importance of abnormal lung perfusion in excessive exercise ventilation in chronic heart failure

Wada et al. March 1993

American Hearl Journal

improve exercise tolerance in patients with mitral stenosis in sinus rhythm. Br Heart J 1987;58:254-8.

9. Hurst JW. The heart. New York: McGraw-Hill, Inc., 1986761,

5. Meister SG, Engel TR, Feitosa GS, Helfant RH, Frank1 WS. 10. Grossman W. Cardiac catheterization and angiography. Phii-

adelphia: Lea & Febiger, 1986:139. Propranofol in mitral stenosis during sinus rhythm. Ah1 HEART J 1977;94:685-8.

6. Barlow JB. Perspective on the mitral valve. Philadelphia: FA Davis Company, 1987:178-g.

7. Klein HO, Sareli P, Schamroth CL, Carim Y, Epstein M, Marcus B. Effects of atenolol on exercise capacity in patients with mitral stenosis with sinus rhythm. Am J Cardiol 1985;56:598-601.

11. Wisenbaugh T, Berk M, Essop R. Middlemost S, Sareli P. Et’- feet of mitral regurgitation and volume loading on pressure half-time before and after balloon valvotomy in mitral stenosis. Am J Cardiol 1991;67:162-8.

12. Dalen JE. Mitral stenosis. In: Dalen JE, Alpert .JS, eds. Val- vular heart disease. Boston: Little, Brown and Company. 1981:49.

8. Braunwald E. Heart disease. A textbook of cardiovascular medicine. Philadelphia: WB Saunders, 1988:1031.

Importance of abnormal lung perfusion in excessive exercise ventilation in chronic heart failure

Whether excessive ventilatory response to exercise is related to the maldistribution of pulmonary blood flow was examined in 23 patients with chronic heart failure and nine age-matched normal subjects. With the use of technetium 99m macroaggregated albumin, the resting distribution of pulmonary blood flow was assessed by the scintigraphic counts ratio of upper to lower lung fields. The ventilatory response to exercise was assessed by the slope of the relationship between minute ventilation and carbon dioxide production during exercise. Eight patients (group A) had slope less than 33, the upper limit of the normal range, and 15 patients had slope of 33 or greater (group B). In group B pulmonary blood flow was distributed more to the upper lung, which made the counts ratio (60%) higher than in normal subjects (34%) or in patients in group A (36%). There was no significant difference in pulmonary flow distribution between normal subjects and patients in group A. In group B tidal volume did not increase during exercise as much as it did in normal subjects and in patients in group A; therefore, the respiratory pattern was rapid and shallow. Although the ratio of physiologic dead space to tidal volume fell by 20% during exercise in normal subjects and by 23% in patients in group A, it failed to decrease in patients in group B (-I%), which indicates a relative increase in dead space respiration during exercise. These data indicate that decreased lung compliance and regional ventilation-perfusion mismatch caused by pulmonary vascular and parenchymal abnormalities would play an important role in the excessive exercise ventilation in chronic heart failure. (AM HEART J 1992;125:790.)

Osamu Wada, MD, Hidetsugu Asanoi, MD, Kyoko Miyagi, MD, Shinji Ishizaka, MD,

Tomoki Kameyama, MD, Hikaru Seto, MD, and Shigetake Sasayama, MD Toyama, Japan

Shortness of breath is a major symptom of congestive heart failure.’ In patients with acute heart failure,

From the Second Department of Internal Medicine and Radiology Depart- ment, Toyama Medical and Pharmaceutical University, Toyama, Japan.

Received for publication June 22, 1992; accepted Sept. 1, 1992.

Reprint requests: Hidetsugu Asanoi, MD, The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University. 2630 Sugitani. Toyama, 930-01 Japan.

