RESUMO
This case demonstrates an alternative approach to cerebral revascularization by performing both intravascular mechanical thrombectomy and local injection of thrombolytics that may reduce mortality, bleeding, and the diminished quality of life experienced by patients following an acute septic embolic stroke.
Assuntos
Endocardite Bacteriana/terapia , Procedimentos Endovasculares/métodos , Embolia Intracraniana/terapia , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica , Idoso , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Angiografia Cerebral , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/microbiologia , Masculino , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/microbiologia , Resultado do TratamentoRESUMO
BACKGROUND: Gap junction protein and extracellular matrix signalling systems act in concert to influence developmental specification of neural stem and progenitor cells. It is not known how these two signalling systems interact. Here, we examined the role of ECM components in regulating connexin expression and function in postnatal hippocampal progenitor cells. RESULTS: We found that Cx26, Cx29, Cx30, Cx37, Cx40, Cx43, Cx45, and Cx47 mRNA and protein but only Cx32 and Cx36 mRNA are detected in distinct neural progenitor cell populations cultured in the absence of exogenous ECM. Multipotential Type 1 cells express Cx26, Cx30, and Cx43 protein. Their Type 2a progeny but not Type 2b and 3 neuronally committed progenitor cells additionally express Cx37, Cx40, and Cx45. Cx29 and Cx47 protein is detected in early oligodendrocyte progenitors and mature oligodendrocytes respectively. Engagement with a laminin substrate markedly increases Cx26 protein expression, decreases Cx40, Cx43, Cx45, and Cx47 protein expression, and alters subcellular localization of Cx30. These changes are associated with decreased neurogenesis. Further, laminin elicits the appearance of Cx32 protein in early oligodendrocyte progenitors and Cx36 protein in immature neurons. These changes impact upon functional connexin-mediated hemichannel activity but not gap junctional intercellular communication. CONCLUSION: Together, these findings demonstrate a new role for extracellular matrix-cell interaction, specifically laminin, in the regulation of intrinsic connexin expression and function in postnatal neural progenitor cells.
Assuntos
Conexinas/metabolismo , Matriz Extracelular/fisiologia , Hipocampo/fisiologia , Neurônios/fisiologia , Células-Tronco/fisiologia , Animais , Western Blotting , Comunicação Celular/fisiologia , Células Cultivadas , Conexinas/genética , Citometria de Fluxo , Imuno-Histoquímica , Laminina/metabolismo , Camundongos , Camundongos Knockout , Neurogênese/fisiologia , Oligodendroglia/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Cell-based therapies are being explored as a therapeutic option for patients with chronic heart failure following myocardial infarction. Extracellular vesicles (EV), including exosomes and microparticles, secreted by transplanted cells may orchestrate their paracrine therapeutic effects. We assessed whether post-infarction administration of EV released by human embryonic stem cell-derived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways. METHODS: Mice underwent surgical occlusion of their left coronary arteries. After 2-3 weeks, 95 mice included in the study were treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM; vehicle control) delivered by percutaneous injections under echocardiographic guidance into the peri-infarct myocardium. functional and histologic end-points were blindly assessed 6 weeks later, and hearts were processed for gene profiling. Genes differentially expressed between control hearts and hESC-Pg-treated and EV-treated hearts were clustered into functionally relevant pathways. RESULTS: At 6 weeks after hESC-Pg administration, treated mice had significantly reduced left ventricular end-systolic (-4.20 ± 0.96 µl or -7.5%, p = 0.0007) and end-diastolic (-4.48 ± 1.47 µl or -4.4%, p = 0.009) volumes compared with baseline values despite the absence of any transplanted hESC-Pg or human embryonic stem cell-derived cardiomyocytes in the treated mouse hearts. Equal benefits were seen with the injection of hESC-Pg-derived EV, whereas animals injected with alpha-MEM (vehicle control) did not improve significantly. Histologic examination suggested a slight reduction in infarct size in hESC-Pg-treated animals and EV-treated animals compared with alpha-MEM-treated control animals. In the hESC-Pg-treated and EV-treated groups, heart gene profiling identified 927 genes that were similarly upregulated compared with the control group. Among the 49 enriched pathways associated with these up-regulated genes that could be related to cardiac function or regeneration, 78% were predicted to improve cardiac function through increased cell survival and/or proliferation or DNA repair as well as pathways related to decreased fibrosis and heart failure. CONCLUSIONS: In this post-infarct heart failure model, either hESC-Pg or their secreted EV enhance recovery of cardiac function and similarly affect cardiac gene expression patterns that could be related to this recovery. Although the mechanisms by which EV improve cardiac function remain to be determined, these results support the idea that a paracrine mechanism is sufficient to effect functional recovery in cell-based therapies for post-infarction-related chronic heart failure.
