A new method of ventilation inhomogeneity assessment based on a simulation study using clinical data on congenital diaphragmatic hernia cases.

Congenital Diaphragmatic Hernia (CDH) is a diaphragm defect associated with lung hypoplasia and ventilation inhomogeneity (VI). The affected neonates are usually born with respiratory failure and require mechanical ventilation after birth. However, significant interindividual VI differences make ventilation difficult. So far, there are no clinical methods of VI assessment that could be applied to optimize ventilation at the bedside. A new VI index is a ratio of time constants T1/T2 of gas flows in both lungs. Pressure-controlled ventilation simulations were conducted using an infant hybrid (numerical-physical) respiratory simulator connected to a ventilator. The parameters of the respiratory system model and ventilator settings were based on retrospective clinical data taken from three neonates (2, 2.6, 3.6 kg) treated in the Paediatric Teaching Clinical Hospital of the Medical University of Warsaw. We searched for relationships between respiratory system impedance (Z) and ventilation parameters: work of breathing (WOB), peak inspiratory pressure (PIP), and mean airway pressure (MAP). The study showed the increased VI described by the T1/T2 index value highly correlated with elevated Z, WOB, PIP and MAP (0.8-0.9, the Spearman correlation coefficients were significant at P < 0.001). It indicates that the T1/T2 index may help to improve the ventilation therapy of CDH neonates.

Automatic air volume control system for ventilation of two patients using a single ventilator: a large animal model study.

The COVID-19 pandemic outbreak led to a global ventilator shortage. Hence, various strategies for using a single ventilator to support multiple patients have been considered. A device called Ventil previously validated for independent lung ventilation was used in this study to evaluate its usability for shared ventilation. We performed experiments with a total number of 16 animals. Eight pairs of pigs were ventilated by a ventilator or anesthetic machine and by Ventil for up to 27 h. In one experiment, 200 ml of saline was introduced to one subject's lungs to reduce their compliance. The experiments were analyzed in terms of arterial blood gases and respiratory parameters. In addition to the animal study, we performed a series of laboratory experiments with artificial lungs (ALs). The resistance and compliance of one AL (affected) were altered, while the tidal volume (TV) and peak pressure (Ppeak) in the second (unaffected) AL were analyzed. In addition, to assess the risk of transmission of pathogens between AL respiratory tracts, laboratory tests were performed using phantoms of virus particles. The physiological level of analyzed parameters in ventilated animals was maintained, except for CO2 tension, for which a permissive hypercapnia was indicated. Experiments did not lead to injuries in the animal's lungs except for one subject, as indicated by CT scan analysis. In laboratory experiments, changes in TV and Ppeak in the unaffected AL were less than 11%, except for 2 cases where the TV change was 20%. No cross-contamination was found in simulations of pathogen transmission. We conclude that ventilation using Ventil can be considered safe in patients undergoing deep sedation without spontaneous breathing efforts.

Virtual and Artificial Cardiorespiratory Patients in Medicine and Biomedical Engineering.

Recently, 'medicine in silico' has been strongly encouraged due to ethical and legal limitations related to animal experiments and investigations conducted on patients. Computer models, particularly the very complex ones (virtual patients-VP), can be used in medical education and biomedical research as well as in clinical applications. Simpler patient-specific models may aid medical procedures. However, computer models are unfit for medical devices testing. Hybrid (i.e., numerical-physical) models do not have this disadvantage. In this review, the chosen approach to the cardiovascular system and/or respiratory system modeling was discussed with particular emphasis given to the hybrid cardiopulmonary simulator (the artificial patient), that was elaborated by the authors. The VP is useful in the education of forced spirometry, investigations of cardiopulmonary interactions (including gas exchange) and its influence on pulmonary resistance during artificial ventilation, and explanation of phenomena observed during thoracentesis. The artificial patient is useful, inter alia, in staff training and education, investigations of cardiorespiratory support and the testing of several medical devices, such as ventricular assist devices and a membrane-based artificial heart.

A Compliant Model of the Ventricular Apex to Study Suction in Ventricular Assist Devices.

