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Russian Journal of Transplantology and Artificial Organs

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Vol 18, No 4 (2016)
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https://doi.org/10.15825/1995-1191-2016-4

Clinical Transplantology

16-25 1562
Abstract

Introduction. Venoarterial extracorporeal membrane oxygenation (VA ECMO) is one of the most widely used methods of temporary mechanical circulatory support (MCS) during the preparation and performance of heart transplant surgery (HT) [Barth E. et al., 2012; Kittleson M.M. et al., 2011].

Aim of this study was to assess the effectiveness of using peripheral VA ECMO as a method of mechanical circulatory support in potential heart transplant recipients that urgently required transplantation.

Materials and methods. The study included 125 potential heart transplant recipients (107 (86%) men and 18 (14%) women) aged from 12 to 72 (43 ± 1.2) years with a peripheral VA ECMO system installed within the period from April 01, 2011 till August 12, 2016. The indication for the start of its use was rapidly progressing congestive heart failure (CHF) of level 1 or 2 by the INTERMACS scale. Femoral blood vessel cannulation was performed using both open (surgical) and closed (puncture) methods. 23 and 25 F venous cannulae were utilized for femoral vein cannulation, and 15 and 17 F arterial cannulae were utilized for femoral artery cannulation. In all cases superfi cial femoral artery catheterization (14 F single-lumen catheter) or cannulation (8 or 10 F arterial cannula) was performed in the descending (anterograde) direction for the prevention of lower limb ischemia on the side of the femoral artery cannulation.

Results. The peripheral cannulation method was used to perform VA ECMO in 100% (n = 125) observations. In 69 (55.2%) patients the severity of progressive CHF corresponded to INTERMACS level 1; in 51 (40.8%) cases it corresponded to INTERMACS level 2. During VA ECMO the average volumetric extracorporeal circulation fl ow rate ranged from 2.2 to 4.5 (3.2 ± 0.4 l/min) or 1.6 ± 0.2 l/min/m2 with the average rotation speed of the centrifugal pump of 3.216 ± 105 rpm. 113 (90.4%) of 125 potential recipients underwent HT. The duration of VA ECMO prior to HT (n = 113) was from 8 hours to 40 (7.1 ± 2.7) days: in 37 (32.7%) of 113 patients – up to 3 days, in 43 (38.1%) cases – from 4 to 7 days, in 21 (18.6%) cases – from 8 to 14 days, in 8 (7.1%) cases from 15 to 21 days, in 4 (3.5%) cases – more than 3 weeks. In the course of VA ECMO, 12 (9.6%) of 125 potential recipients (11 men and 1 women aged from 21 to 63 (40 ± 4) died before they could receive HT. In 2 (16.7%) of 12 cases the cause of death was brain death associated with a thromboembolic cerebrovascular event. The majority of patients (n = 10; 83.3%) died of progressive multiple organ failure and sepsis. 6 of 12 patients showed clinical and instrumental signs of acute unilateral (n = 2) or bilateral (n = 4) polysegmental pneumonia.

Conclusion. Peripheral VA ECMO provides a successful bridge to heart transplant procedure in 90% of potential recipients who need pre-transplant MCS. The timely initiation of VA ECMO before the development of pronounced hemodynamic, organ, electrolyte and metabolic disorders creates the conditions for a successful use of MCS in potential heart transplant recipients.

33-42 2093
Abstract

Aim. To estimate the results of 6-year experience of heart transplantation (HT) in Federal Almazov North-West Medical Research Centre. Methods. From 2010 to 2015 we have performed 65 HT. Mean age was 44.3 ± 14 years old (from 10 to 64 years old). We used biventricular assist device (BIVAD, Berlin Heart Excor) support in 7 heart transplant candidates before HT. 19 patients (29%) received thymoglobulin, whereas 46 patients (71%) had basiliximab to induce immunosuppression.

Results. Extracorporeal membrane oxygenation machines were implanted in 5 patients (7.7%) after HT due to acute right ventricular failure. Suture annuloplasty (the Batista procedure) for tricuspid valve repair was carried out in 3 cases (4.6%). Venovenous hemodiafi ltration was used in 11 patients (16.9%). A total of 598 endomyocardial biopsies (EMB) were performed after HT. Evidence of cellular rejection (R1 and R2) was presented in 286 biopsies (48%). The 30-day in-hospital mortality rate was 3.1%. The 6-month survival rate after HT was 92%, 1-year – 91% and overall survival for the 6-year period of observation – 89.2%. Maximum observation period was 71 months.

