RESUMO
We studied the effects of indirect allorecognition on the induction and maintenance phases of tolerance in miniature swine cotransplanted with heart and kidney allografts. MHC class I-mismatched heart and kidney grafts were cotransplanted in recipients receiving CyA for 12 days. Recipients were unimmunized or immunized with a set of donor-derived or control third-party MHC class I peptides either 21 days prior to transplantation or over 100 days after transplantation. T-cell proliferation, delayed type hypersensitivity reaction (DTH) and antibody production were assessed. All animals injected with donor MHC class I peptides developed potent indirect alloresponses specific to the immunizing peptides. While untreated recipients developed stable tolerance, all animals preimmunized with donor allopeptides rejected kidney-heart transplants acutely. In contrast, when peptide immunization was delayed until over 100 days after kidney-heart transplantation, no effects were observed on graft function or in vitro measures of alloimmunity. Donor peptide immunization prevented tolerance when administered to recipients pre transplantation but did not abrogate tolerance when administered to long-term survivors post transplantation. This suggests that the presence of T cells activated via indirect allorecognition represent a barrier to the induction but not the maintenance of tolerance.
Assuntos
Transplante de Coração/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Tolerância Imunológica , Transplante de Rim/imunologia , Animais , Ensaio de Imunoadsorção Enzimática , Hipersensibilidade Tardia , Suínos , Porco Miniatura , Transplante HomólogoRESUMO
BACKGROUND: We have previously reported the successful induction of renal allograft tolerance in non-human primates using a nonmyeloablative conditioning regimen to produce a mixed-chimeric state in the recipient. In the present study, we applied this same technique to lung allotransplantation in cynomolgus monkeys. METHODS: Nine pairs of fully major histocompatibility complex (MHC)-mismatched cynomolgus monkeys were used. The conditioning regimen consisted of total body irradiation, thymic irradiation, and antithymocyte globulin. The recipients underwent lung and bone marrow transplantation, followed by anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine. The regimen included anti-CD8 mAb in the last 5 recipients and alpha 1-antitripsin in the last 3 recipients. The results were compared with 8 recipients that received kidney allografts using the same regimen. RESULTS: Transient chimerism developed in all lung recipients, as was previously seen in the kidney recipients. Nonetheless, the lung recipients rejected their allografts significant earlier than the kidney recipients (P < .01). CONCLUSIONS: Despite the successful induction of mixed chimerism in recipients of fully MHC-mismatched lung allografts, we have not observed long-term graft survival, as has been seen in an analogous kidney model. Strategies to overcome this problem include organ-specific modifications of the transplant regimen.
Assuntos
Sobrevivência de Enxerto/imunologia , Tolerância Imunológica , Transplante de Rim/imunologia , Transplante de Pulmão/imunologia , Quimeras de Transplante , Sistema ABO de Grupos Sanguíneos , Animais , Soro Antilinfocitário/uso terapêutico , Transplante de Medula Óssea/imunologia , Teste de Histocompatibilidade , Macaca fascicularis , Complexo Principal de Histocompatibilidade/imunologia , Masculino , Irradiação Corporal TotalRESUMO
The use of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL(+) graft cell injury with the infiltration of T cells (including CD3 and TIA-1(+) cytotoxic T cells), CD4(+) cells, CD8(+) cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL(+) dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens.
