Experimental

and laboratory

reports

Cardiorespiratory function and extravascular lung water following acute myocardial infarction

J. W. Warnica, M.D. A. V. M. White, M.D. J. H. Burgess, M.D. Montreal, Quebec, Canada

Oxygen administration has been part of the routine management of patients with acute myocardial infarction for many years. Its use has been justified by the almost invariable presence of arterial hypoxemia in these patients.‘* 2 More recent work suggests that breathing high oxygen mixtures may limit infarct size.3 A potential problem with this management, however, is the reported increase in systemic resistance and decrease in cardiac index accompanying the inhalation of 100 per cent oxygen in patients with acute myocardial infarction,4-7 although no such changes were found by Foster and co-workers8 Left ventricular filling pressures were not measured in any of these studies. A high proportion of patients with apparently uncomplicated acute myocardial infarctions have increased left ventricular filling pressures.9. lo It is therefore possible that the inhalation of high oxygen mixtures may potentiate left ventricular failure in these patients. The accessible extravascular lung water volume has been reported to be normal in patients with uncomplicated acute myocardial infarction”-14 and normal” or elevated with increasing left ventricular failure.12-‘4 We report here the effects of increasing inspired oxygen mixtures on pulmonary and systemic vascular resistance, left ventricular filling pressure, cardiac index, and From the Montreal General Hospital and the University Medical Clinic, McGill University, Montreal, Quebec, Canada. Received for publication Mar. 27, 1978. Accepted for publication May 12, 1978. Reprint requests: Dr. J. W. Warnica, Room 5590, Montreal General Hospital, 1650 Cedar Ave., Montreal H3G lA4, P.Q., Canada.

0002-8703/79/040469

+ 08$00.80/O

0 1979 The

C. V. Mosby

Co.

extravascular uncomplicated

lung water in patients myocardial infarction.

with acute

Methods We studied 11 patients between 46 and 71 years of age. All had proven acute myocardial infarction and were studied within 36 hours of admission to our Coronary Care Unit. Ten were uncomplicated on clinical grounds, while one had evidence of mild left ventricular dysfunction (S, gallop). Patients with clinical or radiological evidence of severe failure, anemia, hypertension, serious dysrhythmias and those receiving cardiac medications, including anti-dysrhythmics, were excluded. None had clinical or radiological evidence of chronic pulmonary disease. Most had received morphine on admission, but low dose diazepam was the only medication allowed during this study. After the procedure was explained and formal consent given, we passed a 7F Swan-Ganz flowdirected triple lumen catheter via the antecubital vein to the pulmonary artery under continuous ECG and pressure monitoring. Pulmonary capillary wedge pressures were measured as indicators of left ventricular filling.*5 We then inserted an intravenous canula into the radial artery for systemic pressure measurements and blood sampling. With the patient supine, and with the zero reference point 5 cm. below the sternal angle,16 we recorded pulmonary and systemic pressures using Statham P23 Db transducers on an Electronics for Medicine recorder previously calibrated in mm. Hg. After the catheters were inserted, the patients rested for 15 minutes breathing room air.

American Heart Journal

469

War&a,

White,

and

Burgess

I. Background information acute myocardial infarction Table

Patient No.

Age

Sex

Surface area (M.2)

1

63

M

2.06

2

65

M

1.78

3

61

M

1.82

4

46

M

2.04

5

61

M

2.14

6

60

M

2.04

7

66

M

2.01

8

55

F

1.70

9

58

M

1.93

10

50

M

2.16

11

71

F

1.42

Inspired o2 Cone. e/oi 21 35 100 21 35 100 21 35 100 21 35 100 21 35 100 21 35 100 21 35 100 21 35 100 21 35 100 21 35 100 21 35 100

and the results of all measurements made in 11 patients with

Arterial blood gases (mm. Hg) Pa 0,

Pa CO,

Ph (units)

56 92 380 58 107 385 40

34 27 29 23 26 25 26 37 28 24 27 22 29 29 24 27 28 27 33 33 33 29 25 28 27 27 27 27 28 30 25 30 27

7.50 7.52 7.52 7.51 7.52 7.51 7.49 7.44 7.49 7.55 7.55 7.55 7.51 7.51 7.58 7.42 7.41 7.40 7.48 7.46 7.46 7.50 7.53 7.51 7.53 7.53 7.54 7.49 7.47 7.48 7.55 7.45 7.47

