RESUMO
To test the alternative possible locations for the placement of a liver graft and the relevant surgical technique issues, we developed a porcine model of auxiliary partial heterotopic liver transplantation (APHLT) and evaluated the difference between 2 styles of liver transplantation, either subhepatic fossa or splenic fossa APHLT, by comparing survival and biochemical indexes. Thirty-eight miniature pigs were randomly divided into 2 groups. A left hemihepatic graft without the middle hepatic vein (HV) was procured from the living donor. In group A (n = 9), an 8 mm diameter polytetrafluoroethylene (PTFE) graft approximately 2.5 cm long was connected to the left HV while another PTFE graft of the same size was connected to the left portal vein (PV). The liver graft was implanted in the right subhepatic fossa following splenectomy and right nephrectomy. In group B (n = 10), a PTFE graft of the same size was connected to the left HV while the liver graft was implanted in the splenic fossa following splenectomy and left nephrectomy. Survival rate and complications were observed at 2 weeks after transplantation. Data were collected from 5 animals in group A and 6 animals in group B that survived longer than 2 weeks. The liver function and renal function of the recipients returned to normal at 1 week after surgery in both groups. Eighty-eight percent (14/16) of the PTFE grafts remained patent at 2 weeks after surgery, but 44% of the PTFE grafts (7/16) developed mural thrombus. No significant differences in the survival rate and biochemistry were found between the 2 groups. In conclusion, the splenic fossa APHLT can achieve beneficial outcomes similar to the subhepatic fossa APHLT in miniature pigs, although it also has a high morbidity rate due to hepatic artery thrombosis, PV thrombosis, and PTEF graft mural thrombus formation. Liver Transplantation 22 812-821 2016 AASLD.
Assuntos
Transplante de Fígado/métodos , Complicações Pós-Operatórias/etiologia , Trombose/etiologia , Transplante Heterotópico/métodos , Enxerto Vascular/métodos , Aloenxertos/patologia , Animais , Prótese Vascular , Estudos de Viabilidade , Feminino , Artéria Hepática/patologia , Veias Hepáticas/cirurgia , Humanos , Estimativa de Kaplan-Meier , Fígado/irrigação sanguínea , Fígado/patologia , Fígado/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Doadores Vivos , Modelos Animais , Nefrectomia/métodos , Politetrafluoretileno , Veia Porta/cirurgia , Distribuição Aleatória , Esplenectomia/métodos , Suínos , Porco Miniatura , Transplante Heterotópico/efeitos adversos , Transplante Heterotópico/mortalidade , Enxerto Vascular/efeitos adversos , Enxerto Vascular/instrumentação , Enxerto Vascular/mortalidadeRESUMO
INTRODUCTION: More than 3 decades have passed since the first heterotopic heart transplantation (HHT) was reported. Nowadays, this surgical technique is used rarely, and only in patients who do not qualify for standard orthotopic heart transplantation (OHT). Current indications mainly comprise refractory pulmonary hypertension and a donor-recipient size mismatch (>20%). The objective of this study was to analyze the United States experience with HHT. PATIENTS AND METHODS: The United Network for Organ Sharing (UNOS) database between 1987 and 2007 was analyzed. Patients who underwent heart transplantation were enrolled in this study. Patients with missing transplant dates or history of retransplantation were excluded. RESULTS: A total of 41,379 patients underwent OHT and 178 HHT; 32,361 and 111 patients, respectively, were enrolled. Overall 1-, 5-, and 10-year survival was significantly (P < .001) better in OHT (87.7%, 74.4%, 54.4%) than HHT patients (83.8%, 59%, 35.1%). Survival in patients with transpulmonary gradients (TPG) >15 mmHg was 86.6 %, 73.3%, and 57.4% in the OHT and 93.8%, 64.8%, and 48.6% in the HHT group (P = .35). Pretransplant criteria (HHT versus OHT) with statistically significant differences (P < .05) were as follows (mean + SD): recipient weight, 78.9 + 19.9 versus 74.1 + 23.4 kg; recipient height, 174.9 + 13.9 versus 168 + 25.1 cm; and TPG 12.1 + 7.2 versus 9.6 + 6.3 mmHg. CONCLUSIONS: The results show that HHT remains a feasible option in a highly selected patient population, with overall good results.