Assuntos
Galactosiltransferases/genética , Galactosiltransferases/fisiologia , Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Papio hamadryas/imunologia , Porco Miniatura/imunologia , Transplante Heterólogo/imunologia , Animais , Animais Geneticamente Modificados , Formação de Anticorpos/fisiologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Transplante de Coração/patologia , Transplante de Coração/fisiologia , Imunidade Celular/fisiologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Células Matadoras Naturais/patologia , Suínos , Porco Miniatura/genética , Trombose/patologia , Transplante Heterólogo/patologia , Transplante Heterólogo/fisiologia , Troponina T/sangueRESUMO
It is well known that interferon-gamma (IFN-gamma) not only plays a critical role in antigen-dependent but also in antigen-independent tissue injury; however, it is not clear how tolerance induction affects the actions of IFN-gamma in the transplant setting. To address this question, we compared the effects of IFN-gamma on porcine recipients of near-syngeneic, rejecting, and tolerant heart transplants. IFN-gamma was infused continuously into the left anterior descending artery of hearts transplanted into 3 groups of major histocompatibility complex (MHC) inbred miniature swine, each treated with a 12-day course of cyclosporine A (CyA). Group 1 recipients received a MHC class I disparate heart, group 2 recipients received a near-syngeneic heart, and group 3 recipients were cotransplanted with a MHC class I disparate heart and kidney, which uniformly induces tolerance to both grafts. An additional group of animals was not transplanted but received intracoronary IFN-gamma infusion into their native hearts. IFN-gamma perfusion not only accelerated the acute rejection of MHC class I disparate hearts (mean survival time = 19 +/- 7.21 vs 38 +/- 8.19 days, P = .025), but caused near-syngeneic heart transplants, which otherwise survive indefinitely, to reject within 35 days (n = 3). In contrast, IFN-gamma perfusion had no demonstrable effects on interstitial rejection, the development of vascular lesions, or graft survival in tolerant heart plus kidney allograft recipients (n = 4) or in autologous hearts (n = 2). These results suggest that tolerance induction mitigates the damaging effects of IFN-gamma itself and that the beneficial effects of tolerance induction on acute and chronic rejection may extend to antigen-independent factors like ischemia/reperfusion injury.
Assuntos
Transplante de Coração/imunologia , Tolerância Imunológica , Interferon gama/farmacologia , Transplante Homólogo/imunologia , Animais , Rejeição de Enxerto/prevenção & controle , SuínosRESUMO
UNLABELLED: We have previously reported that tolerance to class I disparate lung allografts in miniature swine could be induced using an intensive 12-day course of tacrolimus and that pretransplant sensitization with immunogenic MHC class I allopeptides failed to block the induction of tolerance. We also have previously reported the importance of the presence of the thymus in the induction of tolerance to isolated heart, kidney, and combined heart-kidney transplants. In this study, we examined the impact of thymectomy on tolerance induction in lung transplantation. METHODS: Orthotopic left lung transplantation was performed using MHC class I-disparate donors. The recipients received a 12-day course of high-dose tacrolimus (n = 6). Total thymectomies were performed in three of the swine 21 days prior to transplantation. Lung grafts were monitored by chest radiography and serial open lung biopsy. RESULTS: All euthymic recipients maintained their grafts for over 1 year. None of the thymectomized recipients has experienced graft loss in the 6 to 10 months following transplantation. Although isolated lesions of obliterative bronchiolitis were occasionally seen in one thymectomized animal on biopsy, donor-specific unresponsiveness has been observed on assays of cell-mediated lymphocytotoxicity in all recipients. Moreover, co-culture assays have shown that recipient lymphocytes can strongly inhibit the normally robust response of naïve recipient-matched lymphocytes to donor antigen. This inhibition was not seen when using stimulators primed with third-party antigens against appropriate targets. CONCLUSIONS: These data suggest that thymus-independent peripheral regulatory mechanisms may be sufficient to induce and maintain long-term acceptance of the lung allografts.
Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Transplante de Pulmão/imunologia , Timectomia , Transplante Homólogo/imunologia , Animais , Genótipo , Rejeição de Enxerto/imunologia , Homozigoto , Imunossupressores/uso terapêutico , Transplante de Pulmão/patologia , Suínos , Porco Miniatura , Tacrolimo/uso terapêuticoRESUMO
UNLABELLED: Considerable evidence suggests that indirect recognition of MHC allopeptides plays an important role in solid-organ rejection. Here, we examine whether immunization with class I or class II allopeptides accelerates rejection in a fully MHC-mismatched lung transplant model in miniature swine. METHODS: Recipients were immunized with either donor-derived class I or class II peptides. Sensitization to the peptides was confirmed by DTH testing and in vitro proliferation assays. Nonimmunized control (n = 6), class I peptide-immunized (n = 3), and class II peptide-immunized (n = 3) swine were transplanted with fully mismatched lungs using only a 12-day course of tacrolimus. RESULTS: One control animal rejected its graft on postoperative day 103, while the others maintained their grafts for over 1 year. In the class I peptide-immunized group, two recipients rejected their grafts (days 14 and 52). The third animal has not rejected the graft (day 120, experiment is ongoing). In contrast, in the class II-peptide immunized group, only one animal rejected its graft on day 52, while the others maintained their grafts over 1 year. Both anti-donor IgM and IgG antibodies were detectable in all acute rejectors, although no alloantibody was detectable in long-term acceptors. Regardless of the fate of the graft, all animals have maintained their proliferative responses to the peptides. However, only acceptors maintained donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity and mixed lymphocyte reaction assays. CONCLUSIONS: Pretransplant sensitization of lung allograft recipients to donor allopeptides accelerates graft rejection. This appears particularly true for class I-derived allopeptides, suggesting that class II molecules may be less antigenic when presented indirectly.
Assuntos
Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Transplante de Pulmão/imunologia , Animais , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Complexo Principal de Histocompatibilidade , Modelos Animais , Suínos , Porco MiniaturaRESUMO
OBJECTIVES: The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. We have induced robust tolerance to class I-disparate lung allografts in miniature swine using an intensive 12-day course of tacrolimus. Here, we tested whether a tolerant state can be induced in swine receiving fully mismatched lung allografts. METHODS: Orthotopic left lung allografts were performed using MHC class I-disparate (group 1: n = 3) or fully disparate (group 2: n = 6) donors. The recipients received a 12-day postoperative course of tacrolimus (continuous intravenous infusion; target level = 35-50 ng/mL) as their only immunosuppression. RESULTS: All swine in group 1 maintained their grafts long term without developing any lesions of chronic rejection (>497, >432, >451 days). These recipients exhibited donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity (CML) and mixed lymphocyte reaction (MLR) assays. In group 2, five of the six recipients maintained their grafts long term (sacrificed on postoperative days 515, 389, 429, 481, and 438 with viable grafts). Isolated lesions of obliterative bronchiolitis were occasionally seen on biopsy, and donor-specific hyporesponsiveness on assays was consistently observed. The remaining recipient rejected its graft on day 103 with histologic findings of obliterative bronchiolitis. CONCLUSIONS: We report long-term graft acceptance without chronic immunosuppression in five of six recipients across a full MHC disparity, albeit with some evidence of obliterative bronchiolitis. These data suggest that the class II disparity inherent in a fully mismatched transplant increases the requirement for tolerance induction.
Assuntos
Antígenos de Histocompatibilidade Classe II/imunologia , Tolerância Imunológica , Transplante de Pulmão/imunologia , Animais , Rejeição de Enxerto/patologia , Transplante de Pulmão/patologia , Complexo Principal de Histocompatibilidade , Modelos Animais , Suínos , Porco Miniatura , Transplante Homólogo/imunologiaRESUMO
OBJECTIVES: The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. Using a strategy to induce tolerance across strong allogeneic barriers, we have employed a brief, intensive course of immunosuppression to determine whether the induction of donor-specific hyporesponsiveness would prevent allograft rejection in a preclinical model of lung transplantation using MHC-inbred miniature swine. METHODS: Orthotopic left lung allografts were performed using MHC class I-disparate donors. The recipients received a 12-day postoperative course of cyclosporine (n = 6) or a 12-day postoperative course of high-dose tacrolimus (n = 3) as their only immunosuppression. Control animals received no immunosuppression (n = 3). RESULTS: Cyclosporine-treated recipients exhibited graft survival ranging from 67 to >605 days. All six animals developed acute cellular rejection between postoperative days (PODs) 27 and 108. Two animals lost their grafts on PODs 67 and 69, before developing obliterative bronchiolitis (OB). The other four recipients developed OB between PODs 119 and 238. In contrast, all tacrolimus-treated recipients maintained their grafts long term, without developing chronic rejection (>339, >308, and >231). These recipients also exhibited donor-specific hyporesponsiveness in assays of cell-mediated lymphocytotoxity. All untreated control animals lost their grafts to acute rejection by POD 11. CONCLUSIONS: This study demonstrates the ability of a brief course of high-dose tacrolimus to induce long-term graft acceptance with donor-specific hyporesponsiveness in a class I-disparate preclinical lung transplant model.
