Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al. [602277]

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

183Heat Shock Protein 70 and IgE as Inflammatory
Mediators, are Early Predictors of Myocardial
Ischemia and Recovery Markers after
Coronary Artery Bypa ss Grafting (CABG)

Amal A Baalash*, Hala E Hamouda*, Bedir M Ibrahim**,
Ibrahim K Yassein** and Ghada M. Ismail***
Departments of *Medical Biochemi stry, **Cardiothoracic Surgery and
***Physiology, Faculty of Medici ne, Tanta University, Egypt

ABSTRACT

Objective: The aim of the present study was to id entify levels of heat shock protein 70
(Hsp 70), total immunoglobulin E (IgE) and matrix metalloproteinase-9 (MMP-9)
before and after coronary artery bypass grafting (CABG) surgery. Method: Heat
shock protein 70, IgE, MMP-9, creatine phosphokinase-MB (CPK-MB), and lactate
dehydrogenase (LDH) levels were measur ed in normal subjects (n=20), and in
patients with chronic stable angina pectoris who were referred for elective CABG,
before and after performing CABG-surgery (n=20). Result: Compared with normal
subjects, increased heat shock protei n 70 and IgE levels but unchanged MMP-9 level,
and activities of CPK-MB, LDH were found in the pre-operative patient group. Heat
shock protein 70, and IgE levels in the post-operative period were significantly
reduced when compared to pre-operative period. Conclusion: On the basis of these
results it could be conclude that, heat shock protein 70 and IgE might be used as
markers for detection of early minor my ocardial damage, and coronary insufficiency
with less overt damage than myocardial in farction, as significant changes in their
levels appear before occurrence of in any changes in the levels of MMP-9, CPK-MB
and LDH. Besides, heat sho ck protein 70, and IgE returning to the normal levels after
CABG surgery, suggests that they could be helpful to evaluate the effect of CABG
surgery.

INTRODUCTION

The clinical feature of myocardial
ischemia correlates with a particular
biochemical pattern of inflammatory
system activation. Experimental
models of ischemic myocardial injury
indicate that the inflammatory
response after the ischemic event
contributes to tissue damage.(1) So,
inflammation is becoming an intriguing focus of research as a
possible pathogenetic component and
therapeutic target in ischemic heart
disease.
Elevated values of circulating
inflammatory markers, such as C
reactive protein (CRP), serum amyloid A protein, interleukin-6, TNF
and interleukin-1 receptor antagonist,
are commonly found in acute
coronary syndrome (ACS). It have
been suggested that this systemic

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

184inflammatory response may be the
result of the myocardial
microinfarction known to occur in that
case.(2)
Heat -shock proteins (Hsps) are
abundant intracellular proteins found
in both prokaryotic and eukaryotic
organisms. Their main function
appears to be as chaperones, involved
in protein folding and transport.(3)
Upregulation of the synthesis of a number of these proteins occurs upon

