RESUMO
OBJECTIVES: An important cornerstone of the Enhanced Recovery After Cardiac Surgery initiative is a fast-track cardiac anesthesia management protocol. Fast-track failure has been described to have a detrimental impact on immediate postoperative outcomes. The authors here evaluated risk factors for short- and long-term effects of fast-track failure. DESIGN: A retrospective cohort study. SETTING: A single academic center. PARTICIPANTS: Adult cardiac surgery was performed on 7,064 patients between January 2013 and October 2019. INTERVENTION: The inclusion criteria for the fast-track program at the postanesthesia care unit were met by 1,097 patients. MEASUREMENTS AND MAIN RESULTS: Univariate and multivariate logistic regression analyses were used to identify independent risk factors. Fast-track failure occurred in 69 (6.3%) patients. These were associated with significant increases in the incidences of coronary revascularization, cardiac tamponade or bleeding requiring surgical intervention, new-onset atrial fibrillation, pneumonia, delirium, and sepsis. Likewise, the postoperative length of stay, and up to 5-year mortality, were significantly higher in the fast-track failure than the nonfailure group. The European System for Cardiac Operative Risk Evaluation II and transfusion of any blood product could be identified as independent risk factors for fast-track failure, with only limited discriminative ability (area under the curve = 0.676; 95% confidence interval, 0.611-0.741). CONCLUSION: Fast-track failure is associated with increases in morbidity and long-term mortality, but remains difficult to predict.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Adulto , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Seguimentos , Humanos , Incidência , Tempo de Internação , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: Increasing evidence suggests that aortic valve (AV) repair may have better long-term outcomes than AV replacement for aortic insufficiency. However, most literature is limited to centres of excellence and has not sufficiently been replicated in nascent programs. This single-centre experience of a newly established AV repair program aims to compare short-term outcomes of AV sparing versus replacement surgery. METHODS: A retrospective cohort study of patients who underwent elective surgery for aortic regurgitation or aortic root dilatation at the Leuven University Hospital between 2013 and 2018 was performed. Patients with a critically ill presentation, endocarditis, aortic stenosis or requiring redo surgery were excluded. Patients were assigned to repair versus replacement based on preoperative intention to preserve the AV. Nearest neighbour propensity score matching was performed to compare both groups. Safety (mortality, morbidity), efficiency (cross-clamp and bypass times) and efficacy end points (repair rate, postoperative echocardiography) were compared. RESULTS: One hundred and seven patients underwent AV surgery (48 repair, 59 replacement), from which 2 groups of 23 matched patients were created. There were 1 death and 2 reoperations after repair and no death and 1 reoperation after replacement. Extracorporeal circulation and aortic cross-clamp time were significantly longer while ventilation and total hospital stay were significantly shorter after AV repair. Echocardiographic follow-up showed comparable aortic regurgitation but lower transvalvular gradients after repair. Freedom from major complications was comparable in both cohorts. CONCLUSIONS: Early results suggest the feasibility of replicating experienced centres' perioperative and short-term outcomes in nascent programs.
Assuntos
Insuficiência da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Infective endocarditis (IE) remains a severe disease with high mortality. Most studies report on short-term outcome while real world long-term outcome data are scarce. This study reports reinfection rates and mortality data during long-term follow-up. METHODS: A total of 270 patients meeting the modified Duke criteria for definite IE admitted to a tertiary care center between July 2000 and June 2007 were analyzed retrospectively. Early reinfection was defined as a new IE episode within 6 months; late reinfection as a new IE episode beyond 6 months follow-up. RESULTS: Median follow-up was 8.5 years. Early reinfection occurred in 10 patients (3.7%), late reinfection in 18 patients (6.7%). Staphylococci (39.7%) were the most frequent causative microorganisms, followed by Streptococci (30.0%) and Enterococci (17.8%). Independent predictors of any reinfection were heart failure (HR 3.02, 95% CI 1.42-6.41), peripheral embolization (HR 4.00, 95% CI 1.58-10.17) and implanted pacemakers (HR 3.43, 95% CI 1.25-9.36). Survival rates were 71.1%, 55.2% and 43.3% at respectively 1-, 5- and 10-years follow-up. Independent predictors for mortality were age (HR 1.03, 95% CI 1.01-1.04), diabetes mellitus (HR 2.24, 95% CI 1.46-3.45), hemodialysis (HR 2.70, 95% CI 1.37-5.29), heart failure (HR 1.64, 95% CI 1.19-2.26), stroke (HR 1.73, 95% CI 1.18-2.52), antimicrobial treatment despite surgical indication (HR 5.53, 95% CI 3.59-8.49) and non-Streptococci causative microorganisms (HR 1.84, 95% CI 1.28-2.64). CONCLUSIONS: Contemporary mortality rates of infective endocarditis remain high, irrespective of reinfection. Heart failure, peripheral embolization and presence of a pacemaker were predictors of reinfection.
