Lung
154,
65-74
(1976)
Springer-V~
Obstruction of Small Airways in Patients After Acute Myocardial Infarction J. Ressl,
L.
Cernj~,
R.
Jandov~
and
L.
Nikod~mov~
2nd Research Unit of Internal Medicine (Chief: Ass. Prof. J. %Vidimsk~, DrSc) of the Institute for Clinical and Experimental Medicine (Head: Prof. P. M~lek, DrSc), Praque, CSSR
Ab st r act. The closing volume of the small airways was measured using the argon bolus technique by mass spectrography in 20 males 3 to 5 months after acute myocardial infarction. No patient exhibited signs of a manifest heart failure or of a simultaneous pulmonary disease. The closing volume expressed in percent of vital capacity exceeded in only 2 patients the limits of + 2 SD of our own normal values. A slight arterial hypoxemia was established in 45% of patients but its correlation to closing volume was not significant. Also, no correlation was found to the alveoloarterial oxygen pressure gradient, vital capacity, or expiratory forced volume. The hemodynamic changes in the lesser circulation were examined in all patients with floating catheter. The closing volume showed no correlation to the pulmonary artery diastolic pressure (regarded as an index of left ventricular filling pressure), nor to the pulmonary mean pressure both at rest and during effort. Key
words:
Myocardial
infarction
- Airway
obstruction
Zusammenfassung. Das VerschluSvolumen der kleinen Luftwege (closing volume) wurde mittels Argon Bolus-Methode bei 20 Kranken 3-5 Monate nach einem akuten Herzinfarkt mittels Mass Spectrometer gemessen. Keiner der Kranken zeigte klinische Symptome einer manifesten Herzschw~che oder einer gleichzeitigen Lungenerkran.kung. Das Verschluf~volumen iiberstieg nur bei 2 Patienten die Orenze yon + 2 SD eigener Sollwerte. Eine arterielle Hypox~mie, meist leichten Grades, wnrde bet 45% der Kranken festgestellt, lhre Abh~ngigkeit yon der Gr~i2e des Verschlu2volumens wurde statistisch nicht signifikant. Es wurde keine Korrelation zu der alveolo-arteriellen Sauerstoffdruckdifferenz, der Vitalkapazit~t und dem Atemstoff gefundeno
66 Die h~imodynamischen Ver~inderungen irn kleinen Kreislauf wurden bei allen Patienten ambulant rnit dern Einschwernrnkatheter untersucht. Das Verschluf~volurnen zeigte keine Korrelation zur GrOf~e des diastolischen Pulmonalisdruckes, der als ein Index des linksventrikul~iren Filllungsdruckes betrachtet wurde, und zur HShe des rnittleren Pulrnonalisdruckes und zwar in Ruhe oder bei Belastung.
INTRODUCTION Most cases of an acute myocardial infarction (AMI) are accompanied by arterial hypoxemia, which is caused mainly by the disturbance of the ventilation-perfusion ratio and has a certain relation to abnormal hemodynarnic left ventricular function (M&lek et al., 1973). During convalescence the hypoxemia becomes normal in some patients, but in others, however, it perseveres. They are only few data available on the latter group and they are conflicting. McNicol et al. [14]found arterial hypoxernia and an increased alveoloarterial oxygen pressure gradient in 43% of patients 6-12 months after acute myocardial infarction. Higgs ei al. [ 6] described an elevated alveoloarterial oxygen gradient in a part of patients convalescing from AMI. Bazzaz and Kazemi [l] are reporting, on the contrary, nearly normal findings 2-6 months after AMI. In our series a slight arterial hypoxemia was found in 45% of patients 3-5 months after acute myocardial infarction, in w~hich hypoventilation and pulmonary diffusing capacity disturbance could be excluded. The causes of hypoxernia in the convalescence from AMI has not yet been completely elucidated. One of the possible causes could be the augmentation of the closing volume of the small airways. If the closing volume (CV) is larger than the functional residual capacity, the hypoventilation of lower lung zones with a disturbance of gas exchange can occur. Hales and Kazemi [ 5] showed that in AMI a transitory left ventricular failure with a pulmonary congestion can lead to the closure of the small airways and to hypoxernia. Interiano et al. [8] found in the patients with AIViI an increased resistance of peripheral airways with hypoxemia. As yet there is, however, little knowledge available on the changes of closing volume during convalescence from AMI. This has initiated us to investigate the closing volume in patients 3-5 months after acute myocardial infarction and to correlate the results with some changes in ventilation, gas exchange, and hemodynamic findings in the lesser circulation.