environmental stress establishes a unique defense system to maintain

cellular protein homeostasis and to
ensure survival of the cell. In the
cardiovascular system this enhanced protein synthesis leads
a powerful
increase in tole rance to such
endangering situations as ischemia,
hypoxia, oxidative injury, and
endotoxemia. The Hsp 70 family,
located in th e cytosol and the nucleus
of the cell, is the most conserved and
the best-studied class of Hsps.
Myocardial ischemia induces Hsp70
as a stress response,(4) and Hsp 70 is
increased in atrial tissue of patients
with angina.(5) Circulating Hsp 70 is
suggested as a marker of myocardial
damage. In addition, Hsp70 may has a
role in the inflammatory response
after myocardial tissue damage.(6)
Immunoglobulin E (IgE), known
primarily as a mediator of allergy, can
cause platelet activation and arterial
smooth muscle hyperplasia (7). On the
other hand, it has been observed that
myocardial tissue damage is
associated with an immunological
response characterized by rise of
serum immunoglobulin E (IgE). This
behavior of serum IgE bears much
resemblance to that of acute phase
proteins. (8) Matrix metalloproteinases
(MMPs) are a group of
endopeptidases with capacity to cleave
components of extracellular matrix,
such as collagen and elastin. The
ability to modify the tissues is
important for several aspects of
normal and abnormal physiology.
Approximately 20 different MMPs are
identified, and they can be subdivided
into different groups according to
which components of the extracellular
matrix they degrade. Gelatinase B
(MMP -9) belongs to the group of
gelatinases. It readily digests the
denatured collagens, and gelatins. This
group of enzymes has three repeats of
a type II fibronectin domain inserted
in the catalytic domain, which bind to
gelatin, collagens, and laminin.(9)
MMPs are secreted in a latent
proform and require activation for
proteolytic activity(10) .MMPs can be
activated by proteinases, and reactive
oxygens. Low pH and heat treatment
can also lead to activation. (11)
Recently, studies by Gu et al.,(12) have
shown that NO activates proMMP -9
during cerebral ischemia by reacting
with the thiol group of the cysteine
switch and forming an S-nitrosylated
derivative, a demonstration of the
chemical activation of a proMMP in
vivo.
MMP-9 is considered to play a
role in the regulation of migration and
proliferation of vscular smooth muscle cells (VSMCs) and modulates the
cell-to-cell communication with
activated surrounding cells, such as inflammatory cells, endothelial cells
and VSMCs.
(13)
The activity of MMPs is normally
low in healthy tissue, but the
expression and activity of several

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

185MMPs are increased in a range of
pathological processes, such as
inflammation and tissue repair after
ischemic damage.(10) It has been
reported that concentrations of MMPs are elevated not only in affected tissue
and body fluid but also in peripheral
blood in some patients with cancer, liver cirrhosis or rheumatoid
arthritis.
(14, 15)
These findings raise the
possibility that patients with ischemic
myocardial tissue would show
elevated peripheral blood levels of MMPs.
Early and accurate identification
of myocardial damage in patients experiencing symptoms and signs of
coronary insufficiency is an important
challenge. Current diagnostic tests for acute myocardial infarction (AMI) by
conventional criteria are quite
adequate. Evaluation of new and
more-sensitive tests that can detect
early minor myocardial damage
posses a new problem.
Cardiac markers of "minor
myocardial damages" in patients with stable angina pectoris (SAP) are not
confirmed and a marker of coronary
insufficiency is not well established. Besides, the recovery markers after
CABG surgery are also not well
established.
The present work aimed to study
if heat shock protein 70, total Ig E,
and MMP-9 which are proteins sharing in the inflammatory response
after myocardial tissue damage and in
tissue recovery, could be used as possible indicators for minor
myocardial damages, and also to study
if they could be used as markers for
the success of CA BG surgery in
improving the myocardial ischemia. MATERIALS & METHODS

Twenty patients with chronic
stable angina referred for elective
CABG were included in the study.
The patients had angiographically
verified 3-vessels or in a few cases 2-
vessel disease, were <75 years old,
and before surgery had no signs of
infection. Also, emergency cases and
patients undergoing combined
procedures or re-operations were
excluded.
The other exclusion criteria in the
present study included other known
diagnosed disease, acute phase fever,
any allergic disease, oesinophilia or
evidence of parasitic infestation in
stool examination, and complications
in the post-operative course.
Anesthesia and Surgical Procedure
All patients underwent a routine
procedure with median sternotomy
and use of CPB. Anesthesia was
induced with diazepam, fentanyl,
thiopental, and pancuronium and
maintained with isoflurane, fentanyl,
and nitrous oxide until the start of
CPB. The activated clotting time was
maintained >480 seconds during CPB,
and CPB was performed with flow of
2.4 L/min per m2 body surface area.
Patients were cooled down to 34°C at
the beginning of CPB, and active
rewarming was started during the last
distal coronary anastomosis.
Antegrade intermittent warm blood
cardioplegia was used. The left
internal mammary artery was
anastomosed on the left anterior
descending artery, and venous grafts
were used for the rest, with a mean of
2.8 ± 0.8 grafts per patient.
Transit-time flowmetry was done
for all patients intraoperatively to

