RESUMEN
PURPOSE OF REVIEW: With advances in the field of congenital cardiac surgery and in the management of congenital heart defects in early life, the population of adult congenital heart disease (ACHD) patients is increasing. End-stage heart failure is currently the main cause of cardiovascular mortality and is expected to increase in the coming years. This review summarizes recent innovations in transplant techniques, with special attention to what is known in the population of ACHD recipients. RECENT FINDINGS: The use of machine perfusion for heart preservation enables longer preservation times. Normothermic (organ care system - OCS) and hypothermic (hypothermic oxygenated perfusion - HOPE) machine perfusion will alleviate the time pressure associated with heart transplantation in the ACHD population, may allow for expansion of the geographical range in which donors can be matched and may improve graft quality. Donation after circulatory death (DCD) heart transplantation, either through direct procurement-machine perfusion (DP-MP) or thoraco-abdominal normothermic regional perfusion (TA-NRP) is a viable strategy to further expand the donor pool. SUMMARY: The use of machine perfusion and DCD donors in ACHD is feasible and shows promise. Time pressure and shortage of donors is even more critical in ACHD than in other patient populations, making these innovations particularly relevant. Further clinical experience and research is needed to elucidate their impact.
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Cardiopatías Congénitas , Trasplante de Corazón , Preservación de Órganos , Perfusión , Humanos , Preservación de Órganos/métodos , Preservación de Órganos/efectos adversos , Trasplante de Corazón/métodos , Cardiopatías Congénitas/cirugía , Perfusión/métodos , Perfusión/efectos adversos , Resultado del Tratamiento , Donantes de Tejidos/provisión & distribución , Selección de Donante , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/fisiopatologíaRESUMEN
BACKGROUND: This case report documents the first worldwide use of the Hybrid System from Spectrum Medical in a heart transplant procedure, focusing on its safety and efficacy. Traditional cardiopulmonary bypass systems often use an open reservoir, which increases the blood's exposure to air, thereby heightening the risk of an inflammatory response and gas embolism. In contrast, the Hybrid System is designed to improve surgical outcomes by significantly reducing the blood-air interface. This system utilizes a dual-chamber cardiotomy-venous reservoir with a collapsible soft bag, effectively minimizing blood contact with air and foreign materials. However, it is important to note that there is currently no evidence supporting the use of this methodology specifically in heart transplants. CASE PRESENTATION: A 41-year-old male managed with a left ventricular assist device because of dilated cardiomyopathy underwent a heart transplant using the Hybrid System. The perioperative and postoperative data provided evidence of the system's effectiveness. The selection of this patient was due to the absence of significant comorbidities unrelated to his primary cardiac condition, making him an ideal candidate to evaluate the system's performance. CONCLUSION: The Hybrid System is safe and efficient. The successful implementation in this case highlights its advantages over traditional cardiopulmonary bypass systems, suggesting a promising future in cardiac surgery. Further studies with routine cardiac surgery patients are required to validate these findings.
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Circulación Extracorporea , Trasplante de Corazón , Humanos , Masculino , Trasplante de Corazón/métodos , Adulto , Circulación Extracorporea/métodos , Corazón Auxiliar , Cardiomiopatía Dilatada/cirugíaRESUMEN
Due to the discrepancy between patients awaiting a heart transplant and the availability of donor hearts, strategies to expand the donor pool and improve the transplant's success are crucial. This review aims to summarize current knowledge on the ex vivo heart preservation (EVHP) experience as an alternative to standard cold static storage (CSS). EVHP techniques can improve the preservation of the donor's heart before transplantation and allow for pre-transplant organ evaluation.
