Left Ventricular Function in Patients

with Chronic Obstructive Pulmonary Disease

JOHNF. WILLIAMS, JR., RICHARDH. CmLDREss, DANIEL L. BOYD,LAWRENCEM. HIGGs, and RoY H. BEHNKE

From the Medical Service, Veterans Administration Hospital and the Department ofMedicine, Indiana University School of Medicine, Indianapolis, Indiana 46202

A B S T R A C T Left ventricular function was as-sessed in six patients with essentially normalcardiopulmonary function, in five patients withprimary myocardial disease, and in 16 patientswith chronic obstructive pulmonary disease by de-termining the response of the ventricle to an in-creased resistance to ejection. Studies were per-formed at the time of cardiac catheterization andincreased resistance to left ventricular ejection wasproduced by the intravenous infusion of methox-amine.

In the control patients, methoxamine producedan increase in stroke volume index (SVI), instroke work index (SWI), and stroke power in-dex (SPI), whereas left ventricular end-diastolicpressure (LVEDP) increased only moderately.In contrast SVI, SWI, and SPI fell, whereasLVEDP increased inordinately in the patientswith myocardiopathy. The patients with chronicobstructive pulmonary disease responded to theinfusion with an increase in SVI, SWI, SPI, andLVEDPcomparable to the control patients. Fur-thermore, in this latter group of patients, a quan-titatively similar response was observed in thosewith essentially normal resting hemodynamics, inthose with resting pulmonary hypertension, andin those whose disease had progressed to the stageof right ventricular failure.

This study provides no evidence that chronicobstructive pulmonary disease results in chronicimpairment of left ventricular function, but on thecontrary, has demonstrated that the left ventricleresponds normally to an increased pressure loadin these patients.

Received for publication 9 October 1967 and in revisedform 28 December 1967.

INTRODUCTION

Impairment of cardiopulmonary hemodynamics isa well recognized complication of chronic obstruc-tive pulmonary disease (COPD). Although themanifestations of the hemodynamic abnormalitiesusually are related to the development of pulmo-nary hypertension and right ventricular failure,it has been a clinical impression that. left ventricu-lar dysfunction also may occur as a complicationof the lung disease. Indeed, it is stated in a recenttextbook of cardiology that the entire heart is af-fected in cor pulmonale, and not just the rightventricle (1). Evidence to support this impressionhas been gained primarily from the observationthat patients dying with COPDoften have leftventricular hypertrophy at postmortem examina-tion (2-7), and the possible mechanisms for thishave been summarized (7). However, the presenceof myocardial hypertrophy does not necessarilyindicate depressed myocardial function since it hasbeen demonstrated that the hypertrophied myo-cardium can function normally (8) or even su-pernormally (9-13). Furthermore, definitive con-clusions concerning left ventricular function inthese patients cannot be made from the vastamount of hemodynamic data accumulated fromcardiac catheterization studied which have beensummarized recently (14). None of these studieshas been concerned specifically with left ventricu-lar function and the only information pertaining tothe function of this ventricle must be inferred frommeasurements of pulmonary "wedge" pressure atrest and during exercise; this pressure being usedas a reflection of left ventricular filling pressure.Interpretation of these "wedge" pressures, how-ever, is extremely difficult since these patients of-

The Journal of Clinical Investigation Volume 47 1968 1143

ten have increased intrapleural pressure, particu-larly during the hyperventilation of exercise,which, in itself, would be expected to elevate intra-thoracic vascular pressures.

Recently Ross and Braunwald reported that theresponse of the left ventricle in man to an increasein resistance to ejection can be used to character-ize the functional state of the ventricle (15). Em-ploying this technique, the present study was per-formed to provide more definitive informationconcerning left ventricular function in patientswith chronic obstructive pulmonary disease.

METHODS27 patients were the subjects of this study. Six patients,ages 40-52 yr (average, 46) served as controls (GroupA). Five of the patients had small mediastinal lesionsand this study was performed during diagnostic angiogra-phy. The remaining patient in this group had "pure"mitral stenosis with a normal resting pulmonary arterypressure and a calculated mitral valve orifice of 2.5 cm2.Five patients, ages 41-55 yr (average, 46), had primarymyocardial disease (Group B). Each of these patientshad cardiomegaly, whereas three of the five had a historyof congestive heart failure and were receiving a digitalispreparation. None of these patients had congestive heartfailure clinically at the time of the study. 16 patients,ranging in age from 41 to 76 yr (average, 54), hadclinical and radiographic evidence of obstructive pul-monary disease (Group C). None of these patients hadsystemic hypertension, evidence of valvular disease, pre-vious myocardial infarction, or a history of anginapectoris.

