Download Assessment of myocardial injury by serum tumour necrosis factor

European Heart Journal (1996) 17, 1852-1859
Assessment of myocardial injury by serum tumour
necrosis factor alpha measurements in acute
myocardial infarction
M. M. Hirschl*, M. Gwechenbergerf, T. Binderf, M. Binder^, S. Graff,
T. Stefenellit, F. Rauschaf, A. N. Laggner* and H. Sochorf
^Department of Emergency Medicine, University of Vienna, Austria; ^Clinic of Internal Medicine 2, Department of
Cardiology, University of Vienna, Austria; %Department of Dermatology, University of Vienna, Austria
Clinical and experimental data have shown that after
acute myocardial infarction there is a significant release of
tumour necrosis factor alpha. Therefore, an attempt was
made to correlate changes in serum tumour necrosis factor
alpha concentrations with indices of infarct extent in
patients with acute myocardial infarction.
In 50 patients with acute myocardial infarction, blood
samples for evaluation of tumour necrosis factor alpha and
alpha-hydroxybutyrate-dehydrogenase were collected every
6 h until 120 h after admission. Infarct extent was estimated
by clinical parameters such as the occurrence of heart
failure and rhythm disturbances, by enzymatic methods
such as cumulative release of alpha-hydroxybutyratedehydrogenase and imaging techniques, by late resting
single
photon
emission
tomography — 2 0 1 thallium
scintigraphy — using an extent score and by echocardiography using a wall motion index. The maximum change in
serum tumour necrosis factor alpha after infarction
(^JTNF) was calculated by subtracting tumour necrosis
factor alpha concentration on admission from peak tumour
necrosis factor alpha concentration.
Introduction
Evaluation of the extent of acute myocardial infarction
is important for predicting the subsequent clinical course
and the prognosis of patients'1"31. In previous studies,
estimation of infarct extent has been based on serum
enzyme elevation during the acute phase of infarction'4"61. However, there was no strong correlation
applicable for practical clinical use between changes in
enzymes and myocardial infarction extent since the
release of enzymes might be influenced by the degree of
Revision submitted 8 March 1996. and accepted 20 March 1996.
Correspondence: Michael M. Hirschl. MD. Department of
Emergency Medicine. New General Hospital. Wahringer Gurtel
18-20, A-1090 Vienna, Austria.
0195-668X/96/121852+08 S25.00/0
The average peak tumour necrosis factor alpha level was
observed 84 h after admission (median: 1 2 p g . m l ~ ' ) .
Between the 72nd and the 96th h no significant changes
in tumour necrosis factor alpha values were observed.
Analysis of the data showed that larger zl(TNF) values were
found to be associated significantly with signs of heart
failure (P=0003), the presence of rhythm disturbances
(/ > =0001), increased enzymatic infarct extent indicated
by cumulative
release
of
alpha-hydroxybutyratedehydrogenase (r=0-74; / > <0001), large myocardial perfusion defects measured with 201 thallium scintigraphy
(r=0-80; P<0-001), and a considerable number of left
ventricular wall motion abnormalities (r=0-57; / ) <0001).
In conclusion, /f(TNF) is a reliable method of assessing
damage severity in the myocardium after acute myocardial
infarction. As only two blood samples are necessary within
84 h, the method may be one of the more convenient for the
assessment of infarct size in clinical practice.
(Eur Heart J 1996; 17: 1852-1859)
Key Words: Myocardial infarction, tumour necrosis factor.
reperfusion and infarct localization'7 10]. Tumour necrosis factor alpha (TNF-a) is a hormone-like polypeptide
with a variety of activities involved in the defence
against pathogenic microorganisms and in the process of
tissue repair'"1. In-vitro data revealed a significantly
higher release of TNF-a from macrophages in patients
with stable or unstable angina compared to patients
without any evidence of coronary artery disease'121.