Assuntos
Rejeição de Enxerto/mortalidade , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Transplante de Coração/mortalidade , Doadores de Tecidos/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Comorbidade , Intervalo Livre de Doença , Feminino , Transplante de Coração/estatística & dados numéricos , Transplante de Coração/tendências , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida , Transplante Heterotópico/mortalidade , Transplante Heterotópico/estatística & dados numéricos , Transplante Heterotópico/tendências , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Some of the 600,000 patients with solid organ allotransplants need reconstruction with a composite tissue allotransplant, such as the hand, abdominal wall, or face. The aim of this study was to develop a rat model for assessing the effects of a secondary composite tissue allotransplant on a primary heart allotransplant. METHODS: Hearts of Wistar Kyoto rats were harvested and transplanted heterotopically to the neck of recipient Fisher 344 rats. The anastomoses were performed between the donor brachiocephalic artery and the recipient left common carotid artery, and between the donor pulmonary artery and the recipient external jugular vein. Recipients received cyclosporine A for 10 days only. Heart rate was assessed noninvasively. The sequential composite tissue allotransplant consisted of a 3 x 3-cm abdominal musculocutaneous flap harvested from Lewis rats and transplanted to the abdomen of the heart allotransplant recipients. The abdominal flap vessels were connected to the femoral vessels. No further immunosuppression was administered following the composite tissue allotransplant. Ten days after composite tissue allotransplantation, rejection of the heart and abdominal flap was assessed histologically. RESULTS: The rat survival rate of the two-stage transplant surgery was 80 percent. The transplanted heart rate decreased from 150 +/- 22 beats per minute immediately after transplant to 83 +/- 12 beats per minute on day 20 (10 days after stopping immunosuppression). CONCLUSIONS: This sequential allotransplant model is technically demanding. It will facilitate investigation of the effects of a secondary composite tissue allotransplant following primary solid organ transplantation and could be useful in developing future immunotherapeutic strategies.
Assuntos
Transplante de Coração/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Parede Torácica/cirurgia , Transplante Heterotópico/métodos , Animais , Modelos Animais de Doenças , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Frequência Cardíaca , Transplante de Coração/mortalidade , Imunossupressores/uso terapêutico , Masculino , Pescoço , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos WKY , Transplante de Pele/métodos , Taxa de Sobrevida , Transplante Heterotópico/mortalidade , Transplante Homólogo , Resultado do TratamentoRESUMO
BACKGROUND: Along the past few years the number of papers on heterotopic cardiac transplant has been very scarce in the medical literature, including at the international level; this is particularly true in reference to the long term follow-up of these patients and the reason which led to the presentation of our report. OBJECTIVE: To report the initial clinical experience and late evolution of 4 patients undergoing heterotopic heart transplantation, indications for this procedure and its major complications. METHODS: The surgeries were performed between 1992 and 2001, and all had as indication for heterotopic transplantation the PVR, which ranged from 4.8 WU to 6.5 WU, with a transpulmonary gradient above 15 mmHg. In the 3rd patient, a direct anastomosis between the pulmonary arteries was performed without the use of a prostetic tube, and a mitral valvuloplasty and a LV aneurysmectomy were performed in the native heart. The immediate immunosuppressive regimens were double, with cyclosporine and azathioprine in the first 3 patients, and cyclosporine and mycophenolate mofetil in the 4th patient. RESULTS: One immediate death occurred from graft failure, one death occurred after 2 (1/2) years, from endocarditis in an intraventricular thrombus in the native heart, and a third death occurred 6 years after transplantation, from post-operative complications of the aortic valve surgery in the native heart. The remaining patient is well, 15 years after the transplantation. This patient is in functional class II (NYHA), 6 years after a surgical occlusion of the native heart aortic valve. CONCLUSION: Heterotopic heart transplantation results are inferior to those of orthotopic heart transplantation because they present higher RVP. The intraventricular thrombi, in the native heart, which require prolonged anticoagulation, and aortic valve complications, also in the native heart, may require surgical treatment. However, a patient's 15-year survival has demonstrated a long-term effectiveness of this option for selected patients.
