IMMUNE INFLAMMATORY ATTACKS AND UNSTABLE
CARDIOVASCULAR PATHOMORPHOSIS. VERIFICATION AND
COUNTERACTION.
Andriyevskikh I.A., Lukin O.P., Davydov I.V.
Chelyabinsk State Medical Academy and
Chelyabinsk Federal Center of Cardiovascular Surgery. Hospital surgery department. Russia.
MD. PROF. ANDRIYEVSKIKH I.A
Abstract
The research into the peculiarities of the influence of immune inflammation on the formation of severe forms of cardiovascular
diseases, developed by patients, who had a major cardiovascular operation, has been conducted by the authors of this paper.
Significant shifts in the patients’ immune status have been detected. The criteria of unstable cardiovascular pathomorphosis have been
established. The methods of immunodiagnostics and immunotherapy of such conditions have been worked out. Due to the use of these
additional methods the number of intra- and post- operative complications can be reduced by 13,4%.
Key words : immune inflammation; unstable cardiovascular pathomorphosis; cardiovascular operations.
Topicality.
Considerable influence of immune inflammation on the
formation of severe forms of cardiovascular pathology is
completely proven [1,3,8,11,13,14,16]. However, optimal
verification criteria of this negative influence on cardiovascular
catastrophes ( provided that patients undergo major
cardiovascular operations) and counteraction methods to this
pathological component have not been determined yet.
Present day standards and algorithms do not include
evaluation methods of total immune status or immunotherapy
of patients with the hard course of cardiovascular diseases and
risky surgical care. Our paper focuses on this urgent problem.
Materials and methods.
The research is conducted on 492 patients with severe forms
of cardiovascular pathomorphosis. These patients were getting
surgical care in different arterial pools of our clinic from 2005 to
2010. The average patient’s age was 54,9 ± 11,2years. There
were 94,5% of men and 5,5% of women. 50,6% of patients had
heart ischemia as the main disease. 73,8% of patients had multivasal damages. All patients with multivasal damages
simultaneously had ischemic heart, brain and limbs disorders.
63,4% of patients were under conditions of comorbidity with
accompanying pathology of the gastrointestinal tract, lungs,
kidneys, endocrinopathy and autoimmune diseases. The common
standard methods , such as ACS and MCS, intimectomy from the
branches of
the aortic arch and branchycephalic trunk
prosthetics, surgical operations on visceral and renal arteries,
aorto-femoral and femoral-popliteal shuntings were used to cure
such patients. We referred all such cases to the group of patients
with unstable cardiovascular pathomorphosis.
Sign
We regarded unstable cardiovascular pathomorphosis as
availability of clinical and laboratory-instrumental data,
manifesting predominance of the immune inflammatory
component over the adaptation component, which was
accompanied by rapid progress of ischemic disorders n different
arterial pools, also by tolerance to the total amount of traditional
treatment and threat of sudden thrombo-hemorrhagic
complications.
We believe that the clinical markers of unstable
cardiovascular pathomorphosis are as following: multivasal
damages, comorbidity as a whole complex of interrelated
pathologies with marked aggravations, endocrinopathy and
connective-tissue dysplasia.
On the basis of our research and considering the data,
obtained by other authors, we worked out a therapeuticdiagnostic algorithm, which reveals the marked immune
inflammatory component of cardiovascular bed. Besides, we
established the principles of individualized immunotherapy,
applied to such seriously ill patients. The algorithm is as follows:
If patients are examined by standard methods, which detect
direct and indirect indications of predominance of the immune
inflammatory component of cardiovascular bed over
compensation reparative component, in this case we carried out
additional immunodiagnostics and immunotherapy.
This method was worked out on the basis of the preliminary
discrete analyses of clinical laboratory data, collected on 119
patients with cardiovascular diseases during a certain period of
time prior to this research. For integral analyses we used a score
system, whose principle we present in the Table 1.
Table 1. Principle of integral assessment of the presence of
immune inflammatory component of cardiovascular bed.
Index
Score
Indirect
Direct
Connective-tissue dysplasia
0,5
Relative's cardiovascular diseases
0,5
Rapid course (days, weeks) occlusive, stenotic or degenerative changes in vascular walls and cardiac valve structures
0,5
Distal and diffuse damages of cardiovascular bed
0,5
Heightened ESR
1,0
Leukocytosis with deviation of the differential count to the left
1,0
Increased СRP rate
1,0
Thrombocytopenia
1,0
The predominance of the immune inflammatory component
was confirmed if the total sum exceeded 3 scores. In this case in
order to determine the presence of inflammation and the direction
of immunotherapy, we tested the patient’s immune status in the
laboratory conditions. This laboratory examination included the
characteristic of cell link of the immunity (absolute quantity of
lymphocytes, CD3, CD4, CD8, CD 10, CD11в, CD16, CD20,
CD25. CD34, CD56, CD95, HLA-DR), humoral link of the
immunity (immunoglobulins А, М, G, Е, circulating immune
complexes, СН50, С3 и С5 components of complement in the
blood serum); phagocytic neutrophils activity of peripheral
blood (the quantity of cells taking part in phagocytosis,
phagocytic index, phagocytic number and the state of redox
processes in neutrophils and the test, stimulating them [7,12].