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

186ensure graft patency and patients who
showed quantitative or qualitative low
flow were excluded.
Blood samples
Two blood samples were taken
from the patients, the first one was
taken at the day just before the
surgery and the second one was taken
three weeks after CABG performance.
Another 20 healthy normal
persons with matched age and sex were considered as the control group.
All persons gave an informed consent
for participation in the study.
Blood samples were withdrawn from
subjects after overnight fasting and
serum was separated for determination
of the following parameters;
1. Creatine phosphokinase-MB (CPK-
MB), and lactate dehydrogenase
(LDH) using the commercially
available kits;
2. Serum levels of heat shock protein-
70 was determined using Hsp70 ELISA kits, (StressGen
Biotechnologies Corp);
3. IgE levels were determined by solid
phase chemiluminescent
immunometric assay, using Immulite total IgE kits with
IMMULITE 1000 analyzer ;

4. Serum matrix metalloproteinase-9
(MMP-9) was determined using
Ray Bio human MMP-9 ELISA kit
(Ray Biotech. In).
Data were expressed as means ±
standard deviation (SD). A 2-tailed
Student t test for unpaired data was
used to evaluate statistical differences
between control group and the two
patients groups; the significance of the intraindividual change
caused by
CABG was evaluated using a paired t
test. In all cases a difference at p<0.05 was considered statistically
significant.

RESULTS

Table (1): Demographic data and clinic al characteristics of the patients
undergoing elective CABG
Characteristic Value Range
Age, years 57.4±8.5 43–66
Sex, male/female 17/3
CPB time, min 69±17 35–95
Aortic cross-clamping, min 41±15 20–67
Intubation time, hour 5.2±1.8 4.0–8.1
Postoperative in- intensive care unit stay, d 1±0 one day
Postoperative in-hospital stay, d 8.5±4.4 6–15
Distal coronary anastomoses per patient 2.8 ± 0.8 2–4

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

187Table (2): Serum levels of Hsp 70 (pg/ml) in all studied groups.
Control Pre-operative Post-operative
Mean + SD 286 + 112 895 ± 123 311 ± 76
P (compared to control) P < 0.05* P > 0.05
P (compared to postoperative G) P > 0.05 P < 0.05*
*Significant

Table (3): Serum levels of IgE (IU/ml) in all studied groups.
Control Pre-operative Post-operative
Mean + SD 31.6 ± 3.4 99.8 ± 8.6 37.4 ± 5.7
P (compared to control) P < 0.05* P > 0.05
P (compared to postoperative G) P > 0.05 P < 0.05*
*Significant

Table (4): Serum levels of MMP-9 (ng/ml) in all studied groups.
Control Pre-operative Post-operative
Mean ± SD 88.4 ± 5.7 95.7 ± 6.2 91.6 ± 8.1
P (compared to control) P > 0.05 P > 0.05
P (compared to postoperative G) P > 0.05 P > 0.05

Table (5): Serum levels of CPK-MB (IU/L) in all studied groups.
Control Pre-operative Post-operative
Mean ± SD 5.6 ± 1.1 7.2 ± 2.5 6.8 ± 3.1
P (compared to control) P > 0.05 P > 0.05
P (compared to postoperative G) P > 0.05 P > 0.05

Table (6): Serum levels of LDH (IU/L) in all studied groups.
Control Pre-operative Post-operative
Mean ± SD 229 ± 124 311 ± 117 341 ± 126
P (compared to control) P > 0.05 P > 0.05
P (compared to postoperative G) P > 0.05 P > 0.05

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

1880100200300400500600700800900
Control pre-oper. post oper.Hsp 70
IgE
MMP-9

Fig. (1): Serum levels of Hsp 70, IgE, and MMP-9 in the different groups.