Copyright ” 1993 by Mosby-Year Book, Inc. 0002~8703/93/$1.00 + .lO 4/l/43372

790

this is closely related to the magnitude of pulmonary congestion. i, 2 However, in optimally treated patients with chronic heart failure, mechanisms other than increased pulmonary capillary wedge pressure ap- pear to be more important.3-5 Recent clinical studies have demonstrated consistently that the increase in ventilation during exercise is greater in patients with heart failure than in normal subjects and have sug- gested that this abnormal ventilatory pattern con- tributes in part to the sensation of dyspnea in

patients with heart failure.“) 6 Early onset of anaero-

Volume 125, Number 3

American Heart Journal

Table I. Patient characteristics

Patient Age NO. (yr) Gender Disease

NYHA ClUSS Symp

Wada et al. 791

i/E- !%‘02 slope

Control group 1 59 2 57 3 57 4 57 5 72 6 59 7 50 8 47 9 50

Mean f SD 56 f 7 Group A fnormal ventilation) 10 46 11 67 12 61 13 45 14 48 15 65 16 66 17 64

Mean k SD 58 k 9 Group B (excessive ventilation) 18 68 19 65 20 50 21 65 22 42 23 41 24 66 25 58 26 67 27 65 28 46 29 67 30 53 31 76 32 69

Mean k SD 60 + 11

M Normal LEG F Normal SOB M Normal LEG M Normal SOB M Normal LEG M Normal LEG F Normal LEG M Normal LEG M Normal LEG

F MS,AR F AS M OMI M OMI M OMI M DCM M DCM M DCM

F MR M MS,TR F MS M MS,TR F MS F MS F MS M OMI M OMI M DCM M DCM M DCM M DCM M DCM F HHD

II II II I I II II

III

II III II II II

II

I III

II II

SOB LEG LEG LEG LEG SOB LEG LEG

SOB LEG LEG SOB SOB SOB LEG LEG LEG LEG LEG LEG LEG LEG SOB

26 29 30 30 31 31 27 27 24

28 k 2

32 31 31 30 32 31 32 31

31 -+ 1

44 38 40 45 44 43 34 47 38 37 33 43 35 37 39

40 t 4

\iE-iioz slope is calculated from the linear regression analysis of the relationship between minute ventilation and carbon dioxide production during exercise. AR. Aortic regurgitation; AS, aortic stenosis; DCM, dilated cardiomyopathy; HHD, hypertensive heart disease; LEG, leg fatigue; MS, mitral stenosis; NYHA, New York Heart Association; OM, old myocardial infarction; Symp, symptoms at peak exercise; SOB, shortness of breath; 7X, tricuspid regurgitation.

bit metabolism and lactic acidosis would accelerate the ventilatory response to exercise.7 However, the excessive exercise ventilation occurs at work rates lower than those in which respiration begins to com- pensate for exercise-induced lactic acidosis.4* 7,8 Re- cently, an abnormal increase in physiologic dead space has been proposed to be the primary mechanism responsible for exercise hyperpnea in patients with heart failure.3s 9 Intrapulmonary changes such as pulmonary parenchymal abnormalitieslo, l1 or dy- namic ventilation-perfusion mismatchl’-l5 are po- tential causes of increased physiologic dead space. However, there is no evidence that links excessive exercise ventilation directly to intrapulmonary flow

distribution or structural changes in chronic heart failure. The present study was undertaken to deter- mine whether excessive exercise ventilation is related to the maldistribution of pulmonary blood flow in patients with chronic heart failure. For this purpose, we assessed resting pulmonary flow distribution by lung perfusion scintigraphy and examined exercise ventilatory responses during incremental ergometer tests.

