CC BY
34
33. Shukurov D. T. The dynamics of functional and metabolic activity ofperipheral blood neutrophils with protracted course of salmonellosis in children//Infection, Immunity, Pharmacology. - 1999. - № 1. -S. 41-42.
34. Badolato R., Wang J. W., Stornello S. et al.//J. Leukocyte Biol. - 2000. - Vol. 67. - P. 381-386.
35. Gentle T. A., Thompson R. A.//Clinical immunology. A Practical Approach/Eds Gooi H. G., Chapel H. - New York, 1990. - P. 57-59.
36. Miller E. J., Kudowska A., Nagao S.//Agents and Actions. - 1993. - Vol. 40, № 3-4. - P. 200-208.
37. Pick E., Charon I., Mizel D. Arapid densitometric micro assayfor NBT reduction and application ofthe micro assay to macrophage//J. Re-ticuloendotel. Soc. - 1981. - V. 30. - P. 581.
38. Badolato R., Wang J. W., Stornello S. et al.//J. Leukocyte Biol. - 2000. - Vol. 67. - P. 381-385.
Alimdjanova Nelya Yunusovna, doctor-intern of resuscitation and intensive care, Republican Specialized Center of Surgery named by academic V. Vahidov, Uzbekistan, Tashkent E-mail: saodat.us@mail.ru
Dynamics of clinical and immunological parameters of pharmacotherapy of pulmonary hypertension in patients with CHD in the surgical treatment stages
Abstract: Patients with congenital heart disease complicated by pulmonary hypertension in preoperative treatment were administered phosphodiesterase-5 inhibitors (IPDE-5) and ACE inhibitors (ACEl)-captopril, which promote vasodilation of the pulmonary circulation, reduce lung resistance and the pressure in the pulmonary artery by 10-14 %. The use of combined therapy in the postoperative period, including inotropic agents- dopamine, dobutamin, epinephrine; phosphodiesterase^ inhibitors (IPDE-3) — milrenone, enoximone, perfan; IPDE-5, nitrates; prostaglandins E1-vasoprostan, which reduce the development of severe cardiovascular failure in the short term, prevent pulmonary hypertension crises and further reduce residual pulmonary hypertension by another 8-10 %.
Thus, drugs of IFDE-5 can be recommended as the first line drug for the treatment of PH in the preoperative period and as a maintenance therapy in patients with inoperable IIIb-IV level of PH, improving the quality and extending the life span. Combined therapy with these drugs can be recommended in early postoperative period, as an effective therapy aimed at preventing pulmonary hypertensive crisis, treatment of cardiovascular failure, the further reduction of residual PH, and thus, improvement of patients' condition in the late postoperative period.
On 52 patients between the ages of 3 to 14 with congenital heart failure, complicated pulmonary hypertension on 3rd degree are learned dynamic of cellular immunity on surgical treatment depend on different pharmacotherapy. Treatment was consist of traditional therapy in patient who have congenital heart failure with pulmonary hypertension inhibitors of phosphodiesterase-5 (iFDE-5) (Viagra, Pfizer) and inhibitors AFP (iAFP) shows with time length increasing tendency their favorable impact on character and degree of severity in patient with secondary immunodeficiency.
Keywords: congenital heart disease, pulmonary hypertension, cellular immunity, secondary immunodeficiency, pulmonary hypertensive crisis, pulmonary circulation, inhibitors phosphodiesterase-5 (iFDE).
More than 50 % of congenital heart disease is accompanied by fluid overload, pulmonary circulation (PC) with the formation of pulmonary hypertension (PH), which is based on a combination of marked structural abnormalities associated with a wide range of hemodynamic disorders [1; 10; 12]. An important problem of cardiac surgery remains residual pulmonary hypertension (PH) in 15 % of cases, against which in the early postoperative period may develop heart failure and severe as a consequence of it, the occurrence of pulmonary hypertensive crises (PHC). Mortality in PHC is 18-55 % [3; 12]. Pulmonary hypertension, causing the development of various by hypoxia severity and hypoxemia, the de-stabilization of metabolic processes, contributes to the imbalance of almost all parts of the humoral and cellular immunity and development immunodeficiency Immunedeficiency leads to increased susceptibility of various infections, propensity to development of multiple organ lesions, allergic and autoimmune processes, high the risk of complications in cardiac surgery. Many comorbidities in children with CHD, and purulent-septic complications after cardiac
surgery indicate the presence of the original immune deficiency and worsening immune status after surgery [11].