Additionally, an experimental porcine model demonstrated that after an ischaemic event, macrophages
migrate into the ischaemic myocardium and release
TNF-a locally'131. The number of cells migrated into the
myocardium increased until 72 h after vessel occlusion
and remained constant over the next 3 weeks. There
are also clinical data demonstrating a significant increase of TNF-a in patients with acute myocardial
1996 The European Society of Cardiology
lnfarct size and tumour necrosis factor alpha
infarction'1415'. In view of these experimental and clinical data, it can be assumed that after an ischaemic event
macrophages that migrated into the myocardium are the
source for the increased TNF-a in patients with acute
myocardial infarction. The extent of infarcted myocardium is frequently assessed by the integration of clinical
information, amount of non-contractile myocardium
and also more recently by scintigraphic indices of severe
and irreversible perfusion abnormalities in the 'area-atrisk'. Thus, the goal of the present study was to investigate the correlation between parameters of infarct extent
and changes in serum TNF-a concentrations in patients
after acute myocardial infarction.
Methods
1853
infarction. Cumulative release of a-HBDH (HBDHQ72)
within the first 72 h was calculated by a twocompartment model described previously'81.
Echocardiography
Two-dimensional echocardiography was performed on
day 3 after acute myocardial infarction. A 16-segment
model, as proposed by the American Society of
Echocardiography, was used in the present study'18'. The
severity of regional wall motion abnormalities was
graded by a score for each segment: 1= normal, 2 =
hypokinesia, 3 = akinesia, 4=dyskinesia. The wall
motion index was calculated as the mean of visualized
regional wall motion scores. Thus, a normal left ventricle would have a wall motion score index of 1.
Theoretically, the maximal wall motion score index
could be 4 if all segments were dyskinetic.
Patient selection
Between April 1993 and March 1994, 58 consecutive
patients admitted to the emergency department with
acute myocardial infarction were included in the study
protocol. Acute myocardial infarction was diagnosed by
a history of acute chest pain lasting for more than
30 min and persistent ST segment elevation as demonstrated on the ECG. Transmural infarction was confirmed by serial electrocardiographic abnormalities, with
the development of Q waves lasting 004 s or longer as
well as a typical rise and fall in levels of serum creatine
kinase MB. Infarct location was defined as anterior if Q
wave development occurred in leads I, aVL or V, to V6
and as inferior if Q waves occurred in leads II, III or
aVF. All patients received 100 mg rt-PA (Actilyse,
Boehringer Ingelheim, GmbH, Ingelheim am Rhein,
Germany) as thrombolytic therapy administered by accelerated frontloading'161. Treatment was preceded by an
intravenous bolus of 5000 IU of conventional heparin,
5 mg intravenous propanolol and 100 mg aspirin orally.
After thrombolytic therapy, conventional heparin and
nitrates were given intravenously until normalization of
creatine kinase MB (<10 U . 1~ '). Eight patients were
excluded for the following reasons: death within 24 h
due to cardiogenic shock (n = 2), absence of transmural
infarction (n=4), prior myocardial infarction (n = 2). The
remaining 50 patients were 38 men and 12 women with
a mean age of 55 ± 12 years (range: 34-75).
Definition of in-hospital complications after acute
myocardial infarction
The complications studied were the presence of heart
failure (class II, III, or IV according to Killip1'7') on the
first day or persisting longer and the presence of major
rhythm disturbances, which required therapeutic intervention (application of antiarrhythmic drugs, intravenous insertion of a temporary pacemaker, cardioversion
or defibrillation).