Conclusions. The 6-year experience of HT in our Center has shown a high level of survival. BIVAD Excor support can be effectively used as a «bridge» to HT. Prevention of graft loss due to acute rejection in heart transplant recipients can be achieved only through regular EMB monitoring. The rate of viral infection increased in 2 months after HT.

43-55 1823
Abstract

Introduction. Living donor liver transplantation has proved to be an effective, safe and radical treatment modality for patients with end-stage liver diseases. Left lateral section (LLS) of donor’s liver is used in pediatric recipients. Laparoscopic LLS procurement was fi rst described by D. Cherqui in 2002. At present, this technique is routinely used only by 5 hospitals in the world. However, up to date, some authors consider it to be a new standard to perform such a surgery in living donors.

Aim. To analyze the fi rst Russian experience in laparoscopic left lateral sectionectomy (LapLLS) in living related donor.

Materials and methods. From May to September 2016 fi ve LapLLS were performed in living donors. In all cases donors were women (mothers in 4 cases and aunt in 1 case). Recipients were children aged from 6 months through 3 years with body mass from 5.6 to 12.5 kg. Liver transection was carried out under conditions of maintained blood supply. Parenchymal transection was performed using a harmonic scalpel, bipolar coagulation and ultrasound dissection.

Results. Average donor age was 32 ± 5 years. Average operation time was 287 ± 16 min. Average LLS graft weight was 220 ± 16 g. Intraoperative blood loss did not exceed 100 ml (95 ± 5 ml). Donors were discharged on the 3rd–4th post-op day. There were no postoperative complications in donors. Recipients were also characterized by a standard course of the postoperative period.

Conclusion. LapLLS is an effective and safe method with several advantages. Primarily, these are early rehabilitation of the donors and shortening of the hospital stay, which are important for the quick return to normal way of live. Excellent visualization of anatomical structures, including vascular and biliary ones, allows performing precise selection. In addition, good cosmetic effect is also an important aspect.

56-65 1482
Abstract

Introduction. Increase in the number of older patients with terminal CHF results in increase in their proportion among potential recipients requiring mechanical circulatory support and/or heart transplantation (HT) [Abecassis M., Bridges N.D. et al., 2012].

Aim. To analyze our own experience of HT in recipients of older 60 years.

Materials and methods. The study included 63 patients (56 men (93.3% ) and 4 (6.7%) women) aged 60–74 years (63.0 ± 0.8) with body weight of 76.6 ± 1.4 kg, body surface area of 1.7 ± 0.02 m2, and body mass index of 23.4 ± 0.6. Indications for heart transplantation: dilated cardiomyopathy – 24 (38.1%), coronary heart disease – 34 (54.0%), hypertrophic cardiomyopathy – 2 (3.2%), irreversible cardiac graft dysfunction – 3 (4.7%). 46 (73.0%) patients had NYHA functional Class III and 17 (23.0%) patients – Class IV. Transpulmonary pressure gradient was 11.2 ± 2.7 mmHg, pulmonary vascular resistance – 3.5 ± 1.3 Wood units. According to UNOS algorithm 10 (15.9%) patients were listed as Status 1A of urgency of orthotopic cardiac transplantation (VA ECMO, n = 8, and implantable left ventricular assist device, n = 2), 21 (33.3%) patients as Status 1B, and 32 (50.8%) patients as Status 2. Recipients had the following comorbidities: arterial hypertension (n = 51; 81.0%), diabetes mellitus (n = 6; 9.5%), cerebrovascular disease (n = 13; 20.6%), history of stroke (n = 9; 14.3%), dialysisindependent renal dysfunction (n = 21; 33.3%). Before cardiac transplantation 9 (14.2%) recipients underwent various thoracic surgeries, 2 (3.2%) recipients – brain surgery. Heart donors (49 (77.8%) men and 14 (22.2%) women) were aged 18–59 (34.3 ± 10.4) years.