Assuntos
Transplante de Coração/efeitos adversos , Hipertensão Pulmonar/complicações , Transplante Heterotópico/efeitos adversos , Adulto , Seguimentos , Transplante de Coração/mortalidade , Humanos , Hipertensão Pulmonar/patologia , Pessoa de Meia-Idade , Transplante Heterotópico/métodos , Transplante Heterotópico/mortalidade , Resultado do TratamentoRESUMO
FUNDAMENTO: Nos últimos anos o numero de artigos sobre transplante cardíaco heterotópico tem sido escasso na literatura, inclusive internacional, e em particular do seguimento de longo prazo destes pacientes, o que levou ao presente relato. OBJETIVO: Relatar a experiência clínica inicial e evolução tardia de quatro pacientes submetidos a transplante cardíaco heterotópico, sua indicação e principais complicações. MÉTODOS: As cirurgias ocorreram entre 1992 e 2001, sendo que a indicação de transplante heterotópico, em todas, foi pela RVP, variável de 4,8UW a 6.5UW, com gradiente transpulmonar acima de 15mmHg. No 3º paciente, foi realizada uma anastomose direta entre as artérias pulmonares sem emprego de tubo protético e, no coração nativo, foi realizada uma valvoplastia mitral e aneurismectomia de ventrículo esquerdo (VE). O esquema imunossupressor imediato foi duplo com ciclosporina e azatioprina nos três primeiros pacientes e ciclosporina e micofenolato mofetil no 4º paciente. RESULTADOS: Um óbito imediato por falência do enxerto, um óbito após dois anos e meio por endocardite em trombo intraventricular no coração nativo, e um terceiro óbito seis anos após o transplante, por complicações pós-operatórias de cirurgia na valva aórtica do coração nativo. O remanescente, 15 anos após o transplante, encontra-se bem, em classe funcional II (NYHA), seis anos após a oclusão cirúrgica da valva aórtica do coração nativo. CONCLUSÃO: O transplante cardíaco heterotópico é um procedimento com resultado inferior ao transplante cardíaco ortotópico, por apresentarem maior RVP. Os trombos intraventriculares no coração nativo, que exigem anticoagulação prolongada, bem como as complicações de válvula aórtica, também no coração nativo, podem exigir tratamento cirúrgico. Entretanto, em um paciente, a sobrevida de 15 anos mostrou a eficácia de longo prazo desse tipo de alternativa, para pacientes selecionados.
BACKGROUND: Along the past few years the number of papers on heterotopic cardiac transplant has been very scarce in the medical literature, including at the international level; this is particularly true in reference to the long term follow-up of these patients and the reason which led to the presentation of our report. OBJECTIVE: To report the initial clinical experience and late evolution of 4 patients undergoing heterotopic heart transplantation, indications for this procedure and its major complications. METHODS: The surgeries were performed between 1992 and 2001, and all had as indication for heterotopic transplantation the PVR, which ranged from 4.8 WU to 6.5WU, with a transpulmonary gradient above 15mmHg. In the 3rd patient, a direct anastomosis between the pulmonary arteries was performed without the use of a prostetic tube, and a mitral valvuloplasty and a LV aneurysmectomy were performed in the native heart. The immediate immunosuppressive regimens were double, with cyclosporine and azathioprine in the first 3 patients, and cyclosporine and mycophenolate mofetil in the 4th patient. RESULTS: One immediate death occurred from graft failure, one death occurred after 2 ½ years, from endocarditis in an intraventricular thrombus in the native heart, and a third death occurred 6 years after transplantation, from post-operative complications of the aortic valve surgery in the native heart. The remaining patient is well, 15 years after the transplantation. This patient is in functional class II (NYHA), 6 years after a surgical occlusion of the native heart aortic valve. CONCLUSION: Heterotopic heart transplantation results are inferior to those of orthotopic heart transplantation because they present higher RVP. The intraventricular thrombi, in the native heart, which require prolonged anticoagulation, and aortic valve complications, also in the native heart, may require surgical treatment. However, a patient's 15-year survival has demonstrated ...
FUNDAMENTO: En los últimos años el número de artículos sobre trasplante cardíaco heterotópico y, en particular, del seguimiento a largo plazo de estos pacientes, ha sido escaso en la literatura, inclusive internacional, lo que llevó al presente relato. OBJETIVO: Relatar la experiencia clínica inicial y la evolución tardía de cuatro pacientes sometidos a trasplante cardíaco heterotópico, su indicación y principales complicaciones. MÉTODOS: Las cirugías se realizaron entre 1992 y 2001, y la indicación de trasplante heterotópico, en todas, fue mediante RVP, variable de 4,8 UW; a 6.5 UW, con gradiente transpulmonar superior a 15 mmHg. En el tercer paciente, se realizó una anastomosis directa entre las arterias pulmonares sin empleo de tubo prostético, y, en el corazón nativo, se realizó una valvuloplastia mitral y aneurismectomía de VI. El esquema inmunosupresor inmediato fue doble, con ciclosporina y azatioprina en los tres primeros pacientes y ciclosporina y micofenolato mofetil en el cuarto paciente. RESULTADOS: Un óbito inmediato por falla del injerto, un óbito luego de dos años y medio por endocarditis en trombo intraventricular en el corazón nativo, y un tercer óbito seis años después del trasplante, por complicaciones postoperatorias de una cirugía en la válvula aórtica del corazón nativo. El restante, 15 años después del trasplante, se encuentra bien, en clase funcional II (NYHA), seis años después de una oclusión quirúrgica de la válvula aórtica del corazón nativo. CONCLUSIÓN: El trasplante cardíaco heterotópico es un procedimiento con resultado inferior al trasplante cardíaco ortotópico, por presentar mayor RVP. Los trombos intraventriculares en el corazón nativo, que exige anticoagulación prolongada, así como las complicaciones de válvula aórtica, también en el corazón nativo, pueden exigir tratamiento quirúrgico. Sin embargo, en un paciente, la sobrevida de 15 años mostró la eficacia a largo plazo de este tipo de alternativa, ...