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Trasplante de Corazón , Preservación de Órganos , Perfusión , Humanos , Trasplante de Corazón/métodos , Preservación de Órganos/métodos , Perfusión/métodos , Donantes de TejidosRESUMEN
INTRODUCTION: Insufficient supply of cardiac grafts represents a severe obstacle in heart transplantation. Donation after Circulatory Death (DCD), in addition to conventional donation after brain death, is one promising option to overcome the organ shortage. However, DCD organs undergo an inevitable more extended period of warm unprotected ischemia between circulatory arrest and graft procurement. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have shown remarkable protective effects against ischemia-reperfusion injury. Thus, we aimed to enhance grafts preservation from DCD donors, through treatment with MSC-EVs. METHODS: Female pigs were euthanized by barbiturate overdose and after 20â¯min of a flat EKG, the chest was opened, the heart harvested and subsequently connected to an extracorporeal perfusion machine. MSC-EVs, isolated by ion exchange chromatography, were added to the perfusion solution (1×1011 particles) and the heart was perfused for 2â¯h. Then, heart tissue biopsies were taken to assess histological changes, mitochondrial morphology, antioxidant enzyme activity and inflammation mediators' expression. Biochemical parameters of myocardial viability were assessed in the perfusate. RESULTS: The treatment with MSC-EVs significantly prevented mitochondria swelling, mitochondrial cristae loss and oxidative stress in cardiac tissue. The protective effect of MSC-EVs was confirmed by the delayed increase of the cardiac-specific enzymes CK and TnC in the perfusate and the reduction of caspase-3+ cells in tissue sections. CONCLUSION: MSC-EVs improve graft quality by preserving the mitochondrial ultrastructure protecting the myocardium against oxidative stress, reducing apoptosis of cardiac cells and preventing the increase of pro-inflammatory cytokines.
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Vesículas Extracelulares , Células Madre Mesenquimatosas , Animales , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Células Madre Mesenquimatosas/metabolismo , Femenino , Porcinos , Estrés Oxidativo , Trasplante de Corazón/métodos , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/patología , Modelos Animales de Enfermedad , Miocardio/patología , Miocardio/metabolismo , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patologíaRESUMEN
Physical therapy students must learn about heart transplantation. They need to know how to care for these patients' emotions and needs. The study aimed to compare the effectiveness of a narrative photography (NP) program and a traditional learning (TL) program in physical therapy students' knowledge, satisfaction, empathy, and moral sensitivity. A two-armed assessor-blinded randomized controlled trial was carried out. One hundred and seventeen physical therapy students participated in the study. They were divided into two groups: (i) NP group (n = 56) and (ii) TL group (n = 61). At the end of the program, NP group's knowledge increased when compared with the TL group (p = 0.02). 90.57% of the sample was very satisfied/satisfied with the NP method, and 88.68% felt that NP helped them to understand the importance of considering subjective realities. In conclusion, NP improved knowledge and satisfaction compared with the TL group. These results suggest that NP may be a useful method to improve the academic outcomes of physical therapy students in the heart transplantation field; thus, NP may be considered a teaching-learning methodology of choice in physical therapy students.
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Trasplante de Corazón , Fotograbar , Humanos , Femenino , Masculino , Fotograbar/métodos , Trasplante de Corazón/psicología , Trasplante de Corazón/métodos , Adulto , Narración , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Aprendizaje , Evaluación Educacional/métodosRESUMEN
Ex vivo machine perfusion or normothermic machine perfusion is a preservation method that has gained great importance in the transplantation field. Despite the immense opportunity for assessment due to the beating state of the heart, current clinical practice depends on limited metabolic trends for graft evaluation. Hemodynamic measurements obtained from left ventricular loading have garnered significant attention within the field due to their potential as objective assessment parameters. In effect, this protocol provides an easy and effective manner of incorporating loading capabilities to established Langendorff perfusion systems through the simple addition of an extra reservoir. Furthermore, it demonstrates the feasibility of employing passive left atrial pressurization for loading, an approach that, to our knowledge, has not been previously demonstrated. This approach is complemented by a passive Windkessel base afterload, which acts as a compliance chamber to maximize myocardial perfusion during diastole. Lastly, it highlights the capability of capturing functional metrics during cardiac loading, including left ventricular pulse pressure, contractility, and relaxation, to uncover deficiencies in cardiac graft function after extended periods of preservation times (Ë6 h).
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Trasplante de Corazón , Trasplante de Corazón/métodos , Animales , Perfusión/métodos , Atrios Cardíacos/cirugía , Atrios Cardíacos/fisiopatologíaRESUMEN
An orthotopic heart transplant and an aortic operation can be done concomitantly at centres that are experienced in both aortic operations and heart transplants with meticulous surgical strategy.
