RESUMO
OBJECTIVES: To evaluate the interim results of the initial multicenter feasibility trial for trans-apical aortic-valve implantation (TA-AVI) in high-risk elderly patients with severe aortic stenosis. METHODS: A total of 168 patients were prospectively included in three European centers between February 2006 and April 2008. The Cribier-Edwards or Edwards SAPIEN™ Trans-catheter Heart Valve (23 mm and 26 mm) was implanted using an oversizing concept. Interventions were performed in a hybrid operative room (OR) (one center), with a mobile C-arm in the OR (one) and in the catheterization laboratory (one). Inclusion criteria included age ≥70 years and an increased risk profile (additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) ≥9). RESULTS: Patient age was 82.1±5.6 years, 76% were female and the EuroSCORE was 11.3±1.8 (additive) and 27±12.7% (logistic). Cardiopulmonary bypass was used by intention in 14.2% during the initial phase, secondarily in 10.1% and 75% of the patients were treated off-pump. Valve implantation led to a good immediate result in 161 (95.8%) patients and problems were encountered in seven patients (malposition (two patients), migration (three patients) and severe incompetence (two patients)). Nine patients were converted to conventional surgery, early stroke occurred in two (1.2%) patients and 10 (6%) patients received a new pacemaker. At 30 days, 25 patients died, 48% of them due to cardiac-related causes. Overall survival at 30 days, 6 months and 1 year was 85%, 70% and 63%, respectively. CONCLUSIONS: The initial multicenter feasibility trial for TA-AVI (TRAVERCE) shows acceptable results of this promising technique, especially in view of the high-risk profile of the patients.
Assuntos
Estenose da Valva Aórtica/terapia , Valva Aórtica/cirurgia , Bioprótese , Cateterismo/métodos , Implante de Prótese de Valva Cardíaca/métodos , Próteses Valvulares Cardíacas , Idoso , Idoso de 80 Anos ou mais , Insuficiência da Valva Aórtica/etiologia , Estenose da Valva Aórtica/mortalidade , Ecocardiografia , Estudos de Viabilidade , Feminino , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
The influence of an acellular porcine matrix on proinflammatory activation of endothelial cells (EC) during normoxia and hypoxia was investigated by a newly established semi-quantitative electron microscopic procedure. As a model, three adhesion molecules (E-selectin, ICAM-1, and VCAM-1) were localized by silver-enhanced immunogold staining and energy dispersive X-ray microanalysis after normoxic or hypoxic pretreatment of the cells and subsequent stimulation with IL-1beta. Morphology of EC grown on porcine matrix or coverslips was recorded simultaneously using secondary electron imaging. EC appeared tightly attached to the underlying surfaces with their typical cobblestone-like morphology. Statistically significant upregulations upon stimulation with IL-1beta were observed in both groups for all three adhesion molecules. Hypoxic pretreatment of the specimens with subsequent reoxygenation neither induced morphological changes nor caused an upregulation of adhesion molecule expression in cells grown on acellular porcine tissue. Unexpectedly, in cells seeded onto the acellular matrix, IL-1beta failed to upregulate ICAM-1 expression after a short period of hypoxia. The surface expression of VCAM-1 was also significantly lower even under normoxic conditions, which might indicate the development of functional impairment of cells in contact with acellular porcine tissue. The method presented in this study has proven valuable for the determination of antigen expression on scaffold materials in parallel with the characterization of surface morphology.
