Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
1.
Oncogene ; 31(5): 611-23, 2012 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-21706061

RESUMO

The nuclear factor (NF)-κB transcription factor has essential roles in inflammation and oncogenesis. Its ubiquitous RelA subunit is regulated by several post-translational modifications, including phosphorylation, ubiquitination and acetylation. Ubiquitination promotes the termination of RelA-dependent transcription, but its regulation is incompletely understood. Through mass spectrometry analysis of ubiquitinated RelA, we identified seven lysines that were attached to degradative and non-degradative forms of polyubiquitin. Interestingly, lysines targeted for acetylation were among the residues identified as ubiquitin acceptor sites. Mutation of these particular sites resulted in decreased polyubiquitination. Acetylation and ubiquitination were found to inhibit each other, consistent with their use of overlapping sites. Reconstitution of rela(-/-) fibroblasts with wild-type and mutant forms of RelA revealed that modifications at these residues can have activating and inhibitory functions depending on the target gene context. Altogether, this study elucidates that ubiquitination and acetylation can modulate each other and regulate nuclear NF-κB function in a gene-specific manner.


Assuntos
NF-kappa B/metabolismo , Fator de Transcrição RelA/metabolismo , Ubiquitina/metabolismo , Acetilação , Animais , Sítios de Ligação/genética , Linhagem Celular Tumoral , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Immunoblotting , Molécula 1 de Adesão Intercelular/genética , Lisina/genética , Lisina/metabolismo , Camundongos , Camundongos Knockout , Mutação , NF-kappa B/genética , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras Genéticas/genética , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição RelA/genética , Ubiquitinação
2.
J Cardiovasc Surg (Torino) ; 52(3): 411-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21577195

RESUMO

AIM: The combination of the two cardiac support mechanisms of intra-aortic balloon pumping (IABP) and non-pulsatile circulatory extracorporeal membrane oxygenation (ECMO) has been confirmed to improve efficacy of the cardiac support as a whole. However, reports on benefits of diastolic augmentation on coronary vascular bed and graft flowmetry during concomitant use of IABP and ECMO are lacking. The aim of this study was to evaluate the acute impact of IABP support on coronary vascular resistance (CVR) and coronary bypass flows (CBF) in high-risk patients with peripheral ECMO following coronary artery bypass grafting (CABG). METHODS: In eight emergency CABG patients (mean age=67.8±1.9 years; gender: six male and two female; EF=25.5±2.4%) requiring mechanical circulatory support with ECMO hemodynamic parameters, CVR, CBF, diastolic filling index (DFI), graft flow reserve (GFR), and pulsatility index (PI) were analyzed with and without diastolic augmentation using a transit time flowmeter. RESULTS: The addition of IABP to ECMO decreased CVR significantly by 6.5%±1.9% compared to baseline with ECMO alone (1.62±0.2 versus 1.78±0.2; P<0.0045). Accordingly, significant higher mean CBF were found during IABP assist, resulting in a 21.6%±2.6% increase (60.7±8.7 mL/min with versus 51.3±7.4 mL/min without IABP; P<0.0001). IABP also significantly increased DFI by 9.8±0.9% (73.2%±1.4% with versus 66.7%±1.3% without IABP; P<0.0001). GFR was recruited during IABP in all grafts (GFR>1). There were no statistically significant differences in PI with and without IABP assistance (2.6±0.1 versus 2.5±0.2). CONCLUSION: IABP-induced pulsatility significantly improves diastolic filling index and mean coronary bypass graft flows by lowering coronary vascular resistance during non-pulsatile peripheral ECMO. The combination of ECMO with IABP may provide more optimal myocardial oxygen conditions resulting in an improved efficacy of the cardiac support as a whole in critical ill patients with postcardiotomy myocardial dysfunction following CABG.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Circulação Coronária , Oxigenação por Membrana Extracorpórea , Balão Intra-Aórtico , Complicações Pós-Operatórias/terapia , Fluxo Pulsátil , Resistência Vascular , Idoso , Velocidade do Fluxo Sanguíneo , Doença da Artéria Coronariana/fisiopatologia , Estado Terminal , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
3.
J Cardiovasc Surg (Torino) ; 51(6): 895-905, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21124287