Ventricular suction is a frequent adverse event in patients with a ventricular assist device (VAD). This study presents a suction module (SM) embedded in a hybrid (hydraulic-computational) cardiovascular simulator suitable for the testing of VADs and related suction events. The SM consists of a compliant latex tube reproducing a simplified ventricular apex. The SM is connected on one side to a hydraulic chamber of the simulator reproducing the left ventricle, and on the other side to a HeartWare HVAD system. The SM is immersed in a hydraulic chamber with a controllable pressure to occlude the compliant tube and activate suction. Two patient profiles were simulated (dilated cardiomyopathy and heart failure with preserved ejection fraction), and the circulating blood volume was reduced stepwise to obtain different preload levels. For each simulated step, the following data were collected: HVAD flow, ventricular pressure and volume, and pressure at the inflow cannula. Data collected for the two profiles and for decreasing preload levels evidenced suction profiles differing in terms of frequency (intermittent vs. every heart beat), amplitude (partial or complete stoppage of the HVAD flow), and shape. Indeed different HVAD flow patterns were observed for the two patient profiles because of the different mechanical properties of the simulated ventricles. Overall, the HVAD flow patterns showed typical indicators of suctions observed in clinics. Results confirmed that the SM can reproduce suction phenomena with VAD under different pathophysiological conditions. As such, the SM can be used in the future to test VADs and control algorithms aimed at preventing suction phenomena.

How to ventilate preterm infants with lung compliance close to circuit compliance: real-time simulations on an infant hybrid respiratory simulator.

Circuit compliance close to lung compliance can create serious problems in effective and safe mechanical ventilation of preterm infants. We considered what ventilation technique is the most beneficial in this case. A hybrid (numerical-physical) simulator of infant respiratory system mechanics, the Bennett Ventilator and NICO apparatus were used to simulate pressure-controlled ventilation (PC) and volume-controlled ventilation with constant flow (VCVCF) and descending flow (VCVDF), under permissive hypercapnia (PHC) (6 ml kg-1) and normocapnia (SV) (8 ml kg-1) conditions. Respiratory rate (RR) was 36 or 48 min-1 and PEEP was 0.3 or 0.6 kPa. Peak inspiratory pressure (PIP), mean airway pressure (MAP), and work of breathing by the ventilator (WOB) were lower (P < 0.01, 1 - ß = 0.9) using the PHC strategy compared to the SV strategy. The WOB increased (P < 0.01; 1 - ß = 0.9) when the RR increased. The PC, VCVCF, and VCVDF modes did not differ in minute ventilation produced by the ventilator (MVV), but the PC mode delivered the highest minute ventilation to the patient (MVT) (P < 0.01; 1 - ß = 0.9) at the same PIP, MAP, and WOB. The most beneficial ventilation technique appeared to be PC ventilation with the PHC strategy, with lower RR (36 min-1). Graphical abstract The effectiveness of an infant ventilation depending on circuit compliance to lung compliance ratio (Cv CL -1) and inspiration time (Ti). VV, VT, tidal volume set on the ventilator and delivered to patient, respectively.

Gold Nanoparticle-Modified Poly(vinyl chloride) Surface with Improved Antimicrobial Properties for Medical Devices.

Despite the significant technological progress achieved in the past decades in the medical field, device-related infections carry a heavy social and economic burden. Surface modification of medical equipment is one of the most interesting approaches employed to improve the antibacterial activity of a material. Herein, we developed a process for the gold nanoparticle modification of a poly(vinyl chloride) laryngeal tube, which typically serves as an airway management device. In our study, we focused specifically on increasing the antimicrobial properties of the material while maintaining its biocompatibility. We applied two different modification methods to the poly(vinyl chloride) laryngeal tube. An increase in the antimicrobial activity of the surface was observed for both methods. In addition, the adsorption of bacterial cells on the material surface was assessed. We determined that the number of colonies cultured in the presence of the gold nanoparticle-modified samples or absorbed to the material surface decreased significantly compared with the control group. The trend was observed for both Gram-positive and Gram-negative strains. Moreover, it was established that the designed material did not exhibit a lethal impact on a control cell line. Finally, we noted discrepancies in the growth of bacteria cultured in the presence of modified or unmodified PVC material as well as differences in cell adherence to its surface. The proposed poly(vinyl chloride) modifications are most effective against Gram-positive bacteria, especially L. monocytogenes. Nevertheless, it ought to be emphasized that due to their different properties, each strain requires an individual approach.