Assuntos
Antígenos de Superfície/metabolismo , Microanálise por Sonda Eletrônica/métodos , Engenharia Tecidual , Alicerces Teciduais , Animais , Selectina E/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/ultraestrutura , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/farmacologia , Microscopia Eletrônica de Varredura , Sus scrofa , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Expression of the lymphoendothelial marker membrane mucoprotein podoplanin (podo) distinguishes endothelial cells of both blood and lymphatic lineages. We have previously discovered two distinct subpopulations of lymphatic endothelial cells (LECs) in human skin that were defined by their cell surface densities of podoplanin and were designated LEC podo-low and LEC podo-high. LEC podo-low is restricted to lymphatic precollector vessels that originate from initial LEC podo-high-containing lymphatic capillaries and selectively express several pro-inflammatory factors. In addition to the chemokine receptor protein Duffy blood group antigen receptor for chemokines, these factors include the constitutively expressed chemokine CCL27, which is responsible for the accumulation of pathogenic CCR10+ T lymphocytes in human inflammatory skin diseases. In this study, we report that CCR10+ T cells accumulate preferentially both around and within CCL27+ LEC podo-low precollector vessels in skin biopsies of human inflammatory disease. In transmigration assays, isolated CCR10+ T lymphocytes are chemotactically attracted by LEC podo-low in a CCL27-dependent fashion, but not by LEC podo-high. These observations indicate that LEC podo-low-containing precollector vessels constitute a specialized segment of the initial lymphatic microvasculature, and we hypothesize that these LEC podo-low-containing vessels are involved in the trafficking of CCR10+ T cells during skin inflammation.
Assuntos
Quimiocina CCL27/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Vasos Linfáticos/citologia , Glicoproteínas de Membrana/metabolismo , Proliferação de Células , Separação Celular , Células Cultivadas , Quimiotaxia , Derme/irrigação sanguínea , Derme/patologia , Feminino , Rejeição de Enxerto , Humanos , Inflamação/genética , Transporte Proteico , Receptores CCR10/metabolismo , Dermatopatias/imunologia , Dermatopatias/patologia , Linfócitos T/patologiaRESUMO
Decellularization treatment of heart valves has been thought to eliminate tissue immunogenicity. Early failure of tissue-engineered xenogeneic heart valves was seen in children and has been a major drawback in this promising field of research. This study was designed to characterize the effects of acellular porcine heart valve tissue on immune activation in vitro. Incubation of decellularized porcine tissue with human plasma led to adsorption of IgG, activation of the classical complement pathway and adhesion of activated polymorphonuclear leukocytes (PMN). This inflammatory response was strongly inhibited by proteins extracted from native porcine tissue which might indicate that inhibitors of PMN activation present in the extracellular matrix (ECM) are lost during the decellularization process.
Assuntos
Ativação do Complemento/imunologia , Via Clássica do Complemento/imunologia , Granulócitos/imunologia , Valvas Cardíacas/citologia , Valvas Cardíacas/imunologia , Imunoglobulina G/imunologia , Idoso , Animais , Sistema Livre de Células/imunologia , Células Cultivadas , Feminino , Humanos , Masculino , SuínosRESUMO
Tissue-engineered heart valves constructed from a xenogeneic or allogeneic decellularized matrix might overcome the disadvantages of current heart valve substitutes. One major necessity besides effective decellularization is to preserve the biomechanical properties of the valve. Native and decellularized porcine pulmonary heart valve conduits (PPVCs) (with [n = 10] or without [n = 10] cryopreservation) were compared to cryopreserved human pulmonary valve conduits (n = 7). Samples of the conduit were measured for wall thickness and underwent tensile tests. Elongation measurement was performed with a video extensometer. Decellularized PPVC showed a higher failure force both in longitudinal (+73%; P < 0.01) and transverse (+66%; P < 0.001) direction compared to human homografts. Failure force of the tissue after cryopreservation was still higher in the porcine group (longitudinal: +106%, P < 0.01; transverse: +58%, P < 0.001). In comparison to human homografts, both decellularized and decellularized cryopreserved porcine conduits showed a higher extensibility in longitudinal (decellularized: +61%, P < 0.001; decellularized + cryopreserved: +51%, P < 0.01) and transverse (decellularized: +126%, P < 0.001; decellularized + cryopreserved: +118%, P < 0.001) direction. Again, cryopreservation did not influence the biomechanical properties of the decellularized porcine matrix.