Enzymatic infarct extent estimation
Blood samples for determination of a-HBDH were
taken every 12 h until 120 h after acute myocardial
201
thallium scintigraphy
Thallium scintigraphy was performed between the 7th
and 10th day after myocardial infarction. Following
resting injection of 3-3-5 mCi of 20lTl-chloride, single
photon emission tomography (SPECT) was performed
with a rotating gamma camera. Early imaging was
carried out 15 to 30 min after injection and 3^4 h later
(late resting distribution). Only the late tracer distribution was taken into account for this study, as it had been
shown to correlate with absence or presence of residual
viability and thus the amount of severely underperfused
and infarcted myocardium. Cross-sectional images in
three standard slice orientations were obtained (16 slices
for short axis, 8-12 slices for vertical long axis and 8-10
slices for horizontal long axis). From the late distribution of a short axis tracer, polar map analysis was
carried out using count profiles which displayed information on all slices in a 'target-like' fashion1'91. From
this polar map or 'bull's eye' the extent score was
calculated as the ratio of the defect area to the total area
of the left ventricular myocardium in comparison to a
validated normal data base'201.
Coronary angiography
Coronary angiography was performed between the 10th
and 14th day after onset of myocardial infarction. The
infarct-related artery was identified by assessing the
electrocardiogram, the ventriculographic location of
the contractile abnormality and the presence of stenosis
or thrombus in the corresponding artery. Flow in the
infarct-related artery was determined during the initial
injection of the contrast agent and graded as described
in the Thrombolysis in Myocardial Infarction (TIMI)
trial'2'1. According to TIMI grading, the patients were
classified into two groups: patients without reperfusion
of the infarct-related artery (TIMI grade 0 or 1) and
patients with reperfusion of the infarct-related artery
(TIMI grade 2 or 3).
Eur Heart J, Vol. 17, December 1996
1854 M. M. Hirschl et al.
Blood sampling and handling
Blood samples were collected from patients through a
venous cannula inserted in the forearm not used for
administration of treatment, immediately before thrombolytic therapy and thereafter at intervals of 6 h up to
120 h to determine TNF-a. The first 5 ml were discarded
and samples for TNF-a were collected into endotoxinfree evacuated glass tubes with sodium heparin
(Chromogenix AB, Sweden). Samples were centrifuged
within lOmin at 3000 # at 4 °C for 15min. Plasma
specimens of 500 |il were stored at — 70 °C in plastic
tubes. All patients gave their written informed consent
for taking the additional blood samples.
Assay
The concentrations in plasma (pg.ml" 1 ) of TNF-a
were determined with the use of an enzyme immunoassay according to the manufacturers instructions
(Innotest h TNF-a; Innogenetics: Belgium). Purified
TNF-a was used for construction of standard curves.
The lower detection limit of TNF-a was 4 0 pg . ml ~ '.
The calculated overall intra-assay and interassay coefficient of variation was 6-5% and 7-6%, respectively.
Calculation and statistics
As TNF-a is detectable in about 50% of all healthy
subjects'22231, we calculated the difference between the
highest TNF-a concentration and TNF-a concentration
on admission:
= TNF-a (max) - TNF-a
(admission) .
Numerical data are given as mean (standard deviation,
SD) or median (interquartile range, IQR) as appropriate. Differences in the TNF-a concentrations between
the 72nd and 96th h after admission were calculated
using the Wilcoxon signed rank test. Unpaired Student's
t-test was used to investigate differences between
groups'24"261. Simple and multiple regression was used to
investigate associations between variables. All analyses
were performed on the SPSS-release 6.0 statistical package (SPSS Inc., U.S.A.). F-values <005 (two sided) were
considered as statistically significant.
Results
Patients characteristics (Table 1)
Based on electrocardiographic data, myocardial infarction was located in the anterior wall in 24 patients and in
the inferior wall in 26 patients. The location and patency
of the infarct-related artery and the number of diseased
vessels are summarized in Table 1.
