Mast Cell Tryptase Measurements During Cardiac Catheterization and the Effect of Heparin Administrat

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Mast Cell Tryptase Measurements During Cardiac
Catheterization and the Effect of Heparin
Administration
Farhad Ardeshirpour Joseph P. Pye, BS Gregory J.
Dehmer, MD Efthymios N. Deliargyris, MD
 Cardiac Catheterization Laboratory University of
North Carolina School of Medicine Chapel Hill,
North Carolina, USA
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INTRODUCTION
It is now well recognized that inflammation plays
a central role in the development and progression
of atherosclerotic vascular disease (ASVD). Mast
cells are part of this response and are activated
at sites of plaque rupture, the central event in
the genesis of myocardial infarction. (Figure
1). When activated, mast cells release mediators
that regulate plaque inflammation and the
progression to myocardial infarction. We
recently demonstrated that tryptase, a mediator
specific to mast cells, is indeed elevated in
patients with ASVD (Figure 2). Measurement of
tryptase levels may therefore emerge as a novel
means for the detection of ASVD. Tryptase,
which is normally bound to heparin within mast
cells, is released in an unbound state upon
activation. Heparin is routinely used both for
the treatment of patients with myocardial
infarction and also as a prophylactic measure
during cardiac catheterization. We hypothesized
that heparins strong affinity for tryptase might
effect tryptase measurements during cardiac
catheterization. To test this hypothesis we
measured tryptase levels in patients undergoing
cardiac catheterization in the presence or
absence of heparin.
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METHODS
1. Patient Selection Study subjects were
recruited from patients referred for cardiac
catheterization for recognized clinical
indications. All patients provided informed
consent. 2. Sample Collection and Analysis
Blood samples from the left main coronary artery
and coronary sinus were collected in 47 patients
before and after cardiac catheterization. Heparin
was administered to 24/47 patients (51), based
on the operators discretion. Four serial samples
were obtained in patients who did not receive
heparin (control group), while two samples were
obtained both before and after heparin
administration in the test group. Samples were
processed and serum was stored at -80?C for later
analysis. Tryptase was measured by immunoassay
(UniCap?, Pharmacia, Kalamazoo, MI), and values
were expressed in ?g/l. 3. Statistical Analysis
All values are expressed as the mean ? standard
deviation. Paired and unpaired student t-tests
were used to compare differences between groups.
P-values less than 0.05 were considered
significant.
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RESULTS
Table 1. Baseline Characteristics Baseline
characteristics for the two study groups are
shown in Table 1. Patients in the heparin group
were younger and had a lower LVEF, however these
differences were not significant.  
left ventricular ejection fraction
erythrocyte sedimentation rate
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RESULTS (contd)
Tryptase levels before and after cardiac
catheterization in the 23 patients that did not
receive heparin (control group) are shown in
Figure 3. Mean tryptase levels did not
demonstrate a significant difference before and
after cardiac catheterization in either the left
main or coronary sinus sampling sites (8.3 4.0
vs. 7.9 4.1µg/ml, and 8.3 4.1 vs. 7.9 3.8
µg/ml respectively, pns). Samples obtained
before and after cardiac catheterization in the
heparin-treated group are shown in Figure 4.
There was a significant (57) reduction in the
tryptase levels obtained from the left main (7.6
4.5 vs. 3.3 3.5µg/ml, plt0.01). Similarly,
there was a significant (51) reduction in
tryptase levels obtained from the coronary
sinus  (7.6 4.4 vs. 3.7  4.3 µg/ml,  plt0.02).

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DISCUSSION
Heparin administration during cardiac
catheterization resulted in a significant
decrease in measured serum tryptase levels.
Tryptase levels obtained following heparin
administration were gt50 reduced compared to
baseline levels. In the absence of heparin there
was no difference in tryptase levels obtained
before or after cardiac catheterization,
suggesting that it was the presence of heparin
and not the procedure itself that led to the
reduction in tryptase levels.  
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 CLINICAL SIGNIFICANCE
As inflammation emerges as a central mechanism in
the development of ASVD, there is an increasing
need for identification and measurement of
sensitive inflammatory markers. Tryptase is a
promising novel marker for the presence of ASVD,
however, as our study demonstrates, levels
obtained in the presence of heparin may
underestimate the actual underlying risk for
significant ASVD.