MATERIAL
AND
METHODS
There were 20 males, aged 37-64 years (mean age 51 years) examined. The diagnosis of AMI was established in all at our coronary care unit. A coexisting pulmonary disease was excluded by clinical, laboratory, and chest x-ray examinations. No patient was suffering from a manifest heart failure. Hernodynamic examination was performed in supine out-patients by the floating catheter technique [17] 3-5 months after AIV[I. The pulmo-
67
nary artery mean pressure was measured by electrical integration on Mingograph Elema 81 apparatus. The diastolic pulmonary pressure, regarded as an indicator of left ventricular filling pressure~ was obtained by averaging two breathing cycles from at least I0 individual values. The cardiac output was determined by the Fick method. Expired air was collected in a Douglas bag for 3-5 min and analyzed for oxygen and carbon dioxide concentration by means of a Zeiss interpherometer. The oxygen tension in arterial and mixed venous blood from the pulmonary artery was determinded by Micro Astrup Apparatus BMS 2 Radiometer fitted with the Clark electrode. The alveolar oxygen tension was calculated after Riley et al° [19]. The global spirometry was examined in sitting subjects using Godart Pulmotest. For measurement of the closing volume, special methods are necessary [4~ i0]. We employed the argon bolus technique in the sitting position. At the end of maximal expiration, an argon bolus of 50 ml was injected rapidly into the mouthpiece followed by a slow maximal inspiration. During the subsequent slow maximal expiration (flow rate 0.2-0.5 L/s) the argon concentration in the expirate is measured continuously by means of mass spectrometer M3 Varian. Simultaneously, the expired volume and flow rate is determined by Pneumotest Jaeger. All parameters were registered
/.;:::-;;~,.~[:~;~-.{!L:-T/i:i,i~:;\T:~i;i.:iL-:~ ........ ; . . . . .
-
::
...........
~:~ ......... • . . . . . . . .
: : : :: !:'::% i: :-::: ',;-~!::i~: ::i ~-..
-:-~:iP:-:,:
~:
~:ii~!~iii-'!-~-~HF:
IAHGON
;.[.,;,~.~.,.,-.~7.~:,~;~
I ~ :
....~
:~:-:., ~:b
:
- ~-:~
50,.i
........ I . . . . . . . . . . . . . . . .
' ! :
~
~iUi
;~-',~:
; :::::~ " ;
!:- • - : - : -
J.R., C V
?:~::'-:
; ;~i::[ 'r':-"~:~:
• z
7 0 0 ml = 1 2 , 7 ~ V C
- :
:;,..
: ~
:'
-:-
{
: i
! ;
.: / " '
: : _ ~ . ~ : ~ " ;i :' : ~
-i =-.':- l - - ~ : - ~ - ~ : ? i - ~ - . ' ~
i
•
:~
i .
;
..... ~, • I !
.
-
, .::-
"
-
'~
::~: ;
Fig. 1. Estimation of closing v o l u m e by a bolus of 50 m l of argon (arrow). Upper line is argon concentration, m e a s u r e d by m a s s spectrograph. Volu m e and flow are simultaneously registered. Transport delay of m a s s spectrograph is estimated from difference of beginning of inspiration (flow curve) and end of argon concentration curve. This delay is subtracted from breaking point in argon concentration. E x a m p l e of values in n o r m a l subject
Age
years
64 53 39 41 53
42 54 60 53 62 37 53 38 60 41 48 62
57 52 51
Subj.
No.
I 2 3 4 5
6 7 8 9 10 11 12 13 14 15 16 17
18 19 20
13,9 ii,6 15,7
11, 2 9,2 14, 3 8,0 26,3 12,9 20,0 15, 8 21,2 24,1 12, 6 23, 6
16,7 19, 5 9, 2 12, 3 18, 8
%VC
CV
9,6 3,2 ii,2
6, 8 14,6 11, 8 11,6 14,7 8,0 7,0 7, 8 9,1 14,0 13,8 32, 2
torr R 15,0 14, 6 3, 0 12, 6 12, 8
PAPd
34,6 19,2 35,4
10, 0 25,8 35, 5 42,6 34,1 16,6 26,9 14, 6 18,1 26,0 40,0
E 29,3 36, 6 17, 3 35, 0 32, 5
0 7 0 3 0 6 7 5
6 0 6 2 7 8 0 0 0 0 5 9
23 20 8 25 17 13 25 14
15 21 11 12 11 17 19, 20 53 17, 10 14
torr R
PAP
52,4 30,0 49, 0
60,0 46, 0 21, 5 43, 0 20, 8 29,0 30, 0 48,0
43,0 43, 5
50, 5 46, 0 22,0 50, 4 43,1 22,0
E
0 5
75 79
95 0 86, 5 68, 0 70, 0 58,7 81, 0 88, 5 79, 4
0 0 5 0 3 0 5 4 0 5
torr
64 78 79 75 81 73 85, 81. 91 68
R
PaO E
5 0 0 0
66, 0 87, 2 90, 3
81, 80, 76, 74,
83, 5 74, 0
64, 5 77, 1 85, 8 76, 5" 81, 2 74,0 71, 5 71, 0 78,0 64, 0
2
0 2
22,0 30, 3 16,6
52,8
23, 1 33, 0 24, 0 43, 5 11,5 42, 5 28, 0 22, 5
50, 0 27, 1 14, 8 22,3 21, 3
38,0 22, 2 17,7
38, 9 39, 7 34, 0 40, 0 14,5 34, 0 24, 5 20, 0
49, 5 29, 5 19, 1 28,3 29, 5
difference R E
A-a
3 0 2 8 8 1 5 9 8 1 9 2 1 2 1
1
66,2 74, 1
702 74 69 75 71 79 72 67 76 61 84 68 78 64 66 77
%~/C
FEV
96,8 97,2
89,6 I00, 1 I00, 0 95,5 98,0 97,2 90, i 104, 3 78 1 90 3 112 0 85 8 99 9 i01 0 ii0 7 106 9
% norm.