Assuntos
Endocardite Bacteriana , Endocardite , Endocardite/diagnóstico , Endocardite/epidemiologia , Endocardite/terapia , Seguimentos , Humanos , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção TerciáriaRESUMO
BACKGROUND: International electives benefit training of medical residents due to exposure to an increased scope of pathologies, improved physical examination skills, communication across cultural boundaries and more efficient resource utilization. Currently there is no mechanism for Belgian surgical residents to participate in international training opportunities and little research has addressed the international mobility of Belgian residents. The goal of this study was to examine the attitudes of Belgian residents towards international training among surgical residents. METHODS: An anonymous, structured electronic questionnaire was sent to a cohort of Belgian residents, including surgical residents, by e-mail and social media. RESULTS: In total, 342 respondents filled out the questionnaire out of a total of 5906 Belgian residents. The results showed that 334 of the residents came from Flanders (10.8%) and 8 came from French-speaking Brussels and Wallonia (0.28%). Surgical specialties represented 46% of respondents and included surgical, obstetric and anaesthesiology residents. The majority (98%) were interested in an international rotation, both in low- and middle-income countries (LMICs) and in high-income countries. A total of 84% were willing to conduct an international rotation during holidays and 91% would participate even when their international stay would not be recognised as part of their residency training. A minority (38%) had undertaken an international rotation in the past and, of those, 5% went to an LMIC. CONCLUSION: The majority of surgical residents consider an international rotation as educationally beneficial, even though they are rarely undertaken. Our survey shows that in order to facilitate foreign rotations, Flemish universities and governmental institutions will have to alleviate the regulatory, logistical and financial constraints.
Assuntos
Internato e Residência , Atitude , Bélgica , Humanos , Internacionalidade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Chronic pressure overload predisposes to heart failure, but the pathogenic role of microvascular endothelial cells (MiVEC) remains unknown. We characterized transcriptional, metabolic, and functional adaptation of cardiac MiVEC to pressure overload in mice and patients with aortic stenosis (AS). METHODS: In Tie2-Gfp mice subjected to transverse aortic constriction or sham surgery, we performed RNA sequencing of isolated cardiac Gfp+-MiVEC and validated the signature in freshly isolated MiVEC from left ventricle outflow tract and right atrium of patients with AS. We next compared their angiogenic and metabolic profiles and finally correlated molecular and pathological signatures with clinical phenotypes of 42 patients with AS (50% women). RESULTS: In mice, transverse aortic constriction induced progressive systolic dysfunction, fibrosis, and reduced microvascular density. After 10 weeks, 25 genes predominantly involved in matrix-regulation were >2-fold upregulated in isolated MiVEC. Increased transcript levels of Cartilage Intermediate Layer Protein (Cilp), Thrombospondin-4, Adamtsl-2, and Collagen1a1 were confirmed by quantitative reverse transcription polymerase chain reaction and recapitulated in left ventricle outflow tract-derived MiVEC of AS (P<0.05 versus right atrium-MiVEC). Fatty acid oxidation increased >2-fold in left ventricle outflow tract-MiVEC, proline content by 130% (median, IQR, 58%-474%; P=0.008) and procollagen secretion by 85% (mean [95% CI, 16%-154%]; P<0.05 versus right atrium-MiVEC for all). The altered transcriptome in left ventricle outflow tract-MiVEC was associated with impaired 2-dimensional-vascular network formation and 3-dimensional-spheroid sprouting (P<0.05 versus right atrium-MiVEC), profibrotic ultrastructural changes, and impaired diastolic left ventricle function, capillary density and functional status, especially in female AS. CONCLUSIONS: Pressure overload induces major transcriptional and metabolic adaptations in cardiac MiVEC resulting in excess interstitial fibrosis and impaired angiogenesis. Molecular rewiring of MiVEC is worse in women, compromises functional status, and identifies novel targets for intervention.