METHODS Study patients. Twenty-three patients with cardiac dis-

ease (15 men and 8 women) and nine age-matched normal subjects were studied (Table I). The causes of cardiac dis-

792 Wada et al March 1993


75-

-I 500 1000 1500 2000

Gco2 (ml/mini

Fig. 1. Relationship between minute ventilation (irE) and carbon dioxide production fi/COs,J in a normal subject and in patients with chronic heart failure (group A and group B). Group A = patients with normal exercise ventilation (VE-Vco? slope <33); group B = patients with excessive exercise ventilation (VE-VCOz slope 233).

ease were dilated cardiomyopathy in eight patients, valvular heart disease in nine, old myocardial infarction in five, and hypertensive heart disease in one patient. The functional status of the patients was New York Heart Associ- ation functional class I in 8 patients, class II in 12, and class III in 3. Eight patients had chronic atria1 fibrillation, and the others were in sinus rhythm. Patients with anemia, primary lung disease, or angina pectoris were excluded from this study. Diuretics had been administered to 14 patients, and isosorbide dinitrate had been given to 10 patients. These medications were withheld for 48 hours while the patients were observed closely. Every subject terminated progressive exercise because of leg fatigue or dyspnea. All patients gave informed consent for their par- ticipation in the study as approved by our institutional committee on human research.

Exercise testing and expired gas analysis. Each subject was evaluated at least 2 hours after a meal. Patients were asked to perform progressive maximal symptom-limited exertion while seated upright on an electronically braked cycle ergometer (Corival-400, Lode B.V., The Netherlands). Initially, subjects performed unloaded cy- cling for 3 minutes. Then the work rate was increased pro- gressively by 3 to 15 W every minute. The work rate incre- ment was individualized on the basis of the subject’s exercise capacity. The heart rate was monitored together with the blood pressure, which was measured by the cuff method at l-minute intervals throughout the test. Oxygen uptake (~oz), carbon dioxide production (~coz), ventilatory volume (VE), tidal volume, respiratory rate, and mixed expired carbon dioxide concentration were continuously measured on a breath-by-breath basis with a Minato AE- 280 metabolic measurement cart (Minato Medical Science Co. Ltd., Osaka, Japan) equipped with an oxygen and car-

bon dioxide analyzer. Respiratory flow was measured by the thermal dissipation technique. Exercise capacity was evaluated from peak oxygen uptake (peak iroz). In all patients and in six of nine normal subjects, arterial blood was drawn from a radial artery through a 19-gauge cannula at rest, at submaximal exercise (70% to 75% of peak %‘o,), and at peak exercise.

In the present study the exercise ventilatory response was assessed by relating the VE to the corresponding 9~02 below the level of respiratory compensation required for metabolic acidosis. In all subjects the VE and the 9~02 cor- related in a highly linear fashion 0. > 0.96). Accordingly, we used the slope of the 7j,-7jcOa relationship as an index of ventilatory drive during exercise. In our laboratory the slope of this relationship ranged from 24 to 32 (24 rfr 4) and was independent of age or gender. Therefore patients with a ~E-~COZ slope of 33 or greater are considered to have excessive exercise ventilation. Subjects were divided into three groups. The control group consisted of nine normal subjects (VE-VCOs slope: 28 k 2). Group A consisted of eight patients (VE-VCOz slope: 31 + 1) who had a normal ventilatory response to exercise. Group B consisted of I5 patients (VE-VCOs slope: 40 ? 4) who had excessive exercise ventilation. There was no significant difference in age among these three groups, Fig. 1 shows the relationship between the VE and \icoz for three patients in each group. The ratio between physiologic dead space and tidal volume (VD/VT) was calculated at rest and during exercise such that VD/VT = (PacOs - PEcoz)/PacOs - VDMIVT, where PECO~ is the mixed expired carbon dioxide tension, VDM is mechanical dead space, and PacOs is the arterial carbon dioxide tension. Changes in VDIVT that occurred during exercise are expressed as percent resting VDIVT.

