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1.
Am J Physiol Lung Cell Mol Physiol ; 327(1): L79-L85, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38651234

RESUMO

The pathophysiology of pulmonary hypertension (PH) is not fully understood. Here, we tested the hypothesis that hypoxic perfusion of the vasa vasorum of the pulmonary arterial (PA) wall causes PH. Young adult pig lungs were explanted and placed into a modified ex vivo lung perfusion unit (organ care system, OCS) allowing the separate adjustment of parameters for mechanical ventilation, as well as PA perfusion and bronchial arterial (BA) perfusion. The PA vasa vasorum are branches of the BA. The lungs were used either as the control group (n = 3) or the intervention group (n = 8). The protocol for the intervention group was as follows: normoxic ventilation and perfusion (steady state), hypoxic BA perfusion, steady state, and hypoxic BA perfusion. During hypoxic BA perfusion, ventilation and PA perfusion maintained normal. Control lungs were kept under steady-state conditions for 105 min. During the experiments, PA pressure (PAP) and blood gas analysis were frequently monitored. Hypoxic perfusion of the BA resulted in an increase in systolic and mean PAP, a reaction that was reversible upon normoxic BA perfusion. The PAP increase was reproducible during the second hypoxic BA perfusion. Under control conditions, the PAP stayed constant until about 80 min of the experiment. In conclusion, the results of the current study prove that hypoxic perfusion of the vasa vasorum of the PA directly increases PAP in an ex situ lung perfusion setup, suggesting that PA vasa vasorum function and wall ischemia may contribute to the development of PH.NEW & NOTEWORTHY Hypoxic perfusion of the vasa vasorum of the pulmonary artery directly increased pulmonary arterial pressure in an ex vivo lung perfusion setup. This suggests that the function of pulmonary arterial vasa vasorum and wall ischemia may contribute to the development of pulmonary hypertension.


Assuntos
Hipertensão Pulmonar , Hipóxia , Perfusão , Artéria Pulmonar , Vasa Vasorum , Animais , Vasa Vasorum/patologia , Vasa Vasorum/fisiopatologia , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Suínos , Hipóxia/fisiopatologia , Hipóxia/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/patologia , Pressão Arterial , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/fisiopatologia , Artérias Brônquicas/patologia , Artérias Brônquicas/fisiopatologia , Feminino
2.
Eur J Immunol ; 53(7): e2250097, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37119053

RESUMO

Early kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart-transplanted patients were collected before (pre-), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx. Immunophenotyping was performed using flow cytometry. A significant increase was detected for terminally differentiated (TEMRA) CD4+ or CD8+ T cells and CD56dim CD16+ NK cells immediately after HTx linked to a decrease in naïve CD8+ and CM CD4+ T as well as CD56bright CD16- NK cells, returning to baseline levels at T24. More detailed analyses revealed increased CD69+ CD25- and diminished CD69- CD25- CD4+ or CD8+ T-cell proportions at T0 associated with decreasing S1PR1 expression. Passenger T and NK cells were found at low frequencies only in several patients at T0 and did not correlate with lymphocyte alterations. Collectively, these results suggest an immediate, transient shift toward memory T and NK cells following HTx. Opposite migratory properties of naïve versus memory T and NK cells occurring in the early phase after HTx could underlie these observations and may impinge on the development of allo-specific immune responses.


Assuntos
Linfócitos T CD8-Positivos , Transplante de Coração , Humanos , Células Matadoras Naturais , Subpopulações de Linfócitos , Imunofenotipagem , Antígeno CD56/metabolismo
3.
Am J Transplant ; 23(11): 1740-1756, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37225088