Assuntos
Estenose da Valva Aórtica/genética , Vasos Coronários/metabolismo , Células Endoteliais/metabolismo , Átrios do Coração/metabolismo , Ventrículos do Coração/metabolismo , Microvasos/metabolismo , Proteínas ADAMTS/genética , Idoso , Animais , Aorta , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/cirurgia , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Constrição Patológica , Vasos Coronários/patologia , Modelos Animais de Doenças , Células Endoteliais/patologia , Proteínas da Matriz Extracelular/genética , Ácidos Graxos/metabolismo , Feminino , Perfilação da Expressão Gênica , Átrios do Coração/patologia , Implante de Prótese de Valva Cardíaca , Ventrículos do Coração/patologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Densidade Microvascular , Microvasos/patologia , Pró-Colágeno/metabolismo , Prolina/metabolismo , Pirofosfatases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA , Trombospondinas/genéticaRESUMO
BACKGROUND: Vagus nerve (VN) stimulation is currently evaluated as a novel approach to treat immune-mediated disorders. The optimal stimulation parameters, however, largely depend on the VN composition potentially impacting on its clinical translation. Hence, we evaluated whether morphological differences exist between the cervical and abdominal VNs across different species. MATERIALS AND METHODS: The cervical and abdominal VNs of mouse, pig, and humans were stained for major basic protein and neurofilament F to identify the percentage and size of myelinated and non-myelinated fibers. RESULTS: The percentage of myelinated fibers was comparable between species, but was higher in the cervical VN compared with the abdominal VN. The cervical VN contained 54 ± 4%, 47 ± 7%, and 54 ± 7% myelinated fibers in mouse, pig, and humans, respectively. The myelinated fibers consisted of small-diameter (mouse: 71%, pig: 80%, and humans: 63%), medium-diameter (mouse: 21%, pig: 18%, and humans: 33%), and large-diameter fibers (mouse: 7%, pig: 2%, and humans: 4%). The abdominal VN predominantly contained unmyelinated fibers (mouse: 93%, pig: 90%, and humans: 94%). The myelinated fibers mainly consisted of small-diameter fibers (mouse: 99%, pig: 85%, and humans: 74%) and fewer medium-diameter (mouse: 1%, pig: 13%, and humans: 23%) and large-diameter fibers (mouse: 0%, pig: 2%, and humans: 3%). CONCLUSION: The VN composition was largely similar with respect to myelinated and unmyelinated fibers in the species studied. Human and porcine VNs had a comparable diameter and similar amounts of fibrous tissue and contained multiple fascicles, implying that the porcine VN may be suitable to optimize stimulation parameters for clinical trials.
Assuntos
Bainha de Mielina/metabolismo , Nervo Vago/metabolismo , Animais , Humanos , Camundongos , Fibras Nervosas/metabolismo , SuínosRESUMO
BACKGROUND: The clavicle presents a large variability in its characterizing sigmoid shape. Prominent and nonproperly fitting fixation plates (FP) cause soft tissue irritation and lead to hardware removal. It is therefore key in FP design to account for shape variations. Statistical shape models (SSMs) have been built to analyze a cluster of complex shapes. The goal of this study was to describe the anatomic variation of the clavicle using SSMs. METHODS: Two different SSMs of the clavicle were created, and their modes of variation were described. One model contained 120 left male and female clavicles. The other model consisted of 76 left and corresponding right clavicles, 41 originating from men and 35 from women. RESULTS: The model of 120 left clavicles showed that 10 modes of variation are necessary to explain 95% of the variation. The most important modes of variation are the clavicle length, inferior-superior bow, and medial and lateral curvature. Statistically significant differences between male and female clavicles were seen in length, sigmoid shape, and medial curvature. Comparison in men between left and right revealed significant differences in length and medial curvature. For women, a statistically significant difference between left and right was only seen in the length. CONCLUSIONS: Although the operative treatment of displaced midshaft clavicular fractures has clear benefits, the variable anatomy of the clavicle often makes it challenging for the surgeon to make the plate fit adequately. Based on the identified variability in the clavicle's anatomy, it seems unlikely that a clavicle plating system can fit the entire population.