In recent years, intensively studied various options for combination therapy schemes LH and PHC, algorithms on a combination and dosage of drugs that reduce the PH in the preoperative period, and acting on the residual PH in the postoperative period [6; 9; 16; 17]. With this in mind the interest of cardiologists produce enzymes of the family of phosphodiesterases (PDEs) catalyze the hydrolysis of cyclic 3'5'-nucleoside adenosine monophosphate (cAMP) and 3'5'-guanosine monophosphate (cGMP). Currently, the treatment of foreign clinics LH is used in children phosphodiesterase-5 inhibitor (PDEI-5-sildenafil, Pfizer). Sildenafil — a selective inhibitor of cGMP-dependent phosphodiesterase (type 5), preventing the degradation of cGMP increases levels of endogenous nitric oxide, which is a potent vasodilator, selectively acting on the PC vessels [6; 9; 14; 16; 17]. A large number of studies and is dedicated to the combination of different inotropic agents in the treatment of post-operative complications. Besides catecholamines (dopamine,
Dynamics of clinical and immunological parameters of pharmacotherapy of pulmonary hypertension
dobutamine, epinephrine, norepinephrine) currently used nonkate-holamine drugs, which are another group of inotropic agents relating to inhibitors of the phosphodiesterase-3 (3-PDEI) [4; 5; 8; 13; 15]. However, information on the nature of the immune status at the CHD are few and contradictory, and the immune system in patients, depending on the drug therapy on surgical treatment stages are often not examined, and, consequently, does not affect the tactics of surgical correction and the introduction of the patients in the early and later postoperatively. Cardiac surgery has a complex and multi-faceted impact on the immune system, which can be characterized as an activation, and how suppressive, since the operation of different influences functioning immune cells, resulting in a complex of these changes can be summarized as immune dysregulation. In this connection, the study of the dynamics of immunological processes in CHD patients with PH body will allow to prepare them for the complex surgery and prevent possible complications in the postoperative period.
The purpose of research: comparison the results of application of immune preparations in combination with 5-PDEI (sildenafil) and ACE inhibitors, as well as the study of the dynamics of cellular immunity in the complex treatment of PH in patients with CHD in the surgical treatment stages.
Materials and methods of studies: The study included patients department of surgery of congenital heart disease RSCS named by academic V. Vahidov for the period 2007-2014 years. There were 965 patients with CHD characterized by arterio-venous shunt. Of these, PH-II-IV st. — 198 patients. All patients were examined by the standard technique. Patients with high PH performed catheterization of heart cavities and the sample with the inhalation of100 % oxygen with X-ray. According to Fick's method of calculating the indicators that assess the state of the vessels of the pulmonary circulation (Qp/Qs, pulmonary resistance).
The studies were conducted for admission to the start of treatment, before surgery, after surgery and before discharge (at least 3-4 times). The obtained data were statistically processed using the program Statistica 6.0 for Windows. Quantitative indicators are presented in the form of Me (Q25 % - Q75 %), where Me — median value of the index, and (Q25 % - Q75 %) — interquartile spread. Validation of the differences produced by using nonparametric tests, since the distribution of patients by age and body mass different from normal. Differences were considered significant at p > 0.05.
In comparative perspective, patients divided into 2 groups.
Group A, n = 82. By the time of receipt of the mean age was 23.8 ± 22.6 (1-46 years), females — 47 (57.3 %), male — 35 (42.7 %). Ratio of 1.34: 1. All examined patients depending on the diagnosis and the degree of PH were divided into 3 groups. ASD: n = 23 (28 %); VSD: n = 39 (47.6 %); PDA: n = 20 (24.4 %).
All patients in group A preoperative received traditional therapy within 14-20 days (cardiac glycosides, potassium supplements, diuretics, restorative therapy if indicated). At baseline, patients in this group SBP in PA was 87.5 ± 15.2 mm. Hg. Art., the rate of Qp/Qs — 1.3 ± 0.3.
Group B, n = 116 patients. By the time of receipt of the mean age was 25.6 ± 23.1 (2-48 years). female, 76 persons (65.5 %), male — 40 (34.5 %). Ratio 1.9: 1. All examined patients depending on the diagnosis and the degree of PH were divided into 3 groups. ASD: n = 33 (28.4 %); VSD: n = 62 (53.5 %); PDA: n = 21 (18.1 %).
