The hybrid (physical-computational) cardiovascular simulator to study valvular diseases.

To better understand the impact of valvular heart disease (VHD) on the hemodynamics of the circulatory system, investigations can be carried out using a model of the cardiovascular system. In this study, a previously developed hybrid (hydro-numerical) simulator of the cardiovascular system (HCS) was adapted and used. In our HCS Björk-Shiley mechanical heart valves were used, playing the role of mitral and aortic ones. In order to simulate aortic stenosis (AS) and mitral regurgitation (MR), special mechanical devices have been developed and integrated with the HCS. The simulation results proved that the system works correctly. Namely, in the case of AS - the mean pulmonary arterial pressure was increased due to increased preload of the left ventricle and the decrease in right ventricular preload was caused by a decrease in systemic arterial pressure. The severity of AS was performed based on the transaortic pressure gradient as well as using the Gorlin and Aaslid equations. In the case of severe AS, when the mean gradient was above 40 mmHg, the aortic valve orifice area was 0.5 cm2, which is in line with ACC/AHA guidelines. For the case of MR - with increasing severity of MR, there was a decrease in the left ventricular pressure and an increase in left atrial pressure. Using mechanical heart valves to simulate VHD by the HCS can be a valuable tool for biomedical research, providing a safe and controlled environment to study and understand the pathophysiology of VHD.

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.

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.

Impact of lidocaine on hemodynamic and respiratory parameters during laparoscopic appendectomy in children.

We assessed the influence of systemic lidocaine administration on ventilatory and circulatory parameters, and the pneumoperitoneum impact on the cardiopulmonary system during a laparoscopic appendectomy in children. A single-center parallel single-masked randomized controlled study was carried out with 58 patients (3-17 years). Intravenous lidocaine bolus of 1.5 mg/kg over 5 min before induction of anesthesia followed by lidocaine infusion at 1.5 mg/kg/h intraoperatively. Respiratory system compliance (C, C/kg), Ppeak-PEEP and Pulse rate (Pulse), systolic, diastolic and mean blood pressure (NBPs, NBPd, NBPm), assessed in the Lidocaine and Control group, at the: beginning (P1), minimum lung compliance (P2) and at the end of surgery (P3) were compared. The respiratory/hemodynamic parameters did not differ between the groups at any stage of operation. Blood Pressure and Ppeak-PEEP were significantly higher at the P2 compared to P1 and P3 stages (P < 0.001, 1 - ß ≥ 0.895) that correlated with lung compliance changes: C/kg vs. NBPs and Ppeak-PEEP (- 0.42, - 0.84; P < 0.001); C vs. Pulse and Ppeak-PEEP (- 0.48, - 0.46; P < 0.001). Although an increase in intraabdominal pressure up to 12(15) mmHg causes significant changes in hemodynamic/respiratory parameters, there appears to be no risk of fatal reactions in 1E, 2E ASA patients. Systemic lidocaine administration doesn't alleviate circulatory/respiratory alterations during pneumoperitoneum. No lidocaine related episode of anaphylaxis, systemic toxicity, circulatory disturbances or neurological impairment occurred.ClinicalTrials.gov: 22/03/2019.Trial registration number: NCT03886896.

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.

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.

Is the New Infant Jarvik 2015 Suitable for Patients<8 kg? In Vitro Study Using a Hybrid Simulator.