Assuntos
Criopreservação , Valva Pulmonar/fisiologia , Animais , Fenômenos Biomecânicos , Congelamento , Humanos , Técnicas In Vitro , Valva Pulmonar/transplante , Suínos , TransplantesRESUMO
BACKGROUND: This study assessed the feasibility of stent graft treatment of ascending aortic dissections in a porcine in vitro model. METHODS: The entire thoracic aortic aorta including the supraaortic branches was harvested from 12 adult pigs and an intimal tear was artificially created. The aortic annulus was then sewn into a silicon ring of a driving chamber. The distal aorta was connected to tubing with adjustable resistance elements. The circulation was driven by a hydraulic motor piston pump to mimic aortic flow and pressure. After creating a dissection by elevating the systolic aortic pressure to 180 mm Hg, a 2- x 2.6-cm covered stent graft was inserted through the brachiocephalic trunk using a specially designed delivery system. Stent graft placement was performed under continuous ultrasound control. RESULTS: The longitudinal length of the created ascending aortic dissection was 1.8 +/- 0.39 cm. Ultrasound studies revealed successful deployment of the stent graft and closure of the false lumen in all 12 cases. Diameter and area of the true lumen increased from 0.52 +/- 0.15 cm to 2.54 +/- 0.36 cm (p < 0.05) and from 0.78 +/- 0.27 cm2 to 5.13 +/- 1.35 cm2 (p < 0.05), respectively. The circumference of the true lumen increased from 4.50 +/- 0.52 cm to 7.96 +/- 1.2 cm (p < 0.05). Ultrasound studies also revealed uncompromised function of the aortic valve in all cases. No dislodging of stent grafts was observed. CONCLUSIONS: Given ideal anatomy, experimental stent graft placement for ascending aortic dissection is feasible and achieves complete closure of the false lumen.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Stents , Dissecção Aórtica/diagnóstico por imagem , Animais , Aneurisma da Aorta Torácica/diagnóstico por imagem , Prótese Vascular , Modelos Animais de Doenças , Ecocardiografia Doppler , Estudos de Viabilidade , Probabilidade , Sensibilidade e Especificidade , SuínosRESUMO
BACKGROUND: Even after successful single-lung transplantation (SLTx) or bilateral lung transplantation (BLTx), patients continue to have peripheral muscle weakness and exercise impairment. After SLTx, exercise limitation is also attributed to persistent or recurrent pulmonary vascular abnormalities with elevated pulmonary arterial pressures at rest or during exercise. Therefore, the aim of this study was to evaluate systolic pulmonary artery pressures (PASPs) at rest and during supine bicycle exercise, exercise capacity and cardiopulmonary function in post-BLTx patients. METHODS: Nine patients underwent BLTx due to end-stage pulmonary arterial hypertension (PAH) and 37 age- and gender-matched control subjects underwent a physical examination, electrocardiographic (ECG) test, a 6-minute walk test, a lung function test, a cardiopulmonary exercise test and echocardiographic assessment at rest and during exercise. RESULTS: Exercise capacity was significantly reduced in the BLTx group, with an impaired 6-minute walk test and maximal oxygen uptake and workload. Ventilatory factors did not appear to limit exercise capacity. Right and left ventricular size and pump function and PASP values at rest were normal in both groups, but exceeded 40 mm Hg in 3 of 9 BLTx recipients and in 1 of 37 controls during exercise at low workloads. Mean PASP during exercise was only slightly higher in the BLTx group (40 +/- 5 vs 36 +/- 4 mm Hg, p = not statistically significant). CONCLUSIONS: Reduced exercise capacity of patients after BLTx due to end-stage pulmonary hypertension is not attributed to persistent or recurrent manifest pulmonary hypertension or cardiopulmonary dysfunction. Nevertheless, latent pulmonary hypertension with exaggerated pulmonary artery pressures during exercise may occur in some patients.