Eur Heart J. Vol 17. December 1996
Table I Patient characteristics and results of coronary
angiography performed between the 10th and 14th day
after acute myocardial infarction. The infarct-related
artery was identified by assessing the electrocardiogram,
the ventriculographic location of the contractile abnormality and the presence of stenosis or thrombus in
the corresponding artery. Flow in the infarct-related artery was determined during initial injection of contrast
agent and graded as described in the Thrombolysis in
Myocardial Infarction ( TIMI) trial
Age (years)
Gender
LAD
CX
RCA
1-vessel disease
2-vessel disease
3-vessel disease
TIMI-0
TIMI-1
T1MI-2
TIMI-3
Overall
(n = 50)
Anterior Ml
(n = 24)
Inferior MI
(n = 26)
55-1 ± 11-8
38M/12F
26
8
16
12
26
12
12
7
14
17
57 3 ± 11-7
I9M/5F
22
0
2
7
10
7
4
5
11
4
53-4 ± 11-9
19M/7F
4
8
14
5
16
5
8
2
3
13
LAD = left anterior descending coronary artery; CX=circumflex
artery; RCA = right coronary artery
Table 2 Median (interquartile range) TNF-a concentrations (pg. ml'') 12 h (TNF-a(l2)), 48 h (TNF-a<48))
and 72 h (TNF-a(72)) after acute myocardial infarction,
according to the degree of reperfusion
TNF-« (I2I
TNF-« (48)
TNF-a (72)
Reperfusion
(TIMI 2.3)
No reperfusion
(TIMI 0, 1)
8-53 (510-15-75)
1113 (4-75-15-93)
12-86 (8-31-16-23)
7-62 (3-38-10-21)
10 41 (5-65-15-62)
10-22 (7-56-15 98)
0-42
0 37
0-29
Time course of TNF-a after acute
myocardial infarction (Fig. 1)
The peak serum TNF-a concentration was 11-9 (10-116-3 pg . ml ~ ') and was noted 84 h (range: 60 to 108 h)
after admission. No substantial differences were observed between the 72nd and the 96th h after admission
(Wilcoxon signed rank test: F=0-25). Serum TNF-a was
detected in 37 (74%) patients on admission. In contrast,
in 13 (26%) patients serum TNF-a concentration was
below the detection limit of 4 0 pg . ml" '. Analysis of
course of serum TNF-a with regard to the state of
reperfusion is summarized in Table 2. After myocardial
infarction, the course of serum TNF-a differed between
patients with angiographically obtained reperfusion and
patients without successful reperfusion. However, the
differences did not reach statistical significance (12 h:
P=0-43; 48 h: P=0-37: 72 h: P=0-29: Table 2).
Infarct size and tumour necrosis factor alpha
1855
t\J
n = 50
r = 0.74
60 "
•
50 e 40
* n -_
30
20
10
,
,
i
Figure 1 Changes in the median levels of TNF-a after
admission in SO patients with myocardial infarction. Between 72 and 96 h after admission no substantial changes
in the TNF-a values were observed. Thus, it is sufficient to
collect blood in the 24 h interval between 72 and 96 h in
order to obtain meaningful information.
=median
value; } = interquartile range.
,
4500
HBDH,Q72
12 24 36 48 60 72 84 96 108120 132 144156
Hours after admission
,
3000
1500
Figure 2 Linear regression analysis of J(TNF) and
HBDH Q 7 2 in 50 patients with myocardial infarction. A
significant positive relationship is found between zf(TNF)
and the magnitude of HBDH Q 7 2 . The regression coefficient is 0-74 (/ ) <0-001). Dashed lines represent the
95% confidence band.
n = 50
r = 0.57
A(TNF) vs in-hospital complications
To assess the relationship between infarct size and
serum TNF-a concentration measurements, we examined the relationship between zf(TNF) and infarct
extent estimated by clinical parameters such as evidence of congestive heart failure or severe rhythm
disturbances.
1.75 -
•I 1.5
_
•
•
o
• •
>
1.25
•
•
A(TNF) vs congestive heart failure
Congestive heart failure was observed in 18 (36%) out of
50 patients. In patients with evidence of congestive heart
failure zf(TNF) was significantly higher compared to
those without any evidence of congestive heart failure
(24-6 pg. m l " 1 (SD7-3) vs 12-9 pg . ml" 1 (SD 14-3),
/>=0-003).
