Unexplained sudden death in patients on the waiting list for renal transplantation

Background. The incidence of unexplained sudden death (SD) and the factors involved in its occurrence in patients with chronic kidney disease are not well known. Methods. We investigated the incidence and the role of co-morbidities in unexplained SD in 1139 haemodialysis patients on the renal transplant waiting list. Results. Forty-four patients died from SD of undetermined causes (20% of all deaths; 3.9 deaths/1000 patients per year), while 178 died from other causes and 917 survived. SD patients were older and likely to have diabetes, hypertension, past/present cardiovascular disease, higher left ventricular mass index, and lower ejection fraction. Multivariate analysis showed that cardiovascular disease of any type was the only independent predictor of SD (P = 0.0001, HR = 2.13, 95% CI 1.46-3.22). Alterations closely associated with ischaemic heart disease like angina, previous myocardial infarction and altered myocardial scan were not independent predictors of SD. The incidence of unexplained SD in these haemodialysis patients is high and probably a consequence of pre-existing cardiovascular disease. Conclusions. Factors influencing SD in dialysis patients are not substantially different from factors in the general population. The role played by ischaemic heart disease in this context needs further evaluation.

The quality of life of patients on the lung transplantation waiting list

Introduction. Lung transplantation (LTx) candidates present incapacitating symptoms related to their mobility and activities of daily living, thereby affecting their work, social and emotional relations, and quality of life (QoL). Objective. To study the QoL of LTx candidates, seeking to identify domains that suffer the greatest impact and verify if there are differences among these impairments according to the original lung disease. Methods. We applied the Short Form-36 questionnaires and St George`s Respiratory Questionnaire (SGRQ). All data were analyzed by one-way analysis of variance and the Kruskal Wallis test for the probability with significance at P < 0.05. Results. Fifty patients were divided into groups of emphysema (n = 16), bronchiectasis (n = 12), idiopathic pulmonary fibrosis (n = 7), and cystic fibrosis (n = 15). The functional capacity, physical aspects, general status, and vitality domains showed average values below 50 points. The cystic fibrosis group showed higher functional capacity scores (46 +/- 23) than the emphysema (12 +/- 13) or idiopathic pulmonary fibrosis cohort (7 5). The limitation caused by pain affected the bronchiectasis more than the cystic fibrosis group (52 +/- 28 vs 81 +/- 25, respectively). The SGRQ scores showed impairment among all groups in all domains with average values over 50. The activities domain shows the highest score value; the emphysema (92 +/- 10) and idiopathic pulmonary fibrosis cohorts (91 +/- 9) were extremely affected compared with the cystic fibrosis (69 +/- 21) and bronchiectasis subjects (79 +/- 16). The impact domain show that subjects with cystic fibrosis were less emotionally affected by the disease. Conclusion. LTx candidates showed great impairment of their QoL due to their health problems, above all in the physical-functional aspects; the cystic fibrosis patients were the least affected by their health status.

Heart Transplantation in 107 Cases of Chagas` Disease

Introduction. Chagas` disease is endemic in South America. Objective. This research reviewed the experience with cardiac transplantation in Chagas` disease, emphasizing reactivation, immunosuppression, and mortality. Methods. Over 25 years from March 1985 to March 2010, 107/409 (26.2%) patients with Chagas` disease underwent heart transplantation, patients including 74 (71.1%) men and 72 (67.2%), in functional class IV with 33 (30.8%) on vasopressors and 17 (10.7%) on mechanical circulatory support. Results. The diagnosis of disease reactivation was performed by identifying the parasite in the myocardium (n = 23; 71.8%) in the subcutaneous tissue (n = 8; 25.0%), in blood (n = 11; 34.3%), or in central nervous tissue (n = 1; 3.1%). Hospital mortality was 17.7% (n = 19) due to infection (n = 6; 31.5%), graft dysfunction (n = 6; 31.5%), rejection (n 4; 21.1%), or sudden death (n = 2; 10.5%). Late mortality was 27 (25.2%) cases, which were distributed as: rejection (n = 6; 22.2%), infection (n = 6; 22.2%), (n = lymphoma 4; 14.8%), sarcoma (n = 2; 7.4%), for constrictive pericarditis (n = 2; 7.4%) reactivation of Chagas` disease in the central nervous system (n = 1; 7.1%). Conclusions. Transplantation in Chagas` disease has peculiar problems that differ from other etiologies due to the possibility of disease reactivation and the increased possibility of emergence of cancers. However, transplantation is the only treatment able to modify the natural progression of the disease in its terminal phase. Early diagnosis and rapid introduction of benzonidazole reverses the histological patterns. Immunosuppression, especially steroids, predisposes to the development of cancer and disease reactivation.