Assuntos
Ecocardiografia Doppler/métodos , Ecocardiografia sob Estresse/métodos , Hipertensão Pulmonar/cirurgia , Transplante de Pulmão/métodos , Artéria Pulmonar/diagnóstico por imagem , Pressão Propulsora Pulmonar/fisiologia , Adulto , Teste de Esforço , Tolerância ao Exercício/fisiologia , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Prognóstico , Artéria Pulmonar/fisiopatologia , Testes de Função Respiratória , Índice de Gravidade de DoençaRESUMO
Supporting structures derived from biological tissue have been used in numerous tissue-engineering applications. This study focuses on the immune response of human leukocytes toward decellularized or glutaraldehyde (GA) cross-linked vascular tissue in vitro. Porcine and human pulmonary roots were sterilized with antibiotics, decellularized or cross-linked with GA. Proteins of the vascular tissue were extracted and the migratory response of human leukocytes toward protein extracts was examined using an in vitro migration chamber. Transmigrated leukocytes were counted and subsets (lymphocytes, monocytes, granulocytes) analyzed by flow cytometry. Decellularization significantly reduced the migration of monocytes compared to native porcine tissue. Although the proportion of transmigrating lymphocytes was much lower, decellularization again reduced the migratory response. Surprisingly, after decellularization granulocyte migration was still significantly higher than the negative control. Results comparable to those obtained with porcine material were found when human tissue was used for the experiments. Interestingly, migratory behavior toward extracts of GA-fixed porcine tissue was similar to that of decellularized specimens. We have shown that decellularization of vascular tissue reduces lymphocyte and monocyte recruitment comparable to cross-linking treatment. However, the migration of granulocytes, which are also known to be strongly involved in early inflammatory reactions, could be abolished neither by decellularization nor by fixation with GA.
Assuntos
Movimento Celular/fisiologia , Reagentes de Ligações Cruzadas/química , Glutaral/química , Granulócitos/imunologia , Imunidade/fisiologia , Artéria Pulmonar/citologia , Animais , Granulócitos/citologia , Humanos , Leucócitos/citologia , Leucócitos/imunologia , Artéria Pulmonar/química , Suínos , Engenharia TecidualRESUMO
BACKGROUND AND AIM OF THE STUDY: In tissue engineering of heart valves using decellularized xenogenic valves, it has been suggested that cell elimination would result in a biologically inert matrix. The aim of this in-vitro investigation was to evaluate different decellularization methods in regard to the completeness of cell removal, inflammatory response, and thrombocyte activation. METHODS: Decellularized porcine Synergraft valves were compared with porcine pulmonary conduits decellularized with Triton X-100, sodium deoxycholate, Igepal CA-630 and ribonuclease. Completeness of decellularization was evaluated with staining for nuclei and alpha-Gal epitope. Decellularized heart valves with and without seeding with endothelial cells (ECs) were incubated with human platelet-rich plasma and stained for CD41 and PAC-1 to evaluate thrombocyte activation. Samples were processed for laser scanning microscopy (LSM) and scanning electron microscopy (SEM). Migration of human monocytic cells towards extracted valve proteins was tested. RESULTS: In contrast to the Synergraft, complete cell removal and elimination of the alpha-gal epitope was achieved with the new decellularization method. Numerous adherent and activated platelets were found on the decellularized matrix. This was inhibited by seeding with ECs. Even in completely cell-free valve tissue extracellular matrix proteins attracted human monocytic cells as in early inflammation, depending on whether porcine or human tissue was used. CONCLUSION: Important differences were found in the decellularization efficacy of treatment methods. However, even complete elimination of cells and their remnants did not result in a biologically inert matrix. The decellularized porcine heart valve matrix has the potential to attract inflammatory cells and to induce platelet activation. These findings suggest that it will be important to control the different inflammation-stimulating factors if porcine tissues are to be used successfully in tissue engineering.
