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Russian Journal of Transplantology and Artificial Organs

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Vol 17, No 3 (2015)
View or download the full issue PDF (Russian)
https://doi.org/10.15825/1995-1191-2015-3

Editorial

Clinical Transplantology

8-13 1406
Abstract

In cardiac recipients non-invasive monitoring will identify the risk of acute rejection, as well as reduce the number of routine biopsies. The relation between the development of the transplanted heart rejection and the change of elastic properties of common carotid artery has been proved. Aim: to analyze dynamics of iRIG in treatment of graft rejection in heart recipients.

Materials and methods. 59 heart recipients were examined: 21 patients (pts)
without rejection, 20 pts – with rejection after 1st biopsy, 15 pts – with rejection after 1st and 2 biopsies, 3 pts – with persistent rejection after all biopsies. iRIG was estimated using empirical equation.

Results. Dynamics of iRIG in pts. without rejection according to all biopsies over time was not signifi cantly changed 6280 ± 2143, 6083 ± 2388, 6362 ± 1984 and 6188 ± 3012 cm/sec2 (p = 0.11, p = 0.13, p = 0.17 between the 1st and 2nd, 2nd and 3rd, 3rd and 4th values, respectively). In pts. with rejection iRIG decreased during treatment, but was signifi cantly higher even after successful treatment. In patients with persistent rejection iRIG did not decrease and tended to increase (17 459 ± 9702 cm/sec2 on the results of the 1st biopsy to 21 305 ± 10 448 cm/sec2 on the results of the 4th biopsy).

Conclusions. In patients with heart transplant iRIG does not change signifi cantly with the time after transplantation. iRIG increases in all types of rejection, followed by its decrease in the course of therapy; in patients with persistent rejection iRIG remains high. Evaluation of iRIG can be used for non-invasive monitoring of patients after heart transplantations (HTx) and to identify patients at high risk of transplant rejection.

14-23 1436
Abstract

Aim. Identifi cation of possible histological differences of the Quilty effect in acute rejection and its absence as well as studying the proliferation of blood and lymph vessels in the area of Quilty damage.

Materials and methods. 883 endomyocardial biopsy materials from 352 patients were studied. Histological sections were stained with hematoxylin and eosin, Masson method; the endothelium of lymphatic vessels was stained with immunoperoxidase method using a marker D2-40.

Results. The Quilty effect was observed both in acute rejection and in
its absence. In the majority of cases the Quilty effect was of type «A» and it was combined with acute rejection. The Quilty effect of type «B» has been mostly in the G2R. Acute rejection is characterized by diffuse form of endocardium lymphoid infi ltration. Follicular form resembles lymphoid organ tissue. Different types and forms of the Quilty effect may be combined in the same biopsy. Proliferation of blood vessels presents in the area of the Quilty effect. Lymphatic vessels are missing in endocardium and in the area of the Quilty effect. They could be found only in the myocardium of endomiocardial biopsy.

Conclusion. Diffuse lymphoid infi ltration of the endocardium is a characteristic feature of acute rejection of the transplanted heart. Follicular form of the Quilty effect is similar to lymphoid tissue whose role requires further study using immunohistochemical methods.

24-31 1423
Abstract

It was shown that Tacrolimus (Tac) can suppress infl ammation and immune response involved in liver ischemia-reperfusion injury (IRI) (Kristo I., Transpl Int., 2011). Aim. We hypothesize that back-table arterial and portal liver perfusion with Tac can infl uence the incidence and severity of early allograft dysfunction (EAD). A prospective randomized study was conducted (ClinicalTrials.gov Identifi er: NCT01887171).

Materials and methods. Criteria of the inclusion: First liver transplantation from DBD donor with sequential portal-arterial reperfusion. At back-table portal vein and hepatic artery were perfused each by 500 ml of HTK solution containing 20 ng/ml Tac during 10–15 min followed by portal fl ushing with 200 ml 5% solution of Albumin containing 20 ng/ml Tac and by resting of liver in effl uent. No Tac was added in the control group. Primary Outcome: EAD (Olthoff KM, et al. Liver Transpl. 2010) and severe EAD (P.R.Salvalaggio, et al. Transpl. Proceedings, 2012).