Assuntos
Adulto , Humanos , Pessoa de Meia-Idade , Transplante de Coração/efeitos adversos , Hipertensão Pulmonar/complicações , Transplante Heterotópico/efeitos adversos , Seguimentos , Transplante de Coração/mortalidade , Hipertensão Pulmonar/patologia , Resultado do Tratamento , Transplante Heterotópico/métodos , Transplante Heterotópico/mortalidadeRESUMO
OBJECTIVE: To develop a surgical method for establishment of a heterotopic uterine transplantation model in syngeneic rats and evaluate its feasibility. METHODS: Thirty pairs of Wistar rats aged 8 - 10 weeks were used as donor and recipient. Heterotopic uterine transplantation was conducted, and the duration of the operation was recorded. The recipient rats were killed 7 days after surgery. The morphology of the transplanted uteri was evaluated. RESULTS: Thirty heterotopic uterine transplantations were conducted. The survival rate increased from 40% (6/15) in the first 15 pairs of recipient rats to 75% (12/15) in the last 15 pairs of recipient rats. Among the 18 living recipient rats, 15 transplanted uteri were viable. The viable rate of uterine transplantation was 83%. Compared with the first 15 pairs of rats, the duration of donor procedures, recipient procedures vascular anastomosis and the total time of the surgery decreased to (65 +/- 10) min, (89 +/- 22) min, (36 +/- 8) min and (154 +/- 23) min respectively in the last 15 pairs of rats. CONCLUSION: It is feasible to establish the model of heterotopic uterine transplantation in Wistar rats.
Assuntos
Transplante de Tecidos/métodos , Útero/cirurgia , Útero/transplante , Animais , Feminino , Humanos , Modelos Animais , Distribuição Aleatória , Ratos , Ratos Wistar , Transplante de Tecidos/mortalidade , Transplante Heterotópico/métodos , Transplante Heterotópico/mortalidadeRESUMO
BACKGROUND: Current studies provide evidence that a small G protein, RhoAp21, and its target protein, Rho-associated coiled-coil forming protein kinase (ROCK), regulate not only cell shape but also cell migration. However, contribution of Rho/ROCK signaling to graft rejection is unknown. The purpose of this study was to evaluate the inhibitory effect of Y-27632, a highly selective ROCK inhibitor, on rejection of heterotopic cardiac transplantation in mice. METHODS: BALB/c (H-2(d)) hearts were transplanted into C3H/He (H-2(k)) as allografts that were full histoincompatibility combinations. The recipients received several doses of Y-27632, commencing 1 day before cardiac transplantation until rejection. We used immunohistochemical study to detect the expression of myocardial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and we immunoenzymatically measured serum interleukin (IL)-6. Furthermore, we evaluated cardiac allograft vasculopathy treated with either FK506 or Y-27632 at Day 100. RESULTS: The Y-27632-treated (2 mg/kg/day) allografts prolonged the mean survival time (49.6 +/- 10.1 days, n = 12) as compared with the untreated allografts (8.1 +/- 0.4 days, n = 7, p < 0.001). Histologic examinations of the Y-27632-treated allografts at Day 7 showed greatly reduced leukocyte infiltration compared with the untreated allografts. The Y-27632-treated allografts revealed faint expression of myocardial ICAM-1 and VCAM-1 at Day 7. The serum IL-6 levels also decreased in the Y-27632-treated mice. In the long-surviving Y-27632-treated allografts at Day 100, we saw neither active rejection nor apparent thickening of vascular intima. CONCLUSION: Our results suggest that ROCK plays a major role in cardiac rejection in the BALB/c-to-C3H/He mouse model. Inhibition of this Rho/ROCK signaling may be an alternative therapeutic option for managing acute and chronic rejection.