Assuntos
Placas Ósseas , Clavícula/anatomia & histologia , Fixação Interna de Fraturas/instrumentação , Adulto , Clavícula/lesões , Feminino , Fraturas Ósseas/cirurgia , Humanos , Masculino , Modelos Estatísticos , Fatores SexuaisRESUMO
Aims: Transcatheter aortic valve implantation (TAVI) is the preferred treatment modality for patients with severe aortic stenosis at high or prohibitive risk for surgical aortic valve replacement (SAVR). We aimed to evaluate real-world outcomes after treatment according to the decisions of the multidisciplinary heart team in a Belgian health-economic context.Methods and results: Four hundred and five high-risk patients referred to a tertiary centre between 1 March 2008 and 31 December 2015 were screened and planned to undergo SAVR, TAVI or medical treatment (MT). Patients undergoing SAVR had lower Society of Thoracic Surgeons scores and Euroscore-II when compared to TAVI or MT (median [IQR]: 6[4-8]; 7[5-10]; 8[6-13]; p < .001 and 6[4-10]; 8[5-15]; 8[4-16]; p = .006). At 1 year all-cause mortality was 14, 17 and 51% with SAVR, TAVI and MT, respectively (p < .001). Cardiovascular death and disabling stroke occurred in 9, 7 and 35% (p < .001) and 2, 2.7 and 1.7% (p = .91). According to Valve-Academic-Research-Consortium-II criteria, device success was 95 and 92% for TAVI and SAVR. The combined safety endpoint at 30 days favoured TAVI (22% vs. 47%) (p < .001). The combined efficacy endpoint at 1 year was comparable between groups (38 and 40%; p = .703). Finally, hospital stay was shorter with TAVI vs. SAVR (9[6-14] and 16[12-22] days; p < .001).Conclusions: Limited resources for transcatheter valve therapies in Belgium push a significant number of patients to SAVR, while TAVI in even higher risk patients translates into similar outcomes and shorter hospital stay. These findings underscore the need for broadening indications for TAVI, as well as readjustment of the budgetary allocations for hospitals in Belgium.
Assuntos
Estenose da Valva Aórtica/economia , Estenose da Valva Aórtica/cirurgia , Tomada de Decisão Clínica , Implante de Prótese de Valva Cardíaca/economia , Custos Hospitalares , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Equipe de Assistência ao Paciente/economia , Seleção de Pacientes , Substituição da Valva Aórtica Transcateter/economia , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/mortalidade , Bélgica , Orçamentos , Redução de Custos , Análise Custo-Benefício , Feminino , Necessidades e Demandas de Serviços de Saúde/economia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Tempo de Internação , Masculino , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: The optimal aortic substitute in extensive aortic valve active infective endocarditis (AIE) continues to be debated. To determine the surgical approach in aortic valve AIE with infection extension beyond the leaflets, we evaluated the outcome of reconstructive surgery with various valve substitutes in those patients. METHODS: During 2000-2013, 168 patients had surgery for extensive aortic valve AIE. Patients were categorised based on aortic valve substitute: Group A: Stented aortic valve replacement (AVR), Group B: Stented AVR with patch support, Group C: Stentless valve, Group D: Aortic allograft, and Group E: Composite valve graft. Outcome parameters were mortality, postoperative cardiogenic or septic shock, stroke, or reinfection. RESULTS: Stented valves with patch support were more frequently utilised in cases of native valve endocarditis (p<0.001). Postoperative complications were comparable among groups. Concomitant preoperative extension of infection in the mitral valve predicted reinfection (OR 3.6; confidence interval 1.46-8.66; p=0.005). Survival was not affected by operative group (log rank=0.6). Univariable preoperative predictors of mortality were: septic shock (hazard ratio 8.3; 95% confidence interval 3.6-19.2; p<0.001), ejection fraction (hazard ratio 0.96; 95% confidence interval 0.93-0.99; p=0.006), preoperative cardiogenic shock (hazard ratio 1.9; 95%CI 1.1-3.6, p=0.02) and concomitant mitral valve surgery (hazard ratio 1.8; 95% confidence interval 1.2-2.5; p=0.002). CONCLUSIONS: Surgical treatment of extensive aortic valve infective endocarditis remains a challenge. Outcomes were not affected by the surgical complexity of aortic reconstruction procedure or valve substitute. Surgical approach should be tailored to individual patient's characteristics.
