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.

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

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.

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.

Hemodynamic characterization of the Realheart® total artificial heart with a hybrid cardiovascular simulator.

BACKGROUND: Heart failure is a growing health problem worldwide. Due to the lack of donor hearts there is a need for alternative therapies, such as total artificial hearts (TAHs). The aim of this study is to evaluate the hemodynamic performance of the Realheart® TAH, a new 4-chamber cardiac prosthesis device. METHODS: The Realheart® TAH was connected to a hybrid cardiovascular simulator with inflow connections at the left/right atrium, and outflow connections at the ascending aorta/pulmonary artery. The Realheart® TAH was tested at different pumping rates and stroke volumes. Different systemic resistances (20.0-16.7-13.3-10.0 Wood units), pulmonary resistances (6.7-3.3-1.7 Wood units), and pulmonary/systemic arterial compliances (1.4-0.6 ml/mm Hg) were simulated. Tests were also conducted in static conditions, by imposing predefined values of preload-afterload across the artificial ventricle. RESULTS: The Realheart® TAH allows the operator to finely tune the delivered flow by regulating the pumping rate and stroke volume of the artificial ventricles. For a systemic resistance of 16.7 Wood units, the TAH flow ranges from 2.7 ± 0.1 to 6.9 ± 0.1 L/min. For a pulmonary resistance of 3.3 Wood units, the TAH flow ranges from 3.1 ± 0.0 to 8.2 ± 0.3 L/min. The Realheart® TAH delivered a pulse pressure ranging between ~25 mm Hg and ~50 mm Hg for the tested conditions. CONCLUSIONS: The Realheart® TAH offers great flexibility to adjust the output flow and delivers good pressure pulsatility in the vessels. Low sensitivity of device flow to the pressure drop across it was identified and a new version is under development to counteract this.

Impact of therapeutic thoracentesis and pleural pressure changes on breathing pattern, dyspnea, lung function, and arterial blood gases.

INTRODUCTION: Therapeutic thoracentesis is highly effective in providing symptomatic improvement in patients with large volume pleural effusion (PE). However, some physiological effects of pleural fluid (PF) withdrawal are still not fully elucidated. OBJECTIVES: The study aimed to evaluate alterations in the breathing pattern, pulmonary function, and arterial blood gases (ABG) in relation to both withdrawn PF volume and pleural pressure (Ppl) changes in patients undergoing therapeutic thoracentesis. PATIENTS AND METHODS: This prospective, observational, cross­sectional study included 37 patients with large volume PE. Respiratory rate (RR), dyspnea, pulmonary function, and ABG were assessed before the thoracentesis, at the termination of the PF withdrawal and 1, 3, and 24 hours after the procedure. The volume of PF drained, Ppl, and tidal volume (TV) were monitored during the thoracentesis. RESULTS: Thoracentesis resulted in a transient but significant increase in RR directly after the procedure, and a transient decrease, followed by subsequent increase in TV. There was a significant and constant increase in forced vital capacity up to 24 hours after thoracentesis (P = 0.001). Oxygen partial pressure (PaO2) significantly improved directly after PF withdrawal (P = 0.01) and returned to baseline values after 24 hours. Thoracentesis was invariably associated with a significant increase in the amplitude of Ppl (Ppl_ampl) changes during the respiratory cycle (P <0.001). CONCLUSIONS: Therapeutic thoracentesis results in a modest improvement in pulmonary function, tran-sient increase in PaO2 and increase in Ppl_ampl. The improvement in pulmonary function and ABG is closely related to the volume of PF drained and pleural elastance. The increase in Ppl_ampl probably represents a more efficient work of the respiratory muscles.

Modeling of Inhalation Profiles Through Dry Powder Inhaler in Healthy Adults and Asthma Patients As a Prerequisite for Further In Vitro and In Silico Studies.