Assuntos
Amidas/antagonistas & inibidores , Inibidores Enzimáticos/uso terapêutico , Transplante de Coração/mortalidade , Piridinas/antagonistas & inibidores , Transplante Heterotópico/mortalidade , Animais , Anticorpos/efeitos dos fármacos , Anticorpos/imunologia , Modelos Animais de Doenças , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração/imunologia , Transplante de Coração/patologia , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/imunologia , Interleucina-6/sangue , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Modelos Cardiovasculares , Transplante Heterotópico/patologia , Transplante Homólogo , Molécula 1 de Adesão de Célula Vascular/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/imunologiaRESUMO
The induction of immune hyporesponsiveness in transplantation is a complex interaction between the immune system and the alloantigen. The route by which an antigen is introduced to the immune system plays an important role in the immune response. Antigen delivered via the portal circulation has the ability to induce T-cell hyporesponsiveness. In this study we examined the mechanism responsible for the induction of hyporesponsiveness by assessing immune response following portal vein (pv) injection of donor alloantigen. C57B1/6 mice were immunized via pv with splenic mononuclear cells (SMNC) from BALB/c mice. The recipient immune response was assessed in vivo by murine heterotopic heart transplant survival. SMNC and hepatic nonparenchymal cells (NPC) were isolated from pv immunized animals and used as regulatory cells in a one-way mixed lymphocyte culture (MLC) as a measure of in vitro recipient responder SMNC proliferation. Survival of murine heterotopic heart transplants was prolonged following pv injection of alloantigen (p < .04 compared to nonimmunized or systemically immunized mice). Stimulation of responder SMNCs isolated from pv immunized mice resulted in an antigen-specific hyporesponsiveness (p < .05 compared with nonimmunized or systemically immunized mice). Cocultures of responder SMNCs from nonimmunized (naive) mice with hepatic NPC from previously pv immunized mice resulted in attenuation of T-cell proliferation in MLR following stimulation with donor alloantigen (p < .05 compared to coculture with NPC from nonimmunized mice or SMNC from pv immunized mice). These data would suggest that the hepatic NPC plays an important role in the regulation of the immune response. With further identification of cell subtypes responsible for induction of hyporesponsiveness, future therapies may be directed at these specific targets, thereby minimizing the harmful side effects of current immunosuppressive therapies.
Assuntos
Sobrevivência de Enxerto/imunologia , Transplante de Coração/métodos , Hepatócitos/imunologia , Isoantígenos/farmacologia , Transplante Heterotópico/métodos , Animais , Divisão Celular/imunologia , Feminino , Transplante de Coração/imunologia , Transplante de Coração/mortalidade , Hepatócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Veia Porta , Especificidade da Espécie , Baço/citologia , Taxa de Sobrevida , Transplante Heterotópico/imunologia , Transplante Heterotópico/mortalidade , Transplante HomólogoRESUMO
BACKGROUND: Surgery, percutaneous cholangiography, and endoscopic retrograde cholangiopancreatography (ERCP) have been used in the management of biliary complications after orthotopic liver transplantation with varied results. We assessed the role of ERCP in the diagnosis, treatment, and outcome of post-orthotopic liver transplantation biliary complications. METHODS: We retrospectively reviewed the records of 260 patients who underwent orthotopic liver transplantation. We examined the number of patients referred for ERCP and the indication, diagnosis, therapeutic intervention, success, and complication rate of ERCP post orthotopic liver transplantation. We compared the survival and retransplantation rates of the patients who underwent ERCP with a control group of post-orthotopic liver transplantation patients not undergoing ERCP. RESULTS: Of the 260 patients undergoing orthotopic liver transplantation, 64 (24.6%) underwent 137 ERCPs. Two categories of indications for ERCP were identified: bile leak (n = 31) and obstruction (n = 39). ERCP identified the site of the bile leak in 27 of 31 cases (87.1%) and the leak was treated by endoscopic means in 26 of 31 (83.9%). Treatment success differed significantly based on location of the leak (T tube, 95.2% vs. anastomosis, 42.9%; p = 0. 009). ERCP identified the site of obstruction in 37 of 39 cases (94. 9%) and obstruction was relieved by endoscopic means in 25 of 35 cases (71.4%). ERCP was significantly less successful in the treatment of biliary casts (25.0%, p = 0.048). There was no difference in survival or retransplantation between patients who did and did not undergo ERCP. CONCLUSION: ERCP should be the primary method for diagnosis and treatment of post-orthotopic liver transplantation biliary complications. Endoscopic therapy is safe and effective for the majority of post-orthotopic liver transplantation complications and temporizes management for those complications that may require surgery.