Assuntos
Sobrevivência de Enxerto/imunologia , Transplante de Pulmão/imunologia , Animais , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Pulmão/patologia , Suínos , Porco Miniatura , Tacrolimo/uso terapêutico , Transplante Homólogo/imunologia , Transplante Homólogo/patologiaRESUMO
Hearts from alpha1,3-Galactosyltransferase gene-knockout (GaIT-KO) pigs were transplanted heterotopically into 8 baboons that received an anti-CD154 monoclonal antibody (mAb)-based immunosuppressive regimen and heparin. Three baboons died or were euthanized with beating grafts on 16, 23, and 56 days, respectively, and the remaining 5 grafts functioned for 59-179 days. Hyperacute rejection did not occur, and classical features of acute humoral xenograft or acute cellular rejection were rare. However, thrombotic microangiopathy (TM) developed in all cases; its onset was delayed in 2 baboons that received aspirin. Function of a pig organ in a baboon for a period approaching 6 months has not been reported previously and lends encouragement that the barriers to xenotransplantation will be overcome, but TM requires investigation.
Assuntos
Aspirina/uso terapêutico , Fibrinolíticos/uso terapêutico , Galactosiltransferases/deficiência , Galactosiltransferases/genética , Deleção de Genes , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/métodos , Trombose/prevenção & controle , Transplante Heterólogo/métodos , Animais , Sobrevivência de Enxerto , Papio , SuínosRESUMO
The present study determined whether the administration of cyclocreatine phosphate (CCrP) prior to ischemia can enhance the recovery of rat hearts hypothermically preserved for a prolonged period. Rats (n = 6 per group) were injected intravenously with 1 ml saline or CCrP (500 mg/kg). After 2 hr, hearts were excised and arrested by an infusion of University of Wisconsin solution. Saline hearts were then incubated in 40 ml UW, while CCrP hearts were incubated in 40 ml UW containing 100 mg CCrP; a mixture that is now referred to as Hartford Hospital (HH) solution. After 6 hr of storage at 4 degrees C, hearts were reperfused in the Langendorff mode for 15 min and then in the working heart mode for 30 min. Results indicated that the recovery of cardiac function--measured as aortic flow, coronary flow, cardiac output, stroke volume, and stroke work--was significantly better in CCrP group (50-55% baseline) compared with that of saline hearts (20-25%). Although no difference in enzyme leakage (i.e., creatine kinase) or lactate was detected between the two groups, the increase in heart weight after the initial 6-hr storage was significantly higher in saline hearts compared with that of CCrP hearts. Results of this study support the conclusion that CCrP treatment provides improved functional recovery after prolonged hypothermic preservation.
