocol but
without invasive procedures and fluid infusions. We have found no
evidence of significant CO back-pressure effects on serial DLCO, DM,
and VC measurements under the present study protocol.
Study Design
All patients were maintained on stable optimal doses of digoxin and
furosemide (dosing was set at 5 PM), and none had overt signs of
fluid retention. After completion of the screening tests, patients and
controls were placed on a constant isocaloric diet that contained
100 mmol/L Na1, 70 mmol/L K1, and 1500 mL of water per day for
the entire study. After 5 days of a controlled diet, the subjects were
admitted for 6 days and 5 nights to the Heart Failure Unit, where
confirmation of sodium balance was achieved, with urinary Na1, K1,
and creatinine monitoring in the first 24 hours. The protocol included
Figure 1. Duration of the study and temporal sequence of solution infusions.
infusions of 0.9% NaCl and 5% D-glucose solutions, both in amounts
of 150 and 750 mL. The duration of the study and the infusion
sequence are depicted in Figure 1. The investigators were blind to the
patient clinical condition and the type of solution to be infused.
Studies were begun at 8 AM after an overnight fast. A triple-lumen,
flow-directed, thermodilution balloon-tipped catheter was inserted
into an antecubital vein and advanced to the pulmonary circulation
under fluoroscopic control with the subject in the recumbent position. Then, the subject’s chest was elevated at 45°, and this
comfortable position was maintained throughout the studies. For
measurement of water and Na1 excretion, urine was collected in the
3 hours that preceded and in the 3 hours that followed fluid infusion.
The infusion was made into the main stem of the pulmonary artery
at a rate of 0.2 mL z kg21 z min21, and the starting solution was
selected randomly. Right atrial and pulmonary wedge pressures were
monitored throughout each study. The catheter was removed in the
48-hour washout interval between one type of solution and the other.
DLCO, DM, and VC were determined hourly in the 2 hours preceding
the infusion, shortly after the infusion, and hourly for the next 3
hours. Ten minutes before and after each infusion, mixed venous
blood was withdrawn for measurements of hematocrit (Htc) and Hb,
plasma protein and aldosterone concentrations, and plasma renin
activity (PRA); cardiac output (average of 2 determinations) and left
ventricular EF were also measured. An aliquot of the blood sample
was rapidly removed for evaluation of Htc. The remainder of the
blood was immediately sent for the other measurements at a central
laboratory.
Laboratory Methods
Left ventricular EF (Simpson’s rule) was assessed at rest by
2-dimensional echocardiography (Hewlett-Packard Sonos 1500).
Standard color Doppler velocimetry was used to measure the degree
of mitral regurgitation, which was graded subjectively on a scale
from 0 (none) to 5 (severe). All Htc measurements were corrected for
trapped plasma volume and for whole-body Htc. PRA and aldosterone plasma concentrations were determined by radioimmunoassay.
Electrolyte levels in urine were measured by ion-selective electrodes.
Statistical Methods
Data are presented as mean61 SD. x2 analysis was applied to
compare the descriptive parameters. Comparisons of the basal data
were performed by unpaired t test or Wilcoxon rank test, as
appropriate. To analyze temporal changes after infusion, 1-way
ANOVA for repeated measurements followed by the post hoc
Newman-Keuls procedure was used. Comparisons of the responses
to the same solution or to different solutions were tested by unpaired
and paired t test. Differences were considered to be significant at
P,0.05.