RESUMO

AIM: The aim of this study was to evaluate the impact of intermittent warm (IWC) versus intermittent cold blood cardioplegia (ICC) in high-risk patients that require prolonged periods of aortic cross-clamping during on-pump cardiac surgery. METHODS: From 3527 consecutive patients undergoing on-pump cardiac surgery, 520 patients were retrospectively identified that required prolonged aortic cross-clamp ≥ 75 min. Myocardial protection was performed with ICC (N.=280) or IWC (N.=240). Groups were compared regarding clinical outcomes, myocardial injury (CK-MB, cTnT) and multivariate analysis was performed to assess the impact of applied cardioplegia on 30-day all-cause mortality, cardiac death, perioperative myocardial injury (PM) and major adverse cardiac events (MACE). RESULTS: Demographic data, mean logistic Euroscore, aortic-cross-clamping and CPB time were comparable between groups. Patients with ICC needed more intraoperative defibrillations, had more postoperative blood transfusions and a prolonged hospital stay when compared to the IWC-group (P < 0.05). Thirty-day all-cause mortality tended to be higher in IWC (11% vs. 6%; P = 0.083) with significantly higher cardiac mortality (9% vs. 4%; P=0.015) compared to ICC. Myocardial injury was more pronounced in the IWC-group with a higher incidence of PMI (IWC: 17% vs. ICC:6%; P < 0.05) and MACE (IWC:37% vs. ICC:25%; P < 0.05). Groups did not differ regarding other postoperative clinical outcomes. Multivariate analysis revealed IWC to be independently predictive (P < 0.05) for 30-day all-cause mortality (OR:2.42; 95% CI:1.04-5.05), cardiac death (OR:3.57; 95% CI:1.49-8.85), MACE (OR:1.87; 95% CI:1.22-2.87) and PMI (OR:3.46; 95% CI:1.86-6.41). CONCLUSION: ICC results in less myocardial damage and reduced postoperative cardiac mortality and morbidity in patients requiring extended periods of aortic-cross-clamping during on-pump cardiac surgery, suggesting superior cardioprotection when compared to IWC.


Assuntos
Aorta/cirurgia , Procedimentos Cirúrgicos Cardíacos , Soluções Cardioplégicas/administração & dosagem , Parada Cardíaca Induzida/métodos , Cardiopatias/prevenção & controle , Idoso , Transfusão de Sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Constrição , Cardioversão Elétrica , Feminino , Cardiopatias/etiologia , Cardiopatias/mortalidade , Humanos , Itália , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Temperatura , Fatores de Tempo , Resultado do Tratamento
4.
J Cardiovasc Pharmacol ; 54(1): 10-5, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19487957

RESUMO

BACKGROUND: The Na,K-ATPase (NKA) is necessary for maintaining the resting membrane potential by transporting Na and K ions across the cell membrane. Although its 3 isoforms expressed in human heart (alpha1beta1, alpha2beta1, and alpha3beta1) possess similar biochemical properties, their specific functions in human tissues remain unknown. In our search for an isoform-specific agent, which can serve to identify isoform-specific functions, we examined 8-methoxycoumestrol in its ability to inhibit the NKA and to produce inotropism in connection with the possibility to identify the NKA isoform-specific functions. METHODS AND RESULTS: In radioligand binding experiments (membrane preparations of yeast expressing isoforms alpha1beta1, alpha2beta1, and alpha3beta1; backdoor phosphorylation; and [H]-ouabain, n = 3), 8-methoxycoumestrol (1-10 microM) produced no or only little inhibition of specific ouabain binding. However, when NKA activity of the alpha1beta1 isoform was measured in membrane preparations from human kidney (reduced form of nicotinamide adenine dinucleotide-coupled assay, n = 3), a concentration-dependent full inhibition of the activity was induced by 8-methoxycoumestrol (IC50: 90 +/- 97 nM), similar to that observed for classical cardiac glycosides digitoxin, digoxin, methyldigoxin, and beta-acetyldigoxin (IC50 = 287 +/- 190 nM, 409 +/- 171 nM, 282 +/- 482 nM, 587 +/- 135 nM, P > 0.05). However, unlike the classical cardiac glycosides, 8-methoxycoumestrol did not increase cardiac contractility of electrically stimulated human right atrial trabeculae. CONCLUSIONS: These results indicate that 8-methoxycoumestrol inhibits the human alpha1beta1 NKA by a mechanism different to that of cardiac glycosides. In addition, the inhibition of the alpha1beta1 NKA activity seems not sufficient to evoke positive inotropy in human trabeculae, indicating that either the positive inotropic effect of cardiac glycosides is not mediated via the alpha1beta1 isoform or the specific glycoside binding to alpha1beta1 is needed for positive inotropy.