VC
Table i. Individual values in 20 males 3-5 months after acute myocardial infarction. CV % VC = closing volume in percent of vital capacity, PAPd = pulmonary artery diastolic pressure, YAP = pulmonary artery mean pressure, PaO 2 = arterial oxygen pressure, A-a 02 = alveolo - arterial oxygen pressure difference, FEV 1 = foP'ced expiratory volume, VC = vital capacity
O3
69 on the Heloscriptor Hellige and at the same time also on the X-Y recorder Hewlett-Packard. Simultaneous registration of the volume and flow is advantageous, because it enables the control of the inspiratory and expiratory flow rate as well as the transport lag of the mass spectrometer capillary (about 0.5 s), which cannot be done from the X-Y record. The calculation of the closing volume is shown in Figure I. After allowing for the transport lag, the closing volume is measured at the breaking point of the expired argon concentration curve and expressed in the percentage of the vital capacity. An average of at least three examinations is demanded [3]. We have therefore performed four determinations~ the highest and lowest values being ommitted, and an average of the two remaining measurements resulted in the definitive value of the closing volume. It is well known that age will affect closing volume considerable [20]. For that reason we have examined with the same technique, a group of healthy male subjects of varying age, smokers and nonsmokers, to get our own reference values.
RESULTS The examination of healthy males showed a significant relation to age (Fig. 2). In young subjects no closing volume was measurable. In contrast to McCarty et al. [13], no relation to smoking was found. The average value of closing volume +- 2 SD was employed as a normal range for evaluating the findings in patients after AMI. The individual values of 20 males 3-5 months after AMI are summarized in Table I. The closing volume in all patients was in normal range. Only two patients exceeded + 2 SD of the predicted value (Fig. 3). Arterial oxygen tension decreased in nine patients (45%) below the normal value (after Sorbini [21]) according to age (Fig. 4). A certain relation of closing volume to the arterial oxygen tension was, however, not significant (Fig. 5). The alveoloarterial oxygen pressure difference at rest exceeded the predicted value [16] in i0 out of 17 patients examined (Table i). A correlation to the closing volume could not be demonstrated. No relationship was established between the size of closing volume and hernodynamie findings. The pulmonary artery diastolic pressure was elevated in seven patients above the normal value at rest, in others an abnormal elevation occurred only during exercise (Table i). This parameter showed, however, no correlation to closing volume at rest or during effort (Fig. 6). The vital capacity and the forced expiratory volume remained in most of the patients in normal range (Table i) and no correlation of these parameters to closing volume was found.
70 CV %vc
r • 0,606 p < o.ool
25
y.o.:~s x- 2.2?5
20" 15.
....
....---"o
"
-";
.-'"
"'~
-
"~"
o
" "
o
Qg
0%
0
• 'no°°'°
105. 0
/ •
2'0
oet
8
;30
~'~ .
-"
"
.--''""
,.,=. ,,
oSmo er • Nonsmoker
"
4'0
5'0
6'0
iO YEARS
Fig. 2. Closing volume in percent of vital capacity in healthy m a l e s of different age, s m o k e r s and nonsmokers. Dotted: + 2 S D
CV %vc 30.
252015°°.°'°'°°
•
~
•
_.
10-
50-
2()
30
40
5()
60
70 YEARS
Fig. 3. Closing v o l u m e in 20 m a l e s 3-5 m o n t h s after acute myocardial infarction. Dotted _+ 2 S D n o r m a l range
71 Fig. 4. Arterial oxygen pressure in 20 males 3-5 months after AIV[I related to normal values according to Sorbini
~O2 torr 10o
"'-.`-.
90 ¸
80-
~ O R B I N I
70-
60
~
(~0
CV %VC
!
~ YEARS
Fig. 5. Relation of closing volume (CV % VC) to arterial oxygen pressure. The correlation is not signi-
• kk
15 •
\
•
10-
5
:
•
// 50
60
70
•
8~0
•
\
r=- o.386 p > o.o5
g()
l(JO Pa02 torr
72 EFFORT
REST
CV %VC 25"
e
20-
e
15-
oo
00
o
10-
5-
10
2'0
10
2'0
3'0
4'oPAPd torr
Fig. 6. Correlation of closing volume (CV % VC) to pulmonary artery stolic pressure (PAPd), regarded as indirect index of left ventricular filling pressure, is not significant at rest nor during effort
dia-
DISCUSSION In the acute stage of myocardial infarction there are often signs of left ventricular failure with lung congestion and arterial hypoxemia [ii ]. A transsudation occures into the lung interstitium whidh can compromise the blood flow distribution as well as the function of small airways because they are placed together with vessels in the space-limited connective tissue [ 5]. Experimentally, hypoventilation of the dependent lung zones could be demonstrated when pulmonary venous pressure was increased [ 7]. In patients suffering from left heart failure an increase in closing volume was found [ 2] as well as in patients with acute myocardial
infarction [S]. The signs of left heart failure disappear rapidly in the later course of myocardial infarction, but abnormal left ventricular function with passive pulmonary hypertension could be found even months later in a high percentage of patients after AMI [18]. The closing volume becomes, on the other hand, normal in nearly all patients convalescing from AMI. Hales and Kazemi [5] found in the acute stage of myocardial infarction an abnormal closing volume in 25 out of 26 patients, 3-4 weeks later they found this change only in 4 out of 14 and after 4-12 months in none of the 7 patients examined. This is in accordance with our findings of normal closing volume in nearly all patients 3-5 months after AMI.