Long-Term Pulmonary Vascular Reactivity After Orthotopic Heart Transplantation by the Biatrial Versus the Bicaval Technique

Introduction. Advantages of the bicaval versus the biatrial technique have been reported, emphasizing atrial electrical stability and less tricuspid regurgitation. Objective. To analyze the impact of the surgical technique on long-term pulmonary pressures, contractility, and graft valvular behavior after heart transplantation. Methods. Among 400 orthotopic heart transplantation recipients from 1985 to 2010, we selected 30 consecutive patients who had survived beyond 3 years. The biatrial versus bicaval surgical technique groups included 15 patients each. Their preoperative clinical characteristics were similar. None of the patients displayed a pulmonary vascular resistance or pulmonary artery pressure over 6U Wood or 60 mm Hg, respectively. We evaluated invasive hemodynamic parameters during routine endomyocardial biopsies. Two-dimensional echocardiographic parameters were obtained from routine examinations. Results. There were no significant differences regarding right atrial pressure, systolic pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, cardiac index, systolic blood pressure, left ventricular ejection fraction, and mitral regurgitation (P > .05). Tricuspid regurgitation increased significantly over the 3 years of observation only among the biatrial group (P = .0212). In both groups, the right atrial pressure, pulmonary wedge capillary pressure, transpulmonary gradient, and pulmonary vascular resistance decreased significantly (P < .05) from the pre- to the postoperative examination. In both groups cardiac index and systemic blood pressure increased significantly after transplantation (P < .05). Comparative analysis of the groups only showed significant differences regarding right atrial pressure and degree of tricuspid regurgitation; the bicaval group showing the best performance. Conclusions. Both surgical techniques ensure adequate left ventricular function in the long term; however, the bicaval technique provided better trends in hemodynamic performance, as well as a lower incidence and severity of tricuspid valve dysfunction.

Can Tricuspid Annuloplasty of the Donor Heart Reduce Valve Insufficiency following Cardiac Transplantation with Bicaval Anastomosis?

Background: The aim of this study was to evaluate the degree of tricuspid valve insufficiency after orthotopic cardiac transplantation with bicaval anastomosis and prophylactic donor heart annuloplasty. Methods: At present, our cardiac transplantation experience includes 478 cases. After January 2002, we included 30 consecutive patients in this study who had undergone orthotopic cardiac transplantation and survived >6 months. The patients were divided into 2 groups: group I, 15 patients who underwent transplantation with prophylactic tricuspid annuloplasty on the donor heart with the De Vega technique; and group II, 15 patients who underwent transplantation without this procedure. Their preoperative clinical characteristics were the same. During the late postoperative follow-up, the degree of tricuspid insufficiency was evaluated by transthoracic Doppler echocardiography and assessed according to the Simpson scale: 0, absent; 1, mild; 2, moderate; and 3, severe. Hemodynamic parameters were evaluated invasively by means of a Swan-Ganz catheter during routine endomyocardial biopsies. Results: The mean follow-up time was 26.9 +/- 5.4 months (range, 12-36 months). In group I, 1 patient (6.6%) died from infection in the 18th month after the operation; the death was not related to the annuloplasty. In group II, 1 death (6.6%) occurred after 10 months because of rejection (P > .05). After the 24-month follow-up, the mean degree of tricuspid insufficiency was 0.4 +/- 0.5 in group I and 1.7 +/- 0.9 in group II (P < .05). Similarly, the 2 groups were significantly different with respect to the right atrium pressure, which was higher in group II. Conclusions: Prophylactic tricuspid annuloplasty on the donor heart was able to reduce significantly the degree of valvular insufficiency, even in cardiac transplantation with bicaval anastomosis; however, it did not modify significantly the hemodynamic performance of the allograft during the investigation period. It is very important to extend the observation period and casuistics to verify other benefits that this technique may offer.