RESUMO

Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient's waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific antiHLA antibodies (pfDSA) have been managed with repeated IgA- and IgM-enriched intravenous immunoglobulin (IgGAM) infusions, usually in combination with plasmapheresis before IgGAM and a single dose of antiCD20 antibody. This retrospective study presents our 9-year experience with patients transplanted with pfDSA. Records of patients transplanted between February 2013 and May 2022 were reviewed. Outcomes were compared between patients with pfDSA and those without any de novo donor-specific antiHLA antibodies. The median follow-up time was 50 months. Of the 1,043 patients who had undergone lung transplantation, 758 (72.7%) did not develop any early donor-specific antiHLA antibodies, and 62 (5.9%) patients exhibited pfDSA. Among the 52 (84%) patients who completed treatment, pfDSA was cleared in 38 (73%). In pfDSA vs control patients and at 8-year follow-up, respectively, graft survival (%) was 75 vs 65 (P = .493) and freedom from chronic lung allograft dysfunction (%) was 63 vs 65 (P = .525). In lung transplantation, crossing the preformed HLA-antibody barrier is safe using a treatment protocol based on IgGAM. Patients with pfDSA have a good 8-year graft survival rate and freedom from chronic lung allograft dysfunction, similar to control patients.


Assuntos
Anticorpos , Transplante de Pulmão , Humanos , Estudos Retrospectivos , Doadores de Tecidos , Antígenos HLA , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Teste de Histocompatibilidade
4.
Transpl Int ; 36: 11089, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547752

RESUMO

Extending selection criteria to face donor organ shortage in heart transplantation (HTx) may increase the risk of mortality. Ex-vivo normothermic perfusion (EVP) limits ischemic time allowing assessment of graft function. We investigated the outcome of HTx in 80 high-risk recipients transplanted with marginal donor and EVP-preserved grafts, from 2016 to 2021. The recipients median age was 57 years (range, 13-75), with chronic renal failure in 61%, impaired liver function in 11% and previous cardiac surgery in 90%; 80% were mechanically supported. Median RADIAL score was 3. Mean graft ischemic time was 118 ± 25 min, "out-of-body" time 420 ± 66 min and median cardiopulmonary bypass (CPB) time 228 min (126-416). In-hospital mortality was 11% and ≥moderate primary graft dysfunction 16%. At univariable analysis, CPB time and high central venous pressure were risk factors for mortality. Actuarial survival at 1 and 3 years was 83% ± 4%, and 72% ± 7%, with a median follow-up of 16 months (range 2-43). Recipient and donor ages, pre-HTx extracorporeal life support and intra-aortic balloon pump were risk factors for late mortality. In conclusion, the use of EVP allows extension of the graft pool by recruitment of marginal donors to successfully perform HTx even in high-risk recipients.


Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Coração , Obtenção de Tecidos e Órgãos , Humanos , Pessoa de Meia-Idade , Doadores de Tecidos , Perfusão , Preservação de Órgãos , Sobrevivência de Enxerto
5.
Transpl Int ; 36: 11071, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37125386

RESUMO

Donor shortages have led transplant centers to extend their criteria for lung donors. Accepting lung donors ≥70 years of age has previously shown good short-term outcomes; however, no mid- and long-term outcome data on these extended criteria donors has been published to date. In this study, all patients who underwent lung transplantation between 06/2010 and 12/2019 were included in the analysis, and the outcomes were compared between patients receiving organs from donors <70 years of age and patients transplanted with lungs from donors ≥70 years of age. Among the 1,168 lung-transplanted patients, 62 patients received lungs from donors ≥70 years of age. The recipient age of those receiving older organs was significantly higher, and they were more likely to suffer from obstructive lung disease. Older donors were exposed to significantly shorter periods of mechanical ventilation prior to donation, had higher Horowitz indices, and were less likely to have smoked. The postoperative time on mechanical ventilation, time on ICU, and total hospital stay were comparable. The overall survival as well as CLAD-free survival showed no differences between both groups in the follow-up period. Utilization of lungs from donors ≥70 years of age leads to excellent mid- and long-term results that are similar to organs from younger donors when the organs from older donors are carefully preselected.


Assuntos
Transplante de Pulmão , Pulmão , Humanos , Resultado do Tratamento , Fatores Etários , Doadores de Tecidos , Estudos Retrospectivos
6.
Artigo em Inglês | MEDLINE | ID: mdl-36858067

