Editorial
Clinical Transplantology
Introduction. Quality of life (QoL) is a new promising area of clinical medicine that provides the opportunity to assess the state of health of the patient and to have a notion of the surgery effects based on the parameters which are lying at the intersection of scientific approach of the surgeons and subjective point of view of the patient.
Materials and methods. The study included 52 living-related liver fragment donors operated between 2009 and 2014. Donors were surveyed after 2–5 years from the surgery. Comparison group was formed by healthy volunteers, students of the Medical University. The Russian version of the non-specific SF-36 questionnaire was used to assess QoL.
Results. Donors in the postoperative period have demonstrated a high level of physical parameter (57.65 ± 3.8). Parameter of psychological health in the postoperative period was (52.01 ± 5.2). These figures are comparable with the results in the comparison group (p > 0.05). All donors have returned to normal life.
Conclusions. Overall results of this study were similar to those of the foreign colleagues which confirm the high safety of liver resection surgery and the efficacy of SF-36 questionnaire in the assessment of quality of life of the living-related liver fragment donors.
Orthotopic liver transplantation (OLT) is the only treatment for many patients with end-stage chronic liver diseases. In patients with complete vena cava inferior (VCI) cross-clamping veno-venous bypass (VVB) is either used or not depending on the indications. The case management of the patient with complete VCI cross-clamping depends on the initial state of the recipient and the transplant team’s opinion.
Aim. To compare the perioperative period of OLT depending on the method to conduct the main stage of the surgery: with the use of veno-venous bypass and without it with complete VCI cross-clamping.
Materials and methods. In Group 1 (n = 20), OLT was performed without VVB with complete VCI cross-clamping; in Group 2 (n = 26), the surgery was conducted with veno-venous bypass. Patients in both groups were similar in age (46.15 ± 10.22 and 47.3 ± 9.29, respectively), in severity of the disease: Child-Pugh (10.15 ± 1.42 and 10.19 ± 2.45), MELD 16.47 ± 4.41 and 15.8 ± 4.95).
Results. We determined and evaluated hemodynamic parameters, oxygen transport, the quantitative and qualitative infusion composition, urine output, characteristics of the postoperative period.
Conclusion. Our data show that changes in hemodynamic and oxygen transport are associated with reperfusion syndrome and do not depend on the method of transplantation. At the same time, it reduces the blood loss, time of surgery, and the duration of postoperative mechanical ventilation and stay in the ICU after liver transplantation in patients without veno-venous bypass.
Aim. To examine the assumption that significant concentrations of cystatin C in urine are the manifestation of the tubular necrosis and, respectively, the severity of kidney damage after heart transplantation (HTx).
Materials and methods. In this study we evaluated 33 heart recipients (6 women and 27 men, aged from 24 to 68 years old) who had risk factors of acute kidney injury: serum creatinine level >113 μmol/l and/or mechanical circulatory support requirement (20 patients, in 14 cases before HTx). Cystatin C concentration in serum and in urine was measured by DyaSis particle-enhanced immunoturbidimetric assay test «Cystatin C FS».
Results. Recipients were divided into two groups according to the levels of cystatinuria. In the group with the significant (more than 0.18 mg/l) urinary cystatin C concentrations the requirement of renal replacement therapy (RRT) was 2.5-fold higher, and the mean duration of RRT was more than 10-fold longer. In 2 patients with the significant cystatinuria acute kidney injury (AKI) has transformed into end-stage renal disease (ESRD).
Conclusion. Due to data obtained we may suppose that significant concentrations of cystatin C in urine are the marker of the tubular necrosis with the prolonged RRT requirement. Further studies are needed to justify this relationship.
Heart Transplantation and Assisted Circulation
Introduction. One of the main indicators characterizing mechanical circulatory support devices (artificial valve, implantable pumps, etc.) is trauma of blood cells. Therefore, while developing new pumps, one of the key studies in vitro is to evaluate blood hemolysis. For an objective hemolysis analysis of pump it is required to create a standardized methodology of hemolysis studies. The object of the study in this paper is implantable axial pump DON for two-step heart transplantation in children.