Intramyocardial transplantation of fibroblasts expressing vascular endothelial growth factor attenuates cardiac dysfunction

In this study, we analyzed whether transplantation of cardiac fibroblasts (CFs) expressing vascular endothelial growth factor (VEGF) mitigates cardiac dysfunction after myocardial infarction (MI) in rats. First, we observed that the transgene expression lasts longer (45 vs 7 days) when fibroblasts are used as vectors compared with myoblasts. In a preventive protocol, induction of cardiac neovascularization accompanied by reduction in myocardial scar area was observed when cell transplantation was performed 1 week before ischemia/reperfusion and the animals analyzed 3 weeks later. Finally, the therapeutic efficacy of this approach was tested injecting cells in a fibrin biopolymer, to increase cardiac retention, 24 h post-MI. After 4 weeks, an increase in neovascularization and a decrease in myocardial collagen were observed only in rats that received cells expressing VEGF. Basal indirect or direct hemodynamic measurements showed no differences among the groups whereas under pharmacological stress, only the group that received cells expressing VEGF showed a significant reduction in end-diastolic pressure and improvement in stroke volume and cardiac work. These results indicate that transplantation of CFs expressing VEGF using fibrin biopolymer induces neovascularization and attenuates left ventricle fibrosis and cardiac dysfunction in ischemic heart. Gene Therapy (2010) 17, 305-314; doi:10.1038/gt.2009.146; published online 10 December 2009

Massive Degeneration and Atrophy of the Native Heart After Heterotopic Transplantation: A Case Report

Extreme myocardial degeneration leading to advanced stages of cardiomyopathy with extensive atrophy is rarely observed before patients die. However, heterotopic transplantation is a special situation wherein this phenomenon can be observed. The greater part of the failed heart shows recuperation after receiving circulatory assistance by reduction of myocardial work. Herein we have reported an unusual behavior of degenerative cardiomyopathy associated with intense myocardial apoptosis resulting in extreme ventricular atrophy after heterotopic heart transplantation. An 11-year-old girl with end-stage heart failure due to dilated cardiomyopathy of undetermined etiology without pulmonary hypertension underwent heterotopic cardiac transplantation with an undersized (by weight mismatch) donor heart. After 9 years heart failure reappeared due to native heart enlargement leading to allograft compression. The patient underwent native heart replacement leaving her with 2 donor hearts. Despite normal hemodynamic recuperation, the patient experienced massive arterial microemboli which led to death. Pathological studies showed exuberant myocardial degeneration in the native heart with intense atrophy of the muscle and gigantic ventricular enlargement. The left ventricle wall was extremely thin with rarefaction of cardiomyocytes and replacement by fibrosis. The right ventricle showed old extensive thrombosis. In conclusion, this report is not usual as it is not frequent to observe cardiomyopathy with an intense degree of myocardial degeneration and atrophy, because the patient dies earlier. In special situations it is possible that a recipient may have 2 donor hearts with normal hemodynamics. Heterotopic heart transplantation is a surgical alternative in a priority situation offering excellent outcomes; however, the native heart must be removed when there is compromise of the function of the heterotopic allograft.

Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction - MiHeart/AMI study

Background: Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls. Methods: A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 x 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum). Implications: Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required.

Heart transplantation experiences: a phenomenological approach

Aim. The aim of this study was to understand the heart transplantation experience based on patients` descriptions. Background. To patients with heart failure, heart transplantation represents a possibility to survive and improve their quality of life. Studies have shown that more quality of life is related to patients` increasing awareness and participation in the work of the healthcare team in the post-transplantation period. Deficient relationships between patients and healthcare providers result in lower compliance with the postoperative regimen. Method. A phenomenological approach was used to interview 26 patients who were heart transplant recipients. Patients were interviewed individually and asked this single question: What does the experience of being heart transplanted mean? Participants` descriptions were analysed using phenomenological reduction, analysis and interpretation. Results. Three categories emerged from data analysis: (i) the time lived by the heart recipient; (ii) donors, family and caregivers and (iii) reflections on the experience lived. Living after heart transplant means living in a complex situation: recipients are confronted with lifelong immunosuppressive therapy associated with many side-effects. Some felt healthy whereas others reported persistence of complications as well as the onset of other pathologies. However, all participants celebrated an improvement in quality of life. Health caregivers, their social and family support had been essential for their struggle. Participants realised that life after heart transplantation was a continuing process demanding support and structured follow-up for the rest of their lives. Conclusion. The findings suggest that each individual has unique experiences of the heart transplantation process. To go on living participants had to accept changes and adapt: to the organ change, to complications resulting from rejection of the organ, to lots of pills and food restrictions. Relevance to clinical practice. Stimulating a heart transplant patients spontaneous expression about what they are experiencing and granting them the actual status of the main character in their own story is important to their care.

Risk factors for Chagas` disease reactivation after heart transplantation

Background: Chagas` disease is the illness caused by the protozoan Trypanosoma cruzi and it is still endemic in Latin America. Heart transplantation is a therapeutic option for patients with end-stage Chagas` cardiomyopathy. Nevertheless, reactivation may occur after transplantation, leading to higher morbidity and graft dysfunction. This study aimed to identify risk factors for Chagas` disease reactivation episodes. Methods: This investigation is a retrospective cohort study of all Chagas` disease heart transplant recipients from September 1985 through September 2004. Clinical, microbiologic and histopathologic data were reviewed. Statistical analysis was performed with SPSS (version 13) software. Results: Sixty-four (21.9%) patients with chronic Chagas` disease underwent heart transplantation during the study period. Seventeen patients (26.5%) had at least one episode of Chagas` disease reactivation, and univariate analysis identified number of rejection episodes (p = 0.013) and development of neoplasms (p = 0.040) as factors associated with Chagas` disease reactivation episodes. Multivariate analysis showed that number of rejection episodes (hazard ratio = 1.31; 95% confidence interval [CI]: 1.06 to 1.62; p = 0.011), neoplasms (hazard ratio = 5.07; 95% CI: 1.49 to 17.20; p = 0.009) and use of mycophenolate mofetil (hazard ratio = 3.14; 95% CI: 1.00 to 9.84; p = 0.049) are independent determinants for reactivation after transplantation. Age (p = 0.88), male gender (p = 0.15), presence of rejection (p = 0.17), cytomegalovirus infection (p = 0.79) and mortality after hospital discharge (p = 0.15) showed no statistically significant difference. Conclusions: Our data suggest that events resulting in greater immunosuppression status contribute to Chagas` disease reactivation episodes after heart transplantation and should alert physicians to make an early diagnosis and perform pre-emptive therapy. Although reactivation led to a high rate of morbidity, a low mortality risk was observed.