Pulmonary perfusion scintigraphy. Before injecting

Volume 125, Number 3 American Heati Journal Wada et al. 793

U/L (%I = counts of ROI (U)

counts of RO I (L! x 100

Fig. 2. Estimation of the resting distribution of pulmonary blood flow. The distribution of pulmonary blood flow is assessed by the counts ratio of the upper fUj to lower (L) lung fields after the injection of ggmT~ macroaggregated albumin while subjects are in the upright position (left). The apical lung profile is con- firmed by the image when the radioisotope is again injected while the subjects are in the supine position (right). ROI, Region of interest.

technetium 99m macroaggregated albumin, a cobalt-51 source was taped over the C7 vertebral body on the back of the patient. Resting perfusion images were then acquired at 140 KeV 2 minutes after 5 mCi of ggmT~ microaggregates of albumin was injected while the patient was sitting with his or her back placed securely against an Anger Camera (Toshiba Corp., Tokyo, Japan) (large field of view; image 1). After image acquisition, an additional 5 mCi of ggmT~ microaggregated albumin was again injected while the patient was supine to assure that the apex of the lung could be labeled, and then data was acquired again (image 2).

Data analysis. All information for the Anger camera was digitized in a 64 X 64 matrix format with a Digital Equip- ment Corporation computer system (Digital Equipment Corp., Maynard, Mass.). The right lung field in image 2 was divided into two equal sections on the basis of the base-to- apex length on the computer image. Specified regions of interest were positioned over the perfusion image of the right lung while the patient was in the sitting position (image 1) and referenced to the 51Co source. The ratio of upper to lower counts for the right lung (U/L) was calculated to assess the distribution of lung perfusion (Fig. 2).

Statistical analysis. Values are expressed as mean * SD, unless otherwise indicated. The statistical significance of any differences was tested by analysis of variance. Multiple comparisons were made with Ryan’s method only when the F test was significant. Values of p < 0.05 were considered to be statistically significant.

RESULTS Exercise capacity and ventilatory response. Individ-

ual patient data are listed in Table II. Peak Tir02 was comparably reduced in groups A and B when compared with that in normal subjects. Resting respiratory rate and tidal volume were similar among the three groups. At submaximal exercise the tidal vol-

ume was less in group B than in normal subjects, whereas there was no significant difference between patients in group A and normal subjects. At peak exercise the tidal volume in group B remained lower than that in normal subjects. Fig. 3 represents the relationship between tidal volume and respiratory rate during exercise, This relationship in group A approximated that in normal subjects. In group B, however, this relationship shifted downward compared with those in group A and normal subjects, which reflects rapid and shallow respiration during exercise.

The resting VD/VT was similar among the three groups. In group B, however, the VDIVT failed to decrease at both submaximal and peak exercise, whereas it fell normally in group A. Fig. 4 shows the relationship between physiologic dead space and tidal volume. In group B this relationship shifted to the left and had a steeper slope than in group A or in normal subjects, which indicates a relative increase in dead space respiration. Since seven patients in group B and two patients in group A had valvular heart disease, we excluded these patients and examined again their ventilatory response to exercise (Table II). Similarly, the patients in group B exhibited a rapid and shallow respiratory pattern and a relative increase in dead space respiration during exercise.

Distribution of lung perfusion at rest. Lung perfusion images of representative cases from each group are shown in Fig. 5, and individual data are listed in Ta- ble II. In group B pulmonary blood flow was distributed more to the upper lung, which made the U/L higher than in normal subjects or patients in group A. There was no significant difference in pulmonary

794 Wada et al. March 1993

Amencan Heart Journal

Table II. Gas exchange and lung perfusion parameters

Putient Peak i/02

,VCJ. Cm Urnin)

RR (breaths/mini L’?’ irrll)

Rest .%kbmax Peak Rest S’ubmas Prak

Control group 1 2 3 4 5 6 7

8

9

Mean + SD

Group A 10 11

1’