Assuntos
Temperatura Baixa , Coração , Imidazolidinas , Preservação de Órgãos , Fosfocreatina/análogos & derivados , Animais , Biópsia , Coração/anatomia & histologia , Coração/efeitos dos fármacos , Coração/fisiologia , Masculino , Miocárdio/química , Miocárdio/enzimologia , Miocárdio/ultraestrutura , Tamanho do Órgão , Fosfocreatina/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
BACKGROUND: Spleen transplantation (Tx) between some strains of rodents can lead to donor-specific tolerance either spontaneously or after a short course of immunosuppression. This study developed a surgical technique for spleen Tx in miniature swine to investigate its immunologic impact in a large animal model. METHODS: The preferred surgical technique of spleen Tx (n=8) involved excision of the donor spleen with its vascular pedicle to the aorta and portal vein. Carrel patches of donor aorta and portal vein were anastomosed to the abdominal aorta and inferior vena cava, respectively, of the (splenectomized) recipient. The results in four major histocompatibility complex-matched pairs that were mismatched for the porcine allelic antigen are reported. Two recipients were untreated, one received a 12-day course of cyclosporine A (CsA) alone, and one received thymic irradiation (700 cGy) and CsA. Hematopoietic cell chimerism was followed by fluorescence-activated cell sorter, and graft survival was assessed by histology. RESULTS: Spleen Tx was technically successful. In two untreated pigs, chimerism was detected in the blood (maximum 5% for 17 and 25 days) and lymph nodes (maximum 6% for 28 and 56 days), but both grafts showed histologic rejection by day 28. In two treated pigs, chimerism was present in the blood for 47 and 57 days, and rejection was prevented, with follow-up for 57 and 217 days, respectively. CONCLUSION: Spleen Tx in major histocompatibility complex-matched pairs treated with CsA+/-thymic irradiation results in prolonged chimerism and is associated with the development of in vivo unresponsiveness to the transplanted spleen.
Assuntos
Complexo Principal de Histocompatibilidade/imunologia , Baço/transplante , Esplenectomia/métodos , Animais , Biópsia , Ciclosporina/farmacologia , Citometria de Fluxo , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/patologia , Células-Tronco Hematopoéticas/citologia , Teste de Histocompatibilidade , Imunossupressores/farmacologia , Complicações Pós-Operatórias , Transplante de Pele/imunologia , Baço/patologia , Porco Miniatura , Doadores de Tecidos , Quimeras de TransplanteRESUMO
Recent studies from our laboratory have demonstrated the release of neutrophil chemotactic factors from isolated rabbit hearts perfused with cardioplegic solutions and from ischemic dog hearts after coronary artery occlusion for 1 hour. On the basis of these animal studies, a test is now made of the hypothesis that neutrophil chemotactic factors are released by myocardial tissues of patients who undergo surgical myocardial revascularization. By means of modified Boyden chambers, the levels of neutrophil chemotactic factors were measured in effluent collected from the coronary sinuses of six patients undergoing cardiopulmonary bypass during periods of cold cardioplegia. Plain cardioplegic solutions were also analyzed. The standard formyl-methionyl-leucyl-phenylalanine, a stimulant of neutrophil recruitment, was used as a positive control solution. Results indicated the recovery of significantly high levels of neutrophil chemotactic factors in patient samples (i.e., 128% +/- 19% of formyl-methionyl-leucyl-phenylalanine) compared with control plain cardioplegic solution (less than 5% of formyl-methionyl-leucyl-phenylalanine) (p less than 0.0001). A standard checkerboard analysis indicated that the observed activity is chemotactic (i.e., directed migration) and not chemokinetic (i.e., random migration). This study also showed that these factors are proteins of a molecular weight in excess of 300 kd and exhibit in vivo activity by recruiting neutrophils into rabbit skin. The absence of immune cell-derived chemoattractants such as interleukin-1 and leukotriene B4 in these coronary sinus effluents suggests that the observed chemotactic activity is cardiac derived. Results of this investigation therefore demonstrate the release of neutrophil chemotactic factors by ischemic human hearts during cardiopulmonary bypass.