Background: The severity of airway obstruction may affect patient's ability to perform an effective drug inhalation from a dry powder inhaler (DPI). Also, an incorrect inhalation technique may negatively affect the efficacy of asthma treatment. The aims of the study were (1) to analyze and compare inhalation profiles recorded with the use of different inhalation techniques, and thus, (2) to establish model inhalation profiles representative for healthy subjects and subjects with mild and moderate-to-severe asthma. Methods: This study was performed in healthy volunteers, patients with mild and moderate-to-severe asthma. A modified flow-volume test to define two different expiratory levels (to residual volume and half-way to residual volume) was performed. Inspiratory flow parameters were extracted: peak inspiratory flow rate (PIFinh), time at which peak inspiratory flow rate occurs (tPIFinh), total inhalation time (T), and inhaled volume (V). Test of frequency for tPIFinh100% and tPIFinh50% by asthma severity was performed, to provide information about initial flow accelerations. The impact of two different expiratory levels preceding inhalation (with severity of asthma as a categorical factor) on inspiratory flow parameters was examined. Results: PIFinh was dependent upon asthma severity (p = 0.046). Type of exhalation before inhalation had no effect on PIFinh values. V value was significantly affected both by asthma severity (p = 0.024) and type of exhalation before inhalation (p < 0.0001). Mean T value was influenced by type of exhalation before inhalation (p = 0.0003), but not by asthma severity. Mean tPIFinh value was affected by the type of exhalation before inhalation only in healthy subjects (p = 0.01). Conclusions: Both asthma severity and type of exhalation before inhalation have little impact on the dynamics of inhalation through a DPI. An alternative form of equation describing inhalation profiles demonstrating a relationship between lung mechanics and dynamics of inspiratory profile has been proposed.

Independent Lung Ventilation-Experimental Studies on a 3D Printed Respiratory Tract Model.

Independent lung ventilation (ILV) is a life-saving procedure in unilateral pulmonary pathologies. ILV is underused in clinical practice, mostly due to the technically demanding placement of a double lumen endotracheal tube (ETT). Moreover, the determination of ventilation parameters for each lung in vivo is limited. In recent years, the development of 3D printing techniques enabled the production of highly accurate physical models of anatomical structures used for in vitro research, considering the high risk of in vivo studies. The purpose of this study was to assess the influence of double-lumen ETT on the gas transport and mixing in the anatomically accurate 3D-printed model of the bronchial tree, with lung lobes of different compliances, using various ventilation modes. The bronchial tree was obtained from Respiratory Drug Delivery (RDD Online, Richmond, VA, USA), processed and printed by a dual extruder FFF 3D printer. The test system was also composed of left side double-lumen endotracheal tube, Siemens Test Lung 190 and anesthetic breathing bag (as lobes). Pressure and flow measurements were taken at the outlets of the secondary bronchus. The measured resistance increased six times in the presence of double-lumen ETT. Differences between the flow distribution to the less and more compliant lobe were more significant for the airways with double-lumen ETT. The ability to predict the actual flow distribution in model airways is necessary to conduct effective ILV in clinical conditions.

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.

Inhalation Profiles Through a Dry Powder Inhaler: Relation Between Inhalation Technique and Spirometric Measures.