Pulmonary function tests were performed in each ofthe patients with COPDwithin 72 hr of cardiac catheteri-zation. Spirometric measurements of the divisions oflung volume and maximum breathing capacity were

determined in each subject whereas functional residualcapacity was measured by the closed circuit nitrogenwashout technique in 14 of the 16 patients. Alveolar nitro-gen was measured after. breathing 100% 02 for 7 min.In addition, the diffusing capacity of carbon monoxidewas measured by the single breath method in 10 of thepatients. Arterial 02 saturation was determined spectro-photometrically and arterial pC02 and pH with a direct-reading electrode instrument (IL meter, InstrumentationLaboratory, Boston, Mass.) Pulmonary function testswere not performed in the control patients or in thosewith primary myocardial disease, however none hadclinical or radiographic evidence of pulmonary disease.

After right heart catheterization, a catheter was in-serted retrogradely into the left ventricle in each patientfor the measurement of pressure. Brachial arterial pres-sure and a standard limb lead of the electrocardiogramwere recorded in each patient. Cardiac output was deter-mined by the indicator-dilution method with injection ofindocyanine green dye into the pulmonary artery and

sampling from the brachial artery. Left ventricular ejec-tion time was determined from an indirect carotid arterialpulse tracing recorded at a paper speed of 100 mm/sec.All pressures were measured with Statham P23Gb trans-ducers (Statham Instruments, Inc., Los Angeles, Calif.)with the mid-thoracic level used as the zero referencepoint. Pressures were averaged over three completerspiratory cycles. All measurements were recorded on amultichannel oscillograph.

After control observations, methoxamine, a sympatho-mimetic amine without significant beta adrenergic ef-fect (16), was infused intravenously at a rate neces-sary to produce a 40-50% increase in systole arterialpressure. All measurements were then repeated whensystemic arterial pressure, heart rate, and LVEDP hadremained constant for 3-5 min. Left ventricular strokework index (SWI) in g-m/m' was calculated from thefollowing formula:

SWI = SVI X (LVS - LVEDP) X 1.36100

where SVI equals the stroke volume index in millilitersper square meter; LVS equals the mean left ventricularpressure during ejection in mmHg determined by plani-metric integration; and LVEDP equals left ventricularend-diastolic pressure in mmHg. Because it has beenreported that changes in myocardial function can occurwhich may not affect SVI or SWI, but which will pro-duce alterations in parameters dependent on the rate ofventricular contraction (17), stroke power index (SPI)in g-m/sec per m' was determined by dividing SWI bythe ejection period in seconds.

RESULTS

The results of the pulmonary function tests in thepatients with COPDare given in Table I. 15 pa-tients had a reduced vital capacity, while all 16patients had a reduced 1-sec vital capacity andmaximum voluntary ventilation. In addition, theratio of residual volume to total lung capacity wasincreased in each of 14 patients in whom it wasdetermined. Furthermore, an increased total lungcapacity, evidence of impaired distribution of in-spired air, and a reduced diffusing capacity ofcarbon monoxide commonly were observed. Oxy-gen saturation at rest ranged from 60-95 %oand was less than 90%o in 9 of the 16 patients.Arterial pH was within the normal range in eachpatient at the time of the study, while arterial pCO2exceeded 45 mmHg in only four patients (E. Z.,J. C., P. S., and H. L.). Although this group con-sisted of both those patients with predominantchronic bronchitis and those with predominantpulmonary emphysema, their responses to methox-amine were similar; therefore, they have beengrouped together.