Assuntos
Implante de Prótese de Valva Cardíaca/efeitos adversos , Próteses Valvulares Cardíacas , Valva Pulmonar , Trombose/prevenção & controle , Inclusão do Tecido/métodos , Animais , Movimento Celular/efeitos dos fármacos , Ácido Desoxicólico/farmacologia , Detergentes/farmacologia , Modelos Animais de Doenças , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/cirurgia , Microscopia Confocal , Octoxinol/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Desenho de Prótese , Valva Pulmonar/efeitos dos fármacos , Valva Pulmonar/cirurgia , Valva Pulmonar/ultraestrutura , Ribonucleases/farmacologia , Suínos , Trombose/etiologiaRESUMO
An approach in tissue engineering of heart valves is the use of decellularized xenogeneic matrices to avoid immune response after implantation. The decellularization process must preserve the structural components of the extracellular matrix to provide a biomechanically stable scaffold. However, it is known that in vascular lesions platelet adhesion to extracellular matrix components occurs and platelet activation is induced. In the present study we examined the effects of a decellularized porcine heart valve matrix on thrombocyte activation and the influence of re-endothelialisation in vitro. Porcine pulmonary conduits were decellularized using Triton X-100, Na-deoxycholate and Igepal CA-630 followed by a ribonuclease digestion. Cryostat sections of decellularized heart valves with and without seeding with human umbilical vein endothelial cells (HUVEC) were incubated with platelet rich plasma. Samples were either stained with fluorescent antibodies for CD41 and PAC-I (recognizing the activated fibrinogen receptor) or fixed with glutaraldehyde. Thereafter, the samples were processed for laser scanning microscopy (LSM) or scanning electron microscopy (SEM). Examination by LSM showed numerous platelets with co-localized staining for CD41 and PAC-1 on the nonseeded decellularized heart valve matrix whereas after seeding with endothelial cells no platelet activation was detected. SEM revealed platelet adhesion and aggregate formation only on the surface of the non-seeded or partially denuded matrix specimens. We show in this study that the decellularized porcine matrix acts as a platelet-activating surface. Seeding with endothelial cells effectively abolishes the platelet adhesion and activation and therefore is necessary to eliminate thrombogenicity in tissue engineered heart valves.
Assuntos
Valva Aórtica/metabolismo , Plaquetas/metabolismo , Células Endoteliais/transplante , Matriz Extracelular/metabolismo , Próteses Valvulares Cardíacas/efeitos adversos , Ativação Plaquetária , Adesividade Plaquetária , Engenharia Tecidual/métodos , Animais , Valva Aórtica/citologia , Valva Aórtica/efeitos dos fármacos , Bioprótese/efeitos adversos , Células Cultivadas , Técnicas de Cocultura , Células Endoteliais/metabolismo , Doenças das Valvas Cardíacas/terapia , Humanos , Tensoativos/farmacologia , Suínos , Trombose/etiologia , Trombose/prevenção & controle , Fatores de TempoAssuntos
Implantes Absorvíveis , Músculo Liso Vascular , Engenharia Tecidual/métodos , Animais , Cães , SuínosRESUMO
Tissue engineering of heart valves promises to create functional autologous tissue with the potential for regeneration and growth without the limitations of current heart valve prostheses. The appropriate valve matrix is essential. Porcine heart valves are attractive because of their anatomical similarity. Decellularization is used for antigen reduction. The efficacy of published protocols varies, however. The absence of a specific immunological or unspecific inflammatory reaction is mandatory. The porcine cell-specific alpha-Gal epitope is known to be responsible for hyperacute rejection in xenotransplantation. In tissue engineering residual alpha-Gal epitope may induce severe inflammation in humans and may lead to graft failure. In this study porcine pulmonary conduits were decellularized with Triton X-100, sodium deoxycholate, Igepal CA-630, and ribonuclease treatment and were compared with specimens of the commercially available porcine decellularized SynerGraft regarding cell removal and elimination of the alpha-Gal epitope. In addition, samples of a porcine bioprosthesis were examined for the presence of the alpha-Gal epitope. In conclusion, we describe for the first time the presence of the alpha-Gal epitope in clinically used porcine bioprostheses and the first generation of a commercial tissue-engineered heart valve. In contrast, complete cell and alpha-Gal removal was achieved by a decellularization procedure developed by our group.