275 63 102 370 52 92 445 49 78 315 67 132 420 70 128 405 64 109 375 64 97 475 52 88 305

Right to left shunt (75)

Mean pressures (mm. Ppw

@a

3 5 6 0 0 0 3 4 6 7 8 6 4 2 7 16 14 15 6 4 6 1 1 0 8 4 7 2 2 1 14 18 20

13 13 14 7 6 9 16 14 11 21 18 11 12 11 14 23 17 19 10 9 9 8 6 6 14 7 9 6 5 5 21 28 24

17.8

15.0

28.9

15.5

13.6

13.9

16.4

13.9

15.4

9.1

20.1

We then measured pulmonary arterial, pulmonary capillary wedge, and radial arterial pressures, systemic and pulmonary arterial blood gases, cardiac output, central blood volume and extravascular lung water at each of three inspired oxygen mixtures selected in random order: room air (21 per cent), 35 per cent (with mask) and 100 per cent (approximately, with a tight-fitting face mask). Rest periods of 25 to 30 minutes were given between test conditions and a further 20 minutes were allowed at each test oxygen level for equilibration to take effect. We used the standard shunt equation” to estimate the magnitude of the right-to-left shunt in the lungs with the patients 470

W Pba 67 74 81 84 85 92 62 65 71 80 78 78 90 94 113 107 119 118 97 96 97 80 77 81 83 83 89 89 91 92 87 99 99

Cardiac index (LJ min. /M-Z) 2.99 2.99 3.20 3.13 3.47 3.09 2.79 2.48 2.70 3.41 3.52 3.56 3.08 3.27 2.99 3.04 3.54 3.17 3.18 3.22 2.76 2.68 2.43 2.29 2.69 2.75 2.62 3.16 2.67 2.50 1.64 1.67 1.49

Pulmonary vascular resistance (units)

Systemic vascular resistance (units)

1.6 1.3 1.2 1.3 1.0 1.6 2.6 2.2 1.0 1.1 1.4 0.7 1.2 1.3 1.1 1.1 0.4 0.6 0.6 0.8 0.5 1.5 1.2 1.5 1.2 0.6 0.4 0.6 0.5 0.7 3.0 3.1 2.8

10.9 12.0 12.2 15.0 13.8 16.5 12.2 14.4 14.5 11.5 10.9 10.7 12.9 13.4 17.7 17.3 16.5 18.2 15.1 14.8 17.5 17.7 18.7 20.8 16.0 15.7 17.8 13.1 15.8 17.0 37.4 44.4 46.8

Central blood volume (ml.1 M.?)

EVLW (ml./ M.?)

725 745 906 1055 1217 1096 681 652 759 726 733 961 769 775 660 803 930 880 776 763 729 618 635 567 765 905 762 778 635 640 570 547 758

96 114 146 124 151 166 128 133 185 133 135 186 93 105 96 119 143 147 108 103 122 121 129 118 94 94 111 104 104 91 116 123 140

breathing the highest oxygen mixtures. Extravascular lung water was determined using the triple indicator dilution method (%r labelled red cells, I”” labelled albumin and Tritium enriched water) as modified by Goresky and colleagues.‘8 The methods used for the analysis of the blood samples, and the subsequent calculation of cardiac output, central blood volume and extravascular lung water space have been described in detail in our earlier paper.‘$ For each curve, transit times were corrected for in-flow and outflow catheter delay and thus correspond to the right atrial-radial artery passage time. Relative recovery rates for each isotope averaged 100 per April,

1979,

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4

EVL W in myocardial

cent, indicating complete recovery of the label. From the cardiac output and pressure measurements we calculated systemic and pulmonary vascular resistance as described by Wood.‘”

infarction

II. Mean values, -+ 1 standard error, for arterial PaO,, cardiac index, central blood volume, and extravascular lung water volume measured at differing inspired oxygen concentrations