1144 1. F. Williams, Jr., R. H. Childress, D. L. Boyd, L. M. Higgs, and R. H. Behnke

TABLE IResults of the Pulmonary Function Tests in Group C Patients

FEV1.0/ Alv RV/ Art 0:

Patient VC VC MVV N2 RV TLC TLC w DLCO sat

ml %pre- % liters/ %pre- % ml %pre- ml %pre- % mi/min %dicted min dicled dicled dicted per mm

Hg1 R. Wal. 2100 (61) 48 35 (38) 3.0 3972 (227) 6072 (121) 65 19.3 932 R. Wag. 2000 (54) 70 39 (42) - - - - 37.8 923 R. H. 4825 (111) 38 83 (63) 2.8 3690 (186) 8515 (151) 43 42.0 944 L. T. 2400 (63) 48 33 (33) - - - - 21.0 935 K. H. 2825 (77) 46 43 (42) 2.0 2005 (108) 4830 (91) 42 - 926 E. Z. 2225 (57) 26 34 (34) - 4125 (209) 6350 (113) 65 18.7 767 L. W. 1200 (29) 42 14 (12) 3.1 4616 (250) 5816 (109) 79 - 828 W. H. 1830 (51) 39 31 (34) 2.9 2925 (160) 4755 (91) 62 - 869 G. W. 2100 (56) 14 25 (24) 2.3 3152 (192) 5252 (112) 60 23.1 86

10 J. G. 1050 (29) 57 28 (30) - 4307 (240) 5357 (103) 80 - 9211 P.S. 1650 (41) 48 24 (19) 2.8 5049 (246) 6699 (114) 75 - 8012 T. J. 1550 (48) 39 14 (19) 3.2 2204 (134) 3754 (80) 59 15.6 9513 B. L. 2450 (72) 40 49 (76) - 4959 (288) 7409 (151) 67 5.0 8614 M. W. 1000 (28) 12 23 (25) 2.4 5406 (301) 6466 (124) 85 12.1 8515 J. C. 1400 (36) 30 36 (36) 2.6 2409 (136) 3809 (75) 63 20.4 8016 H. L. 1850 (47) 57 25 (23) 4.4 3223 (178) 5073 (98) 64 - 60

VC, vital capacity; FEV 1.0/VC, timed vital capacity; MVV, maximum voluntary ventilation; Alv N2, alveolar nitrogen; RV, residual volume;TLC, total lung capacity; DLCO, diffusing capacity for carbon monoxide; Art OXsat. arterial oxygen saturation.

TABLE I IEffects of Methoxamine on Patients in Group A

Art. press. MeanPatient Heart PA

BSA rate S/D Mean CI LVEDP SVI SWI SPI press.

mmHg lilers/min mmHg mi/m2 g-m/m2 g-m/sec mmHgper m2 per m2

N. S. C 88 147/82 104 4.39 4 50 79 346 181.57 M 60 187/92 124 3.57 5 60 118 378

J. B. C 100 85/55 69 2.46 1 25 24 1101.71 M 80 123/74 92 2.35 0 29 38 177

E. R. C 78 131/81 98 3.41 8 44 61 202 181.84 M 66 184/102 129 2.89 14 44 78 236

H. C. C 70 125/70 88 2.51 9 36 43 155 171.88 M 50 171/80 110 2.05 13 41 69 197 -

G. B. C 76 172/87 115 3.49 7 46 87 310 191.82 M 52 214/93 133 2.90 18 56 121 379

R. B. C 84 130/72 91 5.13 3 61 97 374 191.75 M 60 205/88 127 4.56 12 76 162 451 -

Mean C 83 131/75 94 3.57 5 44 65 250± SEM M 44.3 416.4 :10.43 :11.3 415.0 4116.4 4144.4

M 61* 181/88* 119* 3.05* 10* 51* 98* 303*±4.4 416.3 4i0.37 :1:2.7 ±6.7 ±18.1 ±46.5

BSA, body surface area in mi; Art. press., systemic arterial pressure, s/D, systolic diastolic; CI, cardiac index; LVEDP,left ventricular end-diastolic pressure; SVI, stroke volume index; SWI, stroke work index; SPI, stroke power index; PApress., pulmonary artery pressure. C, control; M, during methoxamine infusion.* Mean significantly different from control (P < 0.05).

Left Ventricular Function and Chronic Lung Disease 1145

The hemodynamic data for each individual be-fore and during methoxamine infusion are pre-sented in Tables II, III, and IV.