73 Against a major role of closure of the small airways in the origin of arterial hypoxemia in myocardial infarction, simultaneous changes in lung perfusion are occurring~ also. In the acute phase there is a hypoventilation of the lower lung zones, but at the same time a decreased perfusion of the same zones could be demonstrated [12]. This diminishes the extent of ventilation-perfusion disturbance in the dependent lung fields. On the contrary, during the convalescence after AIV[I, not only the ventilation but also the perfusion of the lower lung zones improves [ i]. Our results can be influenced by examination of the blood gases in recumbent position in which slightly lower values of arterial oxygen tension are found than in sitting position [15], i.e., in the position in which the closing volume was measured. These differences are, however, not great enough to substantially influence the obtained results. The changes in small airways, in our opinion, don't play a major role in the development of arterial hypoxemia in the convalescence after AMI. The closing volume is, in this phase, in normal range and no correlation to the hemodynamic changes could be found. The origin of arterial hypoxemia in convalescence after acute myocardial infarction still remains to be fully elucidated.
REFERENCES I. Bazzaz AI., F.J., Kazemi, H. : Arterial hypoxemia and distribution of pulmonary perfusion after uncomplicated myocardial infarction. A m e r . Rev. Respir. Dis. 106, 721-728 (1972) 2. Collins, J.V., Clark, T.J.H., M c H a r d y - Y o u n g , S. : Small airways closure in left heart failure. T h o r a x 2__7, 260 (1970) 3. Collins, J.V. : "Closing volume" after myocardial infarction. New Engl. J. Med. 291, 97-98 (1974) 4. Dolfuss, R.E., Milic-Emily, J., Bates, D.V. :Regional ventilation of the lung, studied with boluses of 133Xenon. Respiration Physiol. 2, 2B4-246 (1967) 5. Hales, C.A., Kazemi, H.: Small-airways function in myocardial infarction. New. Engl. J. Med. 290, 761-765 (1974) 6. Higgs, B.E., Clode, M., Campbell, E. J.M. :Changes in ventilation, gas exchange, and circulation during exercise after recovery from myocardial infarction. Lancet 1968/II, 793-795 7. Iliff, L.D., Greene, R.E., Hughes, J.M.B. : Effect of interstitial edema distribution of ventilation and perfusion in isolated lung. J. Appl. Physiol. 9_33, 462-467 (1972) 8. Interiano, B., Hyde, R.W., Hodges, 114., Yu, P.N. :Nature of airway obstruction in patients with acute myocardial infarction. Clin. Res. 20, 578 (1972) 9. Kazemi, H., Parsons, F., Valenca, L.M., Strieder, D. J. : Distribution of pulmonary blood flow after myocardial ischemia and infarction. Circulation 41, 1025-1030 (1970) i0. Konietzko, N., Schlehe, K.H., Gefke, E., Adam, W., ik4atthys, H. : Der Nachweis des VerschlufSes kleiner Luftwege mit Hilfe einer
74
ii.
12.
13.
14.
15.
16.
17. 18.
19.
20. 21.
modifizierten 133Xenon-Bolustechnik. Pneumologie 149, 113-117 (1973) M~lek, I., Stan~k, V., Pavlovi~, J., Smld, J. :Arterial hypoxemia in acute myocardial infarction (in czech). Cas. lek. 5es. 112, 1313-1318 (1973) M~lek, I., Oppelt, A., Stan~k, V., Pavlovi[, J., Srnld, J. :The value of lung perfusion gradient in the detection of acute left heart failure. Progr. Respir. Dis. 9, 232-236 (1975) McCarty, D.S., Spencer, R., Greene, R., Milic-Emily, J. : Measurement of "closing volume" as a simple and sensitive test for early detection of small airway disease. Amer. J. Med. 52, 747-753 (1972) McNicol, M.W., Kirby, B.J., IBhoola, K.D., Fulton, P.M., Tattersfield, A.E. : Changes in pulmonary function 6-12 months after mecovery from myocardial infarction. Lancet 1966/II, 1441-1443 Ou~ednik, A., Parkmannov~, A. : Variations in blood gases and pH change of blody position from sitting to supine in healthy subjects (in czech). Gas. ilk. [es. 113, 677-678 (1974) Raine, J.M., Bishop, J.M, : A-a difference in 02 tension and physiological dead space in normal man. J. Appl. Physiol. 18, 284-288 (1963) Ressl, Jo : Heart catheterization with a floating catheter. Cor Vasa 15, 199-208 (1973) Ressl, J., Jandov~, R., Jebav~, P., Kasalick~, J. The significance of passive pulmonary hypertension in patients 3-5 months after myocardial infarction. Progr. Resp. Res. 9, 225-231 (1975) Riley, R. L. , Cournand, A. , Donald, K.W. : Analysis of factors affecting partial pressures of oxygen and carbon dioxide in gas and blood of lungs: methods. J. Appl. Physiol. 4__ 102-120 (1951) Ruff, F. : Effects of age and posture on closing volume. Scand. J. Resp. Dis., Suppl. 85, 190-200 (1974) Sorbini, C.A., Grassi, V., Solinas, E., Muiesan, G. :Arterial oxygen tension in relation to age in healthy subjects. Respiration 25, 3-13 (1968) v
t
v
t
Dr. J. Ressl Institute for Clinical and E x p e r i m e n t a l Medicine Bud~jovick~ 809 (B 5)
Received
February
23, 1976
CS-146 22 Praha Czechoslovakia
4 - Kr~
154,
65-74
(1976)
Springer-V~
Obstruction of Small Airways in Patients After Acute Myocardial Infarction J. Ressl,
L.