Table

Results

Table I contains background patient data and the results of arterial blood gas measurements, estimated shunt flow, and the pressure, flow, and volume measurements at each experimental condition, Table II gives the mean values (* 1 standard error) for the arterial PO,, cardiac index, central blood volume, and extravascular lung water volume. These latter measurements have been related to body surface area for ease of comparison with previously reported studies. All patients were hypoxemic when breathing room air (mean PaO, 58 t 2.5 mm. Hg). The PaO, remained lower than expected during 100 per cent oxygen breathing, indicating a significant shunt-like effect in the lungs. Mean cardiac index (2.89 +- .14L./min./M.?) and central blood volume (751 +- 37 ml./M.‘) were within the normal range under control conditions (room air), but the accessible lung water space (112 f 4.3 ml./M.‘) was higher than in previously reported normals (80 to 90 ml./ ,.,).I,. ‘I The pulmonary capillary wedge pressure was normal in nine patients, borderline in one (14 mm. Hg) and only slightly elevated (16 mm. Hg) in one. These values were all well below the 20 mm. Hg reported by YuZ1 to be necessary in order to be consistently associated with an increased extravascular lung water volume. The extravascular water in the two patients with borderline or elevated capillary wedge pressures was not significantly higher than those with normal wedge pressure. There was no correlation between the wedge pressures and the extravascular lung water space measurements under any of the experimental conditions, The changes in systemic arterial pressure, systemic vascular resistance, and cardiac index with increasing inspired oxygen mixtures are shown graphically in Fig. 1. Systemic vascular resistances and systemic pressures were different from control valves only during 100 per cent oxygen breathing (p < 0.01 for each case). Cardiac index fell only slightly (p > 0.10) and pulmonary wedge pressure did not change significantly (p > 0.10) with increasing inspired oxygen concentrations with the exception of patient 11 (Ppw 14 mm. Hg to 18 to 20 mm. Hg). This American

Heart

Journal

Inspired 0, concentration m 21 35 100 *All

values

Arterial PO, (mm. W 58 f 2.7* 103 f 5.4 377 + 18.2 = mean

Cardiac index (L./min. /M.‘)

Central blood volume (ml./M.‘)

Extravascular water spaces (mL/M.‘)

2.89 + .I4 2.90 2 .18 2.76 f .19

751 i 37 776 i. 56 793 k 47

112 -+ 4.3 121 + 5.6 137 t 9.9

+ SE.

patient had the highest systemic vascular resistance and lowest cardiac index at control conditions and clearly deteriorated hemodynamitally with increasing inspired oxygen mixture. Central blood volume (Fig. 2) increased only slightly at each inspired O? level, but the mean increase with the highest oxygen mixture ( + 6 per cent) was not significant (p > 0.05). Fig. 3 presents the extravascular lung water volumes under each experimental condition. During inhalation of 35 per cent oxygen, mean extravascular water volume increased 8 per cent to 121 r 5.6 ml./M.’ (0.02 > p > 0.01). During 100 per cent oxygen breathing the accessible water space increased further to 137 +- 9.9 ml./ M.‘, 22 per cent higher than control volume (p < 0.01). The greatest increase in extravascular lung water occurred in those patients with the largest apparent intrapulmonary shunts (Fig. 4) (p < 0.05). Discussion Hemodynamics. In contrast to the frequently reported presence of increased left ventricular filling pressures in “uncomplicated” acute myocardial infarctions,!‘. ‘* we found a normal pulmonary capillary wedge pressure in nine of 11, borderline pressure in one, and a slightly elevated pressure in only one patient. It is possible that our measurements were sufficiently delayed after the acute event for initially elevated filling pressures to return to normal levels. It is also possible that the infarction size was so small in each case that there was no left ventricular dysfunction. With increased inspired oxygen tensions, increased systemic vascular resistances contributed to increased afterload, potentially increasing left 471

Wamica,

White,

and

Burgess

45 40

SYSTEMIC VASCULAR RESISTANCE UNITS

SYSTEMIC ARTERIAL PRESSURE head mmHg

.

. .

35 30 25

140 120

.

100

*

l .

.

80

.:. a.*.

0.: J

t

60

t

t

:ri

II!?lEc .

.

40 20 0.

3.5

CARDIAC INDEX L/min/M*

3

.

. . . .

.::..

.

::

2.5 2

. .

1.5

.

.

21%

35%

..= :. mm. .

-

. .

x

’.5 I 0

INSPIRED Fig.

1. Changes

increasing

inspired

in systemic arterial oxygen mixtures.

OXYGEN MIXTURE I-COMPARE TO ROOM

pressure, systemic vascular The mean values f standard

AIR P( 001

resistance, and cardiac error are also shown.

index

that

occur

with

.