All patients in the group B in the preoperative period (14-20 days) are connected to conventional therapy: inhibitors fosfodiesterazy-5 (PDEI-5) — 2.5-3 mg/kg/day in 3 divided doses depending on the PH and ACE inhibitors (ACEI) (captopril)
12.5-25 mg/day in 2 divided doses. Rationale: inhibitors of phosphodiesterase^ included in the scheme of conventional therapy in order to prevent the degradation of cGMP, increasing the level of the powerful endogenous vasodilator — nitric oxide selectively acting on the vessels of the pulmonary circulation (PC), an ACE inhibitor (captopril) in order — vazodilating effect (venular, arteriolar and capillary), increasing the intensity of capillary blood flow, reducing the aggregation of blood cells, increase in end-diastolic volume (EDV), stroke volume (SV), reducing the total peripheral resistance (OPS), which helps to reduce hypertension ICC.
In order to study the dynamics of cellular immunity, we examined 52 patients with a child aged 3 to 14 years of age with CHD-VSD — 43 (82.7 %) and CAP — 9 (17.3 %) with PH IIIa degree.
All patients according to preoperative preparation were divided into 2 groups: group 1 (24 patients aged 3 to 14 years) — the comparison group in the preoperative period of 10-14 days received traditional therapy. 2 group (28 patients aged 3 to 14 years) — 2-I group in the preoperative period to conventional therapy added: fosfodiesterazy-5 inhibitors (5-PDEI—Viagra, Pfizer) 2.5-3 mg/kg/day. 3 receiving ACE inhibitors (ACEI) 6-12.5 mg. 3 times a day. All the results were compared with a control group — an indicator ofhealthy children by age and gender comparable to treatment groups (n = 22).
All patients on admission to hospital, after the preoperative preparation, after 10-14 days and 3 months after surgery with general clinical tests, and special clinical studies were carried out immunological studies, including definition of the content of cellular immunity in peripheral blood — CD3+, CD4+, CD8+ and CD20+ — lymphocytes using monoclonal antibodies, production of Immunology Research Institute of the Ministry of Health of the Russian Federation (Moscow, company "Sorbent") method Garib F. Y. et al., for a more complete and objective evaluation of cellular immunity calculated value of the immunore gulatory index (IRI = CD4+/CD8+).
Results and their discussion
In group A After the treatment, not recorded significant reduction in systolic blood pressure (SBP) in the pulmonary artery (PA) and was 86,4 ± 14,8 mm Hg, rate Qp/Qs 1.4 ± 0.2.
Central hemodynamics in these patients did not change significantly (Table 1).
Table 1. - The results of preoperative treatment of patients in group A
Indicators Initially Without receiving PDEI-5
Heart rate, beats per minute 121 ± 20 122 ± 22
SBP, mm. Hg. 102 ± 8 100 ± 7
DBP, mm. Hg. 66 ± 5 67 ± 5
SatO2, % 87.4 ± 6.2 88.3 ± 7.1
Qp/Qs 1.3 ± 0.3 1.4 ± 0.2
SBP in PA mm. Hg. 91 ± 6 92 ± 5
Note: Results of operations in group A were analyzed in 74patients.
Postoperatively, the patients of group A was conducted conventional therapy. In group A favorable during the early postoperative period was observed in 56 (76 %) patients, 18 (24 %) had a variety of complications with fatal outcome in 10 (13 %) cases. In group A in the early postoperative period in 10 patients having 16 critical complications, leading to death. Among the causes of mortality pulmonary hypertensive crisis was observed in 6 (8.1 %) patients.
Pulmonary hypertensive crisis (PHC) — a complication that is characterized by paroxysmal sharp increase in pulmonary arteriolar resistance, preventing blood flow in the left heart and accompanied by a sharp increase in pressure in the PA to the level of the
system. Sharp decrease of pulmonary blood flow in conjunction with a decrease in preload of the left ventricle leads to a decrease in cardiac output and coronary perfusion, leading to death. When PHC in 6 (8.1 %) patients experienced: increased pressure in the PA (PPA > 70), system pressure drop, the rise of the central venous pressure above 10 mm. Hg., SraO2 fall below 89 %, a pH below 7, 35, PaCO2 above 35, PaO 2 less than 100, pvO2 below 28, the decline Murray index (PaO2/FiO2 < 2), low cardiac output syndrome, tachycardia, increased airway pressure.