The aim of study is to develop a standardized methodology of hemolysis studies of blood pumps and to conduct research of pediatric axial pump DON.
Materials and methods. To conduct hemolysis research we created a mock circulatory system consisting of a reservoir placed in water bath maintaining a constant working fluid (blood) temperature, hydrodynamic resistance, connecting tubes, ports for blood sampling and pressure and flow measurement systems, and research pump. Test method is to estimate levels of free hemoglobin pHb obtained by blood samples during pump working in operating mode (for pediatric pump: blood flow 2.5 l/min, pressure difference 80 mmHg). Using the data obtained the standardized indices of hemolysis NIH and MIH are calculated based on pHb values, hematocrit, total hemoglobin, blood flow and working pump time.
Results. We developed and realized a standardized methodology of hemolysis research by which we evaluated hemolysis of pediatric axial pump. The results of hemolysis tests allowed us to optimize the design of DON. Obtained values of hemolysis of the latest version of pediatric pump DON-3 have shown that they do conform to the requirements of minimum blood injury and it allows us to proceed to the next step of pediatric pump research – animal experiments.
Conclusion. Developed methods and evaluation tools of hemolysis allow us to provide objective information on one of the most important indicators of developing implantable pediatric axial pump and they could be recommended for hemolysis research of others pumps.
Aim. Experimental evaluation of the viscous friction disk pump efficiency, studying the relationship between inter-disk clearance and sizes of input and output ports and pump performance parameters.
Materials and methods. To assess the characteristics and to optimize the disk friction pump design the pump model and experimental stand were created. Pump dimensions were set on the basis of medical and biological requirements for mechanical heart support systems and with due consideration of the experimental studies of our colleagues from Pennsylvania. Flow volume of the working fluid was measured by float rotameter Krohne VA-40 with measurement error of not more than 1%. The pressure values in the hydrodynamic circuit were measured using a monitor manufactured by Biosoft-M. Expansion device allowed changing the flow resistance of the system simulating the total peripheral resistance of the circulatory system.
Results. Linear direct correlation between the pump performance and the pressure drop of liquid being created at the inlet and outlet of the pump was obtained. The required flow rate (5–7 l/min) and pressure (90–100 mmHg) were reached when the rotor speed was in the range of 2500–3000 rev/min. It has been shown that the increase of the inlet diameter to 15 mm has not resulted in a significant increase in the pump performance, and that the highest efficiency values can be obtained for the magnitude of inter-disk gap of 0.4–0.5 mm.
Conclusion. Designed and manufactured experimental disc pump model for pumping fluid has showed the fundamental possibility to use this model as a system for mechanical support of the heart.
Introduction. Successful liver transplantation including from donors with a sudden irreversible cardiac arrest requires the use of modern hardware and technical support to maintain, select and sustain organ viability for the period from harvesting to transplantation to the recipient.
Materials and methods. Hardware-software system (HSS) developed by the Russian State Scientific Center for Robotics and Technical Cybernetics (RTC) was used for testing of normothermic perfusion of donor’s liver ex vivo. The experiment was conducted on the isolated pig liver (Duroc breed) in accordance with the ethical principles.
Result. During perfusion spontaneous recovery of bile outflow through the cannula installed in the common bile duct (volume of bile released – 240 ml) was observed, and the color and uniformity of the perfused liver did not differ from the normal parameters. Biochemical indicators were stabilized at the physiological values after 40 minutes of perfusion procedure.
Conclusion. Isolated liver transplant was completely restored after 30 minutes of warm ischemia and was functioning well due to ex vivo perfusion procedure on the new perfusion device. The first case of the new device usage for normothermic liver ex vivo demonstrated hopeful results to be further investigated.