Cernj~,
R.
Jandov~
and
L.
Nikod~mov~
2nd Research Unit of Internal Medicine (Chief: Ass. Prof. J. %Vidimsk~, DrSc) of the Institute for Clinical and Experimental Medicine (Head: Prof. P. M~lek, DrSc), Praque, CSSR
Ab st r act. The closing volume of the small airways was measured using the argon bolus technique by mass spectrography in 20 males 3 to 5 months after acute myocardial infarction. No patient exhibited signs of a manifest heart failure or of a simultaneous pulmonary disease. The closing volume expressed in percent of vital capacity exceeded in only 2 patients the limits of + 2 SD of our own normal values. A slight arterial hypoxemia was established in 45% of patients but its correlation to closing volume was not significant. Also, no correlation was found to the alveoloarterial oxygen pressure gradient, vital capacity, or expiratory forced volume. The hemodynamic changes in the lesser circulation were examined in all patients with floating catheter. The closing volume showed no correlation to the pulmonary artery diastolic pressure (regarded as an index of left ventricular filling pressure), nor to the pulmonary mean pressure both at rest and during effort. Key
words:
Myocardial
infarction
- Airway
obstruction
Zusammenfassung. Das VerschluSvolumen der kleinen Luftwege (closing volume) wurde mittels Argon Bolus-Methode bei 20 Kranken 3-5 Monate nach einem akuten Herzinfarkt mittels Mass Spectrometer gemessen. Keiner der Kranken zeigte klinische Symptome einer manifesten Herzschw~che oder einer gleichzeitigen Lungenerkran.kung. Das Verschluf~volumen iiberstieg nur bei 2 Patienten die Orenze yon + 2 SD eigener Sollwerte. Eine arterielle Hypox~mie, meist leichten Grades, wnrde bet 45% der Kranken festgestellt, lhre Abh~ngigkeit yon der Gr~i2e des Verschlu2volumens wurde statistisch nicht signifikant. Es wurde keine Korrelation zu der alveolo-arteriellen Sauerstoffdruckdifferenz, der Vitalkapazit~t und dem Atemstoff gefundeno
66 Die h~imodynamischen Ver~inderungen irn kleinen Kreislauf wurden bei allen Patienten ambulant rnit dern Einschwernrnkatheter untersucht. Das Verschluf~volurnen zeigte keine Korrelation zur GrOf~e des diastolischen Pulmonalisdruckes, der als ein Index des linksventrikul~iren Filllungsdruckes betrachtet wurde, und zur HShe des rnittleren Pulrnonalisdruckes und zwar in Ruhe oder bei Belastung.
INTRODUCTION Most cases of an acute myocardial infarction (AMI) are accompanied by arterial hypoxemia, which is caused mainly by the disturbance of the ventilation-perfusion ratio and has a certain relation to abnormal hemodynarnic left ventricular function (M&lek et al., 1973). During convalescence the hypoxemia becomes normal in some patients, but in others, however, it perseveres. They are only few data available on the latter group and they are conflicting. McNicol et al. [14]found arterial hypoxernia and an increased alveoloarterial oxygen pressure gradient in 43% of patients 6-12 months after acute myocardial infarction. Higgs ei al. [ 6] described an elevated alveoloarterial oxygen gradient in a part of patients convalescing from AMI. Bazzaz and Kazemi [l] are reporting, on the contrary, nearly normal findings 2-6 months after AMI. In our series a slight arterial hypoxemia was found in 45% of patients 3-5 months after acute myocardial infarction, in w~hich hypoventilation and pulmonary diffusing capacity disturbance could be excluded. The causes of hypoxernia in the convalescence from AMI has not yet been completely elucidated. One of the possible causes could be the augmentation of the closing volume of the small airways. If the closing volume (CV) is larger than the functional residual capacity, the hypoventilation of lower lung zones with a disturbance of gas exchange can occur. Hales and Kazemi [ 5] showed that in AMI a transitory left ventricular failure with a pulmonary congestion can lead to the closure of the small airways and to hypoxernia. Interiano et al. [8] found in the patients with AIViI an increased resistance of peripheral airways with hypoxemia. As yet there is, however, little knowledge available on the changes of closing volume during convalescence from AMI. This has initiated us to investigate the closing volume in patients 3-5 months after acute myocardial infarction and to correlate the results with some changes in ventilation, gas exchange, and hemodynamic findings in the lesser circulation.