In 15 % ofpatients had residual pulmonary hypertension in the range of 50 to 60 mm. Hg. (Table 2).
Table 2. -Dynamic parameters depending on the stage of treatment in group A
Indicators Before surgery After surgery Before writing out
Heart rate, beats per min. 115 ± 25 90 ± 15 88 ± 14
SBP, mm. Hg. 110 ± 15 105 ± 9 110 ± 8
DBP, mm. Hg. 62 ± 11 70 ± 9 70 ± 8
SatO2, % 86.0 ± 6.4 95.0 ± 4.2 96.0 ± 3.2
Qp/Qs 1.3 ± 0.3 3.3 ± 0.7 3.4 ± 0.8
SBP in PA, mm. Hg. 88 ± 8 64 ± 5 58 ± 3
In the group B. In conducting group analysis B found that all patients at baseline SBP was from 84 to 102 mm Hg. Art. DBP of 52 to 69 mm. Hg., and after receiving PDEI-5 SBP ranged from 85 to 108 mm. Hg., DBP from 50 to 78 mm. Hg. It shows a lack of effect of the drug on the blood vessels of the systemic circulation, as evidenced by stable indicators of systemic blood pressure and heart rate after administration of 5-PDEI. Combination therapy 5-PDEI with ACE inhibitor drugs let to reduce peripheral vascular resistance, and thus prevent the symptoms that can occur with an increase in shunt across the defect walls (raising blood pressure, tachycardia) (Table 3).
Patients in the group SBP in PA was 65-96 mm. Hg., the rate Qp/Qs 1.0-2.9; after taking PDEI-5 was registered SBP in PA 44-95 mm. Hg. Art. and Qp/Qs 1.0-5.0 (Table 3).
Table 3. - Indicators of hemodynamics in patients group B in the dynamics of complex preoperative treatment PDEI-5 and ACE inhibitors
Indicators Initially After treatment PDEI-5 + ACEI
Heart rate, beats per minute 120 ± 22 122 ± 20
SBP mm Hg. 93 ± 9 94 ± 10
DBP, mm Hg. 58 ± 6 57 ± 7
SatO2, % 88.6 ± 5.3 97.0 ± 1.2
Qp/Qs 1.6 ± 0.4 3.6 ± 1.1
SBP in PA mm Hg. 89 ± 14 76 ± 13
In group B, the results of operations are analyzed in 80 patients. In this group of deaths occurred in 3 (4 %) patients, 77 (96 %) patients — a favorable during the early postoperative period.
In this group, in the early postoperative period, 3 patients having 5 critical complications, leading to death. Prevalent heart failure, in any case, was not observed pulmonary hypertensive crisis.
All patients in the group receiving routine in the pre- and postoperative period PDEI-5 in combination with ACE inhibitors (total duration of treatment — 24.9 ± 4.6 days) in an average dose of 2.6 ± 0.49 mg/kg/day. Postoperatively, were connected to a conventional therapy PDEI-3 (mean dose mil-rinone — 0.4 ± 0.62 ug/kg/min, the duration of treatment — 42.5 ± 24.1 hours); Prostaglandin E1 (vazaprostan in doze — 1.76 ± 0.88 ng/kg/min, duration of therapy 40.8 ± 20.4 hours). Patients also received support cardiotonic: dopamine 6.2 ± 3.6 g/kg/min (67.5 ± 38.7 hours). At ineffectiveness of do-pamine (control echocardiography) connected dobutamine — 4.4 ± 2.2 g/kg/min, duration of therapy — 38.6 ± 19.3 hours. Applies the semi prolonged ventilation (PIVL) with controlled pressure (the PCV), the ratio of inhalation/exhalation 1:2, Pinsp — 22-24 sm. vod. st., FiO2 — 60 %, PEEP — 2-3 mm. rt. st. PIVL efficiency criteria were: PaO2, SaO2, PaO2/the FiO2 (index Murray), pO2 (Ah) ie, pO2 (a/A) f. The effectiveness of the complex pharmacotherapy above drugs are presented in Table 4.