Control of a Pediatric Pulsatile Ventricular Assist Device: A Hybrid Cardiovascular Model Study.

The aim of this work is to study pediatric pneumatic ventricle (PVAD) performance, versus VAD rate (VADR) and native heart rate (HR) ratio Rr (VADR/HR). The study uses a hybrid model of the cardiovascular system (HCS). HCS consists of a computational part (a lumped parameter model including left and right ventricles, systemic and pulmonary arterial and venous circulation) interfaced to a physical part. This permits the connection of a VAD (15 mL PVAD). Echocardiographic and hemodynamic data of a pediatric patient (average weight 14.3 kg, HR 100 bpm, systemic pressure 75/44 mm Hg, CO 1.5 L/min) assisted apically with asynchronous PVAD were used to set up a basal condition in the model. After model tuning, the assistance was started, setting VAD parameters (ejection and filling pressures, systole duration) to completely fill and empty the PVAD. The study was conducted with constant HR and variable VADR (50-120, step 10, bpm). Experiments were repeated for two additional patients' HRs, 90 and 110 bpm and for two values of systemic arterial resistance (Ras ) and Emax . Experimental data were collected and stored on disk. Analyzed data include average left and right ventricular volumes (LVV, RVV), left ventricular flow (LVF), VAD flow (VADF), and total cardiac output (COt). Data were analyzed versus Rr. LVV and RVV are sensitive to Rr and a left ventricular unloading corresponds in general to a right ventricular loading. In the case of asynchronous assistance, frequency beats are always present and the beat rate is equal to the difference between HR and VADR. In the case of pulsatile asynchronous LVAD assistance, VADR should be chosen to minimize frequency beat effects and right ventricular loading and to maximize left ventricular unloading.

A new infant hybrid respiratory simulator: preliminary evaluation based on clinical data.

A new hybrid (numerical-physical) simulator of the respiratory system, designed to simulate spontaneous and artificial/assisted ventilation of preterm and full-term infants underwent preliminary evaluation. A numerical, seven-compartmental model of the respiratory system mechanics allows the operator to simulate global and peripheral obstruction and restriction of the lungs. The physical part of the simulator is a piston-based construction of impedance transformer. LabVIEW real-time software coordinates the work of both parts of the simulator and its interaction with a ventilator. Using clinical data, five groups of "artificial infants" were examined: healthy full-term infants, very low-birth-weight preterm infants successfully (VLBW) and unsuccessfully extubated (VLBWun) and extremely low-birth-weight preterm infants without (ELBW) and with bronchopulmonary dysplasia (ELBW_BPD). Pressure-controlled ventilation was simulated to measure peak inspiratory pressure, mean airway pressure, total (patient + endotracheal tube) airway resistance (R), total dynamic compliance of the respiratory system (C), and total work of breathing by the ventilator (WOB). The differences between simulation and clinical parameters were not significant. High correlation coefficients between both types of data were obtained for R, C, and WOB (γ R  = 0.99, P < 0.0005; γ C  = 0.85, P < 0.005; γWOB = 0.96, P < 0.05, respectively). Thus, the simulator accurately reproduces infant respiratory system mechanics.

The need for hybrid modeling in analysis of cardiovascular and respiratory support.

The analysis of the efficiency and optimum use of cardiovascular and respiratory support systems is of great importance in research and development as well as in clinical practice. To understand the complex interaction between human cardiovascular or respiratory systems and the mechanical assist devices, a number of physical, computational or hybrid (physical-electrical or physical-computational) models/simulators have been developed and used in recent years. The hybrid models combine the advantages of both the physical models (interaction with assist devices) and of the computational/electrical models (accuracy, flexibility). This paper reviews the existing solutions and briefly describes their characteristics, advantages and disadvantages, chiefly emphasizing the features of the hybrid models that are most promising for future development.

