Numerical analysis of the pressure drop across highly-eccentric coronary stenoses: application to the calculation of the fractional flow reserve

Abstract Background Fractional flow reverse (FFR) is the gold standard assessment of the hemodynamic significance of coronary stenoses. However, it requires the catheterization of the coronary artery to determine the pressure waveforms proximal and distal to the stenosis. On the contrary, computational fluid dynamics enables the calculation of the FFR value from relatively non-invasive computed tomography angiography (CTA). Methods We analyze the flow across idealized highly-eccentric coronary stenoses by solving the Navier–Stokes equations. We examine the influence of several aspects (approximations) of the simulation method on the calculation of the FFR value. We study the effects on the FFR value of errors made in the segmentation of clinical images. For this purpose, we compare the FFR value for the nominal geometry with that calculated for other shapes that slightly deviate from that geometry. This analysis is conducted for a range of stenosis severities and different inlet velocity and pressure waveforms. Results and conclusions The errors made in assuming a uniform velocity profile in front of the stenosis, as well as those due to the Newtonian and laminar approximations, are negligible for stenosis severities leading to FFR values around the threshold 0.8. The limited resolution of the stenosis geometry reconstruction is the major source of error when predicting the FFR value. Both systematic errors in the contour detection of just 1-pixel size in the CTA images and a low-quality representation of the stenosis surface (coarse faceted geometry) may yield wrong outcomes of the FFR assessment for an important set of eccentric stenoses. On the contrary, the spatial resolution of images acquired with optical coherence tomography may be sufficient to ensure accurate predictions for the FFR value

Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling

Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single-site, cross-sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I-stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI-stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/β-actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI-stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new-borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function

Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling

Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single-site, cross-sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I-stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI-stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/β-actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI-stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new-borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function

Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling

Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single-site, cross-sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I-stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI-stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/β-actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI-stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new-borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function

Fast, flexible and low-cost multiphase blood analogue for biomedical and energy applications

During the last two decades, several kinds of particulate blood analogue fluids have been proposed, but none of those were able to mimic the multiphase effects of real blood. Hence, it is clear that it is crucial to develop a simple multiphase blood analogue to be used for in vitro experiments at both macro- and microscale level. To the best of our knowledge, the present work shows for the first time a straightforward and extremely stable blood analogue fluid able to mimic multiphase blood flow phenomena. The present work proposes a simple, low-cost and stable multiphase blood analogue with the ability to mimic microscale blood flow phenomena. The proposed analogue fluid is composed of Brij L4 surfactant micelles suspended in pure water and is extremely easy to be produced. To investigate the ability of this analogue to mimic microscale blood flow phenomena, flow visualizations were performed in a microchannel constriction. In vitro blood phenomena were compared with the measurements performed with the proposed analogue fluid. Additionally, rheological measurements of the multiphase blood analogue were acquired by means of a stress-controlled rheometer and compared with in vitro blood sample viscosity curves. Overall, the results indicate that it is possible to produce a stable particulate fluid with geometrical, mechanical and flow properties similar to in vitro blood. Hence, the proposed analogue has a great potential to be used in flow experiments from macro- to nanoscale levelsFundação para a Ciência e a Tecnologia (FCT) under the strategic grants UIDB/04077/2020, UIDB/04436/2020 and UIDB/00532/2020. The authors are also grateful for the funding of FCT through the projects NORTE-01-0145-FEDER-029394, NORTE-01-0145-FEDER-030171 and POCI-01-0145-FEDER-016861 (PTDC/QEQ-FTT/4287/2014) funded by COMPETE2020, NORTE2020, PORTUGAL2020, and FEDER. The authors also acknowledge FCT for partially financing the research under the framework of the project UTAP-EXPL/CTE/0064/2017, financiado no âmbito do Projeto 5665—Parcerias Internacionais de Ciência e Tecnologia, UT Austin Programme. Partial support from the Spanish Ministry of Science and Education (grant no. DPI2016-78887) and Junta de Extremadura (grants no. GR15014 and IB18005, partially financed by FEDER funds) is gratefully acknowledged too