Donor organs shortage leads to extending criteria for deceased liver donation in the whole world.

Aim: to compare results of deceased donor liver transplantation (DDLT) depending of donor age over 60 years old.

Materials and methods: the study includes 390 DDLT from January 2010 to November 2017. All liver donors separated by age for two groups: I – 60 years and older (n = 26); II – younger than 60 years (n = 364). All donors were standardized by demographic, laboratory fi ndings and inotropic drug requirement.

 Results: no difference between both groups in severity of ischemia-reperfusion injury, ICU or in-hospital staying (median 2 and 7,5 days respectively) was found. There is also no difference between biliary or vascular complication rate. 5-year actuarial survival rate found no difference between both groups (I: 70%: II: 76%, p = 0,54).

Conclusion. Using grafts from donors older than 60 years don’t worsen early and late results of DDLT. Care should be taken to avoid other risk factors (cold ischemia time, warm ischemia time).

Aim: to develop an optimal surgical tactic for implantation of “AVK-N” system as a “bridge” to heart transplantation.

Materials and methods. 17 patients were included. They were operated in the period from 2012 to October 2017 in Federal State Budgetary Institution «V.I. Shumakov National Medical Research Center of Transplantology and Artifi cial Organs». A tiny implantable system «Portable device for assisting cardiac circulation» (AVK-N; Russia) was used for replacing the pumping function of the left ventricle. All patients were examined according to the program of potential recipients for heart transplantation, before the applying of prolonged mechanical circulatory support. Among the operated patients there were 16 (94.1%) men and 1 (5.9%) woman, the average age was 52.64 ± 10.56 (from 33 to 67 years). All patients had congestive heart failure III–IV functional class according to NYHA, refractory to optimal drug therapy. Heart failure was triggered by dilated cardiomyopathy in 12 (70,58%) cases, and by postinfarction systolic dysfunction of the left ventricle in 5 (29,42%). Implantation of «AVK-N» system was performed to potential recipients of the donor heart with terminal stage of CHF with a decrease in LV ejection fraction up to 10%.

Results. As a result of this study there were developed several technological aspects facilitating the subsequent heart transplantation.

Conclusion. Our experience in optimizing the surgical tactics of the “AVK-N” system implantation as a bridge to heart transplantation, demonstrated the possibility and safety of its active use in both patients with terminal heart failure on the waiting list of heart transplantation and patients having temporary contraindications to HTX.

Aim: to show the analysis of 10-year heart transplantation experience, the main complications and problems of the heart transplantation evaluation.

 Materials and methods. 66 orthotopic heart transplantations were performed in patients with terminal chronic heart failure in our clinic since 2008. The heart failure causes were dilated cardiomyopathy in 46 cases (70%), postinfarction cardiosclerosis in 20 cases (30%). The recipients were 59 men (89%) and 7 women (11%), the average age was 46 ± 10 years. All patients had a severe left heart dilatation and critical left ventricular systolic dysfunction (left ventricular EDV 283 ± 58 ml, left ventricular ejection fraction 17 ± 5%, cardiac index 1.5 ± 0.3 l/min/m2). In some recipients, heart transplantation is performed in the second stage after preliminary implantation of mechanical circulatory support systems (LVAD, BVAD). The fi rst heart transplantations were performed using the biatrial technique (8 cases (12%)), the others were performed using the bicaval technique (58 cases (88%)). After the operation, patients received a three-component immunosuppressive therapy: the inhibitors of calcineurin, mycophenolate and corticosteroids.

Results. 54 patients (82%) were discharged from the clinic after heart transplantation. The hospital mortality was 12 recipients (18%). The mortality in the long-term period was 10 recipients (15%). The hospital mortality cases were acute graft dysfunction in 5 cases (42%), infectious-septic complications in 4 cases (33%), massive intraoperative bleeding in 2 cases (17%), and total thrombosis of pulmonary artery in 1 case (8%). The death causes in the long-term period were acute transplant rejection in 4 cases (40%), coronary artery disease of the transplanted heart in 3 cases (30%), Kaposi’s sarcoma in 1 case (10%), lung cancer in 1 case (10%), and viral pneumonia in 1 case (10%).

Conclusion. Over a 10-year period, we have gained a lot of experience in heart transplantation; the procedures complications have been studied; the stages of preservation, harvesting and transportation of the donor heart, operative technique and postoperative treatment of patients have been improved to avoid complications in the early and long-term postoperative period.

Aim: to estimate physical capacity and quality of life (QoL) and defi ne factors which impact on their dynamic in recipients after heart transplantation (HTx).