Results
Demographic characteristics, blood pressure, heart rate, renal
function, and urinary output were similar in patients and
controls (Table 1). FEV1, total lung capacity, forced vital
capacity, DLCO, DM and its ratio to effective VA (DM/VA),
cardiac index (CI), and left ventricular EF were lower and
plasma aldosterone and renin activity were higher in CHF
patients compared with controls; mean right atrial pressure
rap and mean pulmonary wedge pressure wpp, Htc, Hb, and
plasma protein concentration (PPC) were similar in the 2
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Hypertension
December 1999
TABLE 1. Demographic, Clinical, and Laboratory Baseline
Variables in Controls and CHF Patients
Controls
(n513)
Variables
Age, y
45.566.4
Patients
(DCM, n516;
IHD, n510)
48.266.0
Gender, M/F
13/0
26/0
Weight, kg
7465
7664
SBP/DBP, mm Hg
Serum creatinine, mg/dL
12868/7864
12467/8263
1.0060.08
1.0860.08
TABLE 2. Average Percent Changes From Baseline in Cardiac,
Pulmonary, Hematological, and Humoral Variables in CHF
Patients vs Controls Immediately After 150 mL and 750 mL
Saline Infusion
Variables
Controls, D%
Patients, D%
P
3.060.3
NS
23.461.0
NS
150 mL saline
LVEF
1.660.25
CI
1.561.0
VA
DM/VA
20.3060.16
6.061.8
20.1060.08
NS
21062.0*
,0.01
FEV1, L
4.460.8
3.260.7*
Htc
20.560.2
20.960.2
NS
VC, L
5.460.5
3.760.7*
Hb
20.760.3
22.361.0
NS
TLC, L
6.260.6
5.960.7*
PPC
zzz
0.2560.03
70640
DLCO, mL z min21 z mm Hg21
zzz
34.666.6
22.964.1*
DM, mL z min21 z mm Hg21
49.8612.0
31.068.0*
LVEF
1.660.26
6.664.0
NS
VC, mL
145.1645.0
151.2643.0
CI
3.461.9
5.262.0
NS
VA, L
5.9361.1
5.6260.6
VA
0.160.06
20.160.04
NS
DM/VA, mL z min21 z mm Hg21 z L21
8.3962
5.5964*
DM/VA
5.864.0
28.962.0*
,0.01
Digoxin, mg/d
Furosemide, mg/d
21.560.7
1.560.8
NS
Aldosterone
225.866.0†
29.268.0†
NS
PRA
218.768.0†
213.769.0†
NS
750 mL saline
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61610
3364*
Htc
24.562.0†
25.662.0†
NS
36256382
22746405*
Hb
23.761.8†
25.862.5†
NS
rap, mm Hg
1.361.2
1.561.0
PPC
27.563.0†
25.962.8*
NS
WPP, mm Hg
966
1164
Aldosterone
235.368.0*
228.869.0*
NS
Htc, %
39.465.0
40.664.0
PRA
236.768.0*
252.3612.0*
NS
Hb, g/dL
13.561.0
13.660.8
Values are mean61 SD. NS indicates not significant.
*P,0.01 vs baseline; †P,0.05 vs baseline.
LVEF, %
CI, mL z min z m
2
PPC, g/dL
6.661.1
6.760.9
Aldosterone, pg/mL
89.0650.4
235.06147.5*
PRA, ng z mL21 z h21
1.0760.48
5.165.2*
Urinary output, mL/24 h
17506205
15906308
Urinary Na1 excretion, mmol/24 h
MR subjective scale
10264
9866
1.860.2
zzz
Values are mean61 SD. DCM indicates dilated cardiomyopathy; IHD,
ischemic heart disease; SBP and DBP, systolic and diastolic blood pressure,
respectively; VC, vital capacity; TLC, total lung capacity; LVEF, left ventricular
EF; and MR, mitral regurgitation.
*P,0.01 vs controls.
populations (Table 1). There were no significant systematic
differences in the preinfusion data between sessions. In the
patient and control groups, with the initial baseline DLCO, DM,
and VC used as the reference values, hourly collections of data
during 2 hours of resting before each session were averaged
for each subject. Mean changes in DLCO, DM, and VC during
this period of observation were minimal in both populations:
DLCO 2.0560.3%, DM 1.660.1%, and VC 1.860.8% in
patients, and DLCO 1.9860.2%, DM 1.760.3%, and VC
1.460.6% in healthy subjects.