Background: The understanding of the real flow profiles through a dry powder inhaler (DPI), generated by asthma patients, is a prerequisite for satisfactory drug delivery to the lungs. The aims of the study were to assess the relationship between spirometric measures and inhalation profiles through a low-resistance DPI, and to compare parameters of those profiles between optimal and suboptimal inhalation technique type. Methods: Both healthy adult volunteers and patients with asthma were included in the study. Spirometry was conducted along with modified flow-volume test to detect expiratory levels (maximum "100%" exhalation to residual volume [RV] and halfway "50%" to RV). These were the reference levels of the depth of exhalation for each patient to simulate the effect of incomplete exhalation. Individual inhalation profiles were recorded using spirometry in-house software as the volumetric airflow through the inhaler versus time. Inspiratory flow parameters were extracted: time to peak inspiratory flow through inhaler (PIFinh), time at which peak inspiratory flow occurs (tPIFinh), total inhalation time (T), and inhaled volume during maneuver (V). Results and Conclusions: There are significant relationships between spirometric indices and parameters of inhalation through a low-resistance, cyclohaler-type DPI (assessed by single-factor analysis of Spearman's rank correlation coefficient). Multiple regression models were constructed, predicting inspiratory flow parameters (including spirometric indices, demographic parameters, and inhaler's usage history as determinants). The exhalation halfway to RV before inhalation did not affect significantly PIFinh and tPIFinh (and, thus, initial flow dynamics) in asthma patients. T and V parameters were then significantly decreased, but seemed sufficient for successful DPI performance. Both exhalation to RV and incomplete exhalation halfway to RV preceding inhalation allow for effective usage of low-resistance DPI.

Doxorubicin-transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells.

Doxorubicin (DOX) is considered one of the most powerful chemotherapeutic agents but its clinical use has several limitations, including cardiomyopathy and cellular resistance to the drug. By using transferrin (Tf) as a drug carrier, however, the adverse effects of doxorubicin as well as drug resistance can be reduced. The main objective of this study was to determine the exact nature and extent to which mitochondrial function is influenced by DOX-Tf conjugate treatment, specifically in human breast adenocarcinoma cells. We assessed the potential of DOX-Tf conjugate as a drug delivery system, monitoring its cytotoxicity using the MTT assay and ATP measurements. Moreover, we measured the alterations of mitochondrial function and oxidative stress markers. The effect of DOX-Tf was the most pronounced in MDA-MB-231, triple-negative breast cancer cells, whereas non-cancer endothelial HUVEC-ST cells were more resistant to DOX-Tf conjugate than to free DOX treatment. A different sensitivity of two investigate breast cancer cell lines corresponded to the functionality of their cellular antioxidant systems and expression of estrogen receptors. Our data also revealed that conjugate treatment mediated free radical generation and altered the mitochondrial bioenergetics in breast cancer cells.

Disturbance of cellular homeostasis as a molecular risk evaluation of human endothelial cells exposed to nanoparticles.

Even though application of nanoparticles in medicine seems to provide unique solutions for drug delivery and diagnosis diseases, understanding interactions between nanoscale materials and biological systems is imperative. Therefore, this study determined the effect of different types of nanoparticles (NPs) on human endothelial cells and examined the types of toxicity responses they can induce. Four different types of NPs were tested (PLA/MMT/TRASTUZUMAB, PLA/EDTMP, PLGA/MDP, and Pluronic F127 MICELLES), representing three putative areas of application: anticancer therapy, scintigraphy, and cosmetology. The experiments were performed on immortalized human umbilical vein endothelial cells (HUVEC-STs). Light contrast phase microscopy as well as cell viability assays showed that only Pluronic F127 MICELLES decreased the number of HUVEC-STs in contrast to PLA/MMT/TRASTUZUMAB, PLA/EDTMP, and PLGA/MDP NPs, which altered cell morphology, but not their confluency. The tested NPs induced not only DNA strand-breaks and alkali-labile sites, but also internucleosomal DNA fragmentation, visualized as a DNA ladder pattern typical of apoptosis. Moreover, generation of free radicals and subsequent mitochondrial membrane potential collapse showed the significance of free radical production during interactions between NPs and endothelial cells. High concentrations of NPs had different degrees of toxicity in human endothelial cells and affected cell proliferation, redox homeostasis, and triggered mitochondrial dysfunction.

Development of a computational simulator of the extracorporeal membrane oxygenation and its validation with in vitro measurements.

In the recent years, the use of extracorporeal membrane oxygenation (ECMO) has grown substantially, posing the need of having specialized medical and paramedical personnel