Assuntos
Antígenos Heterófilos/imunologia , Antígenos Heterófilos/isolamento & purificação , Bioprótese , Dissacarídeos/imunologia , Dissacarídeos/isolamento & purificação , Próteses Valvulares Cardíacas , Valva Pulmonar/citologia , Valva Pulmonar/imunologia , Engenharia Tecidual/métodos , Animais , Fracionamento Celular , Rejeição de Enxerto/prevenção & controle , Valva Pulmonar/transplante , SuínosRESUMO
Autologous cells migrate only slightly into acellular matrix grafts. This study was carried out in small-diameter, allogeneic matrix grafts to investigate the effects on cell repopulation and remodeling caused by increased wall porosity induced by laser perforation. Allogeneic ovine carotid arteries were decellularized by dye-mediated photooxidation (Photofix). Matrix grafts (10 cm x 4 mm i.d.) were perforated with holes of 50 microm diameter at a density of 50 holes/cm(2) using a Ti-sapphire laser. The grafts were implanted in the carotid arteries of 10 sheep and were compared to nonperforated grafts implanted contralaterally. The prostheses were retrieved after 6 weeks or 3 or 6 months following implantation and were evaluated by histologic examination, immunohistochemical staining, and scanning electron microscopy. All grafts, except one of the perforated specimens, remained patent. Perforated implants, examined at 6 weeks, showed faster recellularization with endothelial cells than did the corresponding contralateral controls. Perforated grafts, examined at 6 months, showed a significantly thicker neointima and clear signs of neovascularization: endothelial cells, basal lamina, elastic fibers, circular and longitudinally orientated smooth muscle cells in comparison to nonperforated specimens. Repopulation of the decellularized matrix with host cells was higher in the perforated than in the nonperforated prostheses. These results suggest that the increased matrix porosity induced by laser perforation promotes graft remodeling and reconstitution with host cells.
Assuntos
Materiais Biocompatíveis/química , Prótese Vascular , Artérias Carótidas/patologia , Lasers , Animais , Bioprótese , Proliferação de Células , Endotélio Vascular , Imuno-Histoquímica , Luz , Microscopia Eletrônica de Varredura , Oxigênio/metabolismo , Ovinos , Titânio , Grau de Desobstrução VascularRESUMO
BACKGROUND: Tissue-engineered or decellularized heart valves have already been implanted in humans or are currently approaching the clinical setting. The aim of this study was to examine the migratory response of human monocytic cells toward decellularized porcine and human heart valves, a pivotal step in the early immunologic reaction. METHODS AND RESULTS: Porcine and human pulmonary valve conduits were decellularized, and migration of U-937 monocytic cells toward extracted heart valve proteins was examined in a transmigration chamber in vitro. Homogenized tissue specimens were size fractionated by SDS-PAGE. The decellularization procedure effectively reduced the migration of human monocytes toward all heart valve tissue. However, only the antigen reduction of human pulmonary valves abolished the monocytic response (wall, 0.88+/-0.19% versus 30.20+/-3.93% migrated cells [mean+/-SEM]; cusps, 0.10+/-0.06% versus 10.24+/-1.83%) and was significantly lower (P<0.05) than that of the decellularized porcine equivalent (wall, 5.03+/-0.14% versus 24.31+/-2.38%; cusps, 3.18+/-0.38% versus 10.24+/-1.83%). SDS-PAGE of the pulmonary heart valve tissue revealed that considerable amounts of proteins with different molecular weights that were not detected in the human equivalent remain in the decellularized porcine heart valve. CONCLUSIONS: We describe for the first time that the remaining potential of decellularized pulmonary heart valves to attract monocytic cells depends strongly on whether porcine or human scaffolds were used. These findings will have an important impact on further investigations in the field of heart valve tissue engineering.
