RESUMO
Heart-on-chip is an unprecedented technology for recapitulating key biochemical and biophysical cues in cardiac pathophysiology. Several designs have been proposed to improve its ability to mimic the native tissue and establish it as a reliable research platform. However, despite mimicking one of most vascularized organs, reliable strategies to deliver oxygen and substrates to densely packed constructs of metabolically demanding cells remain unsettled. Herein, we describe a new heart-on-chip platform with precise fluid control, integrating an on-chip peristaltic pump, allowing automated and fine control over flow on channels flanking a 3D cardiac culture. The application of distinct flow rates impacted on temporal dynamics of microtissue structural and transcriptional maturation, improving functional performance. Moreover, a widespread transcriptional response was observed, suggesting flow-mediated activation of critical pathways of cardiomyocyte structural and functional maturation and inhibition of cardiomyocyte hypoxic injury. In conclusion, the present design represents an important advance in bringing engineered cardiac microtissues closer to the native heart, overcoming traditional bulky off-chip fluid handling systems, improving microtissue performance, and matching oxygen and energy substrate requirements of metabolically active constructs, avoiding cellular hypoxia. Distinct flow patterns differently impact on microtissue performance and gene expression program.
Assuntos
Bombas de Infusão , Dispositivos Lab-On-A-Chip , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Perfusão , Animais , Hipóxia Celular , Ratos , Ratos Sprague-Dawley , Técnicas de Cultura de TecidosRESUMO
BACKGROUND: It is particularly difficult to choose the appropriate prosthesis to treat infective endocarditis. OBJECTIVES: To investigate the outcomes after aortic valve replacement with a stented bioprosthesis (Trifecta) in patients with active or previous infective endocarditis. METHODS: We performed a single-centre, retrospective study including consecutive patients with infective endocarditis who underwent aortic valve replacement between July 2011 and June 2019. Survival and reintervention were assessed as of December 2021. Hospital mortality was defined as death in-hospital or within 30-days of surgery. Kaplan-Meier method was used for time-to-event outcome assessment (all-cause mortality and reoperation). Data are median (minimum and maximum) or absolute (relative) frequencies. RESULTS: We included 51 patients, median age of 69 (40 to 87) years, 78% male. The median follow-up time was 5.4 years and the maximum was 10 years. Most patients (71%) had native valve infective endocarditis and 16% had previous endocarditis. Surgery was urgent in 82%. Hospital mortality occurred in 10 patients (20%). After excluding these patients, 1-, 3-, 6-, and 9-years cumulative survival rates were 93%, 78%, 72%, and 72%, respectively. There were five bioprosthesis-related reoperations: 4 due to endocarditis at 1-year, 3-years, and 5-years on follow-up (n=1, 1 and 2, respectively) and 1 due to non-structural deterioration, 6-years after surgery. CONCLUSIONS: Despite the small sample size, this report supports a satisfactory performance profile of the Trifecta bioprosthesis in the treatment of infective endocarditis.