The most characteristic immunologic signs of the presence
of immuno-inflammatory cardiovascular attack were as
following: the increased number of immunoglobulins A and G in
the blood serum, circulating immune complexes, E
immunoglobulin reduction, activation (in case of aggravation) of
oxygen –dependent metabolic processes in neutrophils and the
presence of immune deficiency with phagocytosis disorders
predominating (80-85%). More seldom there occurred changes in
the cell link of the immunity (45-50%). The detection of these
divergences in the immunogram was an additional confirmation
of the discrete analysis results, which allowed us to make final
score assessment in accordance with the above mentioned chart.
The course of immunotherapy was 15-20 days on average,
but never longer than 30 days. The main principle of the
prescription of immunotropic medicines for immuneinflammatory component stabilization was the recovery of redox
processes in immuno-competent cells. If the index of the
neutrophil stimulating test was pushed up, we prescribed
intravenous droplet ejection of antioxidants: polioksidony ( if
Index
CD3,%
CD4,%
CD8,%
CD11,%
CD16,%
CD95,%
HLA-DR,%
PhN of neutrophils, conv. units
Spontaneous NBT-test,%
Induced NBT-test,%
IgA, г/л
IgM, г/л
IgG, г/л
CIC, unit опт. density
CH50, conv. units
ESR , mm/h
Leukocyte number, ×109/l
Eosinophils,%
high rates of immunoglobulins and circulating immune
complexes were simultaneously registered) or emoksipin (in
cases of isolated breaches of antioxidant defence), besides,
discrete plasmapheresis was applied to 178 patients of the 1 st
group. In case of decreasing neutrophils stimulating test index
we used intravenous injection of glutoxim. In case of the low
phagocytic activity rate and lack of immunoglobulin G we used
intravenous injection of human polyvalent immunoglobulin
(with 108 patients of the 1st group). Since the end of the first
week of treatment we added immunomodulators (for all our
patients of the 1st group) with the aim of further immune status
harmonization (Immunofan , Vobenzim, Licopid, vitamin А etc.).
As complex immunotherapy depended on the patient’s
individual characteristics of the immune status, the combination
of immunotherapy remedies was also individual.
This algorithm was used for the patients of the 1 st group, to
other patients (2nd group) only traditional methods of diagnostics
and preoperative preparation were applied before putting into
practice this algorithm. The patients of the both groups were
randomized according to the type of the pathology, surgical
treatment methods, gender and age. When assessing the immune
status of the patients of the 1st group we were guided by regional
standard requirements for a normal immune status of
Chelyabinsk and Chelyabinsk region residents[2].
During the preoperative period all the patients of the 1 st
group got individualized immunotherapy, based on the
peculiarities
of
clinical-laboratory
immunodeficiency
manifestations.
Results.
After immunotherapy we got positive dynamics of the
immune state change with the patients of the 1st group. This
dynamics
is
shown
in
Table
2.
Table 2. Divergences in the immune status and immunotherapy
effectiveness (M±m) with 277 patients of the 1st group.
Before therapy
After therapy
37,31±2,56
38,69±1,06
25,52±1,78
27,71±1,34
21,5±1,31
23,5±0,941
16,5±1,29
16,84±0,81
14,65±0,81
17,31±0,61
19,41±1,61
19,22±0,97
14,54±1,32
14,75±1,66
3,44±0,26
3,45±0,29
27,21±2,1
27,58±1,34
36,53±2,36
38,12±1,24
1,83±1,33
1,78±1,16
1,08±0,05
1,05±0,045
8,43±0,26
8,12±0,41
97,32±8,87
92,32±4,57
61,78±1,99
59,18±1,16
24,11±2,27
11,71±3,59
15,59±3,31
11,34±2,17
9,10±0,64
7,02±0,85
p
0,027*
0,048*
0,040*
0,048*
0,035*
0,050
0,112
0,084
0,048*
0,033*
0,652
0,043*
0,050
0,049*
0,019*
0,306
0,191
0,121
Stab neutrophils,%
СRP, mg/l
11,85±2,77
8,71±,1,26
Note: Valid distinctions (p <0.05) are marked *.
