Complete Unsteady One-Dimensional Model of the Net Aortic Pressure Drop

Background: A large amount of engineering and medical research has been devoted to the assessment of aortic valve stenosis severity in the past decades. The net transvalvular pressure drop has been recognized as one of the parameters that better reflect stenosis effects on left ventricle overload, and its adoption in clinical assessment of stenosis has been proposed. Flow unsteadiness has been shown to have a non-negligible impact on the net drop; however, a simple formulation for net drop calculation that includes not only flow pulsatility but also the effects of valve dynamics is still lacking. Objective: The present contribution is hence aimed at developing a complete unsteady one-dimensional model of the net aortic transvalvular pressure drop that just requires non-invasive data to be implemented. Methods: Transvalvular flow is described as a jet of incompressible viscous fluid through a circular orifice placed in a concentric rigid circular tube. The classical one-dimensional mass and total head conservation equations are applied. The effective orifice area and transvalvular flow rate are assumed to vary with time throughout the ejection period. Results: The model is found to capture pressure drop oscillations occurring when the valve opens/closes and/or leaflets flutter, thanks to the inclusion of valve dynamics effects. The model is also proposed as a numerical tool for the calculation of the instantaneous effective orifice area once net pressure drop and flow rate are known. Conclusion: The model may contribute to the improvement of non-invasive aortic stenosis assessment

Modernization of a Cardiovascular Hydrodynamic Testing System through the Automation of its Peripheral Resistance Device

Cardiovascular hydrodynamic systems, such as pulse duplicators, reproduce the human systemic circulation and they play a pivotal role as in vitro assessment tools for testing heart medical devices such as aortic valves and stents [1]. Hence, spe- cific ISO standards govern their safety assessment, prescribing in vitro experiments aimed at replicating the target operating conditions in humans [2]. In this scenario, the modernization of existing mock circulatory loops, in terms of both hardware and software components, offers new possibilities to dominate their intrinsic complexity, through the rapid exploration of new suitable solutions. This research involves the modernization of an existing non-commercial pulse duplicator in use at the Heal- ing Research Laboratory at the University of Padua, Italy [3]. The cardiovascular hydrodynamic system is characterized by high customizability, modularity, and it allows simulating a wide range of physiological and pathologic conditions. The focus of this research is the automation of a crucial system component that is the periph- eral resistance device, aggregating the system effects of resistance to flow providing a suitable pressure drop. To this aim, a new motorized peripheral resistance valve, equipped with a stepper DC motor, a H-bridge, and Arduino Uno board, replaces the current manual device. Specifically, the problem of valve automatic setting ad- justment is tackled in a data-driven way by means of an Extremum Seeking Control algorithm exhibiting interesting plug and play characteristics. The proposed ap- proach can handle the intrinsic system complexity to fix the incomplete knowledge of certain system characteristics while guaranteeing good performance in a wide range of system configurations and operating conditions. The effectiveness of the automated peripheral resistance device has been verified through experimental tests and the automation of other fundamental system components will be considered in the future

Apoptosome-deficient Cells Lose Cytochrome c through Proteasomal Degradation but Survive by Autophagy-dependent Glycolysis

Cytochrome c release from mitochondria promotes apoptosome formation and caspase activation. The question as to whether mitochondrial permeabilization kills cells via a caspase-independent pathway when caspase activation is prevented is still open. Here we report that proneural cells of embryonic origin, when induced to die but rescued by apoptosome inactivation are deprived of cytosolic cytochrome c through proteasomal degradation. We also show that, in this context, those cells keep generating ATP by glycolysis for a long period of time and that they keep their mitochondria in a depolarized state that can be reverted. Moreover, under these conditions, such apoptosome-deficient cells activate a Beclin 1–dependent autophagy pathway to sustain glycolytic-dependent ATP production. Our findings contribute to elucidating what the point-of-no-return in apoptosis is. They also help in clarifying the issue of survival of apoptosome-deficient proneural cells under stress conditions. Unraveling this issue could be highly relevant for pharmacological intervention and for therapies based on neural stem cell transfer in the treatment of neurological disorders