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Trasplante de Corazón , Humanos , Trasplante de Corazón/métodos , Masculino , Esternón/cirugía , Aneurisma de la Aorta/cirugía , Persona de Mediana Edad , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico , Implantación de Prótesis Vascular/métodos , Aorta/cirugía , Aneurisma de la Aorta AscendenteRESUMEN
Heart transplantation is the definitive treatment for refractory, end-stage heart failure. The number of patients awaiting transplantation far exceeds available organs. In an effort to expand the donor pool, donation after circulatory death (DCD) heart transplantation has garnered renewed interest. Unlike donation after brain death, DCD donors do not meet the criteria for brain death and are dependent on life-sustaining therapies. Procurement can include a direct strategy or a normothermic regional perfusion, whereby there is restoration of perfusion to the organ before explantation. There are new developments in cold storage and ex vivo perfusion strategies. Since its inception, there has been a steady improvement in post-transplant outcomes, largely attributed to advancements in operative and procurement strategies. In this narrative review, the authors address the unique considerations of DCD heart transplantation, including withdrawal of care, the logistics of procuring and resuscitating organs, outcomes compared with standard donation after brain death, and ethical considerations.
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Trasplante de Corazón , Donantes de Tejidos , Obtención de Tejidos y Órganos , Humanos , Trasplante de Corazón/métodos , Obtención de Tejidos y Órganos/métodos , Muerte Encefálica , Preservación de Órganos/métodos , MuerteRESUMEN
Background: Heart transplantation is the preferred treatment for end-stage heart failure. This study investigated the intra-operative risk factors affecting post-transplantation mortality. Methods: This single-center retrospective cohort study examined 239 heart transplant patients over eight years, from 2011-2019, at the oldest dedicated cardiovascular center, Shahid Rajaee Hospital (Tehran, Iran). The primary evaluated clinical outcomes were rejection, readmission, and mortality one month and one year after transplantation. For data analysis, univariate logistic regression analyses were conducted. Results: In this study, 107 patients (43.2%) were adults, and 132 patients (56.8%) were children. Notably, reoperation due to bleeding was a significant predictor of one-month mortality in both children (OR=7.47, P=0.006) and adults (OR=172.12, P<0.001). Moreover, the need for defibrillation significantly increased the risk of one-month mortality in both groups (children: OR=38.00, P<0.001; adults: OR=172.12, P<0.001). Interestingly, readmission had a protective effect against one-month mortality in both children (OR=0.02, P<0.001) and adults (OR=0.004, P<0.001). Regarding one-year mortality, the use of extracorporeal membrane oxygenation (ECMO) was associated with a higher risk in both children (OR=7.64, P=0.001) and adults (OR=12.10, P<0.001). For children, reoperation due to postoperative hemorrhage also increased the risk (OR=5.14, P=0.020), while defibrillation was a significant risk factor in both children and adults (children: OR=22.00, P<0.001; adults: OR=172.12, P<0.001). The median post-surgery survival was 22 months for children and 24 months for adults. Conclusion: There was no correlation between sex and poorer outcomes. Mortality at one month and one year after transplantation was associated with the following risk factors: the use of ECMO, reoperation for bleeding, defibrillation following cross-clamp removal, and Intensive Care Unit (ICU) stay. Readmission, on the other hand, had a weak protective effect.
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Trasplante de Corazón , Humanos , Trasplante de Corazón/estadística & datos numéricos , Trasplante de Corazón/métodos , Trasplante de Corazón/mortalidad , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/tendencias , Masculino , Femenino , Factores de Riesgo , Estudios Retrospectivos , Irán/epidemiología , Niño , Adulto , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Adolescente , Preescolar , Reoperación/estadística & datos numéricos , Reoperación/mortalidad , Reoperación/métodos , Adulto Joven , Complicaciones Posoperatorias/mortalidad , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugíaRESUMEN
Despite important advancements in the diagnosis and treatment of cardiovascular diseases (CVDs), the field is in urgent need of increased research and scientific advancement. As a result, innovation, improvement and/or repurposing of the available research toolset can provide improved testbeds for research advancement. Langendorff perfusion is an extremely valuable research technique for the field of CVD research that can be modified to accommodate a wide array of experimental needs. This tailoring can be achieved by personalizing a large number of perfusion parameters, including perfusion pressure, flow, perfusate, temperature, etc. This protocol demonstrates the versatility of Langendorff perfusion and the feasibility of achieving longer perfusion times (4 h) without graft function loss by utilizing lower perfusion pressures (30-35 mmHg). Achieving extended perfusion times without graft damage and/or function loss caused by the technique itself has the potential to eliminate confounding elements from experimental results. In effect, in scientific circumstances where longer perfusion times are relevant to the experimental needs (i.e., drug treatments, immunological response analysis, gene editing, graft preservation, etc.), lower perfusion pressures can be key for scientific success.