Results. ICU hospitalization lasted for 4–15 (8.2 ± 0.5) days. In 61.9% of cases (n = 39) early postoperative and hospital periods were uncomplicated. Early on-table postoperative activation («early» tracheal extubation) was performed in 32 (50.8%) patients in 48 ± 6 minutes after surgery completion. 2 (3.2%) recipients demonstrated early graft dysfunction and required VA ECMO. Complications other than graft dysfunction were in 24 (38.1%) recipients: renal dysfunction (n = 8; 12.7%), renal and hepatic dysfunction (n = 4; 6.3%), infections (bacterial pneumonia, n = 3, [4.8%]), dyscirculatory encephalopathy (n = 9; 14.3%). 12 (19.0%) patients required continuous renal replacement therapy, 10 of them (15.9%) demonstrated renal function recovery. In 2 (3.2%) cases long-term hemodialysis was used. Hospital lethality (n = 6; 9.5%) was due to multiple organ failure syndrome and sepsis.

Conclusion. Our own experience demonstrates satisfactory short-term and long-term survival after heart transplantation in recipients of 60 years and older.

66-70 1327
Abstract

Aim: to estimate effi ciency of endovascular myocardial revascularization in patients with ischemic chronic heart failure, potential candidates for heart transplantation.

Materials and methods. Survival of 108 patients with ischemic heart disease complicated by chronic heart failure (CHF) after performance of endovascular myocardial revascularization by percutaneous coronary intervention (PCI) is presented. The observation period composed 32.79 ± 6.2 (from 3 to 126) months, age from 33 to 72 (58.9 ± 0.64) years, 102 men, 6 women. Left ventricular (LV) ejection fraction was 34.9 ± 0.6%, EDV 249.75 ± 4.9 ml, ESV 163.27 ± 3.7 ml, mitral regurgitation 1.51 ± 0.07 points. 73% of patients had NYHA Class III CHF, 27% had NYHA Class IV CHF. Duration and quality of life after revascularization were determined. In 2–3 days after PCI dynamics of LV ultrasound parameters were estimated.

Results. At the time of the end of our research 88 from 108 patients (81%) were alive, including 18 patients who underwent heart transplantation (HT). Repeated revascularization was carried out to 19 (17%) patients. 20 patients died: 16 patients with cardiovascular disorders (15%, including 4% of stroke), 3 with pulmonary embolism and 1 with oncological disease. Survival of 90% of the patients composed 4.5 years, 50% survival composed 9 years. At the time of the end of our research the maximum observation period was equal to 126 months. The duration from the fi rst PCI to HT composed from 7.5 to 105 months, mean value – 37 ± 7.5 months. Average life expectancy after HT composed 54.9 ± 24.4 months. Life expectancy from the fi rst PCI composed 87.5 ± 36.9 months. All patients of this group were alive by the time of the end of this research.

Conclusion. Endovascular revascularization in patients with ischemic heart failure in 20% of cases can serve as «bridge» to HT, in 50% of cases it can be considered as an alternative to heart transplantation.

71-76 1483
Abstract

Aim: to determine the association between plasma concentrations of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) with histochemical and immunohistochemical signs of heart rejection.

Materials and methods. The study included 98 heart recipients aged from 12 to 69 (mean age 43 ± 14) years, of which 78 men. In 68 patients dilated cardiomyopathy was diagnosed, 30 recipients were diagnosed with coronary heart disease. The concentrations of placental growth factor (PlGF-1), platelet-derived growth factor (PDGF-BB), soluble CD40 ligand (sCD40L) were measured using xMAP technology. The concentrations of ST2 cardiac biomarker were measured by ELISA.

Results. No correlation was found between the levels of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) and gender, age and diagnosis. The rejection was diagnosed via biopsy in 49 biopsies taken from 37 recipients. 1A rejection was found in 25 patients (34 biopsies), 1B rejection was identifi ed in 2 patients (3 biopsies), 3A rejection was diagnosed in 4 patients. Immunohistochemical signs of humoral rejection were identifi ed in 3 patients. The combination of acute cellular and humoral rejection was found in 4 patients (5 biopsies). The PDGFBB level was measured at the same day as the biopsy was taken, and it was shown to be signifi cantly higher in patients with rejection (p = 0.02). Rejection frequency was signifi cantly higher in patients with high PDGF-BB level (≥2473.7 pg/ml, RR = 1.64 ± 0.23; 95% CI [1.03–2.61]). Rejection frequency increased to 2.11 ± 0.34 [95% CI [1.08–4.11]] in recipients with ST2 and PDGF-BB concentration higher than the median value. The highest predictive value for heart rejection can be reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2 (RR = 2.51 ± 0.38; 95% CI [1.18–5.3]).