MATERIAL
AND
METHODS
There were 20 males, aged 37-64 years (mean age 51 years) examined. The diagnosis of AMI was established in all at our coronary care unit. A coexisting pulmonary disease was excluded by clinical, laboratory, and chest x-ray examinations. No patient was suffering from a manifest heart failure. Hernodynamic examination was performed in supine out-patients by the floating catheter technique [17] 3-5 months after AIV[I. The pulmo-
67
nary artery mean pressure was measured by electrical integration on Mingograph Elema 81 apparatus. The diastolic pulmonary pressure, regarded as an indicator of left ventricular filling pressure~ was obtained by averaging two breathing cycles from at least I0 individual values. The cardiac output was determined by the Fick method. Expired air was collected in a Douglas bag for 3-5 min and analyzed for oxygen and carbon dioxide concentration by means of a Zeiss interpherometer. The oxygen tension in arterial and mixed venous blood from the pulmonary artery was determinded by Micro Astrup Apparatus BMS 2 Radiometer fitted with the Clark electrode. The alveolar oxygen tension was calculated after Riley et al° [19]. The global spirometry was examined in sitting subjects using Godart Pulmotest. For measurement of the closing volume, special methods are necessary [4~ i0]. We employed the argon bolus technique in the sitting position. At the end of maximal expiration, an argon bolus of 50 ml was injected rapidly into the mouthpiece followed by a slow maximal inspiration. During the subsequent slow maximal expiration (flow rate 0.2-0.5 L/s) the argon concentration in the expirate is measured continuously by means of mass spectrometer M3 Varian. Simultaneously, the expired volume and flow rate is determined by Pneumotest Jaeger. All parameters were registered
/.;:::-;;~,.~[:~;~-.{!L:-T/i:i,i~:;\T:~i;i.:iL-:~ ........ ; . . . . .
-
::
...........
~:~ ......... • . . . . . . . .
: : : :: !:'::% i: :-::: ',;-~!::i~: ::i ~-..
-:-~:iP:-:,:
~:
~:ii~!~iii-'!-~-~HF:
IAHGON
;.[.,;,~.~.,.,-.~7.~:,~;~
I ~ :
....~
:~:-:., ~:b
:
- ~-:~
50,.i
........ I . . . . . . . . . . . . . . . .
' ! :
~
~iUi
;~-',~:
; :::::~ " ;
!:- • - : - : -
J.R., C V
?:~::'-:
; ;~i::[ 'r':-"~:~:
• z
7 0 0 ml = 1 2 , 7 ~ V C
- :
:;,..
: ~
:'
-:-
{
: i
! ;
.: / " '
: : _ ~ . ~ : ~ " ;i :' : ~
-i =-.':- l - - ~ : - ~ - ~ : ? i - ~ - . ' ~
i
•
:~
i .
;
..... ~, • I !
.
-
, .::-
"
-
'~
::~: ;
Fig. 1. Estimation of closing v o l u m e by a bolus of 50 m l of argon (arrow). Upper line is argon concentration, m e a s u r e d by m a s s spectrograph. Volu m e and flow are simultaneously registered. Transport delay of m a s s spectrograph is estimated from difference of beginning of inspiration (flow curve) and end of argon concentration curve. This delay is subtracted from breaking point in argon concentration. E x a m p l e of values in n o r m a l subject
Age
years
64 53 39 41 53
42 54 60 53 62 37 53 38 60 41 48 62
57 52 51
Subj.
No.
I 2 3 4 5
6 7 8 9 10 11 12 13 14 15 16 17
18 19 20
13,9 ii,6 15,7
11, 2 9,2 14, 3 8,0 26,3 12,9 20,0 15, 8 21,2 24,1 12, 6 23, 6
16,7 19, 5 9, 2 12, 3 18, 8
%VC
CV
9,6 3,2 ii,2
6, 8 14,6 11, 8 11,6 14,7 8,0 7,0 7, 8 9,1 14,0 13,8 32, 2
torr R 15,0 14, 6 3, 0 12, 6 12, 8
PAPd
34,6 19,2 35,4
10, 0 25,8 35, 5 42,6 34,1 16,6 26,9 14, 6 18,1 26,0 40,0
E 29,3 36, 6 17, 3 35, 0 32, 5
0 7 0 3 0 6 7 5
6 0 6 2 7 8 0 0 0 0 5 9
23 20 8 25 17 13 25 14
15 21 11 12 11 17 19, 20 53 17, 10 14
torr R
PAP
52,4 30,0 49, 0
60,0 46, 0 21, 5 43, 0 20, 8 29,0 30, 0 48,0
43,0 43, 5
50, 5 46, 0 22,0 50, 4 43,1 22,0
E
0 5
75 79
95 0 86, 5 68, 0 70, 0 58,7 81, 0 88, 5 79, 4
0 0 5 0 3 0 5 4 0 5
torr
64 78 79 75 81 73 85, 81. 91 68
R
PaO E
5 0 0 0
66, 0 87, 2 90, 3
81, 80, 76, 74,
83, 5 74, 0
64, 5 77, 1 85, 8 76, 5" 81, 2 74,0 71, 5 71, 0 78,0 64, 0
2
0 2
22,0 30, 3 16,6
52,8
23, 1 33, 0 24, 0 43, 5 11,5 42, 5 28, 0 22, 5
50, 0 27, 1 14, 8 22,3 21, 3
38,0 22, 2 17,7
38, 9 39, 7 34, 0 40, 0 14,5 34, 0 24, 5 20, 0
49, 5 29, 5 19, 1 28,3 29, 5
difference R E
A-a
3 0 2 8 8 1 5 9 8 1 9 2 1 2 1
1
66,2 74, 1
702 74 69 75 71 79 72 67 76 61 84 68 78 64 66 77
%~/C
FEV
96,8 97,2
89,6 I00, 1 I00, 0 95,5 98,0 97,2 90, i 104, 3 78 1 90 3 112 0 85 8 99 9 i01 0 ii0 7 106 9
% norm.