Table 4. - Dynamic parameters depending on the stage of treatment in the group B
Indicators Before surgery After surgery Before writing out
Heart rate, beats per min. 124 ± 20 90 ± 15 88 ± 15
SBP, mm. Hg. 96 ± 10 110 ± 10 115 ± 12
DBP, mm. Hg. 57 ± 7 68 ± 12 69 ± 11
SatO2, % 94.2 ± 1.2 97.0 ± 3.0 98.8 ± 1.2
Qp/Qs 3.6 ± 1.0 3.6 ± 1.1 3.8 ± 1.2
SBP in PA, mm. Hg. 76 ± 13 55 ± 11 45 ± 10
Analysis of the research performance of cellular immunity of patients on admission showed significantly lower values we all studied immunocompetent cells. Thus, the level of T-lymphocytes (CD3+) (1.2 times) was significantly lower than control values at a fairly significant reductions indicators B-lymphocytes (CD20+), subpopulations of T-lymphocytes — T-helpers/inducers (CD4+) and T cytotoxic cells (CD8+) (Table 1).
At the same significant decrease subpopulations of T lymphocytes observed marked reduction in the immunoregulatory index (IRI = CD4+/CD8+ lymphocytes), which is connected, apparently, with a slightly larger decrease in T helper/inducer (1.4 times) than the T-cytotoxic cells (1.3 times), indicating that the suppressive nature of the condition of the immune response (Table 7).
Table 5. - Cellular immunity indicators CHD patients with PH at admission
Groups/indicators CD3+ ( %) CD4+ ( %) CD8+ ( %) IRI CD20+ ( %)
Control (n = 22) 51.36 ± 0.99 30.71 ± 0.85 22.0 ± 0.35 1.40 ± 0.38 18.36 ± 0.57
On admission (n = 52) 42.68 ± 0.58* 21.32 ± 0.56* 17.11 ± 0.33* 1.25 ± 0.02* 14.96 ± 0.38*
Note: * — P < 0.05 — reliability indices in comparison with the control.
The results of the original value of of cellular immunity of patients surveyed indicate the presence ofpronounced secondary immunodeficiency.
Comparative analysis ofcellular immunity ofpatients in the control group (group 1) after traditional preoperative preparation shows a slight increase in all studied parameters of cellular immunity with re-
spect to values at admission, but a significant increase is noted only indicators ofregulatory subpopulations of T-lymphocytes — T-helper cells (CD4+) and T-suppressors (CD8+). Moreover, the multiplicity of the increase of their identical (1.04 times), in this connection, the immunoregulatory index virtually unchanged (1.24 ± 0.02) and the immune response retains the suppressor character (Table 6).
Dynamics of clinical and immunological parameters of pharmacotherapy of pulmonary hypertension ... Table 6. - The dynamics of immunological parameters in CHD patients with PH control group (without taking PDEI-5)
Indicators Control On admision Before surgery After surgery
n = 22 n = 52 n = 24 on 12-14 day After 3 months
CD3+ 51.36 ± 0.99 42.68 ± 0.58* 42.58 ± 0.38* 43.13 ± 0.31* 46.35 ± 0.54*
CD4+ 30.71 ± 0.85 21.32 ± 0.56* 22.25 ± 0.32" 22.67 ± 0.31" 23.65 ± 0.27*
CD8+ 22.0 ± 0.35 17.11 ± 0.33* 17.96 ± 0.25" 17.83 ± 0.31* 18.82 ± 0.32*
IRI 1.40 ± 0.38 1.25 ± 0.02* 1.24 ± 0.02* 1.27 ± 0.02* 1.26 ± 0.01*
CD20+ 18.36 ± 0.57 14.96 ± 0.38* 14.71 ± 0.20* 15.08 ± 0.17* 16.35 ± 0.35*
Note: further on in this document: * — P < 0.05 — reliability indices in comparison with the control; ' — P < 0.05 — the accuracy of the indicators in comparison with indicators of admission; • — P < 0.05 — the accuracy of the indicators in comparison with indicators before surgery; * — P < 0.05 — the accuracy of the indicators in comparison with indicators of research and monitoring
Analysis of the data of immunological examination of patients 12-14 days after the operation shows a slight rise in cellular immunity, while remaining significantly lower than the control values. At the expense of some increase in T-helper cells and a slight decrease of T-suppressor on the previous studies, a slight increase in IRI that indicates a positive trend in the course of the disease (Table 6).
A similar, but more pronounced trend is observed in the dynamics of immunological parameters at 3 months after surgery. Thus, there is a significant increase in the level of T-lymphocytes (CD3+) from previous studies (at admission, after preoperative preparation and 14 days after surgery), B-lymphocytes (CD20+), subpopulations of T-lymphocytes — T.