The demographic data and the
clinical characteristics of the 20
patients who underwent the elective
CABG surgery were shown in table (1)
The results of the current study
revealed a significant difference in the serum levels of Hsp 70 between the
pre-operative and post-operative
samples of the same patient (895±123, & 311±76pg/ml, P<0.05) respectively,
and the pre-operative samples and the
samples taken from the control persons (895±123 and 286±112
pg/ml, P<0.05) respectively, however
there was no statistically significant difference in its levels between both
the control groups and the post-
operative samples, table (2).
Table (3) shows that, total IgE
levels were significantly higher in the pre-operative samples (99.8±8.6
IU/ml) when compared with both the
post-operative samples (37.4±5.7 IU/ml) and the control ones (31.6±3.4
IU/ml), and the post-operative
samples didn't show a statistically significant difference when compared
with the control samples. MMP-9, CPK, and LDH levels
didn't show any statistically
significant difference between the
three groups, tables (4, 5, and 6).

DISCUSSION

The most important finding in the
present study is the release of
inducible Hsp 70 into the circulation
in patients with minor myocardial damage due to coronary insufficiency,
even without myocardial infarction. It
has been reported that just ischemia could induce Hsp 70 in
myocardial
cells; Hsp70 mRNA synthesis
increased when coronary flow is gradually reduced from
normal to zero
flow levels. Anaerobic metabolism
during ischemia causes depletion of
intracellular ATP which plays an
important role in triggering the HSF1-
DNA binding activity.(16) The heat
shock transcription factor 1 (HSF1) is
a transcriptional activator protein which regulates the inducible
synthesis
of Hsps.(17) Once activated
HSF1 monomers start to oligomerize
as homotrimers, which then bind to an

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

189upstream sequence-specific motif,
heat shock element, in the promoter of
all stress-inducible Hsp genes.(18)
It has been hypothesized that
anaerobic metabolism is a strong
stimulus for hsp70-gene transcription,
since the cessation of anaerobic
metabolism is associated with complete shutdown of
Hsp 70 mRNA
synthesis, which may explain its
return to normal levels after performing CABG surgery
(19). Also,
Hsp70 synthesis could be correlated
with the onset of anaerobic
metabolism, but not with enzyme
leakage from the tissue,(19) and this
explains the elevated Hsp 70 levels without an associated increase in the
CPK-MB and LDH enzymes levels in
the pre-operative ischemic patients, absence of significant changes in the
cardiac enzymes levels between the
different groups was in agreement
with the results obtained by Batker et
al.
(20) who measured CK-MB
concentration in patients with or
without ischemic heart disease of
different etiologies. The CK-MB concentration was the same in patients
with stable angina as in those without
ischemic heart disease.
In another study of patients with
severe stable angina, myoglobin
concentration, and the cardiac enzymes, total CK activity, and CK-
MB concentration did not increase in
relation to either spontaneous or exercise-induced ischemia, despite
significant ST segment depression
observed in all patients
(21).
Serum levels of IgE, also, showed
a significant elevation in the
preoperative samples, when compared
with both post-operative and control
ones, it is likely, however, that these results are applicable only to patients
with severe debilitating angina
pectoris those with symptoms severe
enough to consider or warrant
coronary bypass operation. In contrast to our results Korkmaz et
al.,
(7) reported that IgE levels were
found to be significantly higher only in patients with unstable angina and
acute myocardial infarction compared
to the patients with stable angina pectoris and controls. This elevation
in total serum IgE levels could be
explained by the findings of Szczeklik
et al.,
(8) who reported that
immunoglobulin E may act in humans
as an acute phase protein in response to tissue injury.
The role of IgE-mediated events
in the pathogenesis of cardiovascular disease may be, in part, mediated
through mast cells activation, it has
been observed that increased
numbers
of cardiac mast cells were found in
human ischemic hearts. (22) It has been
suggested that in myocardial ischemia
circulating IgE sensitizes mast cells in
the ischemic myocardium; this facilitates release of chemical
mediators.
(8) This paracrine release of
cytokines regulates fibroblast phenotype
and MMP activity.(23) For
example, mast cells contain substantial
stores of tumor necrosis factor-alpha, a cytokine
capable of inducing MMP
synthesis. Also, human cardiac mast
cells contain tryptase, chymase,
carboxypeptidase, and cathepsin G, (24)
these enzymes have been implicated
as being involved in the MMP activation cascade
by several in vitro
studies.(25)
In the current study serum levels
of MMP-9 showed no significant
difference between the different