CHF Patients Versus Controls and 150 Versus 750
mL Saline
After the administration of 150 mL of saline in the CHF
group, we recorded a decrease of circulating aldosterone
(29.2%) and PRA (213.7%), without variations in Htc, Hb,
PPC, left ventricular EF, and CI (Table 2). There was also
(Figures 2 and 3) a reduction of DLCO (25%), DM (26.6%),
and DM/VA (210%) and an increase in VC (19%) (Table 2).
These changes were not associated with variations in right
atrial, pulmonary arterial, and wedge capillary pressures and
disappeared within ,1 hour. The humoral response to 750
mL of saline in the CHF group, compared with 150 mL of
saline in the same patients, consisted of a greater inhibition of
aldosterone secretion (228.8%) and PRA (252.3%) and a
reduction in Htc (25.6%), Hb (2 5.8%), and PPC (25.9%),
without variations in left ventricular EF and CI (Table 2). The
infusion of 750 mL of saline produced an 8.3% decrease of
DLCO, 10.3% decrease of DM, 8.9% decrease of DM/VA, and
20% increase of VC (Figures 2 and 3, Table 2). DLCO and DM
were still reduced 1 hour after infusion and reverted to
baseline in the next hour. Notably, 750 mL of saline did not
raise rap and wpp (Figures 2 and 3).
In the healthy group, effects of 150 and 750 mL of saline
were similar to those in CHF patients, as far as aldosterone,
PRA, Htc, Hb, PPC, left ventricular EF, CI, pulmonary
arterial pressure, rap, and wpp are concerned (Figures 2 and
3, Table 2). In spite of this, we did not observe variations in
DLCO, DM, VC, and DM/VA (Figures 2 and 3, Table 2).
Glucose Versus Saline and 150 Versus 750 mL in
CHF Patients
As shown in Table 3, 150 mL of glucose solution was not
effective on Htc, Hb, PPC, aldosterone secretion, PRA, VA,
and left ventricular EF. Variations from baseline in DLCO, DM,
Guazzi et al
Saline Infusion in CHF
1205
TABLE 3. Average Percent Changes From Baseline in Cardiac,
Pulmonary, Hematological, and Humoral Variables in CHF
Patients Immediately After 150 mL Glucose vs 150 mL Saline
Infusion and Immediately After 750 mL Glucose vs 750 mL
Saline Infusion
Variables
Glucose, D%
Saline, D%
P
150 mL
21.560.5
3.060.3
NS
CI
0.8660.4
23.461.0
NS
VA
0.2060.08
20.1060.04
NS
3.863.0
21062.0
,0.01
Htc
1.160.5
20.960.2
,0.05
Hb
1.1560.08
22.361.0
,0.05
PPC
0.8360.08
1.560.8
NS
Aldosterone
0.9760.6
29.268.0*
,0.05
25.062.0
213.769.0*
,0.05
LVEF
DM/VA
PRA
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750 mL
LVEF
6.662.0
6.664.0
NS
CI
1.7861.5
5.262.0
NS
VA
20.8860.6
20.160.04
NS
4.262.0
28.962.0*
,0.01
Htc
23.4362.0
25.662.0†
,0.05
Hb
22.962.0
25.862.5†
,0.05
PPC
21.9561.70
25.962.8*
NS
Aldosterone
239.7615.0*
228.869.0*
NS
PRA
241.1610.0*
252.3612.0*
NS
DM/VA
Figure 2. DLCO, DM, VC, wpp, and rap in CHF patients (F) and
controls (E) before and after 150 mL and 750 mL saline infusion. *P,0.01 vs controls. DP,0.01 vs baseline.
and DM/VA were not significant, but the differences from
both the corresponding absolute values and the percent
changes with a similar amount of saline were significant
(Figures 4 and 5). Glucose caused a 13.3% reduction of VC,
which was significant compared with the 9% increase with
saline. rap and wpp did not vary.