Assuntos
Valva Aórtica/cirurgia , Endocardite/mortalidade , Endocardite/cirurgia , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Complicações Pós-Operatórias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/microbiologia , Endocardite/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/microbiologia , Valva Mitral/cirurgia , Complicações Pós-Operatórias/microbiologia , Estudos RetrospectivosRESUMO
Cardiovascular disease associated with metabolic syndrome has a high prevalence, but the mechanistic basis of metabolic cardiomyopathy remains poorly understood. We characterised the cardiac transcriptome in a murine metabolic syndrome (MetS) model (LDLR-/-; ob/ob, DKO) relative to the healthy, control heart (C57BL/6, WT) and the transcriptional changes induced by ACE-inhibition in those hearts. RNA-Seq, differential gene expression and transcription factor analysis identified 288 genes differentially expressed between DKO and WT hearts implicating 72 pathways. Hallmarks of metabolic cardiomyopathy were increased activity in integrin-linked kinase signalling, Rho signalling, dendritic cell maturation, production of nitric oxide and reactive oxygen species in macrophages, atherosclerosis, LXR-RXR signalling, cardiac hypertrophy, and acute phase response pathways. ACE-inhibition had a limited effect on gene expression in WT (55 genes, 23 pathways), and a prominent effect in DKO hearts (1143 genes, 104 pathways). In DKO hearts, ACE-I appears to counteract some of the MetS-specific pathways, while also activating cardioprotective mechanisms. We conclude that MetS and control murine hearts have unique transcriptional profiles and exhibit a partially specific transcriptional response to ACE-inhibition.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Aterosclerose/genética , Doenças Cardiovasculares/genética , Síndrome Metabólica/tratamento farmacológico , Receptores de LDL/genética , Idoso , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Cardiotônicos/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Redes e Vias Metabólicas/genética , Síndrome Metabólica/complicações , Síndrome Metabólica/genética , Síndrome Metabólica/fisiopatologia , Camundongos , Camundongos Knockout , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/fisiopatologia , Peptidil Dipeptidase A/genética , Transcriptoma/efeitos dos fármacos , Transcriptoma/genéticaRESUMO
The loss of endogenous cardiac regenerative capacity within the first week of postnatal life has intensified clinical trials to induce cardiac regeneration in the adult mammalian heart using different progenitor cell types. We hypothesized that donor age-related phenotypic and functional characteristics of cardiac progenitor cells (CPC) account for mixed results of cell-based cardiac repair. We compared expression profiles and cell turnover rates of human heart-derived c-kitpos progenitors (c-kitpos CPC) and cardiosphere-derived cells (CDC) from young and adult donor origin and studied their in vitro angiogenic and cardiac differentiation potential, which can be relevant for cardiac repair. We report that 3-dimensional CDC expansion recapitulates a conducive environment for growth factor and cytokine release from adult donor cells (aCDC) that optimally supports vascular tube formation and vessel sprouting. Transdifferentiation capacity of c-kitpos CPCs and CDCs towards cardiomyocyte-like cells was modest, however, most notable in young c-kitpos cells and adult CDCs. Progenitors isolated with different methods thus show cell- and donor-specific characteristics that may account for variable contributions in functional myocardial recovery.
Assuntos
Separação Celular , Perfilação da Expressão Gênica , Miocárdio/citologia , Células-Tronco/citologia , Células-Tronco/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular/genética , Proliferação de Células/genética , Forma Celular , Regulação para Baixo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Fisiológica/genética , Fenótipo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Esferoides Celulares/citologia , Esferoides Celulares/metabolismo , Doadores de Tecidos , Regulação para Cima/genéticaRESUMO
BACKGROUND: Abdominal aortic aneurysms (AAAs) are a potentially deathly disease, needing surgical or endovascular treatment. To evaluate potentially new diagnostic tools and treatments, a large animal model, which resembles not only the morphological characteristics but also the pathophysiological background, would be useful. METHODS: Rodent animal aneurysm models were extrapolated to sheep. Four groups were created: intraluminal infusion with an elastase-collagenase solution (n = 4), infusion with elastase-collagenase solution combined with proximal stenosis (n = 7), aortic xenograft (n = 3), and elastase-collagenase-treated xenograft (n = 4). At fixed time intervals (6, 12, and 24 weeks), computer tomography and autopsy with histological evaluation were performed. RESULTS: The described models had a high perioperative mortality (45%), due to acute aortic thrombosis or fatale hemorrhage. A maximum aortic diameter increase of 30% was obtained in the protease-stenosis group. In the protease-treated groups, some histological features of human AAAs, such as inflammation, thinning of the media, and loss of elastin could be reproduced. In the xenotransplant groups, a pronounced inflammatory reaction was visible at the start. In all models, inflammation decreased and fibrosis occurred at long follow-up, 24 weeks postoperatively. CONCLUSIONS: None of the extrapolated small animal aneurysm models could produce an AAA in sheep with similar morphological features as the human disease. Some histological findings of human surgical specimens could be reproduced in the elastase-collagenase-treated groups. Long-term histological evaluation indicated stabilization and healing of the aortic wall months after the initial stimulus.