13

14

15

16

17

Mean t SD

Group B 18 19

20

21

22

23

24

25

26

27

28

29

30

31

32

Mean rt SD

1429 18 2 1 33 470 118” 1474 1473 17 25 30 650 1416 1713

1730 19 28 35 594 134 1 1950 1613 16 23 36 705 7 707 193%

1129 19 27 32 637 11:1,5 1441

1389 17 “5 29 666 1:3:15 1680

1226 17 “5 32 510 77” 970

2314 19 26 37 592 1716 ‘257

1572 15 26 29 !i1; 1359 1669

1542 +- 325 17 + 1 “5 i 2 33 f 3 593 t 75 1:i29 ” 273 16i6 i 445

943 17 29 35 6.56 1017 1288

855 16 22 97 MO 1044 1428

776 16 19 22 ti44 933 1175

1152 22 “7 33 509 1147 1352

1498 17 28 32 827 1:335 1671

950 18 21 28 565 12.53 1504

789 16 “2 27 552 1121 1397

1016 ‘1 “4 “6 -189 1178 1635

997 t- 222* 18 rt_ 2 24 _t ?I 29 + 4 598 t_ 103 1129 :. 1’2 1431 f 157

(1030 ?I 246) (18 -t 2) (24 t 3) (28 i 4) (598 t 114) (1161 i 124) (1456 i 1701

780 23 24 26 516 1080 1209

947 16 23 29 652 937 1164

580 18 27 28 463 644 840

746 13 31 39 645 942 1090

687 21 27 28 421 832 1008

797 17 34 40 411 657 952

591 14 22 36 624 771 916

1028 22 32 38 4’2’2 1018 1380

972 18 22 42 711 1334 1799

1200 23 30 41 503 1025 1556

1099 16 25 37 718 1084 1562

699 20 26 30 487 846 1011

1467 21 36 54 6”l 1276 1686

532 20 23 24 509 867 1029

711 22 33 40 500 779 813

856 2 252* 19 * 3 28 k 5 35 k 8 547 i 102 939 i- 195* 1201 5 :308*

(964 r 285)* (20 + 2)t (28 2 5) (38 i 8,j (559 i 103) (1029 i_ 187)t (1355 t_ 13371

Numbers in parentheses represent data for patients without valvular heart disease; VD/VT is expressed as percent change of the resting values; VD-VT

represents the relationship between VD and VT during exercise. Peak, Peak exercise; RR, respiratory rate; Submax. 70”~ to 75 (‘( of peak exercise; C ‘IL, counts ratio of upper to lower lung fields; iio?, oxygen uptake; VT,

tidal volume; VI), physiologic dead space.

*p < 0.01 versus control group. tp < 0.05 versus control group. $p < 0.01 versus group A. &I < 0.05 versus group A.

flow distribution between patients in group A and DISCUSSION

normal subjects. In patients who did not have valvu- In the present study we assessed the ventilatory lar heart disease, the U/L was also increased in group response to exercise in patients with chronic heart B compared with those in normal subjects and in failure in terms of the slope of the iTE-gC!Or relation- group A. ship and regarded a slope greater than 33 as indicat -

Volume 125, Number 3

American &?a!7 Journal Wada et al. 795

Rest

VD (ml)

Submax Peak

Change in VDIVT (“r)

Submax Peak Slope of VD- VT

-

210 391 525 -18 -24

- 0.23

205 337 386 -8 -17 0.23 213 376 444 -12 -18 0.23 164 207 271 -17 -13 0.23 172 309 465 -38 -29 0.18 155 340 417 -17 -17 0.23

187 + 23 327 f 60 418 t 78 -18 k 9 -20 f 5 0.22 * 0.02

28 42 29 35 33 49 42 17 32

34 * 9

246 296 357 -22 -26 0.18 44 217 388 430 -7 -25 0.24 32 156 221 251 -2 -12 0.18 35 141 249 286 -22 -23 0.17 45 273 307 368 -30 -33 0.11 39 160 320 340 -10 -20 0.19 47 189 304 365 -21 -24 0.21 29 159 415 424 8 -20 0.23 33

193 + 45 313 + 60 353 t 57 -13 -i- 12 -23 k 6 0.19 + 0.04 38 + 6

(180 + 44) (303 T 61) (339 + 57) (-13 * 13)

4 -4 -5 30

0 7

-15 0

-7 0

-1 7

-24 2

-4 -1 f 11*g

(-3 t 9)

(-22 f 6) (0.18 + 0.04) (38 f 6)