Results. No difference was found between groups (main vs. control) in terms of MELD (16 vs. 16), steatosis (10 vs. 10%), ballooning (45 vs. 40%) of liver grafts, recipient age (50 vs. 50 y.o.), warm ischemia time (50 vs.50 min) and total ischemia time (482.5 vs. 485.0 min). Median donor age was higher in the main group (44.5 vs. 39.0 y.o.). The overall rate of EAD was 27.9%. EAD rate was signifi cantly lower in the main group (6/43 vs. 18/43; p = 0.003). The rate of moderate-to-severe EAD was lower in the main group (1/43 vs. 10/43; p = 0.009). The median levels of AST and ALT in 24 h after reperfusion were signifi cantly lower in the intervention group (1004 vs. 1596; p = 0.03 and 449 vs. 759; p = 0.057).

Conclusion. Portal and arterial back-table liver perfusion with HTK solution with Tacrolimus may contribute to lower EAD incidence and severity.

32-39 2674
Abstract

Introduction. The development of immunological confl ict in the form of host-versus-graft reaction has always been main problem in transplantation. The worst case is the development of humoral rejection with the presence of circulating immune complexes and antibodies. There are several methods for quick removal of antibodies; among those are traditional plasmapheresis (PA) and double fi ltration plasmapheresis (DFPF). In this paper we present our experience with these two methods and give a comparative evaluation of the effectiveness in the treatment of acute humoral rejection in renal allograft.

Aim: to compare the effectiveness of traditional and double fi ltration plasmapheresis while processing different volumes of plasma in the treatment of host-versus-graft disease after kidney transplantation.

Methods. The study included 58 patients after kidney transplantation. All patients had increased activity of humoral immunity, which was confi rmed by immunofl uorescence with luminescence C4d complement component. In 26 patients we performed DFPF, in 32 patients – traditional PA. We divided the DFPF patients into 4 subgroups depending on the amount of processed plasma: > 50% (5 patients), 50–100% (8 patients), 100–150% (7 patients), 150–200% (6 patients) of circulating plasma volume. We also divided PA patients into four subgroups depending on the volume of plasma removed: >50% (8 patients), 50–70% (12 patients), 70–90% (7 patients), 90–110% (5 patients) of the volume of circulating plasma. We monitored the immune status with markers of humoral immunity activation IgM, IgG before and after each of the procedures.

Results. Each procedure of traditional PA and DFPF was accompanied by a marked decrease in blood concentrations of IgM and IgG antibodies. Their level decreased by an average of 30–55% of the original. However, some patients in both groups showed an increase in the concentration of these immunoglobulins in 1–2 days after the fi rst and the second procedures. The effect of rebound was observed during DFPF if in one procedure less than 100% of the circulation plasma volume was processed and during traditional PA if less than 70% was removed. Upon reaching the target values and increasing the processing volumes we managed to avoid growth of IgM and IgG.

Conclusions. DFPF and traditional PA can effectively reduce the high titers of circulating antibodies, which is accompanied by a decrease in the activity of humoral immunity of the recipient. In the case of double fi ltration plasmapheresis at least one volume of circulating plasma should be processed and in traditional plasmapheresis – at least 70% should be removed.

40-42 1261
Abstract

The article deals with the legal protection of inventions in V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs

Heart Transplantation and Assisted Circulation

43-49 1579
Abstract

Introduction. The preliminary study of new developed pumps for circulatory support on the hydrodynamic circulation model is an important step in the process of their designing. Hydrodynamic circulation models that can closely imitate cardio – vascular system are important to defi ne the range of effective functioning of the pumps under normal and heart disease conditions which is of great importance for defi ning the mode of these pumps in real clinical conditions.

The aim of study is to create a new hydrodynamic circulation model of the systemic circulation to study the processes of interaction of heart left ventricle and continuous – fl ow pumps.

Materials and methods. The main components of the mock circulation model (arterial and venous blocks) are designed as closed reservoirs with an air bag providing the necessary elasticity value of these reservoirs. The heart left ventricle was simulated with an artifi cial heart ventricle with a pneumatic drive Sinus-IS which allows to change its options in a wide range. As a test pump we used the fi rst native implantable axial pump VISH – 1. In the course of research we made the registration and recording of the basic hemodynamic parameters (pressure, fl ow) with a multichannel module Pumpax for the measurement of pressure parameters.