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

190groups, the present findings are
consistent with the results of the study
done by Kai et al,(26) who reported
that MMP-9 level in patients with
stable angina was not significantly different from that of control, also
MMP-9 levels measured before,
immediately after and 1 h after the treadmill exercise test did not change
during the exercise test although
exercise induced a ngina and typical
ischemic ECG changes were
documented.
The possibility that ischemia may
cause release and activation of MMPs
in the myocardium could not be
denied. However, it must be recognized that the release and
activity of MMPs involve a highly
compartmentalized process and that
blood MMP levels likely reflect only
spillover from the interstitial
compartment.(27) Furthermore, it is
known that all MMPs require
activation from precursors to attain enzymatic activity. The antibodies
available for serum MMP
immunoassays do not distinguish the active form of these enzymes from
their proenzyme forms; therefore, so it
is supposed that augmented enzymatic activity does not necessarily
correspond to increase in its serum
level.
Cardiac surgery, in particular
cardiopulmonary bypass in coronary
artery bypass grafting (CABG) and
cardioplegia, has been reported to
trigger myocardial inflammation and
apoptosis. This surgery-related
inflammatory reaction appears to be of
extreme complexity with regard to its
molecular, cellular and tissue
mechanisms.(28) The molecular chaperone heat-
shock protein (Hsp 70) has been
detected both in the myocardium and
in the circulation after CABG. It was
reported that serum Hsp 70 reaches its peak levels by about five hours post-
operatively, and returns to its normal
pre-operative levels by about one day after surgery.
(29)
Systemic blood levels for MMP-9
increase significantly from baseline values during CABG,
(30) and remain
elevated until 30 minutes after
cardiopulmonary bypass, MMP-9 levels tends to decrease toward
normal values during the
postoperative period, but there is a significant variability in this
response.
(31)
Also, serum IgE begins to rise
shortly after the operations reaches a
peak by the fifth day, and then
gradually declines.(7) In order to avoid
any changes in the measured
parameters that could be related to the
surgical process itself, and not due to
changes in the myocardial status, the
second blood sample was taken three
weeks after surgery.
Conclusion:
On the basis of these results it
could be concluded conclude that,
heat shock protein 70 and IgE might
be used as markers for detection of
early minor myocardial damage, and
coronary insufficiency with less overt
damage than myocardial infarction, as
significant changes in their levels
appear before occurrence of in any
changes in the levels of MMP-9,
CPK-MB and LDH. Besides, heat
shock protein 70, and IgE returning to
the normal levels after CABG surgery,
suggests that they could be helpful to
evaluate the effect of CABG surgery.

