TY - JOUR
T1 - Initial clinical validation of a hybrid in silico—in vitro cardiorespiratory simulator for comprehensive testing of mechanical circulatory support systems
AU - Fresiello, Libera
AU - Muthiah, Kavitha
AU - Goetschalckx, Kaatje
AU - Hayward, Christopher
AU - Rocchi, Maria
AU - Bezy, Maxime
AU - Pauls, Jo P.
AU - Meyns, Bart
AU - Donker, Dirk W.
AU - Zieliński, Krzysztof
N1 - Funding Information:
This article was funded by support given to Daniel Martin by the Consolidated Research Group on Marine Benthic Ecology of the Generalitat de Catalunya (Ref. 2017SGR378), the CSIC Intramural Project 201630E020, and the ongoing project ‘‘Study of natural systems affected by coastal management and infrastructure projects in the open sea’’ involving the CEAB-CSIC and CREOCEAN. João Gil was funded by a collaborative agreement signed with CREOCEAN. Daniel Martin received funds supporting the payment of the PeerJ publication fees through the CSIC Open Access Publication Support Initiative from the CSIC Unit of Information Resources for Research (URICI). TotalEnergies E&P Congo partly sponsored the field surveys. Staff members of CREOCEAN participated in the study design and in sample collection cruises.
Publisher Copyright:
Copyright © 2022 Fresiello, Muthiah, Goetschalckx, Hayward, Rocchi, Bezy, Pauls, Meyns, Donker and Zieliński.
PY - 2022/10/13
Y1 - 2022/10/13
N2 - Simulators are expected to assume a prominent role in the process of design—development and testing of cardiovascular medical devices. For this purpose, simulators should capture the complexity of human cardiorespiratory physiology in a realistic way. High fidelity simulations of pathophysiology do not only allow to test the medical device itself, but also to advance practically relevant monitoring and control features while the device acts under realistic conditions. We propose a physiologically controlled cardiorespiratory simulator developed in a mixed in silico-in vitro simulation environment. As inherent to this approach, most of the physiological model complexity is implemented in silico while the in vitro system acts as an interface to connect a medical device. As case scenarios, severe heart failure was modeled, at rest and at exercise and as medical device a left ventricular assist device (LVAD) was connected to the simulator. As initial validation, the simulator output was compared against clinical data from chronic heart failure patients supported by an LVAD, that underwent different levels of exercise tests with concomitant increase in LVAD speed. Simulations were conducted reproducing the same protocol as applied in patients, in terms of exercise intensity and related LVAD speed titration. Results show that the simulator allows to capture the principal parameters of the main adaptative cardiovascular and respiratory processes within the human body occurring from rest to exercise. The simulated functional interaction with the LVAD is comparable to the one clinically observed concerning ventricular unloading, cardiac output, and pump flow. Overall, the proposed simulation system offers a high fidelity in silico-in vitro representation of the human cardiorespiratory pathophysiology. It can be used as a test bench to comprehensively analyze the performance of physically connected medical devices simulating clinically realistic, critical scenarios, thus aiding in the future the development of physiologically responding, patient-adjustable medical devices. Further validation studies will be conducted to assess the performance of the simulator in other pathophysiological conditions.
AB - Simulators are expected to assume a prominent role in the process of design—development and testing of cardiovascular medical devices. For this purpose, simulators should capture the complexity of human cardiorespiratory physiology in a realistic way. High fidelity simulations of pathophysiology do not only allow to test the medical device itself, but also to advance practically relevant monitoring and control features while the device acts under realistic conditions. We propose a physiologically controlled cardiorespiratory simulator developed in a mixed in silico-in vitro simulation environment. As inherent to this approach, most of the physiological model complexity is implemented in silico while the in vitro system acts as an interface to connect a medical device. As case scenarios, severe heart failure was modeled, at rest and at exercise and as medical device a left ventricular assist device (LVAD) was connected to the simulator. As initial validation, the simulator output was compared against clinical data from chronic heart failure patients supported by an LVAD, that underwent different levels of exercise tests with concomitant increase in LVAD speed. Simulations were conducted reproducing the same protocol as applied in patients, in terms of exercise intensity and related LVAD speed titration. Results show that the simulator allows to capture the principal parameters of the main adaptative cardiovascular and respiratory processes within the human body occurring from rest to exercise. The simulated functional interaction with the LVAD is comparable to the one clinically observed concerning ventricular unloading, cardiac output, and pump flow. Overall, the proposed simulation system offers a high fidelity in silico-in vitro representation of the human cardiorespiratory pathophysiology. It can be used as a test bench to comprehensively analyze the performance of physically connected medical devices simulating clinically realistic, critical scenarios, thus aiding in the future the development of physiologically responding, patient-adjustable medical devices. Further validation studies will be conducted to assess the performance of the simulator in other pathophysiological conditions.
KW - 0D models
KW - artificial organs
KW - cardiorespiratory simulator
KW - exercise physiology
KW - in vitro simulator
KW - lumped parameter model
KW - mechanical circulatory support
KW - ventricular assist device
UR - http://www.scopus.com/inward/record.url?scp=85140603870&partnerID=8YFLogxK
U2 - 10.3389/fphys.2022.967449
DO - 10.3389/fphys.2022.967449
M3 - Article
AN - SCOPUS:85140603870
VL - 13
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
M1 - 967449
ER -