145 314 326 240 331 440 161 212 225 194 367 403 115 226 266 142 243 310 254 267 286 118 286 375 175 307 602 157 320 498 220 327 480 144 267 294 208 325 499 156 271 315 111 166 174

169 k 43 282 k 52 366 + 114

-4 0.26 77 3 0.39 12

-23 0.17 41 23 0.47 97 -3 0.26 95 -6 0.31 75

-23 0.11 44 -3 0.27 54 36 0.39 39

3 0.32 39 0 0.31 67

-2 0.29 61 -12 0.27 40

0 0.31 50 -4 0.20 51

-1 + 14*t 0.29 i 0.09$ 60 t 19*$

(161 z!z 36) (284 + 50) (405 f 131) (2 zlz 13)“i (0.30 * 0.05)?$ (50 t lo)*3

ing excessive ventilation. Patients with a steeper slope (group B) exhibited a rapid and shallow respiration during exercise and a cephalad distribution of pulmonary blood flow. In these patients physiologic dead space against a tidal volume was relatively increased as exercise became strenuous. These findings indicate that the excessive ventilation that is seen during exercise in patients with chronic heart failure is closely related to the maldistribution of pulmonary blood flow.

Mechanisms for excessive ventilation during exercise. According to the alveolar gas formula, there are two proximate causes of excessive exercise ventila-

U/L (Oi ) Rest

tion.16 The ventilatory equivalent of 9~02 (irE/irCOz)

is regulated by the VDNT ratio and the Paces regu- latory set-point. Rubin et a1.g were the first to dem- onstrate that an increased minute ventilation was closely related to increase in physiologic dead space in patients with chronic heart failure. Recently, Sul- livan et a1.3 also observed that the elevation of physiologic dead space during exercise was responsible for an increase in the vE/vjcO~ in patients with chronic heart failure. By analyzing the hemodynamic deter- minants of the enhanced ventilatory response in these patients, they found that maximum cardiac output was inversely related to vE/vCO2, although



2000-

E = looo- ,o

- Normal

Group A

b-4 Group B

0 1 1 1 10 20 30 40

Respiratory rate ( /min)

Fig. 3. Relationship between tidal volume and respiratory rate at rest, submaximal exercise, and peak exercise in normal subjects and in patients with chronic heart failure (group A and group B). In group B this relationship is shifted downward, indicating rapid and shallow respiration during exercise. Data are expressed as mean values t SEM. Group A = patients with normal exercise ventilation; group B = patients with excessive exercise ventilation.

l-

l-

I-

I-

1

- Normal

3---o Group A

6.4 Group9

500 1000 1500

Tbdal volume (ml)

2000

Fig. 4. Relationship between physiologic dead space and tidal volume at rest, submaximal exercise, and peak exercise in normal subjects and in patients with chronic heart failure (group A and group B). The slope of this relationship is steeper in group B than in the group of normal subjects or in group A. Data are expressed as mean values f SEM. Group A = patients with normal exercise ventilation; group B = patients with excessive exercise ventilation.

only a modest correlation was demonstrated. There i7EfiCO2 and pulmonary capillary wedge pressure. was also a very weak relationship between maximum Additionally, they found that after administration of exercise ~E~COz and pulmonary capillary wedge dobutamine or prazosin, the ~E-~Coz slope does not pressure or pulmonary artery pressure.3 Fink et a1.4 change despite an increase in cardiac output. This also showed no relationship between exercise indicates that pulmonary structural abnormalities,

Voiume 125, Number 3 American Heart Journal Wada et al. 797

Fig. 5. Pulmonary perfusion scintigrams representative of three groups (left: normal subject, case 5; mid- dle: group A, case 15; right: group B, case 21). The pulmonary blood flow is distributed more to the upper lung in group B, whereas it is distributed normally in group A. Group A = patients with normal exercise ventilation; group B = patients with excessive exercise ventilation. U/L, The ratio of upper to lower counts for the right lung.

rather than hemodynamic alterations would be responsible for the excessive ventilation during exercise.4 However, there is no evidence that links intrapulmonary flow distribution or structural changes directly to increased physiologic dead space or 7jE-iiC02 slope in patients with chronic heart failure.