Assuntos
Soluções Cardioplégicas/análise , Interleucina-8/análise , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Revascularização Miocárdica , Miocárdio/metabolismo , Neutrófilos/fisiologia , Ponte Cardiopulmonar , Quimiotaxia de Leucócito/fisiologia , Vasos Coronários , Humanos , Interleucina-1/análise , Leucotrieno B4/análise , Masculino , Pessoa de Meia-Idade , N-Formilmetionina Leucil-FenilalaninaRESUMO
With a limited supply of donor hearts in the United States and a prevalent history of cocaine abuse among potential heart donors, the question of transplanting the hearts of cocaine users presents a dilemma to the surgeon. We report a patient who died of the acute right ventricular failure of a heart from a donor with a history of binge drinking and cocaine abuse and who had sustained traumatic brain death. The donor's serum was positive for cocaine prior to transplantation, and autopsy findings were consistent with cocaine cardiomyopathy. This case illustrates the importance of accurate donor history and toxicologic screen prior to heart transplantation and suggests that hearts of cocaine users should not be transplanted, especially in a setting of traumatic brain death.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Cocaína Crack/efeitos adversos , Transplante de Coração/efeitos adversos , Coração/efeitos dos fármacos , Doadores de Tecidos , Disfunção Ventricular Direita/induzido quimicamente , Adulto , Idoso , Evolução Fatal , Feminino , Insuficiência Cardíaca/cirurgia , Humanos , MasculinoRESUMO
BACKGROUND: Since 1973, more than 75 patients with hypocomplementemic urticarial vasculitis syndrome (HUVS) were reported, but valvular heart disease does not seem to have been noted in these patients. Since 1993, however, five patients with HUVS accompanied by Jaccoud's arthropathy (JA) were found to have serious valvular heart disease. METHODS: To characterize the cardiac valvulopathy of the third patient with HUVS/JA to have undergone valve replacement, this study included the use of routine and special tissue stains, as well as immunohistochemical staining. We compared gross and histologic findings of this patient's valve to those of two other patients with this complex syndrome who underwent valve replacement. Pathologic findings of these latter two patients were described in separate earlier reports. RESULTS: Histologic examination of the resected valves in all three patients showed an acute necrotizing endocarditis and fibrin deposition on the surface of valve leaflets. Beneath the surfaces of the leaflets, there was evidence of chronic inflammation, consisting of lymphocytes and histiocytes. A fibrocalcific degenerative change was also present in all three valves. Positive staining for IgG, IgA, IgM, and light-chain determinant-bearing proteins was detected primarily at the valve surface in special studies of the aortic valve of the patient described in the current report. CONCLUSION: Patients with HUVS and associated JA should be evaluated for the presence of valvular heart disease. The latter is probably a nonrheumatic, inflammatory, and degenerative process, mediated by immune complex, as well as cellular immune mechanisms.
Assuntos
Proteínas do Sistema Complemento/deficiência , Doenças das Valvas Cardíacas/complicações , Artropatias/complicações , Urticária/complicações , Vasculite/complicações , Complexo Antígeno-Anticorpo/metabolismo , Valva Aórtica/imunologia , Valva Aórtica/patologia , Feminino , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/patologia , Humanos , Pessoa de Meia-Idade , Valva Mitral/imunologia , Valva Mitral/patologia , SíndromeRESUMO
Antiatherogenic effects of sex steroids in premenopausal women are not well defined. Therefore, we employed an established rabbit model for atherosclerosis to study the effects of exogenous estrogen and a progesterone analogue (P) on serum lipids and aortic plaque load. Serum cholesterol (C) and triglyceride (T) levels and atherosclerotic plaque loads were compared in 5 groups of male New Zealand White rabbits fed a 12-week, C-rich diet: 1 control group (CG) and 4 groups treated with estriol (E), haloperidol (H), low-dose 17-hydroxyprogesterone (LDP), or high-dose 17-hydroxyprogesterone (HDP). Serum P was measured in the LDP and HDP groups. Serial histologic sections (15 each of 27 ascending aortas) were studied by light microscopy and computerized morphometric analysis. Plaque load is defined as the ratio of intimal area to medial area (I/M). Exogenous E (p<0.001), H (P = 0. 02), LDP and HDP (P<0.001, each) were found to be significantly associated with less aortic plaque load than controls. In a multivariate analysis, after controlling for the differences in serum C and T levels, HDP (p = 0.014) was found to be associated with less aortic plaque load than controls, and this association approached statistical significance in the E (p = 0.052) and H (p = 0.069) groups. These data suggest that the mechanism(s) involved with the antiatherogenic effect of HDP in this animal model is, or are, independent of an alteration in serum lipids.