Clinical Cases
The successful use of donor hearts from people died of methanol poisoning helps reducing the deficit of donor organs for patients requiring urgent cardiac transplantation [3]. We present our experience of successful cardiac transplantations from 2 donors who died due to methanol poisoning. Given the possibility of performing a cardiac transplant from this group of donors a protocol has been developed at the V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs of the Ministry of Healthcare of the Russian Federation which includes clinical, laboratory and instrumental criteria for the selection of heart donor and recipient. The possibility of delayed onset myocardial contractile dysfunction due to methanol poisoning means that a longer conditioning
period is vital as well as compulsory clinical, laboratory and expert chocardiographic examinations of the potential donor heart.
Introduction. Liver transplantation is a multi-component and complex type of operative treatment. Patients undergoing such a treatment sometimes are getting various complications. One of these complications is a portal hypertension associated with portal vein stenosis.
Materials and methods. In 6 years after the left lateral section transplantation from living donor in a pediatric patient the signs of portal hypertension were observed. Stenosis of the portal vein was revealed. Due to this fact percutaneous transhepatic correction of portal vein stenosis was performed.
Results. As a result of the correction of portal blood flow in the patient a positive trend was noted. According to the laboratory and instrumental methods of examination the graft had a normal function, portal blood flow was adequate. In order to control the stent patency Doppler ultrasound and MSCT of the abdominal cavity with intravenous bolus contrasting were performed. Due to these examinations the stent function was good, the rate of blood flow in the portal vein due to Doppler data has reached 80 cm/sec, and a decrease of the spleen size was noted.
Conclusion. Diagnosis and timely detection of portal vein stenosis in patients after liver transplantation are very important for the preservation of graft function and for the prevention of portal hypertension. In order to do that, ultrasound Doppler fluorimetry examination needs to be performed to each patient after liver transplantation. In cases of violation of the blood flow in the portal vein CT angiography performance is needed. Percutaneous transhepatic stenting of portal vein is a minimally invasive and highly effective method of correction of portal hypertension. Antiplatelet therapy and platelet aggregation control are the prerequisites for successful stent function.
The development of kidney injury and the characteristics of renal replacement therapy were considered in patient with dilated cardiomyopathy, who consequently underwent two heart transplantations and two kidney transplantations. Since the number of the patients needed both kidney and heart transplantation increases constantly, the multifaceted thorough research in this specific patient population is extremely important.
Case report of reversible high pulmonary hypertension (PH) in patient with successful kidney transplantation (KT) is presented. The distinction of the case was the functioning arteriovenous fistula (AVF) with excessive blood flow during 15 years in the absence of indications for hemodialysis. Consequently, PH was complicated by serious congestive heart failure (CHF) with high cardiac output. Surgical closure of AVF resulted in complete regression of clinical, instrumental and laboratory signs and symptoms of PH and CHF within 2 weeks. The pathogenic role of excessive AVF blood flow in PH and CHF formation is a point of discussion. Surgical closure of AVF with excessive blood flow is recommended in cases of presence of symptomatic PH and CHF in patients after successful KT.
Regenerative Medicine and Cell Technologies
Aim. To develop technology to create 3D-spheroid multipotent mesenchymal stem cells (MMSC) of limbal cadaveric human eyes, capable of safe and long-term secretion of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF).
Materials and methods. MMSC were obtained by cultivation of limbal fragments, released from cadaveric donor human eye. Cultivation was carried out in DMEM/F12 medium, supplemented with L-glutamine, penicillin, streptomycin, amphotericin B, HEPES, insulin, dexamethasone and 10 vol.% FBS under standard conditions (5% СО2, 37 °C), medium change was performed every 3 days. To determine the phenotype of the received cell culture the method of immunophenotyping by marker proteins to MMSC (CD73, CD105, CD19, CD90, CD133) was used. Stimulation of neurotrophic factor secretion was performed via a twostep procedure. 3D-cell spheroids were created with the help of agarous plates for three groups of comparison, where group I was control group, spheroids of intact 2D-culture MMSK; group II – spheroids of previously induced 2D-culture MMSC; group III – spheroids of 2D-MMSC induced on the 1st day of cultivation. Cell cultures supernatants were selected in different periods for NGF and BDNF follow-up study by ELISA procedure.