Kinetics of elimination and distribution in blood and liver of biocompatible ferrofluids based on Fe(3)O(4) nanoparticles: An EPR and XRF study

In this study, we evaluated the biodistribution and the elimination kinetics of a biocompatible magnetic fluid, Endorem (TM), based on dextrancoated Fe(3)O(4) nanoparticles endovenously injected into Winstar rats. The iron content in blood and liver samples was recorded using electron paramagnetic resonance (EPR) and X-ray fluorescence (XRF) techniques. The EPR line intensity at g=2.1 was found to be proportional to the concentration of magnetic nanoparticles and the best temperature for spectra acquisition was 298 K. Both EPR and XRF analysis indicated that the maximum concentration of iron in the liver occurred 95 min after the ferrofluid administration. The half-life of the magnetic nanoparticles (MNP) in the blood was (11.6 +/- 0.6) min measured by EPR and (12.6 +/- 0.6) min determined by XRF. These results indicate that both EPR and XRF are very useful and appropriate techniques for the study of kinetics of ferrofluid elimination and biodistribution after its administration into the organism. (c) 2007 Elsevier B.V. All rights reserved.

Amino acids change liver growth factors gene expression in malnourished rats

Background: Glutamine and proline are metabolized in the liver and may collaborate on its regeneration. Parenteral nutrition (PN) containing either glutamine or proline was given to partially hepatectomized rats. The total RNA content and growth factor gene expression in hepatic remnants was measured, to determine the effects of these amino acid supplementation on the expression of growth factors during liver regeneration. Methods: Wistar rats nourished (HN) and malnourished (HM) were hepatectomized and divided in two groups: 20 receiving PN enriched with Alanyl-Glutamine (HN-Gln and HM-Gln) and 20 PN enriched with proline+alanine (HN-Pro and HM-Pro). The control groups comprised 7 nourished (CN) and 7 malnourished (CM) rats that didn`t undergo surgery. Growth factor and thymidine kinase mRNA levels were measured by RT-PCR. Results: In nourished rats, total hepatic RNA levels were lower in the HN-Gln and HN-Pro groups (0.75 and 0.63 mu g/mg tissue, respectively) than in control group (1.67 mu g/mg tissue) (P<0.05). In malnourished rats, total hepatic RNA content was higher in the HM-Pro group than FIN-Pro, HM-Gln, and CM (3.18 vs. 0.63, 0.93 and 1.10 mu g/mg, respectively; P<0.05). Hepatocyte growth factor mRNA was more abundant in the HM-Gln group when compared to CM (031 vs. 0.23 arbitrary units) and also in HM-Pro in relation to HM-Gln, HN-Pro, and CM (0.46 vs. 033 and 0.23, respectively, P<0.05). Conclusions: Proline or glutamine supplementation in malnourished rats improves total RNA content in the remnant hepatic tissue. Amino acids administration increased HGF gene expression after partial hepatectomy in malnourished rats, with a greater effect of proline than glutamine.

Human leukemia inhibitory factor upregulates LDL receptors on liver cells and decreases serum cholesterol in the cholesterol-fed rabbit

In a previous study, we found that the cytokine (human) leukemia inhibitory factor (hLIF) significantly reduced plasma cholesterol levels and the accumulation of lipid in aortic tissues of cholesterol-fed rabbits after 4 weeks of treatment. The mechanisms by which this occurs were investigated in the present study. This involved examining the effect of hLIF on (1) the level of plasma cholesterol at different times throughout the 4-week treatment and diet period; (2) smooth muscle cell (SMC) and macrophage-derived foam cell formation in vitro; and (3) LDL receptor expression and uptake in the human hepatoma cell line HepG2. At time zero, an osmotic minipump (2-mL capacity; infusion rate, 2.5 mu L/h; 28 days) containing either hLIF (30 mu g.kg(-1).d(-1)) or saline was inserted into the peritoneal cavity of New Zealand White rabbits (N=24). Rabbits were divided into four groups of six animals each. Group 1 received a normal diet/saline; group 2, a normal diet/hLIF; group 3, a 1% cholesterol diet/saline; and group 4, a 1% cholesterol diet/hLIF. hLIF had no effect on the plasma lipids or artery wall of group 2 rabbits (normal diet). However, in group 4 rabbits, plasma cholesterol levels and the percent surface area of thoracic aorta covered by fatty streaks was decreased by approximate to 30% and 80%, respectively, throughout all stages of the 4-week treatment period. In vitro, hLIF failed to prevent lipoprotein uptake by either SMCs or macrophages (foam cell formation) when the cells were exposed to P-VLDL for 24 hours. In contrast, hLIF (100 ng/mL) added to cultured human hepatoma HepG2 cells induced a twofold or threefold increase in intracellular lipid accumulation in the medium containing 10% lipoprotein-deficient serum or 10% fetal calf serum, respectively. This was accompanied by a significant non-dose-dependent increase in LDL receptor expression in hLIF-treated HepG2 cells incubated with LDL (20 mu g/mL) when compared with controls (P