VC
Table i. Individual values in 20 males 3-5 months after acute myocardial infarction. CV % VC = closing volume in percent of vital capacity, PAPd = pulmonary artery diastolic pressure, YAP = pulmonary artery mean pressure, PaO 2 = arterial oxygen pressure, A-a 02 = alveolo - arterial oxygen pressure difference, FEV 1 = foP'ced expiratory volume, VC = vital capacity
O3
69 on the Heloscriptor Hellige and at the same time also on the X-Y recorder Hewlett-Packard. Simultaneous registration of the volume and flow is advantageous, because it enables the control of the inspiratory and expiratory flow rate as well as the transport lag of the mass spectrometer capillary (about 0.5 s), which cannot be done from the X-Y record. The calculation of the closing volume is shown in Figure I. After allowing for the transport lag, the closing volume is measured at the breaking point of the expired argon concentration curve and expressed in the percentage of the vital capacity. An average of at least three examinations is demanded [3]. We have therefore performed four determinations~ the highest and lowest values being ommitted, and an average of the two remaining measurements resulted in the definitive value of the closing volume. It is well known that age will affect closing volume considerable [20]. For that reason we have examined with the same technique, a group of healthy male subjects of varying age, smokers and nonsmokers, to get our own reference values.
RESULTS The examination of healthy males showed a significant relation to age (Fig. 2). In young subjects no closing volume was measurable. In contrast to McCarty et al. [13], no relation to smoking was found. The average value of closing volume +- 2 SD was employed as a normal range for evaluating the findings in patients after AMI. The individual values of 20 males 3-5 months after AMI are summarized in Table I. The closing volume in all patients was in normal range. Only two patients exceeded + 2 SD of the predicted value (Fig. 3). Arterial oxygen tension decreased in nine patients (45%) below the normal value (after Sorbini [21]) according to age (Fig. 4). A certain relation of closing volume to the arterial oxygen tension was, however, not significant (Fig. 5). The alveoloarterial oxygen pressure difference at rest exceeded the predicted value [16] in i0 out of 17 patients examined (Table i). A correlation to the closing volume could not be demonstrated. No relationship was established between the size of closing volume and hernodynamie findings. The pulmonary artery diastolic pressure was elevated in seven patients above the normal value at rest, in others an abnormal elevation occurred only during exercise (Table i). This parameter showed, however, no correlation to closing volume at rest or during effort (Fig. 6). The vital capacity and the forced expiratory volume remained in most of the patients in normal range (Table i) and no correlation of these parameters to closing volume was found.
70 CV %vc
r • 0,606 p < o.ool
25
y.o.:~s x- 2.2?5
20" 15.
....
....---"o
"
-";
.-'"
"'~
-
"~"
o
" "
o
Qg
0%
0
• 'no°°'°
105. 0
/ •
2'0
oet
8
;30
~'~ .
-"
"
.--''""
,.,=. ,,
oSmo er • Nonsmoker
"
4'0
5'0
6'0
iO YEARS
Fig. 2. Closing volume in percent of vital capacity in healthy m a l e s of different age, s m o k e r s and nonsmokers. Dotted: + 2 S D
CV %vc 30.
252015°°.°'°'°°
•
~
•
_.
10-
50-
2()
30
40
5()
60
70 YEARS
Fig. 3. Closing v o l u m e in 20 m a l e s 3-5 m o n t h s after acute myocardial infarction. Dotted _+ 2 S D n o r m a l range
71 Fig. 4. Arterial oxygen pressure in 20 males 3-5 months after AIV[I related to normal values according to Sorbini
~O2 torr 10o
"'-.`-.
90 ¸
80-
~ O R B I N I
70-
60
~
(~0
CV %VC
!
~ YEARS
Fig. 5. Relation of closing volume (CV % VC) to arterial oxygen pressure. The correlation is not signi-
• kk
15 •
\
•
10-
5
:
•
// 50
60
70
•
8~0
•
\
r=- o.386 p > o.o5
g()
l(JO Pa02 torr
72 EFFORT
REST
CV %VC 25"
e
20-
e
15-
oo
00
o
10-
5-
10
2'0
10
2'0
3'0
4'oPAPd torr
Fig. 6. Correlation of closing volume (CV % VC) to pulmonary artery stolic pressure (PAPd), regarded as indirect index of left ventricular filling pressure, is not significant at rest nor during effort
dia-
DISCUSSION In the acute stage of myocardial infarction there are often signs of left ventricular failure with lung congestion and arterial hypoxemia [ii ]. A transsudation occures into the lung interstitium whidh can compromise the blood flow distribution as well as the function of small airways because they are placed together with vessels in the space-limited connective tissue [ 5]. Experimentally, hypoventilation of the dependent lung zones could be demonstrated when pulmonary venous pressure was increased [ 7]. In patients suffering from left heart failure an increase in closing volume was found [ 2] as well as in patients with acute myocardial
infarction [S]. The signs of left heart failure disappear rapidly in the later course of myocardial infarction, but abnormal left ventricular function with passive pulmonary hypertension could be found even months later in a high percentage of patients after AMI [18]. The closing volume becomes, on the other hand, normal in nearly all patients convalescing from AMI. Hales and Kazemi [5] found in the acute stage of myocardial infarction an abnormal closing volume in 25 out of 26 patients, 3-4 weeks later they found this change only in 4 out of 14 and after 4-12 months in none of the 7 patients examined. This is in accordance with our findings of normal closing volume in nearly all patients 3-5 months after AMI.