Assuntos
Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/induzido quimicamente , Colagenases , Elastase Pancreática , Animais , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/patologia , Aortografia/métodos , Angiografia por Tomografia Computadorizada , Modelos Animais de Doenças , Progressão da Doença , Estudos de Viabilidade , Feminino , Xenoenxertos , Ratos , Carneiro Doméstico , Fatores de TempoRESUMO
OBJECTIVE: With the increasing use of bioprostheses worldwide, continuous efforts have been made to improve tissue durability. We introduce a new treatment for bovine pericardium combining octanediol-ethanol based phospholipid removal with taurine-based glutaraldehyde neutralization and storage in an aldehyde-free solution (FREE). METHODS: Treated tissues were evaluated by mechanical and biochemical characterization, phospholipid content, aldehyde levels, cell cultures on pericardial samples (L929 fibroblasts and human umbilical vein endothelial cells), rat subcutaneous implantations, and long-term juvenile sheep mitral valve implantations (n = 3). Comparisons were made to glutaraldehyde-fixed bovine pericardium or to samples from commercially available biological valves (ie, Trifecta [St Jude Medical, Saint Paul, Minn] and Perimount Magna Ease [Edwards Lifesciences, Irvine, Calif]). RESULTS: FREE-treated pericardium had similar mechanical strength and biochemical properties as commercially available valves. Compared with glutaraldehyde-only samples, FREE-treated samples showed lower phospholipid levels (P < .01), significantly better growth of L929 fibroblasts, and lower calcification levels in rat subcutaneous implants (P < .01). Compared with samples from Linx- (Trifecta) and ThermaFix-treated (Perimount Magna Ease) valves, similar low levels of phospholipids were observed as were similar low calcification levels in subcutaneous implants, but tissue extractions from FREE-treated samples showed the lowest levels of extracted aldehydes (P < .01). Mitral implants of FREE-treated valves in juvenile sheep had excellent hemodynamic behavior without any sign of degeneration or calcification at 5 months. CONCLUSIONS: The new FREE treatment combines an adequate phospholipid reduction and aldehyde neutralization with storage in an aldehyde-free solution. This combination enhances the anticalcification properties and may thereby improve long-term durability of the tissue.
Assuntos
Bioprótese , Calcinose/prevenção & controle , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Pericárdio/transplante , Fixação de Tecidos/métodos , Aldeídos/metabolismo , Animais , Calcinose/etiologia , Calcinose/metabolismo , Calcinose/patologia , Bovinos , Linhagem Celular , Etanol/química , Fibroblastos/metabolismo , Fibroblastos/patologia , Fixadores/química , Glutaral/química , Implante de Prótese de Valva Cardíaca/efeitos adversos , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Hidroxiprolina/metabolismo , Teste de Materiais , Octanóis/química , Pericárdio/metabolismo , Pericárdio/patologia , Fosfolipídeos/metabolismo , Desenho de Prótese , Ratos Wistar , Carneiro Doméstico , Resistência à Tração , Fatores de TempoRESUMO
INTRODUCTION: Available evidence suggests that the renin-angiotensin-aldosterone (RAA) system is a good target for medical intervention on aortic root dilatation in Marfan syndrome (MFS). The effect of Compound 21 (C21), a nonpeptide angiotensin II type 2 receptor agonist, on aneurysm progression was tested. METHODS: Mice with a mutation in fibrillin-1 (Fbn1) and wild-type mice were treated with vehicle, losartan, C21, enalapril, or a combination. Blood pressure, aortic root diameter, and histological slides were evaluated. RESULTS: All groups had a comparable blood pressure. Echographic evaluation of the aortic root diameter revealed a protective effect of angiotensin II type 1 receptor antagonist (losartan) and no effect of C21 treatment. None of the treatments had a beneficial effect on the histological changes in MFS. DISCUSSION: This study confirms that angiotensin II type 1 receptor antagonism (losartan) decreases aortic aneurysm growth in a mouse model of MFS. A nonpeptide angiotensin II type 2 receptor agonist (C21), at the doses studied, was ineffective. Future studies are warranted to further elucidate the exact role of the RAA system in aneurysm formation in MFS and identify alternative targets for intervention.