RESUMO

BACKGROUND: The minimally invasive mitral valve procedure warrants minimal surgical trauma and might influence the postoperative course positively, especially in old patients. In this retrospective study, we reviewed our experience in minimally invasive mitral valve surgery (miMVS) in patients aged ≥ 75 years. METHODS: In this retrospective cohort study, based on propensity score matching, we compared patients aged ≥75 years with patients aged <75 years who underwent miMVS. The primary endpoint was 30-day mortality. Secondary endpoints were myocardial infarction, stroke, and renal failure. RESULTS: Between January 2011 and February 2021, 761 patients underwent miMVS at our institution. After propensity score matching, a study group (≥75 years, n = 189) and a control group (<75 years, n = 189) were formed. Preoperatively patients ≥75 years more often suffered from NYHA III heart failure (60 vs. 46%; p = 0.013). Their valves were more often frequently replaced (48 vs. 32%; p < 0.001), and their postoperative ventilation time was longer (13 hours vs. 11 hours; p < 0.001). There were no statistically significant differences regarding postoperative stroke (3 vs. 0.6%; p = 0.16), myocardial infarction (0 vs. 1%; p = 0.32), renal insufficiency with new dialysis (5 vs. 4%; p = 0.62), and 30-day mortality (4 vs. 2%; p = 0.56). CONCLUSION: miMVS results in satisfactory early postoperative outcomes in elderly patients.

7.
Am J Transplant ; 22(8): 2064-2076, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35426974

RESUMO

Heart transplantation across preformed donor-specific HLA-antibody barriers is associated with impaired short- and long-term survival. Therefore, in recipients with preformed anti-HLA antibodies, waiting for crossmatch-negative donors is standard practice. As an alternative strategy, recipients with preformed anti-HLA donor specific antibodies have been managed at our institutions with a perioperative desensitization regimen. A retrospective analysis was performed comparing heart transplant recipients with preformed donor-specific HLA-antibodies to recipients without donor-specific antibodies. Recipients with a positive virtual crossmatch received a perioperative desensitization protocol including tocilizumab intraoperatively, plasma exchange and rituximab followed by a six-month course of IgGAM. Among the 117 heart-transplanted patients, 19 (16%) patients underwent perioperative desensitization, and the remaining 98 (84%) patients did not. Cold ischemic time, posttransplant extracorporeal life support for primary graft dysfunction, and intensive care unit stay time did not differ between groups. At 1-year follow-up, freedom from pulsed steroid therapy for presumed rejection and biopsy-confirmed acute cellular or humoral rejection did not differ between groups. One-year survival amounted to 94.7% in the treated patients and 81.4% in the control group. Therefore, heart transplantation in sensitized recipients undergoing a perioperative desensitization appears safe with comparable postoperative outcomes as patients with a negative crossmatch.


Assuntos
Transplante de Coração , Transplante de Rim , Anticorpos , Soro Antilinfocitário , Dessensibilização Imunológica/métodos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Antígenos HLA , Teste de Histocompatibilidade/métodos , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos
8.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362059

RESUMO

Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients (n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.


Assuntos
Injúria Renal Aguda , Hemoglobinas , Transplante de Pulmão , Traumatismo por Reperfusão , Animais , Camundongos , Injúria Renal Aguda/diagnóstico , Creatinina/química , Haptoglobinas/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Isquemia/metabolismo , Rim/metabolismo , Transplante de Pulmão/efeitos adversos , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/metabolismo
9.
Am J Transplant ; 21(12): 3831-3839, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34355495

RESUMO

Allogeneic lung transplantation (LuTx) is considered the treatment of choice for a broad range of advanced, progressive lung diseases resistant to conventional treatment regimens. Ischemia reperfusion injury (IRI) occurring upon reperfusion of the explanted, ischemic lung during implantation remains a crucial mediator of primary graft dysfunction (PGD) and early allo-immune responses. Ex vivo lung perfusion (EVLP) displays an advanced technique aiming at improving lung procurement and preservation. Indeed, previous clinical trials have demonstrated a reduced incidence of PGD following LuTx utilizing EVLP, while long-term outcomes are yet to be evaluated. Mechanistically, EVLP may alleviate donor lung inflammation through reconditioning the injured lung and diminishing IRI through storing the explanted lung in a non-ischemic, perfused, and ventilated status. In this work, we review potential mechanisms of EVLP that may attenuate IRI and improve organ quality. Moreover, we dissect experimental treatment approaches during EVLP that may further attenuate inflammatory events deriving from tissue ischemia, shear forces or allograft rejection associated with LuTx.


Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Traumatismo por Reperfusão , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Preservação de Órgãos , Perfusão , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle
10.
Transpl Int ; 34(3): 474-487, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33393142

RESUMO

This study evaluated the impact of unilateral diaphragm elevation following bilateral lung transplantation on postoperative course. Patient data for all lung transplantations performed at our institution between 01/2010 and 12/2019 were reviewed. Presence of right or left diaphragm elevation was retrospectively evaluated using serial chest X-rays performed while patients were standing and breathing spontaneously. Right elevation was defined by a > 40 mm difference between right and left diaphragmatic height. Left elevation was present if the left diaphragm was at the same height or higher than the right diaphragm. In total, 1093/1213 (90%) lung transplant recipients were included. Of these, 255 (23%) patients exhibited radiologic evidence of diaphragm elevation (right, 55%; left 45%; permanent, 62%). Postoperative course did not differ between groups. Forced expiratory volume in 1 second, forced vital capacity and total lung capacity were lower at 1-year follow-up in patients with permanent than in patients with transient or absent diaphragmatic elevation (P = 0.038, P < 0.001, P = 0.002, respectively). Graft survival did not differ between these groups (P = 0.597). Radiologic evidence of diaphragm elevation was found in 23% of our lung transplant recipients. While lung function tests were worse in patients with permanent elevation, diaphragm elevation did not have any relevant impact on outcomes.


Assuntos
Diafragma , Transplante de Pulmão , Diafragma/diagnóstico por imagem , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Transplante de Pulmão/efeitos adversos , Estudos Retrospectivos , Capacidade Vital
11.
Transpl Int ; 33(5): 503-516, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31903646

RESUMO

In this retrospective study, we analyzed the presence of any association of three CD4+ CD25high regulatory T-cell subpopulations at 3 weeks after lung transplantation with the later incidence of chronic lung allograft dysfunction and graft survival. Among lung-transplanted patients between January 2009 and April 2018, only patients with sufficient T-cell measurements at 3 weeks after transplantation were included into the study. Putative regulatory T cells were defined as CD4+ CD25high T cells, detected in peripheral blood and further analyzed for CD127low , FoxP3+ , and CD152+ using fluorescence-activated cell sorting (FACS) analysis. Associations of regulatory T cells with chronic lung allograft dysfunction (CLAD) and graft survival were evaluated using Cox analysis. During the study period, 724 (71%) patients were included into the study. Freedom from chronic lung allograft dysfunction (CLAD) and graft survival amounted to 66% and 68% at 5 years. At the multivariable analysis, increasing frequencies of CD127low were associated with better freedom from CLAD (hazard ratio for each 1% increase of %CD127low , HR = 0.989, 95% CI = 0.981-0.996, P = 0.003) and better graft survival (HR = 0.991, 95% CI = 0.984-0.999, P = 0.026). A higher frequency of CD127low regulatory T cells in peripheral blood early after lung transplantation estimated a protective effect against chronic lung allograft dysfunction, mortality, and re-transplantation.


Assuntos
Sobrevivência de Enxerto , Transplante de Pulmão , Citometria de Fluxo , Humanos , Subunidade alfa de Receptor de Interleucina-2 , Estudos Retrospectivos , Linfócitos T Reguladores
12.
Am J Transplant ; 19(2): 345-355, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30106236

RESUMO

Ex vivo lung perfusion (EVLP) has become routine practice in lung transplantation. Still, running periods exceeding 12 hours have not been undertaken clinically to date, and it remains unclear how the perfusion solution for extended running periods should be composed and which parameters may predict outcomes. Twenty-four porcine lungs underwent EVLP for 24 hours using the Organ Care System (OCS). Lungs were ventilated and perfused with STEEN's solution enriched with erythrocytes (n = 8), acellular STEEN's solution (n = 8), or low-potassium dextran (LPD) solution enriched with erythrocytes (n = 8). After 24 hours, the left lungs were transplanted into recipient pigs. After clamping of the contralateral lung, the recipients were observed for 6 hours. The most favorable outcome was observed in organs utilizing STEEN solution enriched with erythrocytes as perfusate, whereas the least favorable outcome was seen with LPD solution enriched with erythrocytes for perfusion. Animals surviving the observation period showed lower peak airway pressure (PAWP) and pulmonary vascular resistance (PVR) during OCS preservation. The results suggest that transplantation of lungs following 24 hours of EVLP is feasible but dependent on the composition of the perfusate. PAWP and PVR during EVLP are early and late predictors of transplant outcome, respectively.