Materials and methods. From January 2010 to September 2016 we performed 76 HTx (mean age – 45,4 ± 1,6 yrs). Physical activity (PA) was evaluated by IPAQ questionnaire, QoL – by SF-36 (6 months and 1 yr after HTx). Patients underwent cardiopulmonary exercise test (Oxycon Pro, Germany) before, 6 months (n = 32) and 1 yr (n = 31) after HTx.

Results. In 6 months after HTx PC improved (VO2peak – 12,6 ± 0,5 and 17,3 ± 0,6 ml/min/kg, p < 0,001). One yr after HTx physically active recipients (n = 21) showed better results (VO2peak – 18,7 ± 0,9 vs. 16,7 ± 0,4 ml/min/kg, p < 0,05). Moreover, 6 months 59,4% (n = 19) and 1 yr after HTx 77,4% (n = 24) of all patients reached normal values, 20 of them were physically active. We did not fi nd any difference in results depending on heart failure severity, duration of illness and of time spent in HT waiting list. In 6 months after HTx physical health (PH) increased (32,2 ± 1,1 vs. 48,2 ± 1,6, p < 0,001), on the other hand, results of mental health (MH) were the same and remained stable in 1 yr after HTx. In addition, QoL was higher in physically active patients than in sedentary lifestyle ones. There was correlations between PH and PA duration (r = 0,4; p < 0,05), VO2peak (r = 0,3; p < 0,05), VO2 at AT (r = 0,4; p < 0,05) and VE/VCO2 (r = –0,5; p < 0,05).

Conclusion. After heart transplantation physical capacity and physical health improved but physically active recipients showed better results. Factors affecting the increase in physical capacity were improvement in the functional state of the cardiovascular system and physical activity.

Aim: to evaluate clinical effi ciency of percutaneous coronary interventions (PCI) at potential recipients of heart with the chronic ischemic heart failure (CHF).

Materials and methods. In this retrospective study results of treatment at 76 patients with CHF NYHA III and 36 patients with CHF NYHA IV by scheduled PCI are presented. Duration of observation was from 6 to 160 months. The age of patients at the time of intervention was 61,7 ± 0,62 years (from 33 to 76). 108 male and 4 female. Defi ned life expectancy and echocardiography parameters of the left ventricle (LV) of heart.  

Results. 20 patients were died, 16 of them from cardiovascular events. 18 patients during this period undergo orthotopic heart transplantation (HT). The endovascular revascularization leads to LV volumes reduction, increase of ejection fraction and decrease of pulmonary artery pressure. Progress CHF is followed by negative dynamics of these characteristics and need of HT performance. In 74% of cases the effect of myocardial revascularization allows to provide increase in life expectancy of potential recipients of heart with the chronic ischemic heart failure.  

Conclusion. Performance of PCI at patients with the chronic ischemic heart failure can delay heart transplantation or become its alternative.

Aim: to analyze the frequency of different histological diagnoses and it simpact on graft survival in a cohort of patients with renal allograft dysfunction, and to determine pathology features, infl uencing prognosis.

Materials and methods. The data obtained from 1470 biopsies, performed by indication at different time after kidney transplantation (48.8 ± 46.1 months) were analyzed retrospectively according to the Banff 2013 classifi cation.

 Results. The majority of graft dysfunction episodes were attributed to fi ve causes: acute (26,8%) and chronic (12,4%) rejection; chronic nephrotoxicity of СNI (19,3%), interstitial fi brosis/tubular atrophy (15,8%) and recurrent or de novo glomerulonephritis (10,6%). T-cell-mediated acute rejection and functional disorders were the most often cause of dysfunction during the fi rst year after transplantation (40,5% and 21% respectively) but decreased over time. On the other hand, the frequency of chronic rejection, interstitial fi brosis/tubular atrophy with or without СNI nephrotoxicity and recurrent or de novo glomerulonephritis increased from 13%, 26% and 5,5% at the fi rst year to 26,4%, 35,3% and 22,8% respectively at 8 year after transplantation. Chronic rejection represented a major risk for graft loss – 8-year graft survival did not exceed 5%. The prognosis of acute rejection as well as de novo or recurrent glomerular pathologies was more favorable (38% and 42% respectively). In cases of interstitial fi brosis/tubular atrophy with or without СNI nephrotoxicity 8-year graft survival was slightly lower than in the functional disorders (62% and 76%). In acute rejection prognosis for C4d-positive forms was worse compared to C4d-negative, while in chronic rejection there was no difference between C4d-positive and C4d-negative forms. The features of СNI nephrotoxicity did not infl uence the prognosis of non-specifi c interstitial fi brosis and tubular atrophy.