Results. The designed circulation model allows to adequately reproduce the main hemodynamic parameters of the circulatory system in normal (arterial pressure – 110/77 mmHg, left atrium pressure – 7 mmHg and cardiac output – 4.2 l/min) and heart failure conditions (arterial pressure – 79/53 mmHg, left atrium pressure – 15 mmHg and cardiac output – 3.1 l/min). On the circulation model the interaction of heart left ventricle and continuous-fl ow pump in heart failure simulation was studied. The dynamics of the main circulation fi gures is shown under conditions of changing of the pump rotor speed. Meanwhile, the conditions of the closing of aortic valve are identifi ed which is important for the
clinical use of this pump. Using a special separately fl exible camera on the pump inlet we modeled phenomena of negative pressure leading to unstable pump operation and reduction of pump fl ow.

Conclusion. Characteristics of the developed hydrodynamic circulation model allow us to reproduce parameters of systemic circulation in a wide range and to use it in designing of new pumps for circulatory support.

Regenerative Medicine and Cell Technologies

50-57 1587
Abstract

Aim. To study the therapeutic potential of cryopreserved fetal liver cells seeded into macroporous alginategelatin scaffolds after implantation to omentum of rats with hepatic failure.

Materials and methods.Hepatic failure was simulated by administration of 2-acetyl aminofl uorene followed partial hepatectomy. Macroporous alginate-gelatin scaffolds, seeded with allogenic cryopreserved fetal liver cells (FLCs) were implanted into rat omentum. To prevent from colonization of host cells scaffolds were coated with alginate gel shell. Serum transaminase activity, levels of albumin and bilirubin as markers of hepatic function were determined during 4 weeks after failure model formation and scaffold implantation. Morphology of liver and scaffolds after implantation were examined histologically.

Results. Macroporous alginate-gelatin scaffolds after implantation to healthy rats were colonized by host cells. Additional formation of alginate gel shell around scaffolds prevented the colonization. Implantation of macroporous scaffolds seeded with cryopreserved rat FLCs and additionally coated with alginate gel shell into omentum of rats with hepatic failure resulted in signifi cant improvement of hepatospecifi c parameters of the blood serum and positive changes of liver morphology. The presence of cells with their extracellular matrix within the scaffolds was confi rmed after 4 weeks post implantation.

Conclusion. The data above indicate that macroporous alginate-gelatin scaffolds coated with alginate gel shell are promising cell carriers for the development of bioengineered liver equivalents.

58-64 1488
Abstract

Aim. To study in experiment the criteria for transplantability of multicellular spheroid microaggregates of retinal pigment epithelium (RPE), prepared by the method of 3D cell culture.

Materials and Methods. 11 donor eyes (6 of adrenaline index «A», 5 of index «B») were used as a source of RPE cell cultures (group «A» – 6 cultures, group «B» – 5 cultures), of which over 2000 RPE spheroids were obtained by the method of three-dimensional cell culture. 1760 spheroids of them were selected for transplantability investigation (960 – group «A», 800 – group «B»). Among the selected spheroids were equal numbers of spheroids of different morphology («smooth» and «rough») and of the initial cell seeding number (500, 1000, 5000, 25 000, 125 000 cells per hanging drop). We were taking out 12 spheroids of group «A» and 10 spheroids of group «B» of the 3D culture in terms of 7, 14, 21, 28 days of 3D culture to assess their viability. We were transferring the same number of spheroids in the same terms from 3D to 2D culture conditions to assess their adhesive properties. Viability of cells within spheroids was determined using the Trypan blue exclusion. The presence or absence of adhesion was determined by microscopic observation.

Results. «Smooth» spheroids of 7 and 14 days of pretransplantation cultivation and derived from hanging drops containing 500 and 1000 cells showed the highest transplantability (cell viability varied from 0.83 ± 0.38 to 0.94 ± 0.24, a 100% adhesion). «Rough» spheroids were untransplantable in all variants, despite their partial preservation of viability (in comparison to “smooth” ones p < 0.05). 21 and 28 days of pretransplantation culturing and high cell seeding numbers signifi cantly lowered transplantability of obtained spheroids (p > 0.05 for low cell numbers, p < 0.05 for the high ones). Differences in adrenaline indexes A and B of donor eyes which were the primary sources of cellular material had no effect (p > 0.05) on resulting spheroids transplantability.