Assuntos
17-alfa-Hidroxiprogesterona/administração & dosagem , Aorta/metabolismo , Colesterol/sangue , Doença da Artéria Coronariana/metabolismo , Dieta Aterogênica , Hipercolesterolemia/sangue , Triglicerídeos/sangue , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Colesterol na Dieta/administração & dosagem , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Relação Dose-Resposta a Droga , Estriol/administração & dosagem , Haloperidol/administração & dosagem , Hipercolesterolemia/etiologia , Hipercolesterolemia/patologia , Processamento de Imagem Assistida por Computador , Masculino , CoelhosRESUMO
Two patient groups were studied to determine the need to preserve the greater saphenous vein during femoral outflow reconstruction for later aortocoronary bypass procedures. First, 74 patients were followed to the time of death or to a minimum of 5 years after femoral outflow reconstruction was performed. Only four patients (5.4%) underwent subsequent aortocoronary bypass. The previous outflow procedures had no adverse effect on the quality of aortocoronary conduit. Risk factors were analyzed to help predict the incidence of later coronary revascularization after femoral outflow reconstruction was performed. The second group that was analyzed included 500 nearly consecutive patients who underwent aortocoronary bypass. In 15 of these patients (3%), there was inadequate saphenous vein for conduit use. In no case was the inadequacy of saphenous vein due to its previous use as outflow conduit in the leg. Only seven patients (1.4%) had had an outflow reconstruction prior to aortocoronary bypass. In conclusion, continued use of adequate greater saphenous vein as femoral outflow conduit is justified despite the high incidence of coronary artery disease in these patients.
Assuntos
Artéria Femoral/cirurgia , Perna (Membro)/irrigação sanguínea , Veia Safena , Adulto , Idoso , Prótese Vascular , Ponte de Artéria Coronária , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
In this study, 6 anesthetized dogs underwent global cardiac arrest for 1 hour, followed by reperfusion on bypass for 45 minutes. The hearts were then weaned off cardiopulmonary bypass and monitored for an additional 2 hours. Using modified Boyden chambers, high levels of neutrophil chemotactic activity were detected (using a checkerboard analysis) in the coronary sinus effluents obtained during cardiac arrest. The activity tended to decline during reperfusion. Assay of myeloperoxidase (a marker for neutrophils) revealed an accumulation of large numbers of neutrophils in the right (14 +/- 1.1 x 10(4) cells/g wet weight) and left (16 +/- 1 x 10(4) cells/g wet weight) ventricles after 2 hours of reperfusion. Light microscopy evaluation confirmed the presence of neutrophils, not only in the ventricles, but also in a greater number in the right and left atria. Electron microscopy study of these hearts revealed the presence of mild reversible changes, indicating good preservation of the hearts during arrest. Results of this study provide evidence for an acute inflammatory reaction that takes place after cardiac operations and suggest a role for myocardial tissues in the initiation of such a response through their release of neutrophil chemotactic factors.