Assuntos
Aorta/efeitos dos fármacos , Aneurisma Aórtico/prevenção & controle , Síndrome de Marfan/tratamento farmacológico , Receptor Tipo 2 de Angiotensina/agonistas , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Aorta/diagnóstico por imagem , Aorta/metabolismo , Aorta/patologia , Aneurisma Aórtico/genética , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/patologia , Dilatação Patológica , Modelos Animais de Doenças , Progressão da Doença , Ecocardiografia , Fibrilina-1/genética , Losartan/farmacologia , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/genética , Síndrome de Marfan/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Mutação , Receptor Tipo 2 de Angiotensina/metabolismoAssuntos
Fibrilação Atrial/terapia , Bradicardia/terapia , Estimulação Cardíaca Artificial , Doenças das Valvas Cardíacas/cirurgia , Cuidados Intraoperatórios/métodos , Anuloplastia da Valva Mitral , Valva Mitral/cirurgia , Marca-Passo Artificial , Valva Tricúspide/cirurgia , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Bradicardia/complicações , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Desenho de Equipamento , Feminino , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/fisiopatologiaRESUMO
Acceleration signals, collected from the inner and the outer heart wall, offer a mean of assessing cardiac function during surgery. Accelerometric measurements can also provide detailed insights into myocardial motion during exploratory investigations. Two different implantable accelerometers to respectively record endocardial and epicardial vibrations, have been developed by packaging a commercially available capacitive transducer. The same coating materials have been deposited on the two devices to ensure biocompatibility of the implants: Parylene-C, medical epoxy and Polydimethylsiloxane (PDMS). The different position-specific requirements resulted in two very dissimilar sensor assemblies. The endocardial accelerometer, that measures accelerations from the inner surface of the heart during acute animal tests, is a 2 mm-radius hemisphere fixed on a polymethyl methacrylate (PMMA) rod to be inserted through the heart wall. The epicardial accelerometer, that monitors the motion of the outer surface of the heart, is a three-legged structure with a stretchable polytetrafluoroethylene (PTFE) reinforcement. This device can follow the continuous motion of the myocardium (the muscular tissue of the heart) during the cardiac cycle, without hindering its natural movement. Leakage currents lower than 1 µA have been measured during two weeks of continuous operation in saline. Both transducers have been used, during animal tests, to simultaneously record and compare acceleration signals from corresponding locations on the inner and the outer heart wall of a female sheep.
Assuntos
Acelerometria , Endocárdio/fisiologia , Pericárdio/fisiologia , Acelerometria/instrumentação , Acelerometria/métodos , Animais , Dimetilpolisiloxanos/química , Feminino , Polímeros/química , Polimetil Metacrilato/química , Ovinos , Xilenos/químicaRESUMO
BACKGROUND: Abdominal aortic aneurysm (AAA) is a prevalent disease affecting around 5% of the population aged more than 65 years. The exact etiology and physiopathology of AAA still raises questions, and elective surgery is currently the only treatment option for this often progressive disease. In this study, we hypothesized and tested a pathophysiological model that depicts AAA as an inflammation-triggered autoimmune disease with remnant vessel wall peptide fragments as the antigen. METHODS: A pilot study with male AAA patients (n = 14) and male controls (n = 8) was conducted. In both study groups, peripheral blood monocytes and plasma were separated from whole blood by centrifugation. An ELISpot test was performed on cultured white blood cells for the presence of elastin-specific T-lymphocytes. An Enzyme-linked immuno sorbent assay (ELISA) was performed on plasma for the presence of elastin-specific IgG molecules. RESULTS: ELISpot interferon-gamma secretion in AAA (7.7 ± 9.5%) and control (4.6 ± 3.5%) and ELISA anti-elastin IgG titer in AAA (77.5 ± 17.8%) and control (78.2 ± 31.5%) were not significantly different (P = 0.94 and P = 0.55, respectively). Both results are expressed as a percentage relative to the respective positive and negative control. CONCLUSIONS: The results of our pilot study did not indicate a clear and invariable autoimmune process directed against remnant elastin peptide fragments. Further research into the model mechanics and a possible antigen is still necessary. In the mean time, the model as presented here already offers a pathophysiological framework to further research into the possible remnant epitope-driven AAA etiology.