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Perfusión , Animales , Perfusión/métodos , Ratas , Trasplante de Corazón/métodos , Preparación de Corazón Aislado/métodosRESUMEN
Heart transplantation is the gold standard treatment for advanced heart failure. The procurement of extended criteria donors (ECD) increases due to the current organ shortage. Coronary angiography is recommended in ECD at risk for coronary artery disease but is not systematically performed. These hearts are, therefore, either declined for transplant or procured without screening for coronary artery disease. Coronary angiography during normothermic ex-situ heart perfusion (NESP) could be an interesting approach to enhance the rate of ECD procurement and to reduce the risk of primary graft failure in the absence of coronary angiography in ECD. The present protocol aims to provide material details along with optimal imaging views for coronary angiography during NESP. Reproducible angiographic views were observed, including one dedicated to the right coronary artery, two for the left anterior descending artery, two for the circumflex artery, and a spider view. Continuous lactate extraction was observed in all procedures with a final median concentration of 1.10 mmol/L (0.61-1.75 mmol/L) two hours after coronary angiography, consistent with myocardial viability. The median contrast agent volume used for ex-situ imaging of the isolated perfused heart was 48 mL (38-108 mL). This protocol was reproducible for coronary artery imaging and did not impair myocardial viability during NESP.
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Angiografía Coronaria , Trasplante de Corazón , Animales , Porcinos , Angiografía Coronaria/métodos , Trasplante de Corazón/métodos , Perfusión/métodos , Corazón/diagnóstico por imagen , Modelos Animales , Vasos Coronarios/diagnóstico por imagenRESUMEN
INTRODUCTION: Inflammatory responses and coagulation disorders are a relevant challenge for successful cardiac xenotransplantation on its way to the clinic. To cope with this, an effective and clinically practicable anti-inflammatory and anti-coagulatory regimen is needed. The inflammatory and coagulatory response can be reduced by genetic engineering of the organ-source pigs. Furthermore, there are several therapeutic strategies to prevent or reduce inflammatory responses and coagulation disorders following xenotransplantation. However, it is still unclear, which combination of drugs should be used in the clinical setting. To elucidate this, we present data from pig-to-baboon orthotopic cardiac xenotransplantation experiments using a combination of several anti-inflammatory drugs. METHODS: Genetically modified piglets (GGTA1-KO, hCD46/hTBM transgenic) were used for orthotopic cardiac xenotransplantation into captive-bred baboons (n = 14). All animals received an anti-inflammatory drug therapy including a C1 esterase inhibitor, an IL-6 receptor antagonist, a TNF-α inhibitor, and an IL-1 receptor antagonist. As an additive medication, acetylsalicylic acid and unfractionated heparin were administered. The immunosuppressive regimen was based on CD40/CD40L co-stimulation blockade. During the experiments, leukocyte counts, levels of C-reactive protein (CRP) as well as systemic cytokine and chemokine levels and coagulation parameters were assessed at multiple timepoints. Four animals were excluded from further data analyses due to porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) infections (n = 2) or technical failures (n = 2). RESULTS: Leukocyte counts showed a relevant perioperative decrease, CRP levels an increase. In the postoperative period, leukocyte counts remained consistently within normal ranges, CRP levels showed three further peaks after about 35, 50, and 80 postoperative days. Analyses of cytokines and chemokines revealed different patterns. Some cytokines, like IL-8, increased about 2-fold in the perioperative period, but then decreased to levels comparable to the preoperative values or even lower. Other cytokines, such as IL-12/IL-23, decreased in the perioperative period and stayed at these levels. Besides perioperative decreases, there were no relevant alterations observed in coagulation parameters. In summary, all parameters showed an unremarkable course with regard to inflammatory responses and coagulation disorders following cardiac xenotransplantation and thus showed the effectiveness of our approach. CONCLUSION: Our preclinical experience with the anti-inflammatory drug therapy proved that controlling of inflammation and coagulation disorders in xenotransplantation is possible and well-practicable under the condition that transmission of pathogens, especially of PCMV/PRV to the recipient is prevented because PCMV/PRV also induces inflammation and coagulation disorders. Our anti-inflammatory regimen should also be applicable and effective in the clinical setting of cardiac xenotransplantation.