A(TNF) vs rhythm disturbances
Rhythm disturbances were observed in 17 (34%) out of
50 patients. In patients with rhythm disturbances
J(TNF) was significantly higher compared to those
without rhythm disturbances (24-4 pg . ml" ' (SD 13-6)
vs 13-4 pg . ml - ' (SD 87), />=0-001).
A(TNF) and in vivo measures of
infarct size
Infarct extent in-vivo was measured by enzymatic
methods, such as cumulative release of a-HBDH, by
imaging techniques, such as late resting SPECT201
thallium scintigraphy using an extent score, and by
echocardiography using a wall motion index.
10
•
20
30
40
50
60
70
ATNF (pg.mF1)
Figure 3 Linear regression analysis of echocardiographically obtained wall motion index and <4(TNF) in 50
patients with myocardial infarction. A significant positive
relationship is found between the wall motion index and
the magnitude of J(TNF). The regression coefficient
is 0-57 (/><0001). Dashed lines represent the 95%
confidence band.
Relationship between A(TNF) and
HBDHQ72 (Fig. 2)
Simple linear regression analysis revealed a significant association between the magnitude of zf(TNF)
and H B D H Q 7 2 . The regression coefficient was 0-74
Relation between A(TNF) and
echocardiography obtained wall motion
index (Fig. 3)
Simple linear regression analysis revealed a moderate
but significant correlation between the magnitude
Eur Heart J, Vol 17, December 1996
1856 M. M. Hirschl et al.
ATNF (pg.ml"1)
Figure 4 Relationship between extent score (%) and
zi(TNF) in 50 patients with myocardial infarction. A
highly significant positive relationship is found between the
two parameters. The regression coefficient is 0-80
(/><0001). Dashed lines represent the 95% confidence
band.
of z/(TNF) and echocardiographically obtained wall
motion indexes. The regression coefficient was 057
Relationship between A(TNF) and
scintigraphically obtained extent score
(Fig. 4)
Simple linear regression analysis revealed a significant
correlation between the magnitude of J(TNF) and
scintigraphically obtained extent scores. The regression
coefficient was 0-80 (P<0001).
Influence of infarct location and state of reperfusion
The influence of reperfusion and infarct location on the
relationship between extent score and zf(TNF) was
investigated by multivariate regression analysis. Extent
scores did not correlate with the location of myocardial
infarction (r= —013, P=0-\6) or the degree of reperfusion (r= — 0-02, P=0-74). In contrast, extent score was
positively correlated with J(TNF) (r=0-75, P<0-00\).
Discussion
The primary aim of the present study was to evaluate the
relationship between changes in serum TNF-a concentration and parameters of infarct extent in patients with
acute myocardial infarction. The results demonstrate
that the extent of changes in serum TNF-a concentration are significantly related to estimates of infarct
extent obtained scintigraphically. zJ(TNF) also correlates well with other parameters such as the occurrence
of heart failure, rhythm disturbances, enzymatic estimated infarct extent (HBDH Q72 ) and the wall motion
index obtained echocardiographically.