Conclusion. Transplant pathology in patients with allograft dysfunction is heterogeneous and changes over time. Acute and chronic rejection; interstitial fi brosis/tubular atrophy with or without СNI nephrotoxicity and recurrent/de novo glomerular pathology are the most often causes of graft dysfunction, but only rejection (mostly chronic) and glomerular pathology are associated with unfavorable prognosis.

Aim – to perform a comparative study of the long-term results of the combined use of extracorporeal photochemotherapy (photopheresis) and drug immunosuppression and standard immunosuppressive therapy in patients after kidney transplantation.

Materials and methods. An open cohort randomized study was conducted, including 60 patients with chronic kidney disease stage 5D. All patients underwent single-group cadaveric kidney transplantation. Patients were randomly divided into two groups. All transplants were paired, the fi rst kidney transplant was received by the patient of the main group, the second – by comparison group. 30 patients of the main group received standard protocol of immunosuppression and 10–15 sessions of photopheresis during the fi rst six months after transplantation. All patients of the comparison group received standard immunosuppressive therapy only. End points: primary – graft loss, surrogate – the number of acute rejection episodes and infectious complications, the dynamics of creatinine blood concentration, the glomerular fi ltration rate and daily proteinuria, the dynamics of tacrolimus C0 blood concentration. To study the mechanism of photopheresis action in the late postoperative period, we evaluated the immunological parameters: subpopulation of naive T-cells (CD3+CD4+CD45RO–CD28+), the level of CD28 molecule expression (MFI) on these cells and also – subpopulation of T-regulatory cells (CD3+CD4+CD25 (Hi)CD127–).

Results. The use of photopheresis leads to the graft function improvement in the late postoperative period: the creatinine concentration (p = 0.017) in the blood and daily proteinuria (p = 0.011) were lower in patients of the main group, the glomerular fi ltration rate was higher (p = 0.027). The incidence rate ratio (IRR) of rejection in the main group was signifi cantly lower than in the comparison group: 0.2509 (95% CI 0.05386, 0.9167), p = 0.0358. The risk of graft loss was also lower in the main group: IRR 0.2782 (95% CI 0.07562, 0.8657), p = 0.026, as well as the risk of infectious complications: IRR 0.3888 (95% CI 0.2754; 0, 5445), p < 0.0001. Survival rate of transplants was higher in the main group (Log Rank p = 0.009; Breslow p = 0.005). The use of photopheresis made it possible to reduce the concentration of tacrolimus in the late postoperative period (p = 0.0017) without increasing the risk of graft rejection. The photopheresis tolerogenic effect in the late postoperative period may be due to an increase in the population of T-regulatory cells with the CD3+CD4+CD25(Hi)+CD127– phenotype compared to the patients which received only standard immunosuppressive therapy (p = 0.024).

Conclusion. The preventive use of photopheresis contributes to improvement of the kidney transplantation long-term outcomes. Further studies are needed to study the mechanisms of photopheresis action and markers of partial immunological tolerance to the allograft.

Aim: to analyse the results of the initial experience of kidney transplantation of the regional hospital of the Republic of Kazakhstan.

Materials and methods. The results of kidney transplantations which were performed to 31 patients in the Aktobe Medical Center (AMC, Aktobesity) for the period from November 2014 to 2017 are presented. Kidney transplantations were performed in compliance with clinical protocols according to the generally accepted methodology. In 25 cases transplantation performed from a living donor, in 6 cases – from deceased donors. The most of living donors underwent laparoscopic nephroureterectomy with manual assistance (70.8%).

Results. After nephrectomy operations complications were not observed in donors, all patients were discharged in a satisfactory state on the 5th–8th postoperative day. The following complications were observed in recipients in the early postoperative period: acute tubular necrosis – 1, postoperative bleeding (retroperitoneal hematoma) – 2, lymphorrhagia – 2, urinary leakages – 2. One recipient was died in the late postoperative period after infection complications and the development of sepsis.

Conclusions. Kidney transplantation is undoubtedly effective method for treating patients with terminal chronic kidney failure. The results of the initial experience of kidney transplantation in the Aktobe regional hospital of the Republic of Kazakhstan are not differ from the average results of leading domestic and other foreign transplant clinics.

Aim: to show the progress of the experiment of cultivation of human liver cells and adipose-derived mesenchymal stromal cells in perfusion bioreactor.