Glucose and saline infusions of 750 mL similarly inhibited
aldosterone secretion and PRA; Htc and Hb concentrations
were reduced less by glucose, and left ventricular EF, CI, and
Values are mean61 SD.
*P,0.01 vs baseline; †P,0.05 vs baseline.
VA were not affected (Table 3). As depicted in Figures 4 and
5, DLCO showed a 4.4% increase that was significant compared with the 8.3% decrease with the same amount of saline.
Variations of DM (10.6%), DM/VA (4.2%), and VC (29%)
with glucose were also the opposite of those elicited by saline
(DM 210.3%, DM/VA 28.9%, and VC 20%); differences were
highly significant. As shown in Figure 4, DM values with one
solution were still significantly different from those with the
other solution 1 hour after infusion. Right and left ventricular
filling pressures did not vary after 750 mL of glucose.
Urinary output in the 3 hours after, compared with that in the
3 hours before, 150 mL of saline administration was similar
in patients and controls. With the 750 mL infusions, output
was raised by 64610% with glucose and by 5868% with
saline in patients and by 68%612% with saline in controls.
Differences between patients and controls and between saline
and glucose were not significant.
Discussion
Figure 3. Respiratory and hemodynamic average percent variations in CHF patients and controls from before to immediately
after 150 mL and 750 mL saline infusions. *P,0.01 vs before
infusion. DP,0.01 vs the corresponding value in controls.
Several human and animal studies11–14 have investigated the
transition of pulmonary edema or cardiovascular adaptations
during fluid or salt loading. In these studies, liquid volumes
were large enough to induce obvious hemodynamic variations. Because we aimed at avoiding these effects, we chose
to infuse a volume of saline (150 mL) similar to the accepted
value for pulmonary capillary blood volume in normal
humans and a 5-fold greater amount.
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Figure 4. DLCO, DM, VC, wpp, and rap in CHF patients. F indicates saline infusion; and M, glucose infusion. DP,0.01 vs
baseline. #P,0.05 vs corresponding value with saline.
Saline, DLCO, and Its Subdivisions
Conditions causing an increase in circulating blood volume or
movement of blood from the periphery to the thorax, as
during head-down tilting15 and water immersion,16 are associated with an acute increase in VC, DM, and DLCO. During
sustained microgravity, DM may increase even in excess of
the rise in VC17 because of capillary recruitment and uniform
capillary filling. DM in these situations is primarily determined by the surface area available for gas exchange.
Figure 5. Comparative immediate percent changes with glucose vs saline (150 mL and 750 mL infusions) in CHF patients.
*P,0.01 vs before infusion. DP,0.01 vs corresponding value
with saline.
In the present study, saline was not effective in normal
subjects, whereas in patients it reduced DLCO, DM, and DM/VA
and increased the VC. These changes disappeared in ,1 hour
and were relatively greater with the larger volume of saline.
Of surprise to us was the observation that VC was augmented
with the infusion of 150 mL of saline. Because the lung is the
only organ to receive the entire cardiac output, the hemodynamic effect of a fluid load is most pronounced in the
pulmonary circulation12 and this may explain why small
amounts of saline were effective in increasing VC. This,
however, does not seem to apply to normal individuals.
An acute decrease in DM with an increase in VC implies that
the thickness of the alveolar capillary membrane be acutely
augmented, thus impeding the passage of the respiratory
gases. Accordingly, a simple interpretation may be that saline
in CHF patients causes subclinical interstitial pulmonary
edema, which results in the reduction of DM. It is remarkable
that there were no changes in pulmonary hydrostatic forces,
left ventricular EF, and right atrial pressure. During large
volume loading, central venous pressure is generally raised
(Gabel et al13 have used 1500 mL of Ringer’s solution to
impede lymphatic drainage in the dog), opposes lung lymph
flow, and leads to excess of fluid in the lung. These
considerations do not support the interpretation that in our
patients changes in hydrostatic forces were the main reason
for an excess of interstitial fluid and an impedance of gas
transfer and suggest that CHF may be associated with an
upregulation of sodium transport from blood to interstitium
with interstitial edema (or perhaps swelling of the endothelium or epithelium), which reduces DM. The relatively slow
response of the lymphatic system in the interstitium to a rapid
increase in the net fluid filtration rate12 may facilitate accumulation of extravascular fluid in the lung and depression of
DM. The relation linking interstitial fluid volume (or membrane thickness) and DM in CHF is unknown.