Group A (Table II)

Mean systemic arterial pressure increased ineach patient from an average of 94 mmHg at restto 119 mmHg during methoxamine infusion.Heart rate, which averaged 83 beats/min duringthe control period, decreased in each patient toan average of 61 beats/min. Cardiac index (CI)decreased from an average of 3.57 liters/min perm2 at rest to 3.05 liters/min per m2 during druginfusion, decreasing in five or six patients. RestingLVEDPaveraged 5 mmHg and increased to 10mmHg, rising in five patients. During the admin-istration of methoxamine, SVI increased in fivepatients, whereas SWI and SPI increased in allsix. SVI averaged 44 ml/m2 at rest and 51 ml/m2during drug infusion, whereas SWI increasedfrom an average of 65 to 98 g-m/m2, and SPIfrom a mean of 250 to 303 g-m/sec per M2.

Group B (Table III)

Mean systemic arterial pressure averaged 88mmHg at rest and increased in each patient to

an average of 107 mmHg with methoxamine.Heart rate decreased from an average of 88 to 81beats/min, decreasing in each patient. Cardiacindex at rest was reduced (< 2.5 liters/min perm,2) in only one patient and averaged 3.18 liters/min per m2. During methoxamine infusion, CI de-creased in each patient to an average of 2.33liters/min per M2. LVEDP at rest averaged 11mmHg and exceeded 12 mmHg in only two pa-tients. With methoxamine LVEDP rose to ab-normal levels in every patient and averaged 21mmHg. Concomitantly SVI decreased in all fivepatients, whereas both SWI and SPI fell in fourpatients and were unchanged in the remaining one.SVI decreased from a resting average of 37 to 29mi/M2, SWI from 44 to 39 g-m/m2, and SPIfrom 180 to 146 g-m/sec per M2.

Group C (Table IV)

Mean systemic arterial pressure averaged 88mmHg at rest and increased in each patient withmethoxamine to an average of 116 mmHg. Heartrate decreased from a mean of 91 to 80 beats/min,decreasing in 14 patients. CI was less than 2.50liters/min per M2 at rest in four patients and av-eraged 2.58 liters/min per M2. However, CI did

TABLE I I IEffects of Methoxamine on Patients in Group B

Art. press. MeanPatient Heart PA

BSA rate S/D Mean CI LVEDP SVI SWI SPI press.

mmHg liters/min mmHg mi/M2 g-m/m" g-m/sec mmHgper m2 per m2

R. V. C 80 118/68 84 3.03 6 38 45 182 241.67 M 77 157/78 109 2.20 22 29 41 133 -

R. Si. C 95 136/88 102 3.70 3 39 54 256 181.92 M 90 157/92 116 2.70 16 30 44 196 -

R. Sa. C 80 123/77 94 4.00 23 50 61 216 352.00 M 74 143/92 112 3.50 28 47 61 216

F. S. C 88 96/61 72 2.76 18 31 29 119 291.91 M 82 105/74 84 1.87 22 23 23 104 -

C. S. C 95 112/67 87 2.40 4 25 31 128 142.00 M 82 155/91 114 1.40 16 17 24 81 -

Mean C 87 117/72 88 3.18 11 37 44 180± SEM ±3.4 -4:5.0 ±0.30 44.1 ±4.2 46.3 ±26.0

M 81* 143/85* 107* 2.33* 21* 29* 39* 146*±2.7 ±5.9 ±0.36 ±2.2 45.0 ±7.0 ±26.0

See Table II for abbreviations.