Our aim was to study the feasibility of implanting the Infant Jarvik 2015 in patients weighing less than 8 kg. The Infant Jarvik 2015 left ventricular assist device (LVAD) was tested in a hybrid simulator of the cardiovascular system reproducing specific patients' hemodynamics for different patient weights (2-7 kg). For each weight, the sensitivity of the pump to different circulatory parameters (peripheral resistance, left ventricular elastance, right ventricular elastance, heart rate, and heart filling characteristics) has been tested repeating for each experiment a pump ramp (10 000-18 000 rpm). The increase in the pump speed causes a decrease (increase) in the left (right) atrial pressure, an increase (decrease) in the arterial systemic (pulmonary) pressure, an increase in the right ventricular pressure, a decrease (increase) in the left (right) ventricular volume, a decrease in the left ventricular cardiac output, an increase in the LVAD output and an increase in the right ventricular cardiac output (total cardiac output). Suction was observed for lower weight patients and for higher pump speed in the case of vasodilation, left ventricular recovery, bradycardia, right ventricular failure, and left ventricular hypertrophy. Backflow was observed in the case of left ventricular recovery at lower pump speed. In the hybrid simulator, the Infant Jarvik 2015 could be suitable for the implantation in patients lower than 8 kg because of the stability of the device respect to the cardio/circulatory changes (low frequency of suction and backflow) and because of the capability of the device to maintain adequate patient hemodynamics.

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.

A new endotracheal tube for infants--laboratory and clinical assessment: a preliminary study.

BACKGROUND: Conventional endotracheal pediatric tubes offer high resistance due to their small diameters and relatively high flow during ventilation. Any increase of the diameter of the tube lumen decreases the airway resistance and subsequently, the work of breathing (WOB). We compared ventilation mechanics using a new, cone-shaped endotracheal tube of our design to the Cole and standard tubes. METHODS: The study has been divided into three parts: (i) preliminary laboratory tests, (ii) in vitro study with infant lung model, and (iii) clinical study in infants. Flow resistance and WOB were compared, using standard, Cole (in experimental phase only) and cone tubes. RESULTS: We proved that inspiratory (Ri ) and expiratory (Re ) resistance, and WOB, were significantly lower in patients ventilated via a cone tube. Mean Ri decreased by 37%, compared with the baseline values, Re - by 35%, and total WOB - by 12%. CONCLUSION: The cone tube offers lower resistance to gas flow than the standard, used nowadays in clinical practice. It can be especially beneficial to spontaneously breathing patients reducing WOB and improving gas exchange.

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.

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.

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.

Virtual respiratory system in investigation of CPAP influence on optimal breathing frequency in obstructive lungs disease.

BACKGROUND: Continuous Positive Airway Pressure (CPAP) is a commonly accepted method of spontaneous breathing support in obstructive lung disease. Previous work suggested that the cause of the CPAP efficacy in the obstructive lung disease localized in bronchi of middle order (OLDMO) is not as obvious as, for example, in the obstructive sleep apnea. Since CPAP reduces obstruction and the optimal breathing frequency (BF) depends on the obstruction level, it seems to be important to analyze the dependence of the optimal BF on CPAP. AIM: To analyze the support efficacy cause in OLDMO, esp. the relationship between the CPAP value and optimal BF. METHOD: Investigations utilized previously built virtual respiratory system. Its most important factors: nonlinear lungs compliance and changeability of nonlinear airway resistance (Raw). Influence of BF and the CPAP value on the tidal volume and minute ventilation was analyzed for four exemplary virtual patients: healthy ("standard") and suffering from moderate, severe, and the very severe OLDMO (the other parameters, esp. respiratory muscles effort, were unchanged). Minute inspiratory work as a criterion of the BF optimization. RESULTS: CPAP decreased Raw making breathing easier, however, it shifted the working point of the respiratory system towards the smaller lungs compliance making breathing harder. The final result depended on the Raw value: CPAP improved breathing of patients with the serious OLDMO while it worsened healthy person breathing. The optimal CPAP value depended on the Raw value. If a virtual patient suffering from the serious OLDMO was not supported with CPAP, he had to breathe with low frequency because minute ventilation did not rise with BF increase. The optimal BF depended on the CPAP value (the greater the value, the greater the frequency). CONCLUSION: The CPAP efficacy depends on the level of OLDMO. CPAP is efficient in the severe OLDMO because it increases the optimal BF, which makes possible less energy-consuming breathing with frequency close to the normal one (greater BF means smaller tidal volume and thus smaller work against lungs compliance).