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

191REFERENCES

1. Plebani M. (2001): Biochemical
markers of cardiac damage: from
efficiency to effectiveness.
Clin.Chim. Acta, 311:3-7.
2. Michael R., Cusack MB.,
Michael S., Marber F., Pier D.,
Lambiase BA., Clifford A., Bucknall D.,.Simon R. and
Redwood M. (2002): Systemic
inflammation in unstable angina
is the result of myocardial
necrosis. J. Am. Coll. Cardiol.,
39: 1917-1923.
3. Ohtsuka K. and Hata M.
(2000): Molecular chaperone
function of mammalian HSP70 and HSP40: a review. Int. J.
Hyperthermia. 16: 231–245.
4. Jaattela M.(1999) : Heat shock
proteins as cellular lifeguards.
Ann. Med., 31: 261–271.
5. Valen G., Hansson GK.,
Dumitrescu A. et al.,(2000):
Unstable angina activates
myocardial heat shock protein 72,
endothelial nitric oxide synthase,
and transcription factors NFkB and AP-1. Cardiovasc. Res., 47:
49–56.
6. Dybdahl B., Slørdahl SA.,
Waage A., Kierulf P., Espevik
TA. and Sundan A. (2005):
Myocardial ischaemia and the
inflammatory response: release of
heat shock protein 70 after
myocardial infarction. Heart, 91: 299-304.
7. Korkmaz ME., Oto A., Saraçlar
Y., Oram E., Oram A., Ugurlu
S., Karamehmetoglu A. and
Karaagaoglu E. (1991): Levels
of IgE in the serum of patients with coronary arterial disease. Int.
J. Cardiol., 31: 199-204.
8. Szczeklik A. and Jawie ń J.
(1995): Humoral immune
response to tissue injury, characterized by a rise in serum
immunoglobulin E. Pol. Arch.
Med. Wewn., 94:495-505.
9. Allan JA., Docherty AJ.,
Barker PJ., Huskisson NS.,
Reynolds JJ. And Murphy G.
(1995): Binding of gelatinases A
and B to type-I collagen and other
matrix components. Biochem. J.,
309: 299–306.
10. Nagase H. and Woessner JF.
(1999). Matrix metallo-
proteinases. J. Biol. Chem., 274:
21491–21494
11. Nagase H. (1997): Activation
mechanisms of matrix metallo-
proteinases. Biol. Chem., 378:
151–160.
12. Gu Z., Kaul M., Yan B., Kridel
SJ., Cui J., Strongin A., Smith JW., Liddington RC. and
Lipton SA. (2002): S-
Nitrosylation of matrix metalloproteinases: signaling
pathway to neuronal cell death.
Science.297: 1186–1190.
13. Dollery CM., McEwan JR.,
Henney AM. (1995): Matrix
metalloproteases and cardiovascular disease. Circ. Res.,
77: 863– 868.
14. Fujimoto N., Mouri N., Iwata
K., Ohuchi E. and Hayakawa T.
(1993): A one-step sandwich
enzyme immunoassay for human matrix metalloprotease 2 (72-kDa
gelatinase/type IV collagenase)
using monoclonal antibodies.
Clinica Chimica Acta. 221: 91–
103.

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

19215. Fujimoto N., Hosokawa N.,
Iwata K., Shinya T., Okada Y.
and Hayakawa T.(1994): A
one-step sandwich enzyme
immuno assay for inactive precursor and complexed forms
of human matrix metalloprotease
9 (92 kDa gelatinase/type IV collagenase, gelatinase B) using
monoclonal antibodies. Clinica
Chimica Acta. 231: 79–88.
16. Benjamin IJ., Horie S.,
Greenberg ML., Alpern RJ.
and Williams RS.(1992):
Induction of stress proteins in
cultured myogenic cells:
molecular signals for the
activation of heat shock
transcription factor during
ischemia. J. Clin. Invest., 89:
1685–1689.
17. Wu C. (1995): Heat shock
transcription factors: structure
and regulation. Ann. Rev. Cell
Dev. Biol., 11: 441–469.
18. Amin J., Ananthan J. and
Voellmy R. (1988): Key features
of heat shock regulatory
elements. Mol. Cell Biol.,8:
3761–3769.
19. Knowlton AA., Eberli FR.,
Brecher P., Romo GM., Owen
A. and Apstein CS.(1991): A
single myocardial stretch or decreased systolic fiber
shortening stimulates the
expression of heat-shock protein
70 in the isolated, erythrocyte
perfused rabbit heart. J. Clin.
Invest., 88: 2018-2025.
20. Batker HE., Ravkilde J.,
Sogaard P., Jorgensen
PJ.,Horder M. and Thygesen
K. (1991) : Gradation of unstable
angina based on a sensitive immunoassay for serum creatine
kinase MB. Br. Heart J.,65: 72-
76.
21. Norregaard-Hansen K.,
Egstrup K., Nielson JR, et
al.,(1992): Lack of indication of
myocardial cell damage after
myocardial ischaemia in patients with severe stable angina. Eur.
Heart J., 13: 188-193.
22. Dixon IM., Ju H., Reid NL.,
Scammell-La FT., Werner JP.
and Jasmin G.(1997): Cardiac
collagen remodeling in the cardiomyopathic Syrian hamster
and the effect of losartan. J. Mol.
Cell Cardiol., 29: 1837-1850.
23. De Almeida A., Mustin D.,
Forman MF., Brower GL.,
Janicki JS. and Carver W
(2002): Effects of mast cells on
the behavior of isolated heart
fibroblasts: modulation of
collagen remodeling and gene
expression. J. Cell Physiol.,191:51-59.
24. PatellaV., de Crescenzo G.,
Ciccarelli A., Marinò I., Adt M.
and Marone G.(1995): Human
heart mast cells: a definitive case
of mast cell heterogeneity. Int Arch Allergy Immunol., 106:
386-393.
25. Nagase H. (1997): Activation
mechanisms of matrix metallo-
proteinases. J.Biol. Chem., 378:
151-160.
26. Kai H., Ikeda H., Yasukawa H.,
Kai M., Seki Y., Kuwahara F.,
Ueno T. and Imaizumi T.
(1998) : Peripheral blood levels of
matrix metalloproteases-2 and -9
are elevated in pa tients with acute
coronary syndromes. J. Am. Coll.
Cardiol., 32:368-372.