Assuntos
Doenças Biliares/diagnóstico , Doenças Biliares/terapia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Transplante de Fígado/efeitos adversos , Transplante Heterotópico/efeitos adversos , Adolescente , Adulto , Idoso , Doenças Biliares/etiologia , Doenças Biliares/mortalidade , Estudos de Casos e Controles , Colangiopancreatografia Retrógrada Endoscópica/estatística & dados numéricos , Feminino , Seguimentos , Rejeição de Enxerto , Humanos , Incidência , Hepatopatias/diagnóstico , Hepatopatias/cirurgia , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Heterotópico/mortalidadeRESUMO
Heterotopic heart transplantation was initially developed in the laboratory for experimental transplantation. While it was more widely utilized in the pre-cyclosporine era to provide adjunct circulatory support in combination with the native heart, associated complications as well as improved long-term graft survival have now established orthotopic transplantation as the procedure of choice. Heterotopic heart transplantation is currently reserved for highly selected patients. The technique is only performed at selected transplantation centers, and indications include significant donor recipient size mismatch or irreversible recipient pulmonary hypertension. The foreseeable introduction of clinical porcine xenotransplantation may lead to renewed interest in the technique of heterotopic heart transplantation as a bridge to potential native heart recovery or allotransplantation in selected patients.
Assuntos
Transplante de Coração/métodos , Transplante Heterólogo/métodos , Transplante Heterotópico/métodos , Adolescente , Adulto , Animais , Modelos Animais de Doenças , Transplante de Coração/mortalidade , Humanos , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Análise de Sobrevida , Suínos , Transplante Heterólogo/mortalidade , Transplante Heterotópico/mortalidadeAssuntos
Reação Enxerto-Hospedeiro , Intestino Delgado/transplante , Transplante Homólogo/fisiologia , Animais , Intestino Delgado/fisiologia , Transfusão de Linfócitos , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos , Taxa de Sobrevida , Transplante Heterotópico/imunologia , Transplante Heterotópico/mortalidade , Transplante Heterotópico/fisiologia , Transplante Homólogo/imunologia , Transplante Homólogo/mortalidadeRESUMO
The occurrence of graft-versus-host disease (GvHD) following small bowel transplantation (SBTx) can be tuned by the recipient's initial natural killer (NK) cell activity, which modifies the immunogeneic balance between donor and host immunocompetent cells. This study was aimed to investigate the role of host NK cells on the incidence and severity of GvHD following SBTx. Intraperitoneal administration of 50 microl ascites fluid of the highly specific anti-NKR-P1 monoclonal antibody (mAb) 3.2.3 into F1 recipient animals on three consecutive days prior to SBTx was performed to suppress NK activity in F1 hybrids. In vivo treatment with 3.2.3 mAb effectively depleted recipient NK activity for at least 10 days in spleens and mesenteric lymph nodes of F1 hosts. In contrast to nontreated F1 recipients, all 3.2.3 mAb-pretreated F1 animals suffered from severe signs of GvHD, and the mean survival time was decreased significantly from 16.0 +/- 0.9 days to 11.0 +/- 0.8 days (p < 0.01) in nontreated and NKR-P1-depleted F1 animals, respectively. Other sequelae included earlier onset of GvH manifestations, pronounced damage of primary and secondary lymphatic organs, substantial increase in spleen index, and lower CD4(+)/CD8(+ )ratios over the course of progressing GvHD. Our results underline the important immunoregulatory role of NK cells as a first defensive line acting on the alloreactivity of donor-derived immunocompetent cells in this model of solid organ transplantation.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Tolerância Imunológica/imunologia , Intestino Delgado/transplante , Células Matadoras Naturais/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Relação CD4-CD8 , Divisão Celular , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Intestino Delgado/imunologia , Masculino , Ratos , Ratos Endogâmicos Lew , Baço/imunologia , Baço/patologia , Transplante Heterotópico/imunologia , Transplante Heterotópico/mortalidade , Transplante Heterotópico/patologiaRESUMO
This report will focus on seven patients treated with auxiliary liver transplantation. In two cases the indication was severe metabolic disorder and in five cases a fulminant hepatic failure. The clinical course was highly complicated in both cases with metabolic disorder (the transplant was lost, one patient died), but satisfactory in the patients suffering from fulminant hepatic disease: three of five are off immunosuppression, one is under therapy and one patient died of sepsis in the early phase.