1146 J. F. Williams, Jr., R. H. Childress, D. L. Boyd, L. M. Higgs, and R. H. Behnke

TABLE IVEffects of Methoxamine on Patients in Group C

Art. press.Patient Heart

BSA rate S/D Mean CI LVEDP SVI

mmHg liters/min mmHg ml/m2

1 R. Wal. C 70 124/64 841.77 M 72 172/84 113

2 R. Wag. C 85 108/68 811.52 M 56 138/78 98

3 R. H. C 68 122/72 892.04 M 66 196/98 131

4 L. T. C 88 120/68 851.64 M 74 160/106 124

5 K. H. C 88 170/93 1191.75 M 80 203/97 132

6 E. Z. C 81 120/75 901.67 M 62 180/95 123

7 L. W. C 100 125/85 981.78 M 100 170/104 126

8 W. H. C 90 131/78 961.59 M 72 194/100 133

9 G. W. C 104 100/60 731.72 M 92 160/90 113

10 J. G. C 96 166/76 1061.80 M 72 216/83 127

11 P. S. C 84 90/56 702.12 M 74 137/88 102

12 T. J. C 100 100/70 801.52 M 96 150/80 103

13 B. L. C 102 116/78 831.60 M 94 160/92 114

14 M. W. C 88 120/73 931.53 M 78 160/88 118

15 J. C. C 84 105/65 781.60 M 78 160/86 111

16 H. L. C 126 119/67 841.78 M 108 126/71 89

Mean C 91 121/72 884 SEM 4-3.5 413.1

M 80* 168/90* 116*4:3.6 -43.3

per m2

3.053.61

2.702.57

3.423.30

2.572.64

2.843.29

3.162.81

2.943.23

2.822.77

2.902.86

1.902.36

2.623.43

1.94-1.96

1.141.41

2.632.81

1.701.90

3.012.85

2.5840.15

2.741:0.15

0 443 50

6 3211 46

5 5011 50

4 298 36

5 3210 41

10 3913 45

10 2917 32

6 3128 38

5 286 31

5 207 33

6 318 46

12 1916 20

5 115 15

12 3017 36

6 2014 24

7 242 26

7 2910.8

11*4-1.6

SWI SPI

g-m/m2 g-m/secper m2

58 18286 240

39 16366 205

66 219106 379

39 13457 196

59 23690 300

54 21681 272

45 18756 233

44 16276 230

33 14553 222

37 13268 261

31 14169 278

21 9431 114

13 9426 175

38 16760 187

23 11340 166

32 15238 171

40 159

MeanPA

Press.

mmHg

14

15

16

20

16

35

36

24

31

26

30

30

30

58

35

:12.4 1:3.6 :1:10.5

36* 63* 227*:1:2.7 145.6, 4115.8

See Table II for abbreviations.

not fall significantly in any patient during drug mal in any patient at rest and averaged 7 mmHg.infusion and averaged 2.74 liters/min per M2. With methoxamine, LVEDP increased in 14 ofLVEDP did not exceed the upper limits of nor- the 16 patients but only to an average of 11 mm

Left Ventricular Function and Chronic Lung Disease 1147

=1

-4

Hg. In response to the increased afterload, SWIand SPI increased in each patient whereas SVIincreased in 15 subjects and was unchanged in theother. SVI increased from an average of 29 ml/M2at rest to 36 mi/M2, SWI from 40 to 63 g-m/m2,and SPI from 159 to 227 g-m/sec per M2.

Because it seemed possible that impairment ofleft ventricular function in patients with COPDmight occur only in those with the more advancedpulmonary disease, these patients were dividedinto three groups and the results were compared.Furthermore, since this study was concernedwith cardiac function, it appeared more advisableto base this division on the level of pulmonary ar-tery pressure and the occurrence of right ventricu-lar failure, rather than the severity of impairmentof pulmonary function. One group (Cl) consistedof five patients with a resting mean pulmonaryartery pressure of 20 mmHg or less. The second

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group (C2) was composed of five patients witha mean pulmonary artery pressure at rest ofgreater than 20 mmHg, but who had never mani-fest right ventricular failure. The remaining group(C3) consisted of six patients with resting pul-monary hypertension and a history of right ven-tricular failure. The individual hemodynamic databefore and during drug administration are pre-sented in Table IV where Group Cl consists ofpatients 1-5; C2, 6-10; and C3, 11-16. The meanvalues of the various parameters for these threegroups are illustrated in Figs. 1 and 2.

Group C1

Mean systemic arterial pressure averaged 92mmHg during the control period and increased to120 mmHg during methoxamine infusion. Heartrate decreased from a resting average of 80 to 70beats/min. CI was within normal limits at rest in

c M

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FIGURE 1 Hemodynamic changes during the infusion of methoxamine in patientswith chronic obstructive pulmonary disease. Open circles represent patients withnormal resting pulmonary artery pressure; closed circles, those with resting pul-monary hypertension; and closed triangles, those who had demonstrated right ven-tricular failure. Points represent mean values + SEM. CI, cardiac index; MeanArt. Pres., mean systemic arterial pressure; LVEDP, left ventricular end-diastolicpressure; C, control period; M, during methoxamine infusion.