Assuntos
Modelos Animais de Doenças , Circulação Extracorpórea/métodos , Transplante de Pulmão/métodos , Pulmão/fisiologia , Preservação de Órgãos/métodos , Perfusão/métodos , Edema Pulmonar/prevenção & controle , Animais , Soluções para Preservação de Órgãos/administração & dosagem , Suínos , Doadores de Tecidos
13.
Transpl Int ; 32(6): 658-667, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30712278

RESUMO

Lung transplantation from donors with fulminant pulmonary arterial embolism as a cause of death remains controversial. An analysis was performed comparing preoperative characteristics and outcomes of 25 donors with a primary diagnosis of pulmonary arterial embolism to 1085 recipients of donor lungs without pulmonary arterial embolism. No early functional impairment of donor lungs with pulmonary embolism was detectable as depicted by the incidence of primary graft dysfunction immediately after surgery (P = 0.66), 24 (P = 0.79), 48 (P = 0.99) and 72 h (P = 0.99) after transplantation. Pulmonary function testing at 1 year (P = 0.003) and at last outpatient control (P < 0.05) showed superior results in the cohort receiving lungs from donors with pulmonary embolism. Incidence of chronic lung allograft dysfunction (CLAD) showed no difference within the first year after lung transplantation, however, 5 year-CLAD free survival was superior in recipients (70.4% vs. 55.1%, P = 0.006) of donor lungs with pulmonary embolism. Overall survival was similar in both groups. Lungs from donors with fulminant pulmonary embolism prior to brain death can safely be used for lung transplantation without impairing postoperative outcomes. Lung function testing shows favorable midterm results in recipients of donor lungs with pulmonary embolism.


Assuntos
Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Pulmão/fisiopatologia , Pulmão/cirurgia , Embolia Pulmonar/fisiopatologia , Adulto , Idoso , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Disfunção Primária do Enxerto , Embolia Pulmonar/mortalidade , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Resultado do Tratamento , Adulto Jovem
14.
Thorac Cardiovasc Surg ; 67(8): 637-643, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30380574

RESUMO

BACKGROUND: To minimize the surgical damage, minimally invasive mitral valve surgery (MIMVS) has become the therapy of choice. However, this approach is technically more challenging, especially in endocarditis. The data on MIMVS in endocarditis are scarce, we therefore retrospectively analyzed the result at our institute. METHODS: From January 2011 and July 2017, 420 MIMVS were performed, out of which 44 (10%) were for endocarditis. Mean age was 55 ± 17 years and 41% (n = 18) were male. RESULTS: Euroscore II was 7.3 (range: 2-38). Operation times, cardiopulmonary bypass times, and clamp times were 230 (±77), 158 (±56), and 84 (±39) minutes, respectively. Seven cases (16%) were cardiac redo operations. Mitral valve repair and replacement was performed in 46 (n = 20) and 54% (n = 24) of patients, respectively. Overall in-hospital mortality, apoplexy, and reoperation rates (all for bleeding) were 7 (n = 3), 0 (n = 0), and 11% (n = 5), respectively. New onset of dialysis was required in three patients (7%). No patient developed superficial wound infection. Overall intensive care unit and hospital stay was 3 (±3) and 24 (±32) days, respectively. CONCLUSION: MIMVS can be performed with acceptable outcome and low perioperative morbidity in patients with mitral valve endocarditis. Especially absence of any postoperative wound infections and low rate of endocarditis recurrence; use of MIMVS must be encouraged as an eligible approach in most cases.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Endocardite Bacteriana/cirurgia , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Adulto , Idoso , Antibacterianos/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Valva Mitral/microbiologia , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/microbiologia , Insuficiência da Valva Mitral/mortalidade , Duração da Cirurgia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Recidiva , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
Am J Transplant ; 18(9): 2295-2304, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29719115