Assuntos
Ponte Cardiopulmonar , Fatores Quimiotáticos/farmacocinética , Inflamação/metabolismo , Miocárdio/metabolismo , Animais , Procedimentos Cirúrgicos Cardíacos , Cães , Microscopia Eletrônica , Reperfusão Miocárdica , Miocárdio/ultraestrutura , Neutrófilos/enzimologia , Peroxidase/análise , Período Pós-OperatórioRESUMO
We present the case of an angiographically uncomplicated direct stent vein graft intervention in which the Percusurge embolization containment device was used. We performed histological examination of the resulting debris and observed massive particulate atheromatous material. This case illustrates the severity of distal embolization that can go clinically unnoticed after direct stenting and also supports the routine use of distal protection devices for vein graft intervention.
Assuntos
Embolia de Colesterol/prevenção & controle , Oclusão de Enxerto Vascular/terapia , Implantação de Prótese/efeitos adversos , Stents/efeitos adversos , Idoso , Oclusão com Balão/instrumentação , Oclusão com Balão/estatística & dados numéricos , Ponte de Artéria Coronária/efeitos adversos , Embolia de Colesterol/etiologia , Equipamentos e Provisões , Oclusão de Enxerto Vascular/etiologia , Humanos , Masculino , Sucção/instrumentação , Sucção/estatística & dados numéricos , Resultado do TratamentoRESUMO
OBJECTIVE: To describe an unexpected inflammatory process associated with malignancy in the lung and to postulate a new mode of pathogenesis. DESIGN: Retrospective review of surgical pathologic findings. SETTING: Academic hospital pathology department. PATIENTS: Four patients, 2 men and 2 women, ranging in age from 45 to 74 years, each of whom had a solitary mass on chest radiographs. INTERVENTIONS: Pulmonary lobectomy. MAIN OUTCOME MEASURE: Histopathologic identification of bronchocentric granulomatosis. RESULTS: Accompanying a bronchogenic carcinoma in each case was a necrotizing chronic granulomatous reaction centered around bronchioles that were plugged with mucus, necrotic detritus from the tumor, lipid, or a combination of these substances. Eosinophils were present in small numbers in one case. The pathologic findings characterize bronchocentric granulomatosis. CONCLUSIONS: The presence of bronchocentric granulomatosis in the biopsy of a mass does not exclude the presence of an accompanying bronchogenic carcinoma associated with obstruction of bronchioles. Bronchocentric granulomatosis in some cases may represent an immunologic response to tumor detritus or lipid, as well as to mucus impaction.
Assuntos
Broncopatias/patologia , Carcinoma Broncogênico/patologia , Granuloma do Sistema Respiratório/patologia , Neoplasias Pulmonares/patologia , Muco/citologia , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Broncopatias/etiologia , Carcinoma Broncogênico/complicações , Carcinoma Broncogênico/cirurgia , Carcinoma de Células Grandes/complicações , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Evolução Fatal , Feminino , Granuloma do Sistema Respiratório/etiologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: A high-resolution coronary artery imaging modality has the potential to address important diagnostic and management problems in cardiology. Optical coherence tomography (OCT) is a promising new optical imaging technique with a resolution of approximately 10 microm. The purpose of this study was to use a new OCT catheter to demonstrate the feasibility of performing OCT imaging of normal coronary arteries, intimal dissections, and deployed stents in vivo. METHODS AND RESULTS: Normal coronary arteries, intimal dissections, and stents were imaged in five swine with OCT and compared with intravascular ultrasound (IVUS). In the normal coronary arteries, visualization of all of the layers of the vessel wall was achieved with a saline flush, including the intima which was not identified by IVUS. Following dissection, detailed layered structures including intimal flaps, intimal defects, and disruption of the medial wall were visualized by OCT. IVUS failed to show clear evidence of intimal and medial disruption. Finally, the microanatomic relationships between stents and the vessel walls were clearly identified only by OCT. CONCLUSIONS: In this preliminary experiment, we have demonstrated that in vivo OCT imaging of normal coronary arteries, intimal dissections, and deployed stents is feasible, and allows identification of clinically relevant coronary artery morphology with high-resolution and contrast.