Reproduction of continuous flow left ventricular assist device experimental data by means of a hybrid cardiovascular model with baroreflex control.

Long-term mechanical circulatory assistance opened new problems in ventricular assist device-patient interaction, especially in relation to autonomic controls. Modeling studies, based on adequate models, could be a feasible approach of investigation. The aim of this work is the exploitation of a hybrid (hydronumerical) cardiovascular simulator to reproduce and analyze in vivo experimental data acquired during a continuous flow left ventricular assistance. The hybrid cardiovascular simulator embeds three submodels: a computational cardiovascular submodel, a computational baroreflex submodel, and a hydronumerical interface submodel. The last one comprises two impedance transformers playing the role of physical interfaces able to provide a hydraulic connection with specific cardiovascular sites (in this article, the left atrium and the ascending/descending aorta). The impedance transformers are used to connect a continuous flow pump for partial left ventricular support (Synergy Micropump, CircuLite, Inc., Saddlebrooke, NJ, USA) to the hybrid cardiovascular simulator. Data collected from five animals in physiological, pathological, and assisted conditions were reproduced using the hybrid cardiovascular simulator. All parameters useful to characterize and tune the hybrid cardiovascular simulator to a specific hemodynamic condition were extracted from experimental data. Results show that the simulator is able to reproduce animal-specific hemodynamic status both in physiological and pathological conditions, to reproduce cardiovascular left ventricular assist device (LVAD) interaction and the progressive unloading of the left ventricle for different pump speeds, and to investigate the effects of the LVAD on baroreflex activity. Results in chronic heart failure conditions show that an increment of LVAD speed from 20 000 to 22 000 rpm provokes a decrement of left ventricular flow of 35% (from 2 to 1.3 L/min). Thanks to its flexibility and modular structure, the simulator is a platform potentially useful to test different assist devices, thus providing clinicians additional information about LVAD therapy strategy.

IABP timing and ventricular performance--comparison between a compliant and a stiffer aorta: a hybrid model study including baroreflex.

INTRODUCTION: The aim of this study was to investigate the effects of the intra aortic balloon pump (IABP) and of aortic compliance on left ventricular performance, including the effects of baroreflex control.
 METHODS: The study was conducted using a hybrid cardiovascular simulator, including a computational cardiovascular sub-model, a hydraulic sub-model of the descending aorta, and a baroreflex computational sub-model. A 40 cc balloon was inserted into a rubber tube component of the hydraulic sub-model. A comparative analysis was conducted for two aortic compliances (C1 = 2.4 and C2 = 1.43 cm3/mmHg, corresponding to an aortic pulse pressure of 23 mmHg and 35 mmHg, respectively), driving the balloon for different trigger timings.
 RESULTS: Under C1 conditions, the IABP induced higher effects on baroreflex activity (decrement of sympathetic efferent activity: 10% for C1 and 14.7% for C2) and ventricular performance (increment of cardiac output (CO): 3.7% for C1 and 5.2% for C2, increment of endocardial viability ratio (EVR): 24.8% for C1 and 55% for C2). The best balloon timing was different for C1 and C2: inflation trigger timing (from the dicrotic notch) -0.09 s for C1 and -0.04 s for C2, inflation duration 0.25 s for C1 and 0.2 s for C2.
 CONCLUSIONS: Early inflation ensures better EVR, CO, and an increment of the afferent nerve activity, hence causing peripheral resistance and heart rate to decrease. The best balloon timing depends on aortic compliance, thus suggesting the need for a therapy tailored to the specific conditions of individual patients.

Continuous-flow pump model study: the effect on pump performance of pump characteristics and cardiovascular conditions.