Endemic and opportunistic infections in Brazilian solid organ transplant recipients

OBJECTIVE To evaluate the frequency and clinical features of endemic and other opportunistic infections in liver or kidney transplant recipients in four transplant centres in different geographical areas of Brazil. METHODS Retrospective analysis of medical and laboratory records of four transplant centres on endemic and other opportunistic infections in liver or kidney transplant recipients. Analyses were performed with spss statistical software. RESULTS From 2001 to 2006, 1046 kidney and 708 liver transplants were registered in all centres. The average age was 42 years. Among 82 (4.7%) cases with infections, the most frequent was tuberculosis (2.0%), followed by systemic protozoal infections (0.7%), toxoplasmosis (0.4%) and visceral leishmaniasis (0.3%). Systemic fungal infections occurred in 0.6%, of which 0.4% were cryptococcosis and 0.2% were histoplasmosis. Dengue was the only systemic viral infection and was registered in two cases (0.1%), of which one was classified as the classic form and the other as dengue haemorrhagic fever. Nocardiosis was described in one case (0.05%). The infectious agents most frequently associated with diarrhoea were Blastocystis sp., Schistosoma mansoni and Strongyloides stercoralis. CONCLUSIONS Opportunistic Infections in transplant patients have a wide spectrum and may vary from asymptomatic to severe infections with high mortality. A better understanding of the epidemiology of endemic pathogens and clinical manifestations can contribute to the establishment of an early diagnosis as well as correct treatment aimed at decreasing morbidity and mortality.

Endoscopic features in a model of multivisceral xenotransplantation

Introduction: Xenotransplantation and multivisceral transplantation are advanced therapeutic methods that still require a scientific basis. There are no experimental models of multivisceral transplantation available, particularly not the monitoring by endoscopy. Here, we describe the endoscopic features in a model of multivisceral xenotransplantation. Methods: The distal esophagus, stomach, intestine, colon, liver, pancreas, and the kidneys with a common vascular pedicle were harvested from rabbits and implanted in swine (group I, n = 9) or in rabbits (group II, n = 4). Endoscopy was performed in the stomach, jejunum, and ascending colon at four consecutive time points (immediate after surgery and 10, 90, and 180 min after reperfusion). Lesions were macroscopically graded as mild, moderate, and severe. Biopsies were taken following sacrifice at 180 min after reperfusion. Results: In group I, the stomach, jejunum, and colon manifested a progression of lesions with predominance of mild lesions after 10 min, mild to moderate lesions after 90 min, and moderate to severe lesions after 180 min. In animals from group II, endoscopy showed normal features at all time points after reperfusion. Histopathologic analysis confirmed the diagnosis of hyperacute rejection in group I. Grafts from group II animals presented normal or mild ischemic/reperfusion injury. Conclusion: All animals subjected to multivisceral xenotransplantation showed a progression of endoscopic lesions with time after transplantation, while animals subjected to allotransplantation showed no aberrations in endoscopy. We conclude that endoscopy is a useful tool in the assessment of hyperacute rejection of a xenograft.