Materials and methods. The cultivation of a cell-engineered construct, consisting of a biopolymer microstructured collagen-containing hydrogel, human liver cells, adipose-derived mesenchymal stromal cells, and William’s E Medium, was performed in a perfusion bioreactor.

Results. On the 7th day large cells with hepatocyte morphology – of a polygonal shape and a centrally located round nucleus, – were present in the culture chambers of the bioreactor. The metabolic activity of hepatocytes in cell-engineered constructs was confi rmed by the presence of urea in the culture medium on the seventh day of cultivation in the bioreactor and by the resorption of a biopolymer microstructured collagen-containing hydrogel.

The increase in biostability of medical products/materials based on proteins and their derivatives, including resorbable 2Dand 3D-matrices for tissue engineering and regenerative medicine is usually achieved by means of cross-linking with glutaraldehyde (GA). One of the serious fl aws of the products stabilized with GA is their cytotoxicity caused by trace amounts of GA which are diffi cult to remove from cross-linked biopolymer matrices, thus the search for chemical and physical methods of cross-linking of such medical products remains essential. 

Aim: to compare the infl uence of various cross-linking methods on the cytotoxicity of collagen and gelatin samples.

Materials and methods. Samples – fi lms with diameter of 30 mm and thickness of ~ 150 μm, – were obtained by irrigation method usingthesolution of scleral collagen (SC) of Type farm animals or with gelatin with the subsequent drying at 37º С until constant weight on air. Samples of porous matrices in shape of tubes of gelatin and polyoxybutirate-co-valerate with the weight ratio 2:1 were obtained by electrospinning. The cytotoxicity of structurally stabilized samples was studied by fi ve methods: 1) dehydrothermal cross-linking with the residual pressure of 10–20 mm Hg and temperature of 120 °С; 2) injection of GA immediately into the biopolymer solution; 3) with GA vapors; 4) with GA vapors with the subsequent incubation in phosphate buffered saline (PBS) with рН = 7.4; 37 °С; 24 h; 5) with GA vapors with the subsequent incubation in 0.1% lysine solution with рН = 7.4; 37 °С; 24 hour in DMEM medium. Cytotoxicity of samples was evaluated according to the requirements of interstate standard GOST ISO 10993-5-2011 on the culture of mice fi broblasts of NIH 3Т3 line using extracts from samples (37 °С; 24 h) and by means of direct contact of samples with these cells.

Results. Matrices treated hydrothermally demonstrated complete absence of cytotoxicity. Samples, fi xated in GA solution in the range of concentrations from 0.01 to 1.0% demonstrated a high level of cytotoxicity which does not answer the requirements of GOST ISO 10993-5-2011. Fixation of collagen and gelatin matrices with GA vapors during 48 h infl uences their cytotoxicity minimally but with the treatment time increased to 72 hours cytotoxicity escalates to severe levels. With the subsequent incubation of cytotoxic gelatin samples in PBS the decrease in cytotoxicity to the levels corresponding with the requirements of GOST ISO 10993-5-2011 was observed. For the analogous decrease in cytotoxicity of collagen fi lms treated with GA vapors during more than 48 h an additional incubation in lysine solution was needed.

Conclusion. Dehydrothermal cross-linking method is optimal from the view point of absence of cytotoxicity of stabilized biopolymers, however its area of application is limited by the risk of infl uence of high temperatures on the medico-technical properties of the products. Fixation in GA vapors is a universally applicable and a rather simple method of treatment of medical products or biopolymer-based coatings, but it does not resolve the issue of their cytotoxicity at treatment times exceeding 48 h. Rinsing in buffer solution in case of gelatin or treatment with the amino acid (lysine) solution in case of collagen allow to decrease the level of cytotoxicity of products stabilized with GA vapors to the values corresponding with the requirements of GOST ISO 10993-5-2011.

Aim. To develop a safe protocol for cryopreservation of segments of iliac arteries straight after their retrieval from post-mortem donor with the use of polydimethylsiloxane as a coolant and cryoprotectant.

Materials and methods. Eleven segments of iliac arteries were retrieved from post-mortem donor and divided into four groups including control. Based on preliminary heat and cold transfer mathematical modeling and tests with tissueequivalent phantom arterial segments were placed on plastic mounts and cryopreserved by following protocol: groups 1 and 2 were immersed in polydimethylsiloxane and cooled rapidly at 180 °С/min to –75 °С. Group 3 segments were cryopreserved at 1,6 °С/min in PDMS – fi lled cryo-container placed in the freezer at –80 °С. All segments were defrosted by immersion in PDMS at +24 °С and then examined for morphology changes by histological methods and SEM. EDS analysis with the use of AzTech software also was performed for Si – content evaluation. Restricted biomechanical tests were conducted for group 2 segments.