Results. Induction of 3D-spheroids of limbal MMSC promotes short-term increase of the level of BDNF and NGF, but further, the secretion of these factors significantly decreases. Induction leads to a change in the morphology of spheroids: loss of compactness and emergence of «fringed» (debris). Such changes indicate of frailty of received constructions. Spheroids from previously induced MMSC are capable of stable NTF secretion, but the level of secretion is much less as compared to the control group.
Conclusion. 3D-cell culture of intact 2Dculture of limbal MMSC can be considered as cellular medication for a safe and long-term neuroprotection in optic neuropathy treatment.
Aim. To investigate cell reaction to different materials, potentially suitable for intracorneal lens (ICL) production.
Materials and methods. A plane surface (2D) corneal stromal cell culture was performed in the presence of different experimental polymer samples, such as hydroxyethylmethacrylate, oligourethanemethacrylate and polymethylmethacrylate. The dynamics of cell numbers was evaluated over culture time. Conclusion on biocompatibility was made based on obtained data.
Results. In each of the experimental groups there was a trend toward a steady increase in the number of cells from the 1st to 6th day of observation, the shapes of the cell growth curves showed no toxicity of materials and their ability not to interfere with cell proliferation. Cell proliferation in the contact to hydroxyethylmethacrylate and oligourethanemethacrylate materials was statistically significantly lower (p < 0.001) than in the presence of polymethylmethacrylate, which makes a strong case for their preferential usage for implantation into the stroma of the corneal optical area. When comparing the results obtained on the 6th day, the cells in the presence of the implant of hydroxyethylmethacrylate showed significantly less tendency to proliferate, than in the presence of oligourethanemethacrylate (p < 0.001). However, these differences were statistically significant not in all days.
Conclusions. The results obtained have shown the absence of toxicity in experimental material samples and their low adhesive properties with respect to the stromal cell culture, thereby confirming its potential suitability for intracorneal implantation.
Literature Reviews
The study of quality of life of living organ donors in transplantation by questionnaires has increasingly become the subject of clinical studies. However, there are no unified criteria and standard norms of quality of life. Each questionnaire has its own criteria and evaluation scale. This review presents the main general questionnaires that have been applied worldwide for the quality of life assessment of living kidney and liver donors. Special questionnaires used to refine the parameters of quality of life and their coordination with common questionnaires are considered. Optimal questionnaire to detect quality of life in modern research for living organ donors is identified.
In the current situation of the shortage of suitable donor organs, heart transplantation from older donors is one of the ways to increase the performance of more heart transplants, particularly, in patients with urgent need of transplantation. While planning a heart transplantation from older donor one should consider increased risk of early cardiac allograft dysfunction, preexisting coronary artery disease, accelerated transplant vasculopathy which may adversely affect early and long-term survival of recipients. Subject to careful selection of donor–recipient pairs, effective prevention and treatment of early cardiac allograft dysfunction, pre-existing atherosclerosis and transplant vasculopathy the early and long-term survival of heart transplant recipients from older donors is comparable to heart transplantation from young donors.
In most cases, severe left ventricular systolic dysfunction is a consequence of ischemic heart disease. In clinical condition, current recommendations support myocardial revascularization in patients with ischemic cardiomyopathy by performing coronary artery bypass grafting. Information on safety and effectiveness of percutaneous coronary intervention in patients with ischemic heart failure is limited. The aim of this review is to study the current state of this problem.
Bone disease is a serious and common condition in patients after kidney transplantation. The review analyzed the causes of bone disorders in the early and late postoperative period that are associated with renal transplantation: fibroblast growth factor 23, parathyroid hormone, vitamin D, immunosuppressive therapy and imbalance of mineral metabolism. It shows the most common clinical variant of the post-transplant bone disease – secondary osteoporosis, risk factors of its development and complications. It presents the diagnostic algorithm for dynamic monitoring and evaluating the effectiveness of the treatment of bone disorders