This model study evaluates the effect of pump characteristics and cardiovascular data on hemodynamics in atrio-aortic VAD assistance. The model includes a computational circulatory sub-model and an electrical sub-model representing two rotary blood pumps through their pressure-flow characteristics. The first is close to a pressure generator-PG (average flow sensitivity to pressure variations, -0.047 l mmHg(-1)); the second is closer to a flow generator-FG (average flow sensitivity to pressure variations, -0.0097 l mmHg(-1)). Interaction with VAD was achieved by means of two interfaces, behaving as impedance transformers. The model was verified by use of literature data and VAD onset conditions were used as a control for the experiments. Tests compared the two pumps, at constant pump speed, in different ventricular and circulatory conditions: maximum ventricular elastance (0.44-0.9 mmHg cm(-3)), systemic peripheral resistance (781-1200 g cm(-4) s(-1)), ventricular diastolic compliance C p (5-10-50 cm(3) mmHg(-1)), systemic arterial compliance (0.9-1.8 cm(3) mmHg(-1)). Analyzed variables were: arterial and venous pressures, flows, ventricular volume, external work, and surplus hemodynamic energy (SHE). The PG pump generated the highest SHE under almost all conditions, in particular for higher C p (+50 %). PG pump flow is also the most sensitive to E max and C p changes (-26 and -33 %, respectively). The FG pump generally guarantees higher external work reduction (54 %) and flow less dependent on circulatory and ventricular conditions. The results are evidence of the importance of pump speed regulation with changing ventricular conditions. The computational sub-model will be part of a hydro-numerical model, including autonomic controls, designed to test different VADs.

Effects of intra-aortic balloon pump timing on baroreflex activities in a closed-loop cardiovascular hybrid model.

Despite 50 years of research to assess the intra-aortic balloon pump (IABP) effects on patients' hemodynamics, some issues related to the effects of this therapy are still not fully understood. One of these issues is the effect of IABP, its inflation timing and duration on peripheral circulation autonomic controls. This work provides a systematic analysis of IABP effects on baroreflex using a cardiovascular hybrid model, which consists of computational and hydraulic submodels. The work also included a baroreflex computational model that was connected to a hydraulic model with a 40-cm(3) balloon. The IABP was operated at different inflation trigger timings (-0.14 to 0.31 s) and inflation durations (0.05-0.45 s), with time of the dicrotic notch being taken as t = 0. Baroreflex-dependent parameters-afferent and efferent pathway activity, heart rate, peripheral resistance, and venous tone-were evaluated at each of the inflation trigger times and durations considered. Balloon early inflation (0.09 s before the dicrotic notch) with inflation duration of 0.25 s generated a maximum net increment of afferent pathway activity of 10%, thus leading to a decrement of efferent sympathetic activity by 15.3% compared with baseline values. These times also resulted in a reduction in peripheral resistance and heart rate by 4 and 4.3% compared with baseline value. We conclude that optimum IABP triggering time results in positive effects on peripheral circulation autonomic controls. Conversely, if the balloon is not properly timed, peripheral resistance and heart rate may even increase, which could lead to detrimental outcomes.

A modular computational circulatory model applicable to VAD testing and training.

Aim of this work was to develop a modular computational model able to interact with ventricular assist devices (VAD) for research and educational applications. The lumped parameter model consists of five functional modules (left and right ventricles, systemic, pulmonary, and coronary circulation) that are easily replaceable if necessary. The possibility of interacting with VADs is achieved via interfaces acting as impedance transformers. This last feature was tested using an electrical VAD model. Tests were aimed at demonstrating the possibilities and verifying the behavior of interfaces when testing VADs connected in different ways to the circulatory system. For these reasons, experiments were performed in a purely numerical mode, simulating a caval occlusion, and with the model interfaced to an external left-VAD (LVAD) in two different ways: with atrioaortic and ventriculoaortic connection. The caval occlusion caused the leftward shift of the LV p-v loop, along with the drop in arterial and ventricular pressures. A narrower LV p-v loop and cardiac output and aortic pressure rise were the main effects of atrioaortic assistance. A wider LV p-v loop and a ventricular average volume drop were the main effects of ventricular-aortic assistance. Results coincided with clinical and experimental data attainable in the literature. The model will be a component of a hydronumerical model designed to be connected to different types of VADs. It will be completed with autonomic features, including the baroreflex and a more detailed coronary circulation model.