Generally, physiologic dead space increases in normal subjects as exercise becomes strenuous, pre- sumably because of an increase in end-inspiratory lung volume during exercise.17 Patients with maldistribution of pulmonary blood flow at rest exhibited greater physiologic dead space during exercise than that in normal subjects for a comparable tidal volume. Mitral stenosis and severe left ventricular failure often reduce blood flow in the lower zone of the lung so much that the normal flow distribution is inverted.15> 18, lg This reduction in blood flow, which is seen in the lower zones, implies that pulmonary vascular resistance is increased in these areas.r5s lg West et a1.20 demonstrated that increased interstitial perivascular pressure and thickening of the vascular wall, caused by a long-standing increase in pulmonary venous pressure, are important causes of up- ward shift of pulmonary blood flow in these patients. Even under these circumstances, it has been shown that ventilation, as assessed with radioactive xenon, was distributed normally in the lower zones of the lung.lgs 21 These observations suggest that the ventilation/perfusion ratio was decreased in the lung apex and increased in the base in patients with inverted pulmonary flow distribution. Since the lung volume of the base is essentially greater than that of the apex, regional ventilation-perfusion mismatch in the lower lung would predominate over that in the apex and

result in the increase in physiologic dead space in these patients.

Patients with excessive exercise ventilation are unable to increase their tidal volume adequately during exercise. A pattern of rapid and shallow breathing can result from anxiety, even in normal subjects, or from decreased lung compliance, which occurs as a consequence of air in the lung being replaced with blood, interstitial fluid, or both. Both the rapid and shallow respiration and the hypoper- fusion of the lower lung suggest that pulmonary vascular and parenchymal abnormalities and a conse- quent reduction in lung compliance exist. A restric- tive ventilatory defect has been reported, by several investigators, to exist in patients with heart failure. 7, 22 By measuring intraesophageal pressure, Christie and Meakins23 demonstrated that a larger intrapleural pressure was generated to produce a given tidal volume in patients with symptomatic heart failure. A marked increase in lung stiffness is also noted in patients with mitral stenosis.12 These abnormal respirations, which are seen in patients with less compliant lungs, seem to be a compensatory mechanism that minimizes the work of respiratory muscle.24 However, rapid and shallow respiration causes a relative increase in anatomic dead space for tidal volume.7 The increase in anatomic dead space during exercise has recently been documented in patients with chronic heart failure.25 Therefore changes in breathing pattern that were observed in our patients could also be in part related to excessive ventilation during exercise.l

Limitations. First, the anatomic boundary of the lungs was determined from lung perfusion scintigra-



phy with

tilatory response in the remaining patients (Table

ggmT~ macroaggregated albumin. This

II). Excessive exercise ventilation in these patients

method may underestimate any evaluation of the upper lung fields because the apices contain less

was still closely related to the maldistribution of pul-

blood than the bases. This discrepancy is more pro- nounced when the radioisotope is injected with the patient in the sitting position. In the present study we referenced the apical lung profile to the cobalt 51 source placed over the C-7 vertebral body and to an- other image obtained when the radioisotope was injected with the patient in the supine position. These precautions would minimize the error in determining the region of interest in the upper lung. Second, het- erogeneity of the causes of chronic heart failure (my - opathic heart disease, hypertensive heart disease, and valvular heart disease) may also influence the results of this study. We therefore excluded patients with valvular heart disease and again examined the pulmonary blood flow distribution and exercise ven-

-I. Fink LI, Wilson JR, Ferraro h. Exercise ventilation culti pu!-

monary artery wedge pressure in chronic stable c.onge<ti\.c- heart failure. Am d Cardiol 1986;57:249-59.

5. Franciosa JA, Leddy CL, Wilen M, Schwartz DE. Helution between hemodynamic and ventilatory responses in determining exercise capacity in severe congestive heart failure. Am J Cardiol 1984;53:127-34.