RESUMO

This retrospective study presents our 4-year experience of preemptive treatment of early anti-HLA donor specific antibodies with IgA- and IgM-enriched immunoglobulins. We compared outcomes between patients with antibodies and treatment (case patients) and patients without antibodies (control patients). Records of patients transplanted at our institution between March 2013 and November 2017 were reviewed. The treatment protocol included one single 2 g/kg immunoglobulin infusion followed by successive 0.5 g/kg infusions for a maximum of 6 months, usually combined with a single dose of anti-CD20 antibody and, in case of clinical rejection or positive crossmatch, with plasmapheresis or immunoabsorption. Among the 598 transplanted patients, 128 (21%) patients formed the case group and 452 (76%) the control group. In 116 (91%) patients who completed treatment, 106 (91%) showed no antibodies at treatment end. Fourteen (13%) patients showed antibody recurrence thereafter. In case versus control patients and at 4-year follow-up, respectively, graft survival (%) was 79 versus 81 (P = .59), freedom (%) from biopsy-confirmed rejection 57 versus 53 (P = .34), and from chronic lung allograft dysfunction 82 versus 78 (P = .83). After lung transplantation, patients with early donor-specific antibodies and treated with IgA- and IgM-enriched immunoglobulins had 4-year graft survival similar to patients without antibodies and showed high antibody clearance.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Imunoglobulinas Intravenosas/administração & dosagem , Isoanticorpos/imunologia , Transplante de Pulmão/métodos , Doadores de Tecidos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Teste de Histocompatibilidade , Humanos , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Imunoglobulinas Intravenosas/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
16.
Respir Res ; 19(1): 238, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30509256

RESUMO

BACKGROUND: Ex vivo lung perfusion (EVLP) is used by an increasing number of transplant centres. It is still controversial whether an acellular or cellular (erythrocyte enriched) perfusate is preferable. The aim of this paper was to evaluate whether acellular (aEVLP) or cellular EVLP (cEVLP) preserves functional lung ultrastructure better and to generate a hypothesis regarding possible underlying mechanisms. METHODS: Lungs of 20 pigs were assigned to 4 groups: control, ischaemia (24 h), aEVLP and cEVLP (both EVLP groups: 24 h ischaemia + 12 h EVLP). After experimental procedures, whole lungs were perfusion fixed, samples for light and electron microscopic stereology were taken, and ventilation, diffusion and perfusion related parameters were estimated. RESULTS: Lung structure was well preserved in all groups. Lungs had less atelectasis and higher air content after EVLP. No significant group differences were found in alveolar septum composition or blood-air barrier thickness. Small amounts of intraalveolar oedema were detected in both EVLP groups but significantly more in aEVLP than in cEVLP. CONCLUSIONS: Both EVLP protocols supported lungs well for up to 12 h and could largely prevent ischaemia ex vivo reperfusion associated lung injury. In both EVLP groups, oedema volume remained below the level of functional relevance. The group difference in oedema formation was possibly due to inferior septal perfusion in aEVLP.


Assuntos
Citratos/administração & dosagem , Pulmão/fisiologia , Pulmão/ultraestrutura , Modelos Animais , Perfusão/métodos , Preservação de Tecido/métodos , Animais , Feminino , Pulmão/efeitos dos fármacos , Masculino , Respiração com Pressão Positiva/métodos , Distribuição Aleatória , Suínos
17.
Thorac Cardiovasc Surg ; 66(7): 545-551, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29490388