Our hypothesis of an upregulation in sodium handling by
the endothelium disagrees with previous data in the literature.
Townsley et al3 have suggested that alveolar-capillary barrier
remodeling in a canine model of pacing-induced heart failure
constitutes a beneficial adaptation to the pulmonary venous
hyperperfusion that accompanies heart failure. Kaplan et al18
documented a normal transcapillary escape rate of transferrin
in patients with decompensated heart failure. Davies et al19
have shown a reduced transferrin escape. However, it is
unclear whether the mechanisms for transferrin and sodium
transport are the same, ACE inhibitors had a role8 in the
findings of Davies et al, and pacing-induced heart failure in
dogs duplicates CHF in humans.
The reasons for an upregulated pulmonary microvascular
salt transport are unclear. The simplest explanation would be
that of remodeling of the alveolar-capillary membranes,
which occurs in CHF.3,6 Note that epidermal growth factor
upregulates alveolar epithelial sodium transport,1 tumor necrosis factor-a mediates an upregulation of sodium and fluid
transfer in a rat model,20 and cardiac glycosides are potent
inhibitors of alveolar fluid clearance.21
Glucose, DLCO, and Its Subdivisions
Glucose in CHF patients elicited pulmonary changes that
were the opposite of those elicited by saline, ie, reduction in
Guazzi et al
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VC and increase in DM, with a tendency of DLCO to augment.
The inhibition of renin and aldosterone secretion and the
slight reduction of Htc, Hb, and PPC with glucose do not
support the interpretation that VC reduction was due to
systemic water displacement from the intravascular to the
extravascular phase and decline of circulating blood volume.
Although not proven, the explanation of a redistribution of
blood from the central compartment to the periphery seems
more likely. Despite the diminished surface area for gas
exchange, DM rose significantly with D-glucose infusion.
Redistribution of blood from the lungs may have reduced
pulmonary hyperemia and interstitial fluid, thus making the
alveolar-capillary membrane thinner and more conductive.
This interpretation implies that improvement in the membrane conductance was such as to fully compensate (DLCO
tended to be raised) for the reduced volume of blood available
for gas exchange. Another hypothesis may be that in heart
failure the alveolar side of the diffusing membrane is involved in the disturbances in sodium handling and that, with
the infusion of glucose, sodium was taken up from the
alveolar lumen through a sodium-glucose cotransport
system.22–24
In conclusion, although part of the proposed effects are
speculation, results show that (1) saline, even in small
amounts, reduces alveolar-capillary membrane diffusing capacity in CHF; (2) healthy subjects do not possess such a
liability; and (3) glucose improves gas diffusion across the
alveolar-capillary membrane in patients with CHF.
Clinical Perspectives
Because DM significantly correlates with the functional status
of CHF patients,25 prospective studies are required to assess
whether the opposite influence of salt and glucose on the
alveolar-capillary membrane function may be of any clinical
relevance and produce any effect on exercise performance in
cardiac failure.
Acknowledgments
This study was supported in part by a grant from the National
Research Council and the Monzino Foundation, Milan, Italy.
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Impeded Alveolar-Capillary Gas Transfer With Saline Infusion in Heart Failure
Marco Guazzi, Piergiuseppe Agostoni, Maurizio Bussotti and Maurizio D. Guazzi
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Hypertension. 1999;34:1202-1207
doi: 10.1161/01.HYP.34.6.1202
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