Hybrid model analysis of intra-aortic balloon pump performance as a function of ventricular and circulatory parameters.

We investigated the effects of the intra-aortic balloon pump (IABP) on endocardial viability ratio (EVR), cardiac output (CO), end-systolic (V(es)) and end-diastolic (V(ed)) ventricular volumes, total coronary blood flow (TCBF), and ventricular energetics (external work [EW], pressure-volume area [PVA]) under different ventricular (E(max) and diastolic stiffness) and circulatory (arterial compliance) parameters. We derived a hybrid model from a computational model, which is based on merging computational and hydraulic submodels. The lumped parameter computational submodel consists of left and right hearts and systemic, pulmonary, and coronary circulations. The hydraulic submodel includes part of the systemic arterial circulation, essentially a silicone rubber tube representing the aorta, which contains a 40-mL IAB. EVR, CO, V(es), and V(ed), TCBF and ventricular energetics (EW, PVA) were analyzed against the ranges of left ventricular E(max) (0.3-0.5-1 mm Hg/cm(3)) and diastolic stiffness V(stiffness) (≈0.08 and ≈0.3 mm Hg/cm(3), obtained by changing diastolic stiffness constant) and systemic arterial compliance (1.8-2.5 cm(3)/mm Hg). All experiments were performed comparing the selected variables before and during IABP assistance. Increasing E(maxl) from 0.5 to 2 mm Hg/cm(3) resulted in IABP assistance producing lower percentage changes in the selected variables. The changes in ventricular diastolic stiffness strongly influence both absolute value of EVR and its variations during IABP (71 and 65% for lower and higher arterial compliance, respectively). V(ed) and V(es) changes are rather small but higher for lower E(max) and higher V(stiffness). Lower E(max) and higher V(stiffness) resulted in higher TCBF and CO during IABP assistance (∼35 and 10%, respectively). The use of this hybrid model allows for testing real devices in realistic, stable, and repeatable circulatory conditions. Specifically, the presented results show that IABP performance is dependent, at least in part, on left ventricular filling, ejection characteristics, and arterial compliance. It is possible in this way to simulate patient-specific conditions and predict the IABP performance at different values of the circulatory or ventricular parameters. Further work is required to study the conditions for heart recovery modeling, baroreceptor controls, and physiological feedbacks.

A new hybrid electro-numerical model of the left ventricle.

The paper presents a new project of a hybrid numerical-physical model of the left ventricle. A physical part of the model can be based on electrical or hydraulic structures. Four variants of the model with numerical and physical heart valves have been designed to investigate an effect of a heart assistance connected in series and in parallel to the natural heart. The LabVIEW real time environment has been used in the model to increase its accuracy and reliability. A prototype of the hybrid electro-numerical model of the left ventricle has been tested in an open loop and closed loop configuration.

A hybrid mock circulatory system: testing a prototype under physiologic and pathological conditions.

Hydraulic models of circulation are used to test mechanical heart assist devices and for research and training purposes. However, when compared with numerical models, they are rather expensive and often not sufficiently flexible or accurate. Flexibility and accuracy can be improved by merging numerical models with physical models, thus obtaining a hybrid model where numerical and physical sections are connected by an electrohydraulic interface. This concept is applied here to represent left ventricular function. The resulting hybrid model is inserted into the existing closed loop model of circulation. The hybrid model reproduces ventricular function by a variable elastance numerical model. Its interaction with the hydraulic sections is governed by measuring left atrial and systemic arterial pressures and computing the left ventricular output flow by the resolution of the corresponding equations. This signal is used to control a flow generator reproduced by a gear pump driven by a DC motor. Results obtained under different circulatory conditions demonstrate the behavior of the ventricular model on the pressure-volume plane and report the trend of the main hemodynamic variables.