1148 1. F. Willams, Jr., R. H. Childress, D. L. Boyd, L. M. Higgs, and R. H. Behnke

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FIGuRE 2 The effect of methoxamine on stroke volume index (SVI), stroke work index(SWI), and'stroke power index (SPI) in patients with chronic obstructive pulmonary disease.For symbols see Fig. 1.

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each patient, averaging 2.92 liters/min per m2,whereas with methoxamine CI averaged 3.08liters/min per M2. LVEDPaveraged 4 mmHg atrest and increased to an average of 9 mmHg.With increased afterload, SVI increased from a

resting average of 37 to 45 ml/m2, SWI from 52to 81 g-m/m2, and SPI from 187 to 264 g-m/secper M2. Resting mean pulmonary artery pressureaveraged 16 mmHg and arterial oxygen saturation93%o.

Group A

N.

80 i Group B

60

40

20

10 15 20 25 30

L V E D P

00 5

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40

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Group C2

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40

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Group C3

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FIGuRE 3 The effect of methoxamine on the relationship of stroke volume index (SVI) to left ven-

tricular end-diastolic pressure (LVEDP) in each individual patient. Arrows point to values duringmethoxamine infusion. For classification of group see text.

Left Ventricular Function and Chronic Lung Disease

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Group C2

Mean systemic arterial pressure averaged 93mmHg and increased to 124 mmHg with methox-amine. Heart rate decreased from an average of94 to 80 beats/min. CI at rest was less than 2.50liters/min per M2 in only one patient and averaged2.74 liters/min per M2. During methoxamine infu-sion, CI averaged 2.81 liters/min per M2. LVEDPaveraged 7 mmHg during the control period and14 mmHg during drug administration. One pa-tient, W. H., did demonstrate an inordinate in-crease in LVEDP, from 6 to 28 mmHg. Withmethoxamine, SVI rose from an average of 29 to36 ml/m2, SWI from 43 to 67 g-m/m2, and SPIfrom 168 to 244 g-m/sec per M2. Mean pulmonaryartery pressure at rest averaged 30 mmHg andarterial oxygen saturation 86%.

Group C3

Mean systemic arterial pressure averaged 81mmHg and increased to an average of 106 mmHg during methoxamine, whereas heart rate de-creased from a control average of 97 to 88 beats/

min. Resting CI was less than 2.50 liters/min perm2 in three of the six patients and averaged 2.17liters/min per M2. With methoxamine CI aver-aged 2.39 liters/min per M2. LVEDPaveraged 8mmHg at rest and 10 mmHg during the in-crease in resistance to ejection. This was ac-companied by an increase in SVI from an averageof 23 to 28 mi/M2, in SWI from 26 to 44 g-m/m2,and in SPI from 127 to 182 g-m/sec per M2.Mean pulmonary artery pressure at rest averaged37 mmHg in the five patients in whom it wasdetermined. Right ventricular systolic pressurewas 41 mmHg in the remaining patient. Arterial02 saturation averaged 81 %.

For comparative purposes, the relationship ofSVI and SWI to LVEDP, i.e. ventricular func-tion "curves," for each subject in all groups areillustrated in Figs. 3 and 4. Since the relationshipof SPI to LVEDP was essentially identical tothat of SWI and LVEDP in each patient, theseare not presented. In the control patients, an in-crease in LVEDPwas associated with an increasein SWI in each patient and an increase in SVI

Group A

d

180

120

60 -

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90

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1201 Group C3Group C2

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FIGURE 4 The effect of methoxamine on the relationship of stroke work index (SWI) to left ventric-ular end-diastolic pressure (LVEDP) in each individual patient. Arrows point to values during me-

thoxamine infusion. For classification of group see text.

1150 1. F. Williams, Jr., R. H. Childress, D. L. Boyd, L. M. Higgs, and R. H. Behnke

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in five of the six subjects. In contrast, in patientswith myocardiopathy, although LVEDPgenerallyincreased to an even greater extent, SVI fell ineach patient and SWI decreased in four of the five.With one exception, these relationships in all pa-tients with COPDwere quite similar to those ofthe control patients, comparable increases inLVEDP being associated with increases in SWIin each patient and SVI in 15 of the 16 patients.