Assuntos
Aneurisma da Aorta Abdominal/imunologia , Autoanticorpos/sangue , Autoimunidade , Elastina/imunologia , Epitopos , Imunoglobulina G/sangue , Fragmentos de Peptídeos/imunologia , Adulto , Idoso , Aneurisma da Aorta Abdominal/sangue , Estudos de Casos e Controles , Células Cultivadas , Elastina/metabolismo , ELISPOT , Humanos , Testes de Liberação de Interferon-gama , Masculino , Fragmentos de Peptídeos/metabolismo , Projetos Piloto , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
OBJECTIVES: Wrapping with various materials was an early treatment for aortic aneurysms. Wrapping with low-porosity vascular grafts has been associated with graft migration and vascular erosion. An alternative is to use a macroporous mesh (MPM) made of the same polymer (polyethylene terephalate). We compared the histological outcome 1 year after wrapping sheep aortas with low-porosity grafts versus MPM fabrics. METHODS: The 2 different fabrics were wrapped around the aorta of 3 sheep. After 1 year the aortas were excised. The 2 wrapped segments of aorta were compared with each other and control aorta. Histological examinations and measurements were made of the layers of the aortic wall in 36 prespecified locations in each of the 3 sheep. RESULTS: Both fabrics were consistently surrounded by foreign body reaction and well-vascularized fibrosis. This was more pronounced with the low-porosity vascular graft material which was poorly incorporated and caused buckling at the transition between wrapped and unwrapped aorta. Conversely, the MPM was fully incorporated, resulting in a composite mesh/biological aortic wall. There was reduction of medial thickness with both materials but it was locally more extreme due to the corrugations in the vascular graft material. The findings were consistent between sampled locations and were similar in the 3 animals. CONCLUSIONS: The different porosity and rigidity of the materials influences their incorporation into the aortic wall. The incorporation of the pliable MPM precludes the complications of migration and erosion which are seen after wrapping with low-porosity prosthetic vascular graft material.
Assuntos
Aorta Torácica/patologia , Aneurisma da Aorta Torácica/patologia , Prótese Vascular , Polietilenotereftalatos/química , Telas Cirúrgicas , Animais , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Modelos Animais de Doenças , Músculo Liso Vascular/patologia , Porosidade , OvinosRESUMO
BACKGROUND: Pelvic organ prolapse affects half of vaginally parous women. Several animal models are used to study its pathophysiology and treatment. Sheep are interesting because they develop spontaneously prolapse with similar risk factors as women and can be used for vaginal surgery. This study describes ovine pelvis anatomy and compares it to women's pelvis to provide anatomical tools for translational researchers. METHODS: MRI, pelvic dissections, and histology were used for detailed macro- and microscopic analysis of relevant anatomical structures in 6 nulliparous ewes. RESULTS: Although sheep are quadrupeds, the gross and microscopic anatomies are similar to the female pelvis. Principal differences are the shape and its orientation, the absence of the sacrospinous ligament and the internal obturator. The levator ani (except for the puborectalis) and the coccygeus muscle are present, yet the latter is more developed - coinciding with the tail. The dimensions and morphology of the ovine vagina is comparable. The retropubic and the rectovaginal space are accessible transvaginally. There is a wide expression of estrogen receptors with low or absent immunoreactivity in the urethral epithelium, bladder, anus and internal anal sphincter. CONCLUSION: The ovine pelvic floor has many anatomical and ultrastructural similarities to the female pelvic floor.
Assuntos
Cavidade Abdominal/anatomia & histologia , Parede Abdominal/anatomia & histologia , Pelve/anatomia & histologia , Bexiga Urinária/anatomia & histologia , Vagina/anatomia & histologia , Animais , Feminino , Humanos , Imageamento por Ressonância Magnética , Diafragma da Pelve/anatomia & histologia , Prolapso de Órgão Pélvico , OvinosRESUMO
We have characterized both acute and long-term vascular and metabolic effects of unilateral common carotid artery occlusion in mice by in vivo magnetic resonance imaging and positron emission tomography. This common carotid artery occlusion model induces chronic cerebral hypoperfusion and is therefore relevant to both preclinical stroke studies, where it serves as a control condition for a commonly used mouse model of ischemic stroke, and neurodegeneration, as chronic hypoperfusion is causative to cognitive decline. By using perfusion magnetic resonance imaging, we demonstrate that under isoflurane anesthesia, cerebral perfusion levels recover gradually over one month. This recovery is paralleled by an increase in lumen diameter and altered tortuosity of the contralateral internal carotid artery at one year post-ligation as derived from magnetic resonance angiography data. Under urethane/α-chloralose anesthesia, no acute perfusion differences are observed, but the vascular response capacity to hypercapnia is found to be compromised. These hemispheric perfusion alterations are confirmed by water [15O]-H2O positron emission tomography. Glucose metabolism ([18F]-FDG positron emission tomography) or white matter organization (diffusion-weighted magnetic resonance imaging) did not show any significant alterations. In conclusion, permanent unilateral common carotid artery occlusion results in acute and long-term vascular remodeling, which may have immediate consequences for animal models of stroke but also vascular dementia.