Assuntos
Movimento Celular , Valvas Cardíacas/citologia , Valvas Cardíacas/imunologia , Monócitos/fisiologia , Engenharia Tecidual/métodos , Animais , Linhagem Celular , Eletroforese em Gel de Poliacrilamida , Valvas Cardíacas/química , Humanos , Proteínas/imunologia , Proteínas/isolamento & purificação , Especificidade da Espécie , SuínosRESUMO
OBJECTIVE: Pulmonary hypertension eventually leads to severe distortion of the cardiac geometry with consequent impact on cardiac function. The purpose of this study was to prove reverse cardiac remodelling after isolated bilateral lung transplantation (LuTX) in patients with advanced primary pulmonary hypertension (PPH) and severe alterations of cardiac morphology and function. METHODS: In the period of 2000-2002 17 (10 female, seven male) patients with advanced PPH underwent isolated bilateral LuTX. Median age was 30 years (range 16-53). All patients were in NYHA III or IV, most of them with intractable ascites, established renal impairment, malnutrition and immobility, continuously deteriorating despite various forms of pharmacological treatment including i.v. and inhalative prostacyclin, diuretics, Ca-antagonists, bosentan and catecholamines. Echocardiography and Doppler echocardiography measurements were performed before and 3 months after transplantation. Left and right ventricular diameters and function were assessed and tricuspid valve regurgitation was determined. RESULTS: Mortality after 3 months was 17.5% (cerebral bleeding, multi-organ failure and diffuse myocardial infarction in one patient each). Three months after LuTX the 14 surviving patients were in NYHA I or II. Echocardiography showed normal left ventricular function and markedly improved right ventricular function with normal size of the RV. The leftward shifted flattened interventricular septum had returned in its physiological position and the high-grade tricuspid insufficiency had disappeared in all patients. CONCLUSIONS: Advanced alterations of cardiac morphology and function normalize completely and pre-existing tricuspid insufficiency disappears in PPH patients after isolated bilateral LuTX. Quality of life is excellent. Therefore, LuTX is preferred and safe in patients with advanced PPH even with severe cardiac dysfunction.
Assuntos
Hipertensão Pulmonar/cirurgia , Transplante de Pulmão , Remodelação Ventricular , Adolescente , Adulto , Débito Cardíaco , Ecocardiografia , Ecocardiografia Doppler , Feminino , Ventrículos do Coração/patologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Artéria Pulmonar/fisiopatologiaRESUMO
BACKGROUND AND AIM OF THE STUDY: EuroSCORE is widely used to assess operative risk. Combined cardiac procedures carry increased perioperative mortality, but the influence of preoperative factors on mid-term outcome is not well known for these patients. The study aim was to determine if EuroSCORE risk influences mid-term survival after combined coronary artery bypass grafting (CABG) and valve surgery. METHODS: Follow up (mean 23.7 months) was obtained in 258 consecutive hospital survivors (148 males, 110 females; median age 72.29 years; mean EuroSCORE 7 points) operated on between January 1998 and March 2001. CABG + aortic valve replacement (AVR) was performed in 171 patients, CABG + mitral surgery in 72, and CABG + double valve surgery in 15. Kaplan-Meier estimates were calculated for survival and combined freedom from death and NYHA class III/IV. The Cox regression model was applied to prove the influence of EuroSCORE risk and a number of preoperative and operative variables on mid-term outcome. RESULTS: Thirty patients (11.63%) died during follow up, and 34 (13.17%) were in NYHA class III/IV. Freedom from death and NYHA class III/IV was 89.3%, 74.7% and 55.2% at 12, 24 and 36 months, respectively. The significant predictor for combined death and NYHA class III/IV was EuroSCORE risk (p = 0.0004). In the subgroup of patients with CABG + mitral valve surgery, age was identified as a significant risk factor for death (p = 0.0346), whereas in the subgroup of patients with CABG + AVR EuroSCORE was detected as significant risk factor for combined death and NYHA class III/IV. CONCLUSION: EuroSCORE is an important predictor for poor mid-term outcome after combined CABG and valve surgery.