73 Against a major role of closure of the small airways in the origin of arterial hypoxemia in myocardial infarction, simultaneous changes in lung perfusion are occurring~ also. In the acute phase there is a hypoventilation of the lower lung zones, but at the same time a decreased perfusion of the same zones could be demonstrated [12]. This diminishes the extent of ventilation-perfusion disturbance in the dependent lung fields. On the contrary, during the convalescence after AIV[I, not only the ventilation but also the perfusion of the lower lung zones improves [ i]. Our results can be influenced by examination of the blood gases in recumbent position in which slightly lower values of arterial oxygen tension are found than in sitting position [15], i.e., in the position in which the closing volume was measured. These differences are, however, not great enough to substantially influence the obtained results. The changes in small airways, in our opinion, don't play a major role in the development of arterial hypoxemia in the convalescence after AMI. The closing volume is, in this phase, in normal range and no correlation to the hemodynamic changes could be found. The origin of arterial hypoxemia in convalescence after acute myocardial infarction still remains to be fully elucidated.
REFERENCES I. Bazzaz AI., F.J., Kazemi, H. : Arterial hypoxemia and distribution of pulmonary perfusion after uncomplicated myocardial infarction. A m e r . Rev. Respir. Dis. 106, 721-728 (1972) 2. Collins, J.V., Clark, T.J.H., M c H a r d y - Y o u n g , S. : Small airways closure in left heart failure. T h o r a x 2__7, 260 (1970) 3. Collins, J.V. : "Closing volume" after myocardial infarction. New Engl. J. Med. 291, 97-98 (1974) 4. Dolfuss, R.E., Milic-Emily, J., Bates, D.V. :Regional ventilation of the lung, studied with boluses of 133Xenon. Respiration Physiol. 2, 2B4-246 (1967) 5. Hales, C.A., Kazemi, H.: Small-airways function in myocardial infarction. New. Engl. J. Med. 290, 761-765 (1974) 6. Higgs, B.E., Clode, M., Campbell, E. J.M. :Changes in ventilation, gas exchange, and circulation during exercise after recovery from myocardial infarction. Lancet 1968/II, 793-795 7. Iliff, L.D., Greene, R.E., Hughes, J.M.B. : Effect of interstitial edema distribution of ventilation and perfusion in isolated lung. J. Appl. Physiol. 9_33, 462-467 (1972) 8. Interiano, B., Hyde, R.W., Hodges, 114., Yu, P.N. :Nature of airway obstruction in patients with acute myocardial infarction. Clin. Res. 20, 578 (1972) 9. Kazemi, H., Parsons, F., Valenca, L.M., Strieder, D. J. : Distribution of pulmonary blood flow after myocardial ischemia and infarction. Circulation 41, 1025-1030 (1970) i0. Konietzko, N., Schlehe, K.H., Gefke, E., Adam, W., ik4atthys, H. : Der Nachweis des VerschlufSes kleiner Luftwege mit Hilfe einer
74
ii.
12.
13.
14.
15.
16.
17. 18.
19.
20. 21.
modifizierten 133Xenon-Bolustechnik. Pneumologie 149, 113-117 (1973) M~lek, I., Stan~k, V., Pavlovi~, J., Smld, J. :Arterial hypoxemia in acute myocardial infarction (in czech). Cas. lek. 5es. 112, 1313-1318 (1973) M~lek, I., Oppelt, A., Stan~k, V., Pavlovi[, J., Srnld, J. :The value of lung perfusion gradient in the detection of acute left heart failure. Progr. Respir. Dis. 9, 232-236 (1975) McCarty, D.S., Spencer, R., Greene, R., Milic-Emily, J. : Measurement of "closing volume" as a simple and sensitive test for early detection of small airway disease. Amer. J. Med. 52, 747-753 (1972) McNicol, M.W., Kirby, B.J., IBhoola, K.D., Fulton, P.M., Tattersfield, A.E. : Changes in pulmonary function 6-12 months after mecovery from myocardial infarction. Lancet 1966/II, 1441-1443 Ou~ednik, A., Parkmannov~, A. : Variations in blood gases and pH change of blody position from sitting to supine in healthy subjects (in czech). Gas. ilk. [es. 113, 677-678 (1974) Raine, J.M., Bishop, J.M, : A-a difference in 02 tension and physiological dead space in normal man. J. Appl. Physiol. 18, 284-288 (1963) Ressl, Jo : Heart catheterization with a floating catheter. Cor Vasa 15, 199-208 (1973) Ressl, J., Jandov~, R., Jebav~, P., Kasalick~, J. The significance of passive pulmonary hypertension in patients 3-5 months after myocardial infarction. Progr. Resp. Res. 9, 225-231 (1975) Riley, R. L. , Cournand, A. , Donald, K.W. : Analysis of factors affecting partial pressures of oxygen and carbon dioxide in gas and blood of lungs: methods. J. Appl. Physiol. 4__ 102-120 (1951) Ruff, F. : Effects of age and posture on closing volume. Scand. J. Resp. Dis., Suppl. 85, 190-200 (1974) Sorbini, C.A., Grassi, V., Solinas, E., Muiesan, G. :Arterial oxygen tension in relation to age in healthy subjects. Respiration 25, 3-13 (1968) v
t
v
t
Dr. J. Ressl Institute for Clinical and E x p e r i m e n t a l Medicine Bud~jovick~ 809 (B 5)
Received
February
23, 1976
CS-146 22 Praha Czechoslovakia
4 - Kr~