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

19327. Bremer C, Tung C-H,
Weissleder R. (2001): In vivo
molecular target assessment of
matrix metalloproteinase
inhibition. Nat. Med., 7: 743–748.
28. Czerny M., Baumer H., Kilo J.,
et al. (2000): Inflammatory
response and myocardial injury following coronary artery bypass
grafting with or without
cardiopulmonary bypass. Eur. J. Cardiothorac Surg.,17: 737–742.
29. Dybdahl B., Wahba A., Lien E.,
Flo T., Waage A., Qureshi N., Sellevold O.and Sundan T.
(2002): Inflammatory response
after open heart surgery: release of heat-shock protein 70 and
signaling through toll-like receptor-4. Circulation 105: 685 –
690.
30. Lalu M., Pasini E., Schulze C.,
Vivaldi M., Vivaldi G., Bachetti
T.and Schulz R.(2005):
Ischaemia–reperfusion injury
activates matrix metallo-
proteinases in the human heart. European Heart Journal 26: 27-35
31. Joffs C., Gunasinghe HR.,
Multani MM., Dorman BH., Kratz JM., Crumbley AJ.,
Crawford FA. and Spinale FG.
(2001): Cardiopulmonary bypass
induces the synthesis and release
of matrix metallo-proteinases.
Ann. Thorac Surg., 71:1518–1523.

Bull. Egypt. Soc. Physiol. Sci. 28 (1) 2008 Baalash et al.

194 الحرارية الصدمة بروتين الأللتھاب وسائط ٠٧استخدام الجلوبيولين و
و القلب لعضلة الدموية التروية لنقص مبكرة كدالالت ، ھـ المناعي
التاجية الشرايين زراعة عمليات لنجاح كمؤشر

* ، بعلش أحمد أمل* ھالة ، حمودة، السيد** ابراھيم، مصطفى بدير
** و يس خيري ابراھيم* ** اسماعيل محمود غادة
* الطبية، الحيوية الكيمياء أقسام** الصدر و القلب جراحة *** كلية الفسيولوجى، قسم و
الطب –طنطا جامعة