Eur Heart J, Vol. 17. December 1996
A substantial increase of TNF-a in patients with
acute myocardial infarction was observed, which is in
line with a previously published report demonstrating a
similar course of TNF-a in these patients'14'. Additionally, in-vitro data from a porcine model demonstrated
that after an ischaemic event macrophages migrated into
the myocardium and released TNF-a locally. The
number of cells immigrating into myocardium increased
until the 3rd day after vessel occlusion and then remained constant over the next weeks. Accordingly, a
proportional increase of TNF-a concentration in the
myocardium was observed'131. Our data are in line with
these experimental data as peak TNF-a concentration
was noted between the 60th and the 108th h after
admission. We therefore assume that macrophages,
which migrated into the myocardium after acute myocardial infarction, are the main source for the increased
serum TNF-a concentration in these patients. Our
hypothesis is in line with experimental and postmortem
data, which provide evidence for an accumulation of
macrophages in ischaemic myocardium'27'281. However,
recent experimental data suggested that some of the
TNF-a released during myocardial ischaemia is produced by myocytes'29'30'. This is in contrast to clinical
data illustrating that macrophages are the main source
for the release of TNF-a into the coronary sinus of the
heart allograft'311. Therefore, the exact cellular source of
TNF-a in patients with acute myocardial infarction
remains controversial. Additionally, TNF-a may also be
produced by activated macrophages circulating in the
peripheral blood. Experimental data about the production of TNF-a from circulating macrophages in
ischaemia/reperfusion models are lacking. However,
Mazzone et al. demonstrated a transcardiac increase in
the surface expression of CD lib/CD 18 in coronary
sinus monocytes and granulocytes when compared with
simultaneous control samples drawn from aortic
blood'321. Therefore, it may be assumed that most
TNF-a is produced either by cells invading the myocardium or by resident cells. Our data, nevertheless, support the hypothesis that the release of TNF-a into
circulation is not confined to severe bacterial and
parasitic infection, but occurs also as a result of
non-infectious tissue injury'33'.
Applicability of the method
An essential limitation of enzymatic infarct extent estimation is the requirement of multiple blood samples
collected at precise moments during the acute phase of
myocardial infarction'481. Van der Laarse et al. reported
that HBDH-infarct extent could be calculated correctly
only in 68% of all patients due to missing values'81. As
the TNF-a-kinetic reveals no substantial changes in the
TNF-a values between the 72nd and the 96th h after
admission, a period of 24 h seems suitable for blood
sampling the maximum TNF-a level. Therefore, the
estimation of infarct extent using TNF-a requires two
blood samples only. We therefore assume that our
method is convenient and easily applicable to daily
clinical routine.
Infarct size and tumour necrosis factor alpha
Influence of reperfusion
Previously published reports using enzymatic infarct
extent estimation demonstrated the important influence
of the degree of reperfusion on the kinetic of enzymes
(e.g. CK, CK-MB, LDH and LDH-isoenzymes) since
changes in myocardial blood flow contributed to the
extent of released enzymes from infarcted myocardium191034"361. In studies on dogs, however, the
amount of CK in serum was twice as high per gram of
infarcted myocardium after reperfusion, as compared
with values in permanent occlusion'101. Only about 15%
of the CK activity depleted from the myocardium
appears in the circulation, owing to inactivation during
transport in the lymph. The increased rate of enzyme
transit into the systemic circulation during a 'wash-out'
could have reduced the extent of enzyme inactivation'371.
The ratio of the amount of CK depleted from myocardium to the amount that appears in serum differs for
reperfused and non-reperfused animals'101. Thus, the use
of serial CK values for calculating infarct sizes is limited.
Calculation of infarct size in reperfused patients is also
complicated by the possibility that patients might have
less than total coronary occlusion and that clot formation and spontaneous or drug-induced lysis may be a
dynamic process. Analysis of the course of TNF-a
according to the grade of reperfusion revealed a difference in TNF-a concentrations 12 and 48 h after myocardial infarction between patients with TIMI grade 2 or 3
and those with TIMI grade 0 or 1. Our data therefore
support experimental findings which demonstrated a
significantly higher number of macrophages in reperfused myocardium compared to non-reperfused myocardium'28'. However, the difference between the groups
did not reach statistical significance. We therefore
assume that the degree of reperfusion (expressed as
TIMI grades) in the infarct-related artery might alter the
course of TNF-a concentrations within the first 48 h, but
not influence the final relationship between serum
TNF-a and infarct extent obtained scintigraphically.