Assuntos
Glicosídeos Cardíacos/farmacologia , Cumestrol/análogos & derivados , Cumestrol/farmacologia , Inibidores Enzimáticos/farmacologia , Miocárdio/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Idoso , Cumestrol/síntese química , Cumestrol/química , Cumestrol/metabolismo , Relação Dose-Resposta a Droga , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/fisiopatologia , Humanos , Concentração Inibidora 50 , Isoenzimas/antagonistas & inibidores , Isoenzimas/genética , Isoenzimas/metabolismo , Rim/metabolismo , Rim/cirurgia , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Contração Muscular/fisiologia , Nefrectomia , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Temperatura , Fatores de Tempo
5.
Eur Respir J ; 33(3): 625-33, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19010995

RESUMO

The optimal timing of exogenous surfactant application to reduce pulmonary injury and dysfunction was investigated in a rat lung ischaemia and reperfusion injury model. Lungs were subjected to flush perfusion, surfactant instillation, cold ischaemia (4 degrees C, 4 h) and reperfusion (60 min). Animals received surfactant before (group 1) or at the end (2) of ischaemia, or during reperfusion (3) or not at all (4). Control groups included "worst case" without Perfadex and surfactant (5), "no injury" without (6) or with surfactant (7), and ischaemia with pre-ischaemic surfactant (8). Intra-alveolar oedema and blood-air barrier injury were estimated by light and electron microscopic stereology. Perfusate oxygenation and pulmonary arterial pressure (P(pa)) were determined during reperfusion in groups 1 to 4. Intra-alveolar oedema was almost absent in groups 1, 6, 7 and 8, pronounced in 2, 3 and 4, and severe in 5. Blood-air barrier injury was moderate in groups 1 and 8, slightly pronounced in 2, 3 and 4, extensive in 5 and almost absent in 6 and 7. Perfusate oxygenation was significantly higher in group 1 compared with groups 2 to 4. P(pa) did not differ between the groups. In conclusion, exogenous surfactant attenuates intra-alveolar oedema formation and blood-air barrier damage and improves perfusate oxygenation in the rat lung, especially when applied before ischaemic storage.


Assuntos
Surfactantes Pulmonares/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Animais , Citratos/farmacologia , Edema/patologia , Humanos , Isquemia/patologia , Pulmão/patologia , Lesão Pulmonar/tratamento farmacológico , Masculino , Microscopia Eletrônica/métodos , Microscopia Eletrônica de Transmissão/métodos , Perfusão , Ratos , Ratos Sprague-Dawley
6.
Thorac Cardiovasc Surg ; 53(6): 334-40, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16311969

RESUMO

BACKGROUND: The risk of neurological complications is still a life-threatening event for patients undergoing proximal aortic arch or total aortic arch surgery. To prevent these complications, axillary artery cannulation and antegrade selective cerebral perfusion were utilized. We compared the effects of using hypothermic circulatory arrest (HCA) alone or with selective cerebral perfusion (SCP/AX) via right side axillary artery direct cannulation. METHODS: 120 patients, mean age 61 +/- 12 years (range 26 - 80), underwent proximal aortic or total aortic arch replacement between 1999 and 2004; 46 were female. We retrospectively compared the results of the two patient groups comparable for preoperative risk factors: 71 pts were operated using HCA beginning in 1999 and 49 pts using HCA/SCP via axillary artery direct cannulation since 2002. The indication for surgery was an aortic aneurysm in 80 (67 %) patients and aortic dissection in 36 (30 %) patients. The groups were well matched with regard to median age (60 vs. 62 yrs), urgency (emergent/urgent 36 vs. 44 %; elective 64 vs. 65 %), and several other known risk factors ( p = ns). RESULTS: Overall in-hospital mortality was 13 %: 10 % with HCA vs. 6 % with SCP/AX. Permanent neurological dysfunction occurred in 10 % with HCA vs. 6 % with SCP/AX. Transient neurological dysfunction (TND) in patients surviving without stroke was lower with SCP/AX (10 %) than with HCA (17 %) ( p = ns). Mean duration of HCA was 28 +/- 12 min when isolated HCA was used, and significantly shorter with 21 +/- 6 min when the combination of SCP/AX ( p = 0.03) was used. Mean duration of CPB was 202 +/- 55 min with HCA vs. 192 +/- 50 min with SCP/AX ( p = ns). Comparison of the groups who had comparable preoperative risk factors showed a trend towards lower in-hospital mortality, stroke and TND rates, a significant reduction in cardiac ( p = 0.034), infectious ( p = 0.025) and bleeding complications ( p = 0.04) in SCP/AX compared with HCA, as well as a significantly shorter duration of hospitalization ( p = 0.046) and shorter ICU stay ( p = ns). CONCLUSION: Our results suggest that HCA/SCP is superior to HCA alone for preventing cerebral injury during operations on the aortic arch. By reducing embolic risk, as well as the duration of HCA, SCP with axillary artery direct cannulation may be the optimal technique for averting cerebral events, reducing complications, and shortening hospital stays following aortic arch repair.