Results. There were no signifi cant morphological differences between segments of the control and cryopreserved groups except for the segment with slow cooling.

Conclusion. Mobile cryopreservation may allow increasing the effi ciency of retrieval of a large number of donor tissues for possible later use in the processing of bioprostheses of blood vessels; or, after decellularization, as well as tissue-specifi c matrices for tissue-engineering blood vessels.

Aim. To evaluate the potential synergistic effects of basic fi broblast growth factor (bFGF) and stromal cell-derived factor-1α (SDF-1α) complemented with VEGF compared to VEGF alone when being added into poly(3-hydroxybutyrateco-3-hydroxyvalerate) / poly(ε-caprolactone) vascular grafts implanted into rat abdominal aorta for 3, 6, or 12 months.

Materials and methods. Utilizing emulsion electrospinning, we fabricated one-layer vascular grafts with either VEGF, bFGF, or SDF-1α, and two-layer vascular grafts with VEGF incorporated into the inner layer and bFGF and SDF-1α incorporated into the outer layer following structural evaluation, tensile testing, and in vivo testing using a rat abdominal aorta replacement model.

Results. Grafts containing all three growth factors had a 100% primary patency rate. The combination of bFGF, SDF-1α and VEGF improved morphology and mechanical properties of the grafts. Furthermore, such combination of the bioactive factors promoted endothelialization compared to VEGF alone. In addition, bFGF induced a rapid formation of a SMC layer.

Conclusion. Taking together, these fi ndings show that the incorporation of bFGF and SDF-1α into the vascular grafts in combination with VEGF enhances vascular tissue regeneration and provides a higher primary patency rate.

Heart transplantation is the gold standard for the treatment of terminal heart failure. The main method of the donor heart preservation is cold perfusion. The recommended maximum time for cold ischemia of the donor heart is 240 minutes. Exceeding this safe limit increases the risk of postoperative allograft dysfunction and death. However, there are reports positing a possibility to prolong the time of ischemia of the donor heart without a signifi cant risk of complications. The article presents the experience of successful transplantation of the donor heart with the cold ischemia time was 440 minutes.

Diabetes mellitus is one of the most prevalent chronic metabolic disorders. Its role in patients with heart transplantation is not unifi ed. According to some authors, post-transplantation diabetes mellitus increases the risk of acute rejections and infections, increases the incidence of coronary artery disease of the graft and reduces long-term survival of patients with heart transplantation. On the other hand other studies did not confi rm these fi ndings. However, when diabetic patients were stratifi ed by disease severity, recipients with less severe disease achieved better survival. Accordingly, posttransplant survival was not signifi cantly different between recipients with uncomplicated diabetes and nondiabetic recipients. Diabetes alone should not be a contraindication to heart transplantation. Well-selected diabetic patients achieve the same survival as nondiabetic patients. Conversely, patients with complicated diabetes have signifi cantly worse survival. Therefore, given the critical shortage of transplantable organs, maximal benefi t may be achieved by exploring alternative treatment options in individuals with severe diabetes. These include use of high-risk transplant lists and destination therapy.

Heart transplantation is the «gold standard» of treatment severe heart failure. Immunosuppressive therapy aimed at the prevention of acute allograft rejection is the cornerstone of post-transplant management. In addition to its direct effects, immunosuppressive therapy is also involved in the generation of a number of post-transplant morbidities that limit the long-term outcome of heart transplant recipients. Given these data it appears that the individual tailoring of immunosuppressive therapy is of paramount importance in determining the outcome of heart transplantation. The goal of immunosuppressive therapy is to prevent rejection of the transplanted heart, while minimizing drug-related effects, such as infection, malignancy, diabetes, hypertension, and renal insuffi ciency. This review aimed is to analyze the protocols for the appointment of immunosuppressive therapy in various groups of recipients after heart transplantation.

The method of mechanical circulation support using non-pulsating fl ow pumps, built on the principle of rotary (centrifugal and axial) pumps, took the leading direction (94%) in the world clinical practice for the treatment of the patients with terminal heart failure. Despite this, the clinic application of these pumps in a number of cases faced with the numbers of negative problems associated with this technology. This is stimulated of a new direction of principles for a control of the rotary pumps, based on the modulation of the speed pumps. The article analyzes the negative factors of the clinical application of non-pulsating fl ow pumps and gives an overview of the methods the optimization of the control pump based on the modulation of the output fl ow.