Conclusion. PDGF-BB has moderate predictive value for heart rejection. The highest predictive value for heart rejection was reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2.

77-86 1356
Abstract

Introduction. Kidney transplant (KTx) with reduced functional reserve is more sensitive to the toxic effects of calcineurin inhibitors (CNI). Immunosuppressive therapy (IST) approach with m-TOR inhibitors in case of KTx from expanded criteria donors (ECD) leads to decreasing levels of cyclosporine (CsA) in the blood. Despite the presence of international pilot studies we do not have yet clear recommendation as to combination of CsA and Everolimus. In this article, we presented 5-year results of the fi rst Russian experience of systematic administration of Everolimus as a basic IST in KTx from ECDs.

Materials and methods. The group of recipients (n = 41) having received bilateral kidney transplants from the same ECDs was analyzed. Comparison group (n = 19) received standard IST consisting of CsA, MMF and steroids. Study group included 22 recipients who received kidneys from the same ECDs and IST based on early (starting from the 90th day after transplantation) conversion from MMF to Everolimus – 1.5 mg/day (target concentration – 3–6 ng/mL). Simultaneously with the administration of Everolimus, dosing of Neoral dropped immediately by 50%, and then, in accordance with the target concentration (C0 30–50 ng/mL). Dosage of steroids in patients of the study group was gradually minimized.

Results. Both groups were comparable in terms of serum creatinine level and glomerular fi ltration rate (GFR) up to 3 months after transplantation. As a result of the introduction of a new IST scheme in the study group, serum creatinine level in 60 months after KTx was 149.27 ± 42.68 μmol/L, in the comparison group – 209.87 ± 39.56 μmol/L; р < 0.05. In the control group GFR reduced to 27.50 ± 7.39 mL/min/1.73 m2, in the study group it was 46.21 ± 15.17 mL/min/1.73 m2, p < 0.05.

Conclusion. Early administration of Everolimus is strongly recommended in all cases of ECD KTx. This approach helps minimize CNI nephrotoxicity, provides the prevention of chronic allograft nephropathy, enables the stable renal function, and contributes to the survival of renal transplant recipients.

Heart Transplantation and Assisted Circulation

87-92 1621
Abstract

Aim: to prove the possibility of increasing the diffusion of insulin through the skin in vitro with pre-applying microneedles.

Materials and methods. Microemulsion for transdermal therapeutic system of insulin has been used in vitro studies. Genetically engineered human insulin has been used in this research. Applicators with silicon microneedles (40 and 150 microns long) have been used to enhance the diffusion fl ux of drug substance. The dynamics of insulin release from the transdermal therapeutic systems through the rabbit skin has been studied in glass Franz diffusion cells in analyzer diffusion of drugs HDT 1000 (Copley Scientifi c Ltd., UK). Insulin has been labeled with fl uorescein isothiocyanate to separate the insulin absorption spectrum from the spectra of native skin proteins at spectrophotometer measurements.

Results. The amounts of insulin delivered through the skin in vitro after previous application of microneedles of 40 and 150 microns are 282.5 ± 61.1 and 372.3 ± 7.0 microgram, respectively. This is 1.4 and 1.9 times more than in the transdermal system without microneedles.

Conclusion. The conditions for increasing the diffusion of insulin through the skin in a model transdermal therapeutic system with microneedles (length – 150 microns, duration of pre-application – 1 hour) have been found.