1.2DO

.

.

1KQ CENTRAL BLOOD

100s

: 600

.*

.

VOLUME

i:

ml/M2

. .

600

0:.

t

+

.*.

.i.

zz

.

t .

35%

100%

01

21% INSPIRED

2. Changes error shown.

Fig.

472

in central

blood

volume

with

OXYGEN

increasing

inspired

MIXTURE

oxygen

mixtures

with

the mean

April,

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1979,

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EVLW

. . EVLW

09 .

T*

ml/M*

-T-

in myocardial

infarction

Y*

. . .

.

. .

35%

100%

01 21% INSPIRED x. P(

0.02

OXYGEN

MIXTURE y-+ P(O.01

Fig. 3. Changes in accessible extravascular lung water volume with increasing inspired oxygen mixtures. The mean values f standard errors are shown. At 35 per cent, and at 100 per cent inspired oxygen, the mean EVLW is significantly higher than that measured during room air breathing.

ventricular oxygen demand. However, this was uniformly well tolerated with no significant decreasein cardiac index or change in pulmonary capillary wedge pressure. In one patient, who had a depressed cardiac index and borderline filling pressure, the increased afterload accompanying increased inspired oxygen resulted in a further decrease in cardiac index and rise in wedge pressure to 24 mm. Hg. This suggests that the administration of increased oxygen mixtures to patients with acutely compromised left ventricular function requires further investigation. The degree of arterial hypoxemia (58 t 2.7 mm. Hg) is lower than that previously reported in patients with acute uncomplicated myocardial infarctions in this hospital.’ The mechanism for this hypoxemia is unclear. No patient was grossly obese, over-sedated, or unusually immobilized. It is difficult to ascribe this hypoxemia to congestion or embolization in the absence of other clinical evidence. Diffuse micro-atelectasis seems the most likely cause, perhaps related to the increased extravascular lung water. American

Heart

Journal

Volumes: Central Blood Volume. The right atria1 to radial artery volume is a poor index of central blood volume. However, the technique for measuring the pulmonary artery to left atria1 volumez3 requires transseptal catheterization of the left atrium; an unacceptable risk in patients with acute myocardial infarction. The mean control central blood volume (751 ? 37 ml./M.*) was identical to that reported by Braunwald and Kelly*’ in resting supine normal subjects. It was also equal to the mean maximum value for central blood volume reached by our upright exercising normal subjects.19 With increasing inspired oxygen mixtures, the mean central blood volume did not change significantly. This stability might be expected since pulmonary venous pressuresand blood flows did not change. Inspiration of high oxygen mixtures has no significant effect on the systemic venous capacitance vessels so that venous return is not altered. Extravascular lung water volume. Primarily because of the variety of techniques and experimental conditions employed, considerable discus473

Warnica,

volumes

1971. 23.

24.

25. 26.

476

White, and Burgess

in

resting

- patients. _

Am.

J.

Cardiol.

28:295,

Luepker, R., Leander, B., Korsgren, M., and Vamouskas, E.: Pulmonary intravascular and extravascular fluid volumes in exercising cardiac patients, Circulation 44626, 1971. Braunwald, E., and Kelly, E. R.: Effect of exercise on central blood volume in man, J. Clin. Invest. 39:413, 1960. Staub, N. C.: Pathogenesis of pulmonary edema, Am. Review Resp. Dis. 109:358, 1974. Singer, M. M., Wright, F., Starley, L. K., et al.: Oxygen toxicity in man; a prospective study in patients after

27.

28. 29.

30.

open heart surgery, N. Engl. J. Med. 283:1473, 1970. Barber, R. E., Lee, J., and Hamilton, W. K.: Oxygen toxicity in man; a prospective study in patients with irreversible brain damage, N. Engl. J. Med. 283:1478, 1970. Hedley-White, J.: Causes of pulmonary oxygen toxicity (Editorial), N. Engl. J. Med. 283:1518, 1970. Nixon, P. C. F.: Pulmonary edema with low left ventricular diastolic pressure in acute myocardial infarction, Lancet 2:148, 1968. West, J. B.: New advances in pulmonary gas exchange, Anesth. Analg. 54:409, 1975.

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1979, Vol. 97, No. 4