Influence of infarct location
The relationship between enzymatic estimation by previous approaches and infarct extent has been moderate
to weak in patients with inferior wall infarction'4'381. De
Boer presented data about the correlation of cumulative
LDH and infarct size in patients undergoing either
intravenous thrombolytic therapy or percutaneous
transluminal angioplasty. There was no correlation
between left ventricular function and cumulative LDH
in patients with inferior wall infarction undergoing
thrombolytic therapy'381. Our data reveal no influence of
infarct location on the relationship between J(TNF) and
infarct size. This would offer a potential assessment
advantage in the clinical setting.
Pathophysiological significance of TNF-a
Previous experimental and clinical studies have
suggested that there is an association between depressed
myocardial function and elevated levels of TNF-a'39'401.
1857
Our data support these findings, as the evidence of
congestive heart failure was associated with higher
TNF-a values compared to patients without heart
failure. As indicated by Yokoyama et al, TNF-a induced abnormalities in the contractile function of myocytes due to an increase of intracellular calcium'291.
From this we assume that TNF-a is partially responsible
for the development of congestive heart failure in
patients with acute myocardial infarction. In experimental studies it has been demonstrated that TNF-a is an
important stimulus for the expression of ICAM-1 on
myocytes'411. ICAM-1 is an adhesion molecule, which
initiates the adherence of neutrophils on myocytes after
reperfusion. This mechanism seems mainly responsible
for the initiation of a reperfusion injury after successful
reopening of an occluded coronary artery. We therefore
assume that TNF-a may play an important role in the
inflammatory cascade after establishment of reperfusion
as well as in the development of reduced myocardial
contractility.
Limitations of the study
Several limitations of the study concerning the analysis
of TNF-a and in-vivo infarct size assessment have to be
emphasized. As TNF-a is also present in peripheral
blood cells, inappropriate handling of the blood samples
may result in wide variations of TNF-a measurements.
Therefore, TNF-a measurement requires some laboratory experience and extremely careful handling of the
samples such as early and thorough centrifugation. In
vivo infarct extent estimation has certain obvious limitations, as the optimal standard for infarct extent determination would be postmortem examination'41. The
early assessment of wall motion indices by echocardiography is certainly limited, as the wall motion index
contains a significant number of 'stunned' myocardium
and thus would overestimate true infarct extent. However, radionuclide imaging by 201Tl-scintigraphy, or
more recently by 99Tc-Sestamibi scintigraphy, delineates
the area-of-risk in patients after acute myocardial
infarction and corresponds to ejection fraction'42"441. As
recently demonstrated after resting injection, regional
activities of both 201Thallium and 99Tc-Sestamibi scintigraphy, as assessed by quantitative analysis, are similar
in reversibly dysfunctional myocardium and irreversibly
dysfunctional myocardium'45'461. Therefore, the total
amount of severely underperfused myocardium, as evidenced by resting 201Tl-scintigraphy, should provide a
reasonable estimate of myocardium unlikely to recover
and thus of infarct extent. Also, our study did not
provide any postmortem examinations. We therefore
could not establish an exact correlation between changes
in serum TNF-a and gram of necrotic myocardium. On
the other hand, it has been the purpose of the study
to investigate the relationship of clinically frequently
used parameters of myocardial injury and this novel
sampling approach to assess the amount of irreversible
myocardial damage.
Eur Heart J, Vol. 17, December 1996
1858 M. M. Hirschl et al.
Conclusion
Delta-(TNF) provides valuable data about the extent of
severely injured myocardium after acute myocardial
infarction. In contrast to other enzymatic methods, only
two blood samples are necessary to obtain zf(TNF-a).
Therefore, the number of expensive laboratory determinations can be markedly reduced. Additionally, the
discomfort for the patient concerning frequent blood
samples can be avoided. In contrast to other methods,
localization of infarct does not influence the relationship
between TNF-a and infarct extent. In summary, the
advantages of zJ(TNF-a) include easy performance in
clinical routine, reduction of blood samples and laboratory investigations, clinically relevant information
about infarct extent and independence from infarct
localization.
[14]
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