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Animales Modificados Genéticamente , Trasplante de Corazón , Inflamación , Papio , Trasplante Heterólogo , Animales , Trasplante Heterólogo/métodos , Trasplante de Corazón/métodos , Porcinos , Inflamación/inmunología , Coagulación Sanguínea/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Humanos , Xenoinjertos/inmunología , Galactosiltransferasas/genética , Inmunosupresores/farmacología , Citocinas/metabolismoRESUMEN
Pediatric heart transplantation is hampered by a chronic shortage of donor organs. This problem is further confounded by graft rejection. Identification of earlier indicators of pediatric graft rejection and development of subsequent strategies to counteract these effects will increase the longevity of transplanted pediatric hearts. Heart transplant reject is due to a complex series of events, resulting in CAV, which is thought to be mediated through a host immune response. However, the earlier events leading to CAV are not very well known. We hypothesize that early events related to ischemia reperfusion injury during pediatric heart transplantation are responsible for CAV and subsequent graft rejection. Identification of the molecular markers of ischemia reperfusion injury and development of subsequent therapies to block these pathways can potentially lead to a therapeutic strategy to reduce CAV and increase the longevity of the transplanted heart. To accomplish this goal, we have developed a perfusable vascular graft model populated with endothelial cells and demonstrated the feasibility of this model to understand the early events of ischemia reperfusion injury.
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Cardiopatías Congénitas , Trasplante de Corazón , Trasplante de Corazón/métodos , Trasplante de Corazón/efectos adversos , Humanos , Cardiopatías Congénitas/cirugía , Daño por Reperfusión Miocárdica/etiología , Células Endoteliales , Rechazo de Injerto , AnimalesRESUMEN
AIM: Heart transplantation (HT) in patients with failing univentricular circulation is often challenging. This is compounded by the ever-increasing number of patients with prior Norwood-type reconstruction of the aorta, large aortic root, and often dense adhesions from multiple prior operations. We aimed to elucidate differences in outcomes of HT in patients with prior univentricular palliations, with and without prior Norwood-type aortic arch reconstruction (ArchRec). METHODS: All patients who underwent HT for failed univentricular palliation during the 1990-2022 period were included in the study. RESULTS: Of 45 patients, 18 had undergone ArchRec. Hospital mortality improved in the recent era (17.4% before 2006 vs 0% after 2006; p=0.11), despite a higher proportion of patients with ArchRec (17.4% before 2006 vs 60.8% after 2006, p=0.002). Patients with ArchRec had a higher number of prior cardiac surgeries (4.1±1.5 vs 3.2±1.3, p=0.04), longer cardiopulmonary bypass time (320±23 vs 242±21 min, p=0.02), more concomitant arch reconstruction (33.3% vs 0%, p=0.02), greater need for post-HT extracorporeal membrane oxygenation (33.3% vs 3.7%; p=0.01) and longer hospital stay (37.1±30.5 days vs 23.6±11.8 days, p=0.04). Freedom from death or retransplantation for all patients was 91%, 73%, 67%, and 53% at 1, 5, 10, and 15-years, respectively. Prior ArchRec, Fontan procedure, and earlier eras were not risk factors for death. CONCLUSIONS: The outcomes of HT after univentricular palliation have improved in recent times and low operative mortality can be achieved. Despite increased complexity, good similar outcomes can be achieved in patients with and without prior arch reconstruction regardless of the palliation stage.
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Trasplante de Corazón , Humanos , Trasplante de Corazón/métodos , Masculino , Femenino , Mortalidad Hospitalaria/tendencias , Lactante , Estudios Retrospectivos , Cuidados Paliativos/métodos , Corazón Univentricular/cirugía , Procedimientos de Norwood/métodos , Tasa de Supervivencia/tendencias , Recién Nacido , Estudios de SeguimientoRESUMEN
In 1984, 21 years after the first liver transplantation, Thomas Starzl achieved a milestone by performing the world's first combined heart-liver transplantation. While still uncommon, the practice of combined heart-liver transplants is on the rise globally. In this review, the authors delve into the current literature on this procedure, highlighting the evolving landscape and key considerations for anesthesiologists. Over the years, there has been a remarkable increase in the number of combined heart-liver transplantations conducted worldwide. This surge is largely attributed to the growing population of adult survivors with single-ventricle physiology, palliated with a Fontan procedure, who later present with late Fontan failure and Fontan-associated liver disease. Research indicates that combined heart-liver transplantation is an effective treatment option, with reported outcomes comparable with isolated heart or liver transplants. Managing anesthesia during a combined heart-liver transplant procedure is challenging, especially in the context of underlying Fontan physiology. International experience in this field remains somewhat limited, with most techniques derived from expert opinions or experiences with single-organ heart and liver transplants. These procedures are highly complex and performed infrequently. As the number of combined heart-liver transplants continues to rise globally, there is a growing need for clear guidance on periprocedural surgical and anesthetic management. Anesthesiologists overseeing these patients must consider multiple factors, balancing various comorbidities with significant hemodynamic and metabolic shifts. An increase in (multicenter) studies focusing on specific interventions to enhance patient and organ outcomes is anticipated in the coming years.