ةѧالحراري الصدمة بروتين من كل مستويات كانت إذا ما معرفة الى الدراسة ھذه ٠٧تھدف ولينѧالجلوبي و
الميتالوبروتينيز و ، ھـ ٩المناعي كد تصلح احѧلنج رѧكمؤش و بѧالقل لةѧلعض الدموية التروية لنقص مبكرة الالت
التاجية الشرايين زراعة عمليات .
ةѧبعملي امѧللقي درجونѧم و تقرةѧالمس الصدرية الذبحة من يعانون مريضا عشرين على الدراسة ھذه أجريت
التاجية الشرايين زراعة . سنه تجاوز مريض أي استبعاد تم بحيث المرضي اختيار ٥٧تم ةѧأي من يعاني أو عاما،
أو ةѧطفيلي أو ةѧمناعي راضѧأم أية وجود أو غيرھا، أو الكلى أمراض و السكرى البول مثل اخرى مزمنة أمراض
أية لھم حدثت الذى أو األولى للمرة الجراحة ھذه باجراء يقومون ال اللذين المرضى استبعاد تم كذلك و ، حساسية
العملي اجراء بعد حمى أو ةمضاعفات .
من استبدال تم و للمرضى الجراحة ٢اجريت ٤الى بمعدل وريدية أو شريانية بوصالت أما ٢شرايين .٨
بشكل عملھا من للتأكد الوصالت ھذه في الدم سريان اختبار تم الجراحية العملية انھاء قبل و مريض، لكل وصلة
سري يكن لم الذى المرضى استبعاد تم قد و جيدجيد، بشكل يتم لھم المزروعة الوصالت في الدم ان .
و ة،ѧالعملي راءѧإلج رةѧمباش ابقѧالس اليوم صباح كانت األولى العينة مريض كل من الدم من عينتين أخذ تم
العملية اجراء من أسابيع ثالثة مضي بعد كانت الثانية العينة . متوافقا صحيحا شخصا عشرون اختيار تم قد و ھذا
ال مجموعة منھممع الدم عينات أخذ تم و ضابطة كمجموعة الجنس و العمر حيث من مرضى .
ةѧѧالحراري دمةѧѧالص روتينѧѧب نѧѧم لѧѧك اسѧلقي اѧѧمنھ لѧѧالمص لѧѧفص مѧѧت اتѧѧالعين حبѧѧس ورѧ٠٧ف ولينѧѧالجلوبي و
الميتالوبروتينيز إنزيم و ھـ ٩المناعي . القلب عضلة احتشاء على الدالة األنزيمات قياس كذلك و CPK-MB و
LDH .
دمةѧالص روتينѧب من كل مستويات في احصائية داللة ذو ارتفاعا ھناك كان أنه الدراسة ھذه نتائج أظھرت
٠٧الحرارية اѧمقارنتھ دѧعن ةѧالعملي راءѧإج لѧقب ىѧالمرض نѧم المأخوذه الدم عينات في ھـ المناعي الجلوبيولين و
وѧѧالموج توياتѧѧالمس و ابطةѧѧالض ةѧѧالمجموع يѧѧف ودةѧѧالموج توياتѧѧبالمس راءѧѧاج دѧѧبع ىѧѧالمرض سѧѧنف اتѧѧعين يѧѧف دة
الميتالوبروتينيز انزيمات من كل مستويات بين اختالف اي ھناك يكن لم األخرى الجھة من لكن و ٩الجراحة، و
CPK-MB و LDH الثالث المجموعات بين .
نѧم لѧك ان تنتاجѧاالس نѧيمك السابقة النتائج من ةѧالحراري دمةѧالص روتينѧ٠٧ب ا ولينѧالجلوبي و ـѧھ اعيѧلمن
دمѧال في مستوياتھما ان الدراسة أظھرت حيث القلب، لعضلة الدموية التروية لنقص مبكرة كداللة استخدامه يمكن
احتشاء حدوث قبل حتى و الدموية التروية في نقص حدوث بمجرد ترتفع توياتھماѧمس ودةѧع أن اѧكم لة،ѧالعض في
ا نѧѧم لѧѧيجع ةѧѧالجراح راءѧѧاج دѧѧبع اѧѧتقريب يѧѧالطبيع دلѧѧللمع ةѧѧالحراري دمةѧѧالص روتينѧѧب انѧѧب راحѧѧاالقت نѧѧ٠٧لممك و
التاجية الشرايين زراعة عمليات لنجاح كمؤشرين اتخاذھما يمكن ھـ المناعي الجلوبيولين .