60 50 40 30 20 10
4^51,36 —control
46,3?S/SSs after 3 months
30,71
23,65 ■- ----- 22 18,36
18,82m a 16,35
CD3+
CD4+
CD8+
CD20+
Fig. 1. The dynamics of cellular immunity in patients with conventional preoperative preparation of 3 months after the operation (in %)
Analysis of increasing multiplicity of all our studies of cellular immunity cells showed the same level of relative values on admission (1.1 times). It should be noted that in this case, the restoration and normalization of the immunological status of patients ofvalues does not occur, since the analysis of the results shows a highly significant difference to their performance in healthy children (Tab. 6, Fig. 1).
Studying the dynamics of cellular immunity in CHD patients with PH Ilia st. in the 2nd group (2nd group — 28 patients), which in the preoperative period to conventional therapy added: PDEI-5 and ACE inhibitors has shown that orientation changes are identical to those of group 1 patients studied, but also the severity of the dynamics of the studied parameters It differs only slightly among themselves, having basically the same fold increase relative to the initial values of the indicators. Thus, if the level of T-lymphocytes (CD3+) 1 group examined after traditional
preoperative preparation is 42.58 ± 0.38 %, then in the 2nd group — 43.82 ± 0.59 %, 1.0 times higher than the corresponding figures in admission (42.68 ± 0.58 %, respectively, P > 0.05). Also, only an order of magnitude higher than the level of B lympho cytes (CD20+), identical in 1.0 times lower than the values on admission, subpopulations of T-lymphocytes — T-helpers/inducers (CD4+) and T-cytotoxic cells (CD8+) (Tab. 7).
However, it should be noted that in group 2 fold increase of T-helpers/inducers (CD4+) subpopulations of T-lymphocytes relatively higher degree ofincrease ofthe indicator in group 1 (1.05 and 1.8 times, respectively), and that it is important to intensity increasing up for enhancing the cytotoxic T-cells (CD8+) in the group, resulting in an increase of the immunoregulatory index IRI regarding admission that, in turn, is a favorable sign in dynamics immunological studies (Table 7).
Table 7. - The dynamics of immunological parameters in CHD patients with PH receiving PDEI-5
Indicators Control n = 22 On admission n = 52 Before surgery n = 24 After surgery
on 12-14 day After 3 months
CD3+ 51.36 ± 0.99 42.50 ± 0.45* 43.82 ± 0.59* 44.04 ± 0.53* 47.62 ± 0.58*
CD4+ 30.71 ± 0.85 21.23 ± 0.34* 23.07 ± 0.30" 23.39 ± 0.40" 24.43 ± 0.41*
CD8+ 22.0 ± 0.35 17.17 ± 0.22* 18.04 ± 0.27" 18.07 ± 0.29* 18.24 ± 0.28*
IRI 1.40 ± 0.38 1.24 ± 0.01* 1.29 ± 0.02* 1.30 ± 0.01* 1.34 ± 0.02*
CD20+ 18.36 ± 0.57 14.67 ± 0.24* 15.75 ± 0.20* 16.07 ± 0.33* 16.62 ± 0.38*
Fig. 2. The dynamics of cellular immunity of patients in group 2 while taking PDEI-5 at 3 months after surgery (in %)
This is a small, but positive dynamics observed in the 2nd group of studied patients and in 12-14 days and 3 months after surgery (Table 7). As in group 1 patients studied all the indicators of cellular immunity are significantly lower with respect to indicators of healthy individuals, i.e, eliminate the cause of the disease is not enough to restore the disturbed balance of the immune system in such a short period of time (Fig. 2).
Thus, the analysis of the dynamics of cellular immunity (T-lym-phocytes (CD3+); B lymphocytes (CD20+); subpopulations of T lymphocytes — T-helpers/inducers (CD4+) and T-cytotoxic cells (CD8+) CHD patients with PH 2 - the second group, which in the preoperative period to conventional therapy added: PDEI-5 and ACE inhibitors, shows no significant effect on their nature and severity of secondary immunodeficiency may have to restore the disturbed balance of the immune system requires a longer application PDEI-5.
Conclusions:
1. Treatment PDEI-5 (sildenafil) in combination with an ACE inhibitor (captopril) preoperatively revealed a decrease in pulmonary resistance and SBP in PA by an average of 10-14 % in patients of group B compared with patients of group A.
2. The main complications after radical correction of CHD are the residual pulmonary hypertension, heart failure and pulmonary — hypertensive crises.