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Anestesia , Trasplante de Corazón , Trasplante de Hígado , Humanos , Trasplante de Hígado/métodos , Trasplante de Hígado/tendencias , Anestesia/métodos , Trasplante de Corazón/métodos , Trasplante de Corazón/tendencias , Procedimiento de Fontan/métodos , Procedimiento de Fontan/tendenciasRESUMEN
Heart transplantation is associated with major hurdles, including the limited number of available organs for transplantation, the risk of rejection due to genetic discrepancies, and the burden of immunosuppression. In this study, we demonstrated the feasibility of permanent genetic engineering of the heart during ex vivo perfusion. Lentiviral vectors encoding for short hairpin RNAs targeting beta2-microglobulin (shß2m) and class II transactivator (shCIITA) were delivered to the graft during two hours of normothermic EVHP. Highly efficient genetic engineering was indicated by stable reporter gene expression in endothelial cells and cardiomyocytes. Remarkably, swine leucocyte antigen (SLA) class I and SLA class II expression levels were decreased by 66% and 76%, respectively, in the vascular endothelium. Evaluation of lactate, troponin T, and LDH levels in the perfusate and histological analysis showed no additional cell injury or tissue damage caused by lentiviral vectors. Moreover, cytokine secretion profiles (IL-6, IL-8, and TNF-α) of non-transduced and lentiviral vector-transduced hearts were comparable. This study demonstrated the ex vivo generation of genetically engineered hearts without compromising tissue integrity. Downregulation of SLA expression may contribute to reduce the immunogenicity of the heart and support graft survival after allogeneic or xenogeneic transplantation.
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Vectores Genéticos , Trasplante de Corazón , Antígenos de Histocompatibilidad Clase I , Lentivirus , Animales , Lentivirus/genética , Trasplante de Corazón/métodos , Vectores Genéticos/genética , Porcinos , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Perfusión/métodos , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/metabolismo , Antígenos de Histocompatibilidad Clase II/inmunología , Microglobulina beta-2/genética , Citocinas/metabolismo , Ingeniería Genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/inmunología , Humanos , ARN Interferente Pequeño/genética , Supervivencia de Injerto/inmunología , Supervivencia de Injerto/genética , Células Endoteliales/metabolismo , Células Endoteliales/inmunología , Proteínas Nucleares , TransactivadoresRESUMEN
Gas-loaded nanocarriers (G-LN) show promise in improving heart transplantation (HTx) outcomes. Given their success in reducing cell death during normothermic hypoxia/reoxygenation (H/R) in vitro, we tested their integration into cardioplegic solutions and static cold storage (SCS) during simulated HTx. Wistar rat hearts underwent four hours of SCS with four G-LN variants: O2- or N2-cyclic-nigerosyl-nigerose-nanomonomers (CNN), and O2- or N2-cyclic-nigerosyl-nigerose-nanosponges (CNN-NS). We monitored physiological-hemodynamic parameters and molecular markers during reperfusion to assess cell damage/protection. Hearts treated with nanomonomers (N2-CNN or O2-CNN) showed improvements in left ventricular developed pressure (LVDP) and a trend towards faster recovery of the rate pressure product (RPP) compared to controls. However, nanosponges (N2-CNN-NS or O2-CNN-NS) did not show similar improvements. None of the groups exhibited an increase in diastolic left ventricular pressure (contracture index) during reperfusion. Redox markers and apoptosis/autophagy pathways indicated an increase in Beclin 1 for O2-CNN and in p22phox for N2-CNN, suggesting alterations in autophagy and the redox environment during late reperfusion, which might explain the gradual decline in heart performance. The study highlights the potential of nanomonomers to improve early cardiac performance and mitigate cold/H/R-induced stunning in HTx. These early improvements suggest a promising avenue for increasing HTx success. Nevertheless, further research and optimization are needed before clinical application.