DISCUSSION

Recently Ross and Braunwald demonstrated thatit was possible to characterize the functional stateof the left ventricle in man by determining itsresponse to an increased afterload produced bythe infusion of angiotensin (15). They observedthat the normal ventricle responded to an in-creased resistance to ejection with an increase inSWI and SVI, whereas LVEDP increased onlymoderately. In contrast, although LVEDP in-creased to an even greater extent, SWI and SVIfell in those patients with abnormal left ventricu-lar function. These observations were supportedby previous experiments using isolated hearts(18), intact hearts (19), and isolated musclepreparations (19, 20).

The results of the present study in which me-thoxamine was employed to increase afterload inpatients with essentially normal cardiac function(Group A) and those with myocardiopathy(Group B), therefore, are in agreement with theresults obtained by Ross and Braunwald. It is ofinterest that such distinctly abnormal responseswere observed in each of the patients with myo-cardiopathy, even though left ventricular functionoften appeared normal at rest, i.e., CI was normalin four and LVEDP in three of these patients.The infusion of methoxamine into patients withCOPDrevealed that the left ventricular responsein these patients was similar to that of the controlpatients with no statistically significant differencesexisting between these two groups in the responseof LVEDP, SVI, SWI, or SPI. In contrast, highlysignificant differences exist between the patientswith COPDand those with myocardiopathy in theresponse of each of these variables.

However, it must be appreciated that the de-crease in heart rate during methoxamine infusionwas significantly greater in the control patientsthan in those with COPD. Since differences in the

response of heart rate might well produce differ-ences in the response of SVI, and consequentlySWI and SPI, comparison of these responses inthese two groups must be made with caution. Thenecessity for making a truly quantitative compari-son between these two groups is evident from theobservations of Ross and Braunwald. They ob-served patients, classified as having depressedmyocardial function, in whom SVI and SWI in-creased with increased pressure load but not toan appropriate degree when compared to the in-crease in LVEDP (15). Therefore although thepatients with COPDclearly do not have left ven-tricular dysfunction of the severity manifest byGroup B, it could not be established conclusivelythat left ventricular function is normal in the pul-monary disease patients by comparing their re-sponse solely with that of the controls. However,when the patients with lung disease were dividedinto groups on the basis of their impairment ofcardiopulmonary hemodynamics at rest and theresults compared, strong evidence is provided thatleft ventricular function is well maintained in thisdisease.

Regardless of whether these patients withCOPDhad essentially normal resting hemody-namics or whether they had progressed to the stageof right ventricular failure, essentially identicalresponses to methoxamine were observed. Duringthe infusion of methoxamine, similar increases insystemic arterial pressure and decreases in heartrate occurred in these three groups of patients(C1, C2, and C3). SVI, SWI, and SPI rose,whereas LVEDP increased moderately in eachgroup with no statistically significant differencesobserved between these groups in the response ofany of these variables. Further statistical analysescomparing the response with methoxamine of eachof the group of patients with COPDwith that ofthe control patients revealed that the decrease inheart rate in Group C3 was the only one of theabove variables significantly different statisticallyfrom those of the Group A patients. In contrast,even in the patients with COPDwho had mani-fest right ventricular failure (Group C3), highlysignificant differences in the response of SVI,SWI, SPI, and LVEDPand insignificant differ-ences in the changes in heart rate and systemicarterial pressure were observed when comparedwith those of the patients with myocardiopathy.

Left Ventricular Function and Chronic Lung Disease 1151

It is apparent that the resting cardiac index ofthe patients with COPDwas less than that of thecontrol patients and that this variable decreasedprogressively as the severity of pulmonary hemo-dynamics increased. In view of the results of thisstudy, this most likely represents the effect ofchronic pulmonary hypertension on right ven-tricular function. If this were due to left ven-tricular dysfunction, it would not be expectedthat SVI, SWI, and SPI would increase with in-creased afterload, since impairment of left ven-tricular function, which is not even of the severityto reduce resting CI or elevate LVEDP, still pro-duces such distinctly abnormal responses to in-creased resistance to ejection (Group B). The ef-fect that the decrease in CI and consequent de-crease in SVI might have on the left ventricularresponse to increased resistance to ejection canbe ascertained from previous studies in animals.In experiments in which stroke volume was con-trolled, it was demonstrated that as the restingstroke volume was increased in the normal ven-tricle, greater increases in stroke work were pro-duced by similar increases in resistance to ejec-tion (18, 19). Therefore, the observation that theresponse of SWI and SPI was no less in GroupsC2 and C3, with their lower resting stroke vol-umes, than in the controls or Group Cl eventhough a somewhat diminished response mighthave been expected only strengthens the conclu-sion that left ventricular function was normal inthese patients.