Assuntos
Aorta Torácica/cirurgia , Circulação Cerebrovascular/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/cirurgia , Artéria Axilar , Cateterismo , Feminino , Humanos , Hipotermia Induzida , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral
7.
Clin Exp Immunol ; 138(2): 221-9, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15498030

RESUMO

Sepsis is associated with depression of T cell-dependent immune reactivity with proinflammatory cytokines, such as tumour necrosis factor (TNF)-alpha, playing an important role. Recent investigations describe an association between these immunological alterations and disturbances of the endocrine system, related most frequently to sex steroid hormones. Dehydroepiandrosterone (DHEA), one of the most abundant adrenal sex steroid precursors, seems to have a protective immunological effect towards septic insults. In this study, both the role of TNF-receptor I (RI) and possible interactions in the protective role of DHEA were investigated in a murine model of polymicrobial sepsis. Polymicrobial sepsis was induced by caecal ligation and puncture (CLP) in a murine model. The effects of DHEA on survival, clinical parameters and cellular immunity (T lymphocytes and natural killer (NK) cells) were investigated. CLP was performed in genetically modified TNF-RI knock-out (TNF-RI(-/-)) and genetically unmodified (wild-type, WT) mice. DHEA application was associated with a decrease in the mortality rate in WT animals. A mortality rate of 91.7% was observed in TNF-RI(-/-) mice after CLP. This mortality rate was reduced to 37.5% by the application of DHEA. In sham-operated TNF-RI(-/-) animals, a significantly higher proportion of NK cells within the lymphocyte population was measured compared with the corresponding WT group. After CLP, a significant increase in the percentage cell count of NK cells was recorded in WT mice. Overall, following DHEA application in WT mice, an alteration in the cellular immune response was characterized by a reduction in the percentage counts of CD4(+), CD8(+) and NK cells. In the group of TNF-RI(-/-) mice treated with DHEA, no increase in the percentage cell count of NK cells was observed after CLP. No data for cell analysis were available from the CLP-TNF-RI(-/-) mice treated with saline, due to the high mortality rate in these animals. DHEA reduces the complications of sepsis in a TNF-RI-independent manner. Our study suggests that NK cells are involved in the protective mechanism of DHEA in WT mice. It would therefore seem that DHEA represents a feasible alternative therapy for the dysregulated immune system in sepsis.


Assuntos
Desidroepiandrosterona/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia , Sepse/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Temperatura Corporal/imunologia , Peso Corporal/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Desidroepiandrosterona/uso terapêutico , Hipersensibilidade Tardia/imunologia , Imunidade Celular/imunologia , Imunofenotipagem/métodos , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sepse/mortalidade , Sepse/prevenção & controle
8.
Eur J Cardiothorac Surg ; 20(4): 877-9, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11574248

RESUMO

We report the one-stage surgical management in a 68-year-old patient with a renal cell carcinoma with extended intravascular growth into the inferior vena cava combined with severe triple coronary artery disease. After nephrectomy the resection of the intravascular tumor and caval reconstruction were performed in deep hypothermic circulatory arrest. Coronary revascularization was accomplished while rewarming. The postoperative course was uneventful. Nine months after this operation there are no signs of reoccurrence.