Assuntos
Valva Aórtica/cirurgia , Ponte de Artéria Coronária , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Valva Mitral/cirurgia , Risco Ajustado , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Doenças das Valvas Cardíacas/mortalidade , Humanos , Masculino , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: We compared 3 different decellularization protocols in porcine heart valves for efficiency of complete cell removal and potential for recellularization. METHODS: Porcine aortic and pulmonary roots were treated with trypsin, sodium-dodecyl-sulphate, or a new method using 0.25% tert-octylphenyl-polyoxyethylen in combination with sodium-deoxycholate. After a subsequent ribonuclease digestion, specimens were seeded with in vitro expanded human saphenous vein endothelial cells and myofibroblasts. RESULTS: After treatment with trypsin and subsequent ribonuclease digestion, endothelial attachment took place; however, xenogenic cells were still visible within the matrix. Unexpectedly, when human cells were seeded onto specimens that had been decellularized with sodium-dodecyl-sulphate, the matrices were surrounded by nonviable endothelial cell fragments, indicating a toxic influence of the ionic detergent; 0.25% tert-octylphenyl-polyoxyethylen together with sodium-deoxycholate completely removed porcine cells and enabled host recellularization. CONCLUSION: Compared with trypsin and sodium-dodecyl-sulphate involving decellularization procedures, reported to be effective in cell removal and susceptible to recellularization with human cells, only the porcine matrix treated with a new detergent-based decellularization method using 0.25% tert-octylphenyl-polyoxyethylen/sodium-deoxycholate followed by nuclease digestion presented an excellent scaffold for recellularization with human cells.
Assuntos
Valva Aórtica/citologia , Valva Aórtica/cirurgia , Bioprótese , Endotélio Vascular/citologia , Matriz Extracelular/química , Próteses Valvulares Cardíacas , Valva Pulmonar/citologia , Valva Pulmonar/cirurgia , Valva Aórtica/ultraestrutura , Materiais Biocompatíveis/farmacologia , Quelantes/farmacologia , Ácido Desoxicólico/farmacologia , Desoxirribonucleases/farmacologia , Detergentes/farmacologia , Ácido Edético/farmacologia , Endotélio Vascular/ultraestrutura , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/ultraestrutura , Humanos , Microscopia Eletrônica , Octoxinol/farmacologia , Desenho de Prótese , Valva Pulmonar/ultraestrutura , Ribonucleases/farmacologia , Veia Safena/citologia , Veia Safena/ultraestrutura , Dodecilsulfato de Sódio/farmacologia , Tensoativos/farmacologiaRESUMO
BACKGROUND: Sixteen patients (mean age, 30.9 +/- 12.9 years; range, 9-79 years) with incompetent bicuspid aortic valves underwent valve-sparing correction between 1992 and 1995. METHODS: All patients underwent triangular resection of the enlarged leaflet. In addition, 13 patients underwent commissuroplasty. In 3 patients leaflet perforations were corrected with glutaraldehyde-fixed autologous pericardial patch. All patients underwent annual echocardiographic and clinical examinations at our institution. RESULTS: During follow-up 1 patient died of heart failure, and 3 patients underwent reoperations because of valve incompetence or dilatation of the sinus. Two patients underwent reoperation perioperatively. At long-term follow-up (mean, 10.06 +/- 1.01 years) the remaining 10 patients were in New York Heart Association class I. No patient was receiving anticoagulation, and no thromboembolic, bleeding, or endocarditis events were observed in 107.2 cumulative patientyears of follow-up. Mean grade of regurgitation was 0.7 +/- 0.5; mean aortic flow velocity was 2.29 +/- 0.47 m/s. Optimal valvular function led to normal ventricular diameters (left ventricular end systolic diameter, 39.2 +/- 4.3 mm; left ventricular end diastolic diameter, 56.2 +/- 5.9 mm) and normal ventricular function (fractional shortening, 31.5% +/- 0.1%). The dimensions of the aortic root were stable from 1-year to late followup (mean aortic annulus, 27.1 +/- 6.8 mm; sinus of Valsalva, 33.0 +/- 7.1 mm; sinotubular junction, 34.1 +/- 7.7 mm; ascending aorta, 31.6 +/- 7.4 mm). CONCLUSION: In contrast to early follow-up results of 5 reoperations, clinical and echocardiographic results were excellent for 10 patients who had undergone reconstruction of bicuspid incompetent aortic valves, and the patients were in stable condition after 10 years. However, the mode of early failure is unknown. Reconstruction of bicuspid valves is possible in selected patients.