RESUMO

BACKGROUND: Minimally invasive mitral valve surgery (MIMVS) is superior to "classical" mitral valve surgery via a sternotomy regarding wound healing and postoperative pain. It is however a more challenging procedure. Patients' preference is leading clearly toward minimally invasive approaches, and surgeons are driven by upcoming new technologies in interventional procedures such as the MitraClip. Especially in re-do cases, the access via right mini-thoracotomy, as previously non-operated situs, is a possible advantage over a re-sternotomy. We therefore retrospectively analyzed our result regarding MIMVS in re-do cases at our institute. METHODS: From January 2011 and June 2016, 33 operations were MIMVS re-do procedures. Mean age was 60 years (±16 years), and 51% were male. RESULTS: Sixty-one percent were elective cases, 29% were urgent cases, and 9% were emergency operations. Operation times, cardiopulmonary bypass (CPB) times, and clamp times were 235 minutes (±51 min), 149 minutes (±42 min), and 62 minutes (±45min), respectively. Mitral valve repair and replacement was performed in 24% (n = 8) and 76% (n = 25), respectively. Overall in-hospital mortality, apoplexy, and re-operation rates (all for bleeding) were 0% (n = 0), 3% (n = 1), and 9% (n = 3). New onset of dialysis was required in two (6%) patients. Two (6%) patients developed superficial wound infection. Overall intensive care unit (ICU) and hospital stay was 3 days (±4 days) and 15 days (±7 days), respectively. CONCLUSION: MIMVS for re-do cases can be performed with minimal mortality and morbidity and therefore represents a safe alternative to conventional mitral valve surgery in cardiac re-do operations. However, postoperative morbidity is highly dependent on preoperative patient status.


Assuntos
Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Anuloplastia da Valva Mitral , Valva Mitral/cirurgia , Toracotomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ponte Cardiopulmonar , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/mortalidade , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Anuloplastia da Valva Mitral/efeitos adversos , Anuloplastia da Valva Mitral/mortalidade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Toracotomia/efeitos adversos , Toracotomia/mortalidade , Fatores de Tempo , Resultado do Tratamento
18.
Transpl Int ; 30(4): 420-431, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28095640

RESUMO

Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism.


Assuntos
Transplante de Coração/métodos , Transplante de Pulmão/métodos , Tolerância ao Transplante , Aloenxertos/imunologia , Animais , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Tolerância Imunológica , Terapia de Imunossupressão , Leucócitos/metabolismo , Masculino , Baço/citologia , Baço/metabolismo , Suínos , Porco Miniatura , Tacrolimo/farmacologia , Fatores de Tempo , Doadores de Tecidos , Quimeras de Transplante , Transplante Homólogo
19.
Transpl Int ; 29(1): 88-97, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26264867

RESUMO

Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition.


Assuntos
Isquemia Fria/métodos , Circulação Extracorpórea/métodos , Transplante de Pulmão/métodos , Pulmão/patologia , Preservação de Órgãos/métodos , Animais , Modelos Animais de Doenças , Feminino , Citometria de Fluxo/métodos , Rejeição de Enxerto , Sobrevivência de Enxerto , Imuno-Histoquímica , Transplante de Pulmão/efeitos adversos , Soluções para Preservação de Órgãos/farmacologia , Perfusão/métodos , Distribuição Aleatória , Medição de Risco , Sensibilidade e Especificidade , Sus scrofa , Suínos , Fatores de Tempo , Doadores de Tecidos
20.
Transplant Proc ; 56(4): 802-805, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582719

RESUMO

INTRODUCTION: Chronic renal failure is one of the most common complications after solid organ transplantation. It is associated with multiple pre-, peri-, and post-transplant factors. In some patients, the available methods of conservative treatment are insufficient and kidney transplantation (KTx) is necessary. The aim of this study was to present our experience in the treatment of renal failure by KTx after lung transplantation (LTx). METHODS: Our study is a single-center retrospective review of clinical data of all 7 LTx recipients who underwent a KTx between the years 2013 and 2021. Patients' clinical condition, pulmonary function, renal function, and survival were examined. RESULTS: There were a total of 7 patients with medium age 36 years (±15). In 3 patients, the period of time from LTx to KTx was less than 3 years, and in 4 of them less than 13 years. Dialysis therapy was required in 4 patients. One patient had pre-LTx renal disease, while 6 patients had renal dysfunction related to post-transplant factors, including the use of calcineurin inhibitors. CONCLUSIONS: Renal protection is a very important aspect among LTx recipients; therefore, physicians must show a holistic and individual approach to patients and minimize exposure to nephrotoxic medication. Patients at high risk of developing chronic renal failure should be identified and, if required, renal replacement therapy should be initiated, including KTx.


Assuntos
Falência Renal Crônica , Transplante de Rim , Transplante de Pulmão , Humanos , Transplante de Pulmão/efeitos adversos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Masculino , Adulto , Feminino , Falência Renal Crônica/cirurgia , Pessoa de Meia-Idade , Adulto Jovem , Resultado do Tratamento
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