The observation that the resting LVEDP washigher and the resting CI lower in Groups C2and C3 than the control patients or those in GroupC1 might be used as evidence that myocardial func-tion was depressed in the former two groups.However conclusions based on single measure-ments of LVEDP in patients with obstructivelung disease are potentially erroneous since thesevalues probably do not reflect the true end-dia-stolic pressure in this chamber. The use of thesame fixed point on the thoracic cage as the refer-ence point for zero pressure in patients with nor-mal thoracic cages and in those with increasedanteroposterior diameter could lead to apparentdifferences in intravascular pressure if the geo-metric relationship of the left ventricular cavityto the reference point were different. Also, it iswell known that intrathoracic pressure may be

elevated in patients with COPD. This in itselfcould result in an apparent elevation of LVEDP,although transmural pressure might be normal.Regardless of whether the LVEDP as measuredin the patients with COPDrepresents the trueLVEDP, the determination of changes in LVEDPin these patients should be accurate in the absenceof changes in ventilation or airway resistance.Respiratory rate was not affected significantly bymethoxamine infusion in any of the patients in thepresent study. Furthermore, minute ventilationwas determined in three patients with lung diseaseand intra-esophageal pressure in three other pa-tients with COPDand no changes were observedduring drug administration.

The usefulness of employing changes in LVEDPto assess left ventricular function as performed inthis study is dependent upon the ability of thisvariable to reflect changes in end-diastolic ven-tricular volume. Although direct measurement ofend-diastolic volume would be preferable whenpossible, considerable evidence has been presentedthat changes in LVEDPdo reflect changes in end-diastolic fiber length (17, 21, 22).

One patient in Group C2 (W. H.) responded ina manner similar to that of patients with de-pressed myocardial function using the criteria ofRoss and Braunwald (15). This patient, age 57,had a resting CI of 2.82 liters/min per M2, a meanPA pressure of 24 mmHg and an arterial oxygensaturation of 86%, values much less abnormalthan those of several other patients with COPD.Although this single abnormal response remainsunexplained, it would not be surprising if one of16 male patients in this age group had coronary ar-tery disease of such hemodynamic significance thatimpairment of left ventricular function might oc-cur under the stress of an increased afterload.

The results of this study should not be inter-preted as indicating that COPDnever depressesleft ventricular function. It is indeed possible, ifnot likely, that severe hypoxia and acidosis whichdevelop during episodes of acute respiratory in-sufficiency could impair the functional ability of themyocardium at that time. However, if this doesoccur, it is highly unlikely that it leads to chronicimpairment of left ventricular function. Each ofthe patients in Group C3 had been admitted to thehospital on more than one occasion (range 2-5)for episodes of acute respiratory insufficiency with

1152 J. F. Williams, Jr., R. H. Childress, D. L. Boyd, L. M. Higgs, and R. H. Behnke

acidosis, yet a normal left ventricular response wasobserved in each of these patients. Also the sub-sequent course of these patients makes it improb-able that the lung disease was not of the severitynecessary to produce chronic left ventricular dys-function. Four of the six patients died of respira-tory insufficiency with right ventricular failurewithin 7-23 months of the time of this study.Postmortem examination revealed marked rightventricular hypertrophy in all, and the left ven-tricle appeared normal in three. Left ventricularhypertrophy was described in the remaining pa-tient although measurements of wall thicknesswere not made. This latter finding has been ob-served in a significant percentage of these patientsby several investigators (2-7), although it hasnot been a universal finding (23). If left ventricu-lar hypertrophy does occur as a result of COPD,it would appear from the present study that thiscompensatory mechanism is sufficient to maintainnormal left ventricular performance in thesepatients.

ACKNOWLEDGMENTSThis work was supported in part with the facilities pro-vided by Public Health Service research grant HE06308 from the National Heart Institute, postgraduateCardiovascular research training grant HTS-5363 fromthe National Heart Institute, and the Indiana HeartAssociation.

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