Assuntos
Carcinoma de Células Renais/cirurgia , Doença das Coronárias/cirurgia , Neoplasias Renais/cirurgia , Veia Cava Inferior/cirurgia , Idoso , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Terapia Combinada , Ponte de Artéria Coronária , Humanos , Hipotermia Induzida , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Imageamento por Ressonância Magnética , Masculino , Nefrectomia , Veia Cava Inferior/patologia
9.
J Heart Lung Transplant ; 20(8): 876-88, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11502410

RESUMO

BACKGROUND: Although administration of nitric oxide (NO) has been suggested to reduce pulmonary reimplantation response, concerns remain about cytotoxic side effects. METHODS: Using light and electron microscopy, we examined the effects of the NO donor nitroglycerin (NTG) (0.1 mg/ml) as a supplement to the preservation solution Celsior on the structural integrity of rat lungs after extracorporeal ischemia (4 hours at 10 degrees C) and reperfusion (50 minutes) (IR). We performed evaluation in comparison with Celsior alone after IR using either standard antegrade perfusion through the pulmonary artery or retrograde perfusion through the left atrium as an alternative way to improve the preservation quality. Untreated, non-ischemic lungs served as controls (n = 5 per group). We recorded respiratory and hemodynamic parameters during reperfusion. Tissue collection using systematic uniform random sampling was representative for the whole organ and allowed stereologic quantification of structures. RESULTS: After IR, histochemistry revealed no breaks in the alveolo-capillary barrier and we detected no alveolar flooding. Edema formed in the peribronchovascular cuffs, of which the volume fraction was increased (p =.008). Vasoconstriction of the smaller arteries accompanied antegrade flush, which occurred neither after administration of NTG nor after retrograde flush, as shown by immunostaining for alpha-smooth muscle actin. Treatment with NTG was associated with focal disintegration of Type II cells, which displayed edematous swelling of distinct cell compartments and lysis of mitochondria and cells. Nitroglycerin prevented alveolar collapse, which was increased in the other IR groups (p = 0.013). We observed alterations in intra-alveolar surfactant components. CONCLUSION: These findings indicate pathologic effects of NTG treatment on alveolar epithelial integrity. Therefore, we suggest further critical evaluation of NTG/NO for therapeutic use in lung transplantation.


Assuntos
Transplante de Pulmão/fisiologia , Pulmão/irrigação sanguínea , Óxido Nítrico/toxicidade , Nitroglicerina/toxicidade , Alvéolos Pulmonares/efeitos dos fármacos , Traumatismo por Reperfusão/patologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Dissacarídeos , Eletrólitos , Epitélio/efeitos dos fármacos , Epitélio/patologia , Glutamatos , Glutationa , Histidina , Masculino , Manitol , Microscopia Eletrônica , Óxido Nítrico/fisiologia , Alvéolos Pulmonares/patologia , Ratos , Ratos Sprague-Dawley
10.
Ann Thorac Surg ; 71(3): 1004-6, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11269410

RESUMO

Preexisting pulmonary hypertension in pediatric patients is associated with poor outcome after cardiac transplantation because of donor right ventricular dysfunction. To avoid a combined heart-lung transplantation in a 17-year-old patient, we used an intensified pretreatment with intravenous prostacyclin and dobutamine combined with an inhalative therapy with the aerosolized prostacyclin-analog Iloprost. With this regimen, the patient was hemodynamically stabilized for the waiting period of 21 days after which an uneventful cardiac transplantation was performed.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Transplante de Coração , Hipertensão Pulmonar/tratamento farmacológico , Iloprosta/administração & dosagem , Cuidados Pré-Operatórios , Adolescente , Aerossóis , Humanos , Masculino , Índice de Gravidade de Doença
11.
Eur J Cardiothorac Surg ; 18(4): 447-52, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11024383