6. Killian Kd, Campbell .JM. Dyspnea and exercise. .4nnu Rr\ Physiol 1983;45:465-79.

7. Weber KT, Kinasewititz CT, danicki JS, Fishman AI’. Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure. Circulation 1982;65:1213-23.

8. Wilson JR. Ferraro N. Exercise intolerance in patients with chronir left heart failure: relation to oxygen transport and ventilatory abnormalities. Am .J Cardiol 1983;51:1358-63.

9. Rubin SA. Brown HV \:entilation and gas exchange during exercise in severe chronic heart failure. Am Rev Respir Dis 1984;129(suppl):S63-S64.

12. Olsen EG.1. I’erivascular fibrosis in lungs in mitral valve disease. Br .I Dis Chest 1966;60:129-36.

18. Raine .J. Bishop .JM. The distribution of alveolar ventilation in mitral stenosis at rest and after exercise. Clin Sci 1963:

10. Ingram RH, McFadden ER. Respiratory changes during exercise in patients with pulmonary venous hypertension. Prog Cardiovasc Dis 1976;19:109-15.

11. Palmer WH. Gree JB, Bates DV. Disturbances in pulmonary function in mitral valve disease. Can Med Assoc J 1963;89:744- 50.

monary blood-flow, as in all patients that were studied. Finally, we assessed pulmonary perfusion at rest but not during exercise. In this regard, Mohsenifar et al.“’ found that there was no significant difference in regional distribution of pulmonary perfusion between periods of rest and periods of exercise. There- fore resting distribution of pulmonary blood flow could be reasonably substituted for the exercise flow distribution.

Conclusions. Excessive ventilation during exercise in patients with chronic heart failure was closely related to the maldistribution of pulmonary blood flow and was caused by a limited increase in tidal volume and by a relative increase in physiologic dead space during exercise. These data indicate that in patients with chronic heart failure, pulmonary vascular and parenchymal abnormalities would make the lungs less compliant and cause regional ventilation-perfusion mismatch, which would result in excessive ventilation during exercise.

%4:63-8. 14. Tatterfield AE. McNicol MW, Sillett RW. Relationship be-

tween hemodynamic and respiratory function in patients with myocardial infarction and left ventricular failure. Clin Sci 1972;42:751-68.

15. Dawson A, Rocamora JM. Morgan JR. Regional lung function in chronic pulmonary congestion with and without mitral stenosis. .4m Rev Respir Dis 1976;113:51-9.

16. Whipp BJ. Ventilatory control during exercise in humans. Annu Rev Physiol 198$4X93-413.

17. Shepard RH, Campbell EJM. Martin HB, Enns T. Factors af- fecting the pulmonary dead-space as determined by single breath analysis. d Appl Physiol 1957;11:241-4.

18. dames AE Jr. Cooper M. White RI, Wagner HN dr. Perfusion changes on lung scans in patients with congestive heart failure. Radiology 1971;100:99-106.

19. Huhges JMB, Glazier .JB, Rosenzweig DY, West JB. Factors determining the distribution of pulmonary blood flow in patients wit.h raised pulmonary venous pressure. Ciin Sci 1969:37:847-58.

20. West JB, Dollery CT, Heard BE. Increased pulmonary vascular resistance in the dependent zone of the isolated dog lung caused by perivascular edema. Circ Res 1965;3:191-206.

21. Mohsenifar Z. Amin DK, Shah PK. Regional distribution of lung perfusion and ventilation in pat,ients with chronic congestive heart failure and its relationship to cardiopulmonary hemodvnamics. A~I HE.u?~ .J 1989:117:887-91.

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2. Gazetopoulos N, Davies H, Oliver C, Deuchar D. Ventilation and haemodynamics in heart disease. Br Heart J 1966;28:1-15.

3. Sullivan MJ, Higginbotham MB, Cobb FR. Increased exercise ventilation in patients with chronic heart failure: intact ven-

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importance of abnormal lung perfusion in excessive exercise ventilation in chronic heart failure

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