3. Risk factors for the development of PHC and adverse outcome in the early postoperative period is the presence of residual pulmonary hypertension (PAP/BP > 0.5), decrease in the index Murray (pa02/Fi02) of less than 2, increasing the average values of CVP greater than 10 mm. Hg.
4. Use of 5-PDEI (sildenafil) and an ACE inhibitor in combination with infusional PDEI-3 (milrenon, enoximone
0.3-1.0 mg/kg/min), with inotropic drugs (dopamine, dobu-tamine 5-15 mg/kg/min) and prostaglandin E1 (vazapros-tan 1-6 ng/kg/min), in the development of acute left and/or right ventricular failure with residual pulmonary hypertension is accompanied by a decrease in average CVP values, heart rate, increased blood pressure and the rate of diuresis, Murray index, decreased pulmonary artery pressure and leads to the stabilization of the patients.
5. Keeping patients in the early postoperative period in pressure modes with limited peak inspiratory pressure, decrease PEEP to 2-3 mm. Hg. and increasing FiO2 > 60 % more efficient in relation to the correction of hypoxemia in heart failure and prevention of pulmonary hypertensive crises and reduce the duration of PIVL after radical correction of CHD complicated with high PH.
6. Inclusion in the traditional therapy of CHD patients with PH inhibitors fosfodiesterazy-5 (PDEI-5) (Viagra, Pfizer) and ACE inhibitors (ACEI) shows a rising trend over time favorable impact of them on the nature and severity of existing secondary immunodeficiency patients.
7. Based on the above, PDEI-5 (sildenafil) can be recommended as the primary drug in the treatment of PH in the preoperative period, in the treatment of post-operative period in combination with the above drugs, and as maintenance therapy in patients with congenital heart disease complicated by high PH not be surgical treatment. Thus, expanding the indications for surgical treatment, there is a more favorable trend in the early postoperative period, reduces mortality, improves condition and prolongs the life of patients who are not subject to surgical intervention. The objectivity of the information obtained was confirmed by repeated echocardiography and catheterization of cardiac cavities.
References:
1. Abdullaeva S. H. Doppler echocardiography and invasive diagnostic methods in the evaluation ofpulmonary hypertension in patients with congenital heart. Diss. of the candidate of medical sciences. - M., 2009. - P. 27-105.
2. Abrams D., Schulze-Neick I., Magee A. G. Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension/Heart. - 2000. - V. 84. - P. E4.
3. Babadjanov C. B., Sobirov M. B., Makhmudov M. M. Ventricular septal defect with a high or critical pulmonary hypertension - surgery and immediate results//Surgery Uzbekistan. - B., 2007. - № 3. - P. 47.
4. Barst R.J., Maislin G., Fishman A. P. Vasodilator therapy for primary pulmonary hypertension in children//Circulation. - 1999. -V. 99. - P. 1197-12089.
5. Boswell-Smith V. et al. Phosphodiesterase inhibitors//British Journal of Pharmacology. - 2006. - № 4. - P. 252-258.
Endoprosthesis of the knee joint without use of metallic modular blocks in the elderly patients with axial deformations
6. Garcia Martinez E., Ibarra De La Rosa I., Perez Navero J. L. et al. Sildenafil in the treatment of pulmonary hypertension//An Pediatr (Barc). - 2003, Jul. - V. 59, № 1. - P. 110-113.
7. Garib F. Y., Gurarii N. I., Garib V. F. The method of determining lymphocyte subpopulations//Rasmiy ahborotnoma. - Tashkent, 1995. - № 1. - P. 90.
8. Ghofrani H. A., Wiedemann R., Rods F. et al. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension//Ann Intern Med. - 2002. - V. 136. - P. 515-522.
9. Ghofrani H. A., Wiedemann R., Rose F. et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomized controlled trial//Lancet. - 2002. - 360: 895-900.
10. Gorbachev S., Belkin N. V. Examination of the patient with pulmonary hypertension in the clinic of cardiovascular surgery: guidelines for physicians/edited. Acad. RAMS L.A Bokeria. - M.: SCCS them. A.N Bakulev RAMS, 2008. - P. 64.
11. Gulyamov M. G., Akhmedova M. D., Akhmedova H. U., Mirzaev U. N. Options and clinical assessment of secondary immunodeficiencies in intestinal infections//Practitioners Messenger. - Samarkand, 2002. - № 2. - P. 22-24.