Assuntos
Emergências , Encefalopatia Hepática/cirurgia , Transplante de Fígado , Transplante Heterotópico , Adolescente , Adulto , Causas de Morte , Criança , Pré-Escolar , Feminino , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/mortalidade , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Taxa de Sobrevida , Transplante Heterotópico/mortalidadeAssuntos
Constituição Corporal , Transplante de Coração/fisiologia , Hemodinâmica , Doadores de Tecidos , Transplante Heterotópico/fisiologia , Adolescente , Adulto , Função do Átrio Esquerdo , Peso Corporal , Débito Cardíaco , Seguimentos , Transplante de Coração/métodos , Transplante de Coração/mortalidade , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Pressão Propulsora Pulmonar , Volume Sistólico , Taxa de Sobrevida , Fatores de Tempo , Transplante Heterotópico/mortalidadeRESUMO
UNLABELLED: We compared hemostatic changes during OLT and HLT after various periods of graft storage, to investigate whether the host liver in HLT protects the recipient from hemostatic deterioration induced by severe graft storage damage. In particular, the mechanism of fibrinolytic deterioration was investigated. The effect of prostaglandin E1 (PGE1) on these parameters was also studied. MATERIAL AND METHODS: 69 pigs underwent either OLT (N = 32) or HLT (N = 37) with a graft stored for 2 hr (N = 31), 24 hr (N = 16), 48 hr (N = 7), or 72 hr (N = 15). PGE1 was given intravenously to both donor and recipient animals and was added to the preservation and flushing solutions. Fibrinolysis (euglobulin clot lysis time, t-PA activity and alpha 2-antiplasmin) and coagulation parameters (activated partial thromboplasmin time, prothrombin time, fibrinogen and platelet count) were measured at several intervals during transplantation. STATISTICS: Univariate non-parametric tests were used for analysis of coagulation and fibrinolysis parameters. For the three main variables- i.e., the type of transplantation, the use of PGE1, and the preservation time, multiple regression analysis was performed. RESULTS: Fibrinolytic activity increased during the anhepatic period of OLT. Graft reperfusion was followed by a rise in t-PA in both OLT and HLT. In HLT, t-PA quickly returned to normal, whereas a continuous increase was found in OLT. The coagulation parameters, in turn, remained unchanged during the anhepatic period and deteriorated in OLT compared to HLT. The duration of graft storage was directly related to the severity of the hemostatic changes, although this effect was more apparent in OLT than in HLT. CONCLUSIONS: Changes in hemostasis are more pronounced in OLT than in HLT. This suggests that the host liver protects the recipient from the effects of graft storage damage, even after long preservation times. Early postreperfusion fibrinolytic activity was presumably due to t-PA release from the graft both in OLT and HLT. The further rise t-PA in OLT might be caused by the release of cytokines from the graft, that subsequently evoke endothelial t-PA release. In HLT, t-PA and cytokines may be cleared by the native liver. No positive or negative effect of PGE1 on coagulation or fibrinolysis parameters was noticed.
Assuntos
Hemostasia , Transplante de Fígado , Preservação de Órgãos , Transplante Heterotópico , Alprostadil/administração & dosagem , Animais , Perda Sanguínea Cirúrgica , Feminino , Fibrinogênio/análise , Fibrinólise , Período Intraoperatório , Transplante de Fígado/mortalidade , Transplante de Fígado/fisiologia , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Tempo de Protrombina , Suínos , Ativador de Plasminogênio Tecidual/análise , Transplante Heterotópico/mortalidade , Transplante Heterotópico/fisiologia , alfa 2-Antiplasmina/análiseRESUMO
Eleven cardiac transplant candidates (all male; mean age, 43.3 years) with multiorgan (hepatic, pulmonary, and/or renal) dysfunction were sustained for prolonged periods (> 30 days) with the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist device. We evaluated the effect of extended support on end-organ recovery and on the ultimate outcome of cardiac transplantation. In addition to cardiac failure, 9 patients had hepatic dysfunction, 8 had pulmonary dysfunction, and 6 had renal dysfunction (4 of whom required hemodialysis before left ventricular assist device support). Mean duration of support was 115 days (range, 31 to 233 days). All patients underwent successful transplantation; 10 of these patients survived a mean of 24 months. One patient, who had required hemodialysis and ventilatory support during and after support, experienced progressive multiorgan failure and died 7 weeks after transplantation. Two late deaths after transplantation were unrelated to the device. Overall, patients experienced improvement in cardiac functional class status, and most participated in cardiac rehabilitation programs before transplantation. During left ventricular assist device support, hepatic function returned to normal in 8 patients, pulmonary function recovered in 7, and renal function returned to normal in 4. One patient who required hemodialysis underwent renal transplantation after cardiac transplantation and had complete recovery of renal function. In the current era of donor shortages, gravely ill patients can benefit from a strategy of prolonged left ventricular assist device support. This strategy has proved safe, has allowed for reversal of multiorgan dysfunction, and has produced healthier transplant candidates.
Assuntos
Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/fisiologia , Coração Auxiliar , Hemodinâmica/fisiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Adulto , Débito Cardíaco/fisiologia , Pressão Venosa Central/fisiologia , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Transplante de Coração/mortalidade , Humanos , Testes de Função Renal , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Complicações Pós-Operatórias/mortalidade , Pressão Propulsora Pulmonar/fisiologia , Diálise Renal , Taxa de Sobrevida , Transplante Heterotópico/mortalidade , Transplante Heterotópico/fisiologia , Resistência Vascular/fisiologiaAssuntos
Antiarrítmicos/efeitos adversos , Transplante de Coração/mortalidade , Complicações Pós-Operatórias/mortalidade , Pré-Medicação , Adolescente , Adulto , Idoso , Amiodarona/administração & dosagem , Amiodarona/efeitos adversos , Antiarrítmicos/administração & dosagem , Aprindina/administração & dosagem , Aprindina/efeitos adversos , Causas de Morte , Criança , Feminino , Seguimentos , Humanos , Masculino , Mexiletina/administração & dosagem , Mexiletina/efeitos adversos , Pessoa de Meia-Idade , Propafenona/administração & dosagem , Propafenona/efeitos adversos , Quinidina/administração & dosagem , Quinidina/efeitos adversos , Sotalol/administração & dosagem , Sotalol/efeitos adversos , Taxa de Sobrevida , Transplante Heterotópico/mortalidadeRESUMO
As the number of heart transplants and the number of transplant programs has increased, so has the waiting time for a suitable organ. To more accurately assess the magnitude of this increase and the influence of recipient size, we reviewed waiting times for large (body surface area greater than or equal to 1.95 m2) and small (body surface area less than 1.95 m2) patients with respect to era of transplantation. Patients who underwent transplantation early (1984 to December 31, 1986) waited 35 +/- 47 days (mean +/- standard deviation), whereas patients who underwent transplantation in the late era (1987 to September 30, 1989) waited 83 +/- 102 days (p = 0.001). Large patients waited longer (130 +/- 142 days) in the late era than did small patients (60 +/- 67 days; p = 0.008). During the heterotopic era (October 1, 1989 to June 30, 1990), waiting times for large patients who received a heterotopic transplant (67 +/- 46 days) were significantly shorter than those for patients who received an orthotopic transplant (166 +/- 157 days; p = 0.05). Waiting times for small patients remained unchanged. In addition, waiting time mortality decreased from 24% to 9% (p less than 0.05). Comparison of orthotopic and heterotopic procedures performed during the same era revealed no significant differences in recipient age, preoperative status, graft ischemic time, donor age, early and midterm survival, or early postoperative functional status. Heterotopic heart transplantation may effectively increase the size of the donor pool, decrease the waiting time, and decrease waiting time mortality without increasing the morbidity of the procedure.
Assuntos
Transplante de Coração , Transplante Heterotópico , Superfície Corporal , Transplante de Coração/mortalidade , Humanos , Pessoa de Meia-Idade , Fatores de Tempo , Transplante Heterotópico/mortalidadeRESUMO
The role of heterotopic heart transplantation in coronary heart disease has not been defined. Between 1983 and 1988, 28 patients with end-stage ischemic heart disease were managed by heterotopic heart transplantation and adjunctive operation on the recipient heart: coronary artery bypass grafts and aneurysmectomy, 20; coronary artery bypass grafts, 5; and aneurysmectomy, 3. Indications were feasibility of operative procedures to the recipient heart and small donor size (61% of the donors were less than 15 years). The 1-year and 5-year actuarial survival was 79% and 63%. Of the 22 patients who survived to 2-year follow-up, all of whom had been severely limited (New York Heart Association grade III/IV) preoperatively, 20 were in grades I or II at 2-year follow-up (p less than 0.001). In 14 of 22 patients (64%), the recipient heart augmented the donor cardiac output substantially, and in 4 the recipient heart supported the patient when the donor heart failed to eject. In conclusion, this series demonstrates the efficacy of heterotopic transplantation combined with operation to the recipient heart in the management of patients with end-stage ischemic heart disease.