Conclusion. Among RPE spheroids obtained by our method the spheroids cultivated in a 3D environment for 7 to 14 days prior to transplantation and derived from hanging drops containing 500 and 1000 RPE cells showed the highest transplantability.

Clinical Cases

65-69 1417
Abstract

Extracorporeal membrane oxygenation is considered either as a linking procedure restoring functioning of an organ or as a link to organ grafting. If there is no expectancy to bring back pulmonary or cardiac functioning and grafting is out of feasibility, one should consider ECMO to be meaningless. In this paper we have demonstrated a successful application of ECMO in a 55 y. o. female patient with terminal stage of critical mitral valve stenosis with left atrial thrombus and her left ventricular ejection fraction (LVEF) was 16%. Following 4-day perfusion due to a noticeable positive dynamics the patient underwent mitral valve replacement and LA thrombus removal. In fi ve days after the surgery ECMO was disconnected. At discharge LV ejection fraction was 43%.

Conclusions: we believe ECMO should be more widely applied in cardiac surgery.

70-75 1565
Abstract

Aim: To estimate results of kidney transplantation in city clinical hospital No. 7 of Almaty.

Materials and methods. 100 patients who underwent kidney transplantation in our institution were analyzed; males – 54 (54%), females – 46 (46%), aged from 14 till 58 years old (39 ± 10.3). In 91 cases hand – assisted laparoscopic nephrectomy (HALN) was performed and in 3 cases – open method (2 with mini-lumbotomic and 1 with pararectal access) was used.

Results. The survival rate was 98% (98 patients). The causes of death were the nonfunctioning transplant due to noncompliance of immunosuppression, post traumatic septic complications, multiple organ failure. The most frequent complications were hematoma (12%), acute rejection (8%), and tubular necrosis (2%). Less aggressive schemes of immunosuppressive therapy allow reducing risk of drug toxic impact on the patient's organism and, thus, can extend functioning of a transplant.

Conclusion. Kidney transplantation is an effective treatment method of end stage renal diseases. The use of modern immunosuppressive therapy protocols and adequate immunological selection of donor – recipient provide high survival of transplants. Operative treatment and further case management of this group of patients are possible in highly specialized medical hospital.

Literature Reviews

76-82 1721
Abstract

This review summarizes the current literature devoted to the analysis of the role of transforming growth factor beta 1 (TGF-β1) at liver transplantation. TGF-β1 plays a key role in the development of liver fi brosis, as well as in development of the immune response; its concentration in the blood and tissue changes in liver diseases. TGF-β1 levels in the blood of the recipients are associated with the development of liver fi brosis, the formation of immune tolerance and immune response to active infection. Measuring the level of TGF-β1 at liver transplantation may have diagnostic and prognostic value for assessing the graft condition. Currently, clinical data on the role of the cytokine at liver transplantation are not accumulated enough and further research on the relation of TGF-β1 levels with different clinical and laboratory parameters in liver transplant patients is needed. The review analyzed 54 sources of literature, more than half of which were published in the last fi ve years.

83-88 1363
Abstract

This review contains analysis of current approaches to HCV treatment in liver transplant recipients. The authors explore key limitations associated with the usage of available treatment options and benefi ts related to the implementation of IFN-free regimens. The review summarizes results of published up-to-date studies on the usage of direct antiviral agents after liver transplantation.

89-111 2662
Abstract

Angiogenesis is the process of new capillary formation by migration and proliferation of differentiated endothelial cells from pre-existing microvascular network. A number of angiogenic molecules and cell populations are involved in this complex of new vessel formation cascades resulting in the determination and organization of new tridimensional vascular network. The goal of therapeutic angiogenesis is to stimulate angiogenesis to improve perfusion, to deliver survival factors to sites of tissue repair, to mobilize regenerative stem cell populations, and
ultimately to restore form and function to the tissue. Growth factors and bone marrow as a source of bone marrow mononuclear cells represent a very interesting research fi eld for the realization of therapeutic angiogenesis in ischemic tissues. They provide a potential key component in the healing processes of ischemic injured tissues.

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ISSN 1995-1191 (Print)