12. Ivanickiy A. V., Garbachevskiy S. V., Sobolev A. V., and etc. Integrated approach in diagnostics and treatment of congenital heart failure with high pulmonary hypertension//6th All-Russian Congress of heart surgeons: Thesis made - M., 2000. - P. 9.
13. Kleinsasser A., Loeckinger A., Hoermann C. et al. Sildenafil modulates hemodynamics and pulmonary gas exchange//Am J Respir Crit Care Med. - 2001. - 163: 339-343.
14. Robinson I. M. et al. Positive inotropic/vasodilatator agents//Cardiol. Clinic. - 2009. - P. 131-144.
15. Trachte A. L., Lobato E. B., Urdaneta F. et al. Oral Sildenafil Reduces Pulmonary Hypertension After Cardiac Surgery//Ann. Thorac. Surg. - 2005. - V. 79. - P. 194-197.
16. Yanulevich O. S. Use of an inhibitor of phosphodiesterase in the diagnosis and treatment of pulmonary hypertension in children with congenital heart disease. Diss. of the candidate of medical sciences. - Tomsk, 2010. - P. 110-118.
17. Yanulevich O. S., Ivanov S. V., Kovalev I. A., Krivoshchekov E. V., Filippov G. P. Pharmaceutics test with sildenafil in the evaluation of pulmonary hypertension in children with congenital heart disease. Research Institute of Cardiology, RAMS, Tomsk//Bulletin of the Siberian medicine. - 2010. - № 5. - S. 117-120.
Alimov Aziz Pulatovich, Azizov Mirhakim Javharovich, Scientific Research Institute of Traumatology and orthopedics, Ministry of Health of the Republic of Uzbekistan E-mail: dr.alimov@bk.ru
Endoprosthesis of the knee joint without use of metallic modular blocks in the elderly patients with axial deformations
Abstract: The purpose of this research was to evaluate the results of endoprosthesis of the knee joint without use of modular metal blocks in the elderly patients. It was determined that in the endoprosthesis of the knee joint with defects of the tibial plateau condyles with use of metal modular blocks the positive results may be achieved after endoprosthesis in minor and middle defects of the tibia. In the elderly patients (75-84 years) the cement replacement was preferable, and at the more younger age (61-74 years) the bone autoplasty with additional osteotropic therapy is more rational.
Keywords: knee joint, endoprosthesis, tibial condyle, scales, elderly patients.
Introduction
Stable pain in the knee joint with presence of accompanied diseases at the aged age is the indication to the endoprosthesis, ignoring the principles of the further revision interventions [4; 8].
The use of modular metallic blocks resulted in significant improvement of the knee joint endoprosthesis in the axial deformations. However, use of these constructions in the patients with accompanying osteoporotic bone tissue leads to the early instability of the tibial component. The efforts of the surgeons to save the osseous mass for further revision intervention do not always prove their value, and, on the contrary, shorten the time for early intervention in the elderly patients with this pathology [2; 5; 9; 12; 13; 14; 16; 17; 19].
Introduction of the principle of resection of the tibial plateau along "the bottom of defect" with insertion of the polyethylene inset of the more size at this age resulted in significant improvement of the outcomes of endoprosthesis of the knee joint in this category of patients. At large defects the use of bone plasty taking into account the bone mineral density showed also satisfactory clinical-functional outcomes of the endoprosthesis of the knee joint [1; 5; 8; 10; 20].
The prior type of fixation in the endoprosthesis of the knee joint is cement, which was required for biomechanics of the joint when mutual pulling out of the joint components occurs under the effect of force of the antagonistic muscles [1; 13; 15].
In the elderly age the bone mineral density reduces and use of the endoprosthesis with modular metal blocks induced doubts of fixing stability of the endoprosthesis components.
Purpose ofthis research is the assessment ofthe results ofendo-prosthesis of the knee joint without use of modular metal blocks in the elderly patients with axial deformation of the knee joint.
Materials and methods
In the department of adult orthopedics of the Scientific Research Institute of Traumatology and Orthopedics of the Ministry of Health of the Republic of Uzbekistan in 45 patients (29 women, 16 men; of the minimal age 61 years old, maximal age 84 years old, and average age 67 years old) with axial deformations and defects of the condyles of tibia there were performed endoprosthesis of a knee joint: with autobone plasty in 15, and with cement filling in 30 patients.
