Initial clinical validation of a hybrid in silico—in vitro cardiorespiratory simulator for comprehensive testing of mechanical circulatory support systems

Figures

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  FIGURE 1. Schematic of the hybrid simulator: in vitro interface with an LVAD connected between two hydraulic chambers (left panel) and in silico lumped parameters cardiorespiratory model and its main controls (right panel). The two middle hydraulic chambers represent the left ventricle and the aorta and exchange pressure and flow data in real-time with the remainder in silico cardiorespiratory model. Physical exercise level is input into the system as oxygen consumption.

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  FIGURE 2. Schematic of the in silico simulator. Left and right atria (LA, RA) and ventricles (LV, RV) contraction is regulated by activation functions (ac, vc). Valves are represented by a diode and a resistance (Rmv, Rav, Rtv, Rpv). The ith vascular compartment is represented by resistance (Ri), inertance (Li), and compliance (Ci). Suffix refer to: ascending and descending aorta (aa, da), upper body (ub), kidneys (kid), splanchnic circulation (sp), left and right legs (ll, rl), inferior and superior vena cava (ivc, svc), arterial, and pulmonary circulation (pa, pv). The baroreflex control uses the difference ascending aortic pressure (Paa)—reference pressure (Paa Ref ) as input, and controls heart rate, heart contractility, arterial resistances and venous tone. The metabolic control acts locally in the upper body, kidneys, splanchnic circulation and legs. In the figure it is represented only for the left leg for brevity. It takes the difference O2 concentration (C O2llv )—reference concentration (C O2llvRef ) as input, and controls R lla and R llv as output. The ventilation control takes the arterial O2 and CO2 partial pressure in the upper body as input and controls the tidal volume and…

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  FIGURE 3. Hydraulic interface of the hybrid simulator. The system includes four hydraulic chambers, each actuated by a gear pump and a DC motor. The HVAD is connected between two chambers, one representing the left ventricle and the other the aorta.

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  FIGURE 4. User interface of the simulator. Hemodynamic data are plot on the top right panel: heart rate (HR), systemic arterial pressure (BP), pulmonary arterial pressure (PAP), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), arterial oxygen saturation (SatO2 ). Respiratory parameters (saturation of O2, partial pressure of CO2 and concentration of O2) are plot on the left panel. A dedicated window (bottom right panel) is used to activate control mechanisms, change cardiorespiratory parameters, and to input the exercise level either manually as a constant value or as a slope of increase over time.

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  FIGURE 5. Continuous line: oxygen consumption measured on LVAD patients at different time points for the Group2 exercise test from 10 to 90 W. Dashed line: linear model of VO2 increase fed into the cardiorespiratory simulator.

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  FIGURE 6. Workflow of the simulation steps for the Group1 and Group2 exercise tests.

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  FIGURE 7. Trend of cardiorespiratory parameters over time during the Group2 exercise test (from 10 to 90 W): heart rate (A), arterial systemic pressure (B), ventilation (C), ventilation frequency (D). Black lines refer to clinical data from Group2 (average and standard deviation), blue lines refer to simulations data. For the arterial systemic pressure, average values are shown for the clinical data and waveforms are reported for the simulations.

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  FIGURE 8. Simulated ventricular pressure-volume loops of the left ventricle supported by an HVAD for different conditions. Also the end-systolic elastance (Els) and the diastolic filling curves of the left ventricle are shown.

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  FIGURE 9. Upper panel: left ventricular pressure (black), ascending aorta pressure (grey), and intrathoracic pressure (dashed line plot against the secondary y-axis) measured on the simulator. Lower panel: flow waveforms measured from the HVAD connected to the simulator. Data from the left to the right column refers to: rest condition with HVAD at baseline speed Group1 exercise (44 W) with HVAD at baseline speed, Group1 exercise (44 W) with HVAD at increased speed, Group2 exercise (90 W) with HVAD at baseline speed.