Our next step was to compare the number of intra- and
postoperative thrombo-hemorrhagic
8,31±1,12
6,25±0,26
0,146
0,042*
and reparative complications in both the groups of patients. This
is
shown
in
Table
3.
Table 3. Types of operative interventions and peculiarities of intraoperative unstable pathomorphosis manifestations
I st group
II nd group
n =277
n =215
Types of
operations
CS and CABG
Operative
interventions on
brachycephalic
arteries
Aorto-femoral
and femoralpopliteal
shuntings
Intervention ons
on visceral
branches of aorta
TOTAL
Thrombosis
of shunts
Diffuse
hemorrh
age
Incision of
the vessel
suture
Total of
operated
patients/
complication
s
(%)
4
8
10
133/16,5
-
1
2
3
6
7
Diffuse
hemorrhage
Incision of
the vessel
suture
Total of
operated
patients/
complication
s
16
21
22
116/42,2
50/6
-
4
7
41/26,8
7
77/20,7
8
14
18
46/86,9
1
1
17/11,7
1
4
3
12/66,6
16
20
277/15,5
25
43
50
215/54,8
All the above mentioned complications in both the
groups of patients were overcome due to local hemostatic
means, using of sutures on pads and thrombectomy. Therefore, in
Thrombosis
of shunts
the 1st group there were considerably fewer complications after
the
immunotherapy. This is shown in Table 4.
Table 4. Patient’s distribution according to the character of postoperative complications in the 1st experimental group and the IInd group for
comparison
I group
II group
n =277
n =215
Total of
Total of
operated
Types of
PurulentPurulentoperated
Acute
patients/
Acute
interventions
Multiorgan
septic
Multiorgan
septic
patients/
heart
complication
heart
insufficiency
complicati
insufficiency
complicatio complications
failure
s
failure
ons
ns
(%)
(%)
ACS and CABG
Operative
interventions on
brachycephalic
arteries
Aorto-femoral and
femoral-popliteal
shuntings
Interventions on
visceral branches of
aorta
TOTAL
5
2
3
-
1
-
-
1
7
1
1
6
5
133/7,5
9
7
4
-
3
1
77/10,3
1
2
12
46/32,6
1
17/17,6
1
2
2
12/41,6
11
277/9,4
11
14
19
215/20,4
50/2
None of the patients in both groups died during the
intraoperative period. During the postoperative period 22 (9,4%)
patients of the experimental main group and 44 (20,4%) patients
in the 2nd comparative group developed hemorrhagic and
reparative complications. In the majority of cases we cured these
complications with the help of traditional methods of treatment.
Nevertheless, 2 (0,7%) patients of the experimental main group
and 7 (3,2%) patients in the 2 nd comparative group died from
heart failure or multiorgan insufficiency.
116/17,2
41/9,7
Discussion: There remains a lot of problems to solve in the
present day immunodiagnostics and immunotherapy of cardiovascular pathology [3,5,9,11]. However, the obtained new data
on the cell-molecular level of many pathological states give hope
for evolving more effective and selective methods of influence on
the immune component of severe forms of cardiovascular
pathomorphosis [4,6,7,8,17,18].
The majority of present day medicines, used for
cardiovascular pathology treatment, influence only separate links
of pathogenesis. Immunotherapy has a lot of advantages over
traditional medical care due to its simultaneous influence on the
key moments of the main pathogenetic links in cell-humoral
associations [3,13,15]. Therefore, we believe that due to
immunotherapy it is possible to raise the level of phagocytosis of
this group of seriously ill patients.
So far, methods of immunodiagnostics and immunotherapy
are put into clinical practice with difficulty because of their
systemic, nonselective influence. Nevertheless, simultaneous
organism-molecular synthesis of data [3,6,10,14] and medical
proficiency in the analysis and synthesis of data according to
general pathological principles, angiology peculiarities, functions
of monocyte- macrophage system and immune status assessment
allow to achieve good success [2,3,8,12].
The data, which we obtained, give a good chance to look
with optimism upon the perspective of developing this trend of
medical science.
6.
7.
8.
9.
10.
Conclusion:
1. It is advisable to single out patients with the hard course
of cardiovascular pathology into a separate group of
unstable cardiovascular pathomorphosis.
2. In the overwhelming majority of cases patients with
unstable cardiovascular pathomorphosis evince marked
immune inflammation of cardiovascular bed.
3. The immunogram of this status of patients allows to
determine individual peculiarities of the secondary
immunodeficiency.
4. Individualized immunotherapy for the patients with
unstable cardiovascular pathomorphosis gives the
patients effective defence against sudden cardiovascular
catastrophes and surgical aggression.
11.
12.
13.
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