93-101 1551
Abstract

The relevance of the use of circulatory support systems for the treatment of chronic heart failure (CHF) has increased over the recent years. Up to 20% of the patients from the waiting list for a donor heart die each year before they could get one. In our country, there is a huge need for mechanical heart support systems. However, the acquisition of foreign systems is associated with the excessive fi nancial costs. In addition, nowadays, there is no system that would meet all medical and technical requirements in full, and at the same time, would be of high safety for the patient. Therefore, research on the development of the systems of auxiliary circulation is highly relevant and is in demand in our country. One of the promising directions in this fi eld is disk pumps of viscous friction, which are based on the operation principle of Tesla disk pump. This article describes the creation and operation of the current model of the disk pump. The results of the bench tests confirmed that the expendable pressure characteristics of our disk pump are capable of providing the necessary parameters of blood circulation. The findings confi rm the perspective of the selected research area and provide the basis for further development and testing of this model of pump.

Editorial

Literature Reviews

102-122 2498
Abstract

Some of the most pressing health problems of the industrial society are the damage and degeneration of articular cartilage associated with the limited capacity of tissues to regenerate. The review describes the existing and developing technologies for the recovery and replacement of damaged joint cartilage tissue. The results obtained are analyzed covering two major areas: the stimulation of regeneration of damaged cartilage tissue and the growing of cartilage tissue elements in bioreactors.

123-132 2652
Abstract

Organ shortage remains to be a crucial issue in transplantation. However, it’s not the only challenge that modern transplantation is facing. There are critical issues to be solved, such as, choosing optimal patient-specific immunosuppressive regimen, preventing or coping effectively with graft rejection and improving graft and patient survival rates. There are still a number of ongoing studies on ischemia-reperfusion injury mechanisms. It is also unknown what the true limitations of organ viability are and what mechanisms actually regulate it. The upcoming era of personalized medicine dictates the necessity for individualized approach to these issues. The creation of transplant biobanks followed by different studies on their base may be the key option to resolve problems of modern transplantation. Biobanks are an essential basis of personalized medicine, which allows largescale population studies, discovery of new biomarkers and therapy targets as well as new drugs development. The importance of this relatively new fi eld has increased over last decades making its way from small collections of samples to large national and international biorepositories. There are biobanks of different types and purposes. In this article a systematic review is given covering historical reference, term definition, and classifi cation variants. Furthermore, the current state of the industry is highlighted along with current issues and perspectives with respect to transplantation.

133-145 1694
Abstract

Allotransplantation of pancreatic islets remains the most effective method of treatment of diabetes mellitus type 1 being capable under combination of favorable conditions (suffi cient number of isolated islets, effective combination of immunosuppressive drugs) to reach the recipients’ insulin independence for several years. However, the overwhelming shortage of donor pancreas and limited post-transplantation islet survival do not allow increasing the number of such transplants and their effectiveness. This review presents a critical analysis of the work done by Russian and foreign authors onto creation of tissue-engineered pancreatic constructs that may lead to the resolution of the three main pancreatic islet transplantation issues: 1) lack of donor material; 2) necessity of immunosuppressive therapy; 3) limited survival and functional activity of the islet.

146-156 2413
Abstract

In this article, the review of the literature on various aspects of the noncompaction cardiomyopathy is presented. Non-compaction cardiomyopathy is a relatively rare congenital heart disease characterized by an excessive prominence of trabecular meshwork, and deep recesses of the ventricular myocardium. The most frequent is left ventricular noncompaction (LVNC). LVNC can occur in isolation or coexist with other cardiac and systemic anomalies. Noncompaction can be detected with an echocardiography or cardiac magnetic resonance imaging. The clinical presentation varies ranging from asymptomatic patients to patients who develop ventricular arrhythmias, heart failure, thromboembolism.

157-169 5468
Abstract

Nowadays, kidney transplantation is the best approach of renal replacement therapy for the majority of patients with end-stage renal disease that significantly improves the quality and length of life. Advances in the field of organ donation, immunosuppression, transplant surgery and immunology have improved short-term graft and patient survival. But the long-term graft survival remains static over last two decades. The disparity between low graft and high patient long-term survival led to increasing number of transplant recipients with failed grafts. Repeat renal transplant is presumed to be a good option for many patients losing their grafts, but it is associated with higher complication rates. Unfortunately, there are no evidence-based recommendations or guidelines for renal retransplantation procedure. This review is based on 100 scientifi c publications related to various aspects of the kidney retransplantation and provides the recent data on this matter.

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ISSN 1995-1191 (Print)