Assuntos
Insuficiência Cardíaca , Animais , Doença Crônica , Células-Tronco Embrionárias , Vesículas Extracelulares , Humanos , Camundongos , Infarto do Miocárdio , Miocárdio , Miócitos CardíacosRESUMO
Aortic valve repair can be a good option in younger patients who have severe aortic regurgitation. A systematic, disease-directed approach can simplify repair. This case report describes how a simplified approach can be successfully applied to complex pathologic conditions of the aortic valve. A 49-year-old man with a bicuspid aortic valve and a history of endocarditis presented with severe aortic regurgitation and evidence of recurrent infection. Intraoperatively, we found congenital and degenerative aortic anatomy with endocarditis and perforation. We performed aortic valve repair to enable leaflet coaptation and to adjust the coaptation height. After 24 months, the patient remained well, with an intact repair and trivial aortic regurgitation. We describe our systematic repair approach and rationales for targeting repairs to identified lesions. To our knowledge, this is the first description of complex aortic valve repairs in a patient who had simultaneous congenital, degenerative, and infectious conditions.
Assuntos
Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/anormalidades , Procedimentos Cirúrgicos Cardíacos , Endocardite Bacteriana/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Infecções Estreptocócicas/cirurgia , Estreptococos Viridans/isolamento & purificação , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/etiologia , Doença da Válvula Aórtica Bicúspide , Ecocardiografia Doppler em Cores , Ecocardiografia Transesofagiana , Endocardite Bacteriana/complicações , Endocardite Bacteriana/diagnóstico , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Postoperative neurocognitive deficits (POCDs) have been found to occur frequently after cardiac surgery. Although POCDs have received significant attention in the medical literature and public media, the true clinical impact of these deficits on patient outcomes and quality of life (QOL) is not well defined. METHODS: Neuropsychometric testing was performed on 696 patients undergoing coronary artery bypass surgery using a battery of tests divided into 4 domains; memory, attention, speed, and psychomotor function. These were performed preoperatively, at hospital discharge, and at 3 months postoperatively. POCDs were defined as a drop in scores by 1 standard deviation in 1 domain or more. QOL was assessed using Short Form 36 and clinical outcomes were recorded. RESULTS: POCDs were identified in 265 (38%) patients at discharge and in 132 (19%) at 3 months. There was no observed difference in mortality or major morbidity in patients with or without POCDs. Predictors of POCDs at discharge were elevated preoperative creatinine (P = .04), increased cardiopulmonary bypass time (P = .005), and diabetes (P = .003). At 3 months, patients had improvements in both physical and mental components of QOL, independent of the occurrence of POCDs (P > .5). Independent predictors of improved QOL included younger age, severe preoperative anginal symptoms, normal left ventricular function, absence of postoperative wound infection, but not POCDs. CONCLUSIONS: Neurocognitive deficits can be frequently detected on comprehensive neuropsychometric testing after cardiac surgery. However, they are not associated with any clinically important differences in patient outcome or in QOL after surgery.
Assuntos
Transtornos Cognitivos/diagnóstico , Ponte de Artéria Coronária/psicologia , Qualidade de Vida , Distribuição de Qui-Quadrado , Creatinina/sangue , Diabetes Mellitus/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valor Preditivo dos Testes , Fatores de Risco , Estatísticas não Paramétricas , Inquéritos e Questionários , Fatores de TempoRESUMO
OBJECTIVES: This study sought to evaluate the main baseline and procedural characteristics, management, and clinical outcomes of patients from a large cohort of patients undergoing transcatheter aortic valve implantation (TAVI) who suffered coronary obstruction (CO). BACKGROUND: Very little data exist on CO following TAVI. METHODS: This multicenter registry included 44 patients who suffered symptomatic CO following TAVI of 6,688 patients (0.66%). Pre-TAVI computed tomography data was available in 28 CO patients and in a control group of 345 patients (comparisons were performed including all patients and a cohort matched 1:1 by age, sex, previous coronary artery bypass graft, transcatheter valve type, and size). RESULTS: Baseline and procedural variables associated with CO were older age (p < 0.001), female sex (p < 0.001), no previous coronary artery bypass graft (p = 0.043), the use of a balloon-expandable valve (p = 0.023), and previous surgical aortic bioprosthesis (p = 0.045). The left coronary artery was the most commonly involved (88.6%). The mean left coronary artery ostia height and sinus of Valsalva diameters were lower in patients with obstruction than in control subjects (10.6 ± 2.1 mm vs. 13.4 ± 2.1 mm, p < 0.001; 28.1 ± 3.8 mm vs. 31.9 ± 4.1 mm, p < 0.001). Differences between groups remained significant after the case-matched analysis (p < 0.001 for coronary height; p = 0.01 for sinus of Valsalva diameter). Most patients presented with persistent severe hypotension (68.2%) and electrocardiographic changes (56.8%). Percutaneous coronary intervention was attempted in 75% of the cases and was successful in 81.8%. Thirty-day mortality was 40.9%. After a median follow-up of 12 (2 to 18) months, the cumulative mortality rate was 45.5%, and there were no cases of stent thrombosis or reintervention. CONCLUSIONS: Symptomatic CO following TAVI was a rare but life-threatening complication that occurred more frequently in women, in patients receiving a balloon-expandable valve, and in those with a previous surgical bioprosthesis. Lower-lying coronary ostium and shallow sinus of Valsalva were associated anatomic factors, and despite successful treatment, acute and late mortality remained very high, highlighting the importance of anticipating and preventing the occurrence of this complication.