RESUMO

OBJECTIVE: Patients with primary pulmonary hypertension (PPHT) have a worse natural outcome compared with those with secondary pulmonary hypertension in Eisenmenger's syndrome (ES) and chronic pulmonary embolism (CPE). Lung transplantation (SLTx, DLTx, HLTx) still remains the only therapeutical option for patients with this type of endstage lung disease. METHODS: From 1988 to 1998, 63 patients underwent lung transplantation for PPHT (n=29, 9 m, 20 f, 2 SLTx, 14 DLTx, 13 HLTx), ES (n=29, 13 m, 16 f, 2 SLTx, 3 DLTx, 24 HLTx) or CPE (n=5, 2 m, 3 f, 1 SLTx, 2 DLTx, 2 HLTx). Groups were comparable for NYHA functional class, preoperative pulmonary arterial pressure, recipient and donor age, ischemic time, necessity and duration of cardiopulmonary bypass and cross-match. RESULTS: The 1-, 3- and 5-year survival was 52, 40 and 35% for the PPHT-group, 83, 78 and 74% for the ES-group and 80, 60 and 60% for the CPE-group, respectively (P=0.026, P=0.033, P=0.082 for 1-, 3- and 5-year survival). Patients following DLTx showed a lower 1-year survival rate as compared with patients after HLTx both in PPHT patients (36 vs. 62%, P=0.091) and in ES patients (67 vs. 83%, P=0.213). The incidence of bronchiolitis obliterans syndrome was 29% at 1 year and 45% at 3 years for the PPHT-group vs. 17 and 65% for the ES-group (n. s. in between groups). Excluding postoperative ventilation time (PPHT-group: 26.8+/-24.0 days vs. ES-group: 16.1+/-30.8 days, P=0. 011) and a higher incidence of infectious causes of death (PPHT-group n=8 vs. ES-group n=1, P=0.017) groups were comparable with regard to their postoperative courses. CONCLUSIONS: It is concluded, that predominantly the underlying primary disease influences graft survival after lung transplantation in patients with pulmonary hypertension compared with all other patient and procedure dependent factors. Lung transplantation in patients with PPHT requires further investigations to achieve results comparable with other indications.


Assuntos
Complexo de Eisenmenger/cirurgia , Sobrevivência de Enxerto , Transplante de Coração , Transplante de Coração-Pulmão , Hipertensão Pulmonar/cirurgia , Adulto , Bronquiolite Obliterante/etiologia , Feminino , Transplante de Coração/mortalidade , Transplante de Coração-Pulmão/mortalidade , Humanos , Masculino , Estudos Retrospectivos , Análise de Sobrevida
12.
J Heart Lung Transplant ; 19(10): 976-83, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11044693

RESUMO

BACKGROUND: Optimal preservation of post-ischemic organ function is a continuing challenge in clinical lung transplantation. Retrograde instillation of preservation solutions has the theoretic advantage of achieving homogeneous distribution in the lung because of perfusing both the pulmonary and the bronchial circulation. So far, we have seen no experimental studies that include stereologic analysis of intrapulmonary edema concerning the influence of retrograde preservation on post-ischemic lung function after preservation with Perfadex and Celsior. METHODS: In an extracorporeal rat model, we perfused 8 lungs, each, using either antegrade or retrograde perfusion technique with Celsior (CE(ant)/CE(ret)) and Perfadex (PER(ant)/PER(ret)). Results were compared with low-potassium Euro-Collins. Post-ischemic lungs were reventilated and reperfused mechanically. We continuously monitored relative oxygenation capacity (ROC), pulmonary artery pressure, flush time, and wet/dry ratio. Furthermore, we used stereologic means to evaluate edema formation. Statistics comprised different analysis of variance models. RESULTS: Relative oxygen capacity of CE(ant)-protected lungs was superior to that of PER(ant) preservation (p = 0.05). Use of PER(ret) resulted in significantly higher ROC as compared with PER(ant) (p < 0.001) and was comparable to results obtained with CE-preservation, which was not further improved with retrograde application. CONCLUSIONS: Celsior provides better lung preservation than does Perfadex when administered antegradely. Retrograde application of Perfadex results in significant functional improvement as compared with antegrade perfusion, which reaches the standard of Celsior-protected organs. Additional in vivo experiments in combination with ultrastructural analysis are warranted to further evaluate retrograde delivery of preservation solutions, which could be used in clinical lung transplantation to further optimize current results.


Assuntos
Citratos/administração & dosagem , Pulmão , Soluções para Preservação de Órgãos/administração & dosagem , Preservação de Tecido , Animais , Dissacarídeos/administração & dosagem , Eletrólitos/administração & dosagem , Glutamatos/administração & dosagem , Glutationa/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Histidina/administração & dosagem , Pulmão/metabolismo , Pulmão/patologia , Masculino , Manitol/administração & dosagem , Modelos Animais , Oxigênio/metabolismo , Ratos , Ratos Sprague-Dawley
13.
Ann Thorac Surg ; 69(6): 1787-91, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10892924

RESUMO

BACKGROUND: The quality of surgical beating heart revascularization is frequently questioned, especially when the surgical access is limited. Nevertheless, the number of off-pump coronary procedures is expanding worldwide. METHODS: Since getting started with minimally invasive direct coronary artery bypass to anterior myocardial vessels in June 1996, 306 patients received left internal mammary artery grafting through an anterior minithoracotomy. Risk increasing comorbidities were present in 168 of them. Particular attention was paid to early postoperative angiographic results and complications. RESULTS: The 30-day mortality summed up at 1.0% and was limited to patients with additional risks for conventional bypass grafting. Early postoperative control angiographies in 232 patients confirmed a global patency rate of 97.8%, revealing in addition four unexpected malinsertions to diagonal branches. In surviving patients major complications like myocardial infarction, stroke, or multiorgan failure were completely absent. CONCLUSIONS: Minimally invasive direct coronary artery bypass grafting appears to allow for a safe and effective revascularization of the left anterior descending artery by use of the left internal mammary artery. Especially patients with risk increasing comorbidities should benefit from this approach, provided the surgical indication based on a dominating left anterior descending artery lesion. Angiographic minimally invasive direct coronary artery bypass results seem to fulfill the expectations generated by results obtained in conventional left internal mammary artery grafting and appear to be superior to interventional means.


Assuntos
Doença das Coronárias/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Revascularização Miocárdica , Idoso , Causas de Morte , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/mortalidade , Feminino , Parada Cardíaca Induzida , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/mortalidade , Taxa de Sobrevida
14.
Am J Respir Crit Care Med ; 161(6): 2058-65, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10852788

RESUMO

Ischemia/reperfusion (I/R) injury results in the impairment of surfactant activity. The hypothesis that the differences in lung preservation quality obtained by EuroCollins (EC) and Celsior (CE) solutions were related to surfactant alterations was tested. To avoid extensive structural damage and edema formation, which can secondarily affect the surfactant system, lungs were stored for a short ischemic period (2 h at 10 degrees C) and reperfused (50 min) in an isolated perfused rat lung model after preservation with either potassium-reduced (40 mmol) EC40 or with CE. Using a modified stereological approach ultrastructure, total amount and distribution of phospholipid membranes composing tubular myelin (tm) and small (s) and large (l) unilameliar vesicles (ul) were investigated in the organ in lungs fixed by vascular perfusion either in situ (controls) or after I/R (n = 5 per group). The total amount of intraalveolar surfactant was increased after I/R. However, a significant amount (p = 0.008) of tm was displaced into the alveolar lumen and showed wider meshes of the tm lattices than did the controls (p = 0.023) where almost all tm was epithelial. In lungs preserved with EC40, epithelial tm was significantly reduced (p = 0.018), resulting in a higher ratio (p = 0.034) of surface-inactive small ul (0.05 to 0.3 microm) to surface-active epithelial tm. In the CE group approximately 50% of the total tm pool was epithelial. This was accompanied by higher parenchymal air space and improved functional parameters. Epithelial and endothelial cell-specific immunostaining did not reveal any gross damage of the blood-gas barrier. In summary, improved lung function during reperfusion was associated with beneficial effects of lung preservation on tm integrity after I/R. These observations suggest that preservation solutions ameliorate events leading to surfactant disturbance even before extensive lung injury is manifested.


Assuntos
Produtos Biológicos , Isquemia/patologia , Pulmão/irrigação sanguínea , Preservação de Órgãos , Proteínas , Surfactantes Pulmonares/ultraestrutura , Traumatismo por Reperfusão/patologia , Animais , Dissacarídeos/farmacologia , Eletrólitos/farmacologia , Glutamatos/farmacologia , Glutationa/farmacologia , Histidina/farmacologia , Soluções Hipertônicas/farmacologia , Pulmão/patologia , Masculino , Manitol/farmacologia , Bainha de Mielina , Ratos , Ratos Sprague-Dawley
16.
Heart ; 83(1): 58-63, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10618337

RESUMO

OBJECTIVE: To expand the benefits of the minimally invasive direct coronary artery bypass (MIDCAB) concept to patients with multivessel disease, a hybrid procedure combining surgical revascularisation of the left anterior descending artery with interventional procedures for additional coronary lesions has recently been introduced. Preliminary results in patients undergoing this hybrid procedure are presented. DESIGN AND PATIENTS: Since December 1996, 35 patients (29 male, 6 female, mean (SD) age 56.7 (17) years) underwent a hybrid revascularisation performed as a primary MIDCAB procedure for grafting of the left anterior descending artery with the left internal mammary artery, followed by staged angioplasty and stenting of additional coronary lesions. RESULTS: After MIDCAB grafting the postoperative course was uneventful in all patients. Coronary reangiography after a median of seven days revealed patent and functioning left internal mammary artery grafts in all patients. Applying subsequent percutaneous transluminal coronary angioplasty and occasional stenting (n = 14), a total of 47 lesions were treated successfully. Procedure related complications did not occur. All patients remained free from angina and no stress ECG changes were recorded. CONCLUSIONS: The preliminary results of this hybrid approach to myocardial revascularisation suggest that this is a safe and effective procedure for complete revascularisation in selected patients with multivessel disease. Elderly and reoperative patients with significant comorbidity may benefit especially from such hybrid procedures by avoiding cardiopulmonary bypass and mid sternotomy.


Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/cirurgia , Anastomose de Artéria Torácica Interna-Coronária/métodos , Revascularização Miocárdica/métodos , Adulto , Idoso , Comorbidade , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Stents
17.
Thorac Cardiovasc Surg ; 48(6): 356-9, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11145404

RESUMO

BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) grafting is an accepted therapeutical option especially in multimorbid, elderly and reoperative patients with single vessel disease. To expand the benefits of M


Assuntos
Doença das Coronárias/cirurgia , Revascularização Miocárdica/métodos , Adulto , Idoso , Angiografia Coronária , Eletrocardiografia , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Período Pós-Operatório , Grau de Desobstrução Vascular
18.
J Heart Lung Transplant ; 18(12): 1198-201, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10612378

RESUMO

BACKGROUND: Optimal preservation of post-ischemic organ function is a continuing challenge in clinical lung transplantation. METHODS: Using an established extracorporeal rat lung screening model, the results after preservation of 8 lungs, each with the extracellular-type preservation solutions Celsior and Perfadex using ischemic periods of 2 and 4 hours were compared to the results obtained after 2 hours of preservation with low-potassium Euro-Collins with prostacyclin. RESULTS: Oxygenation capacity of all Celsior-preserved organs was significantly higher as compared to LPEC lungs (p < 0.01), and after 4 hours of ischemia, lung preservation in terms of post-ischemic oxygenation ability was significantly higher in the Celsior group compared with Perfadex-protected organs (p < 0.01). CONCLUSION: Especially at extended ischemic times Celsior can provide significantly better pulmonary preservation in terms of oxygenation capacity compared to Perfadex solution, which is associated with a post-ischemic lung function only comparable to preservation with modified Euro-Collins solution.


Assuntos
Citratos/farmacologia , Transplante de Pulmão , Pulmão/fisiologia , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos/métodos , Animais , Pressão Sanguínea , Dissacarídeos/farmacologia , Eletrólitos/farmacologia , Glutamatos/farmacologia , Glutationa/farmacologia , Histidina/farmacologia , Soluções Hipertônicas/farmacologia , Masculino , Manitol/farmacologia , Oxigênio/metabolismo , Artéria Pulmonar/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Soluções , Fatores de Tempo
20.
Ann Thorac Surg ; 68(2): 470-2, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10475414

RESUMO

BACKGROUND: Coronary revascularization in patients with pectus excavatum is technically difficult through a median sternotomy secondary to the posterior displacement of the sternum and the asymmetric angulation that it produces. The role of minimally invasive coronary artery bypass grafting (MIDCABG) in this subset of patients was evaluated. METHODS: In 1998, four patients with pectus excavatum underwent revascularization of the left anterior descending artery without cardiopulmonary bypass through a left anterior minithoracotomy. RESULTS: All patients underwent the procedure without intraoperative complications and postoperative angiography demonstrated adequate graft patency. CONCLUSIONS: The advantages of MIDCABG in patients with pectus excavatum is the superior exposure to the LAD and LIMA and avoidance of a median sternotomy and cardiopulmonary bypass. This procedure is deemed safe and effective in patients with such deformities of the chest wall.


Assuntos
Doença das Coronárias/cirurgia , Tórax em Funil/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Revascularização Miocárdica , Ponte Cardiopulmonar , Doença das Coronárias/diagnóstico por imagem , Tórax em Funil/diagnóstico por imagem , Humanos , Anastomose de Artéria Torácica Interna-Coronária , Masculino , Pessoa de Meia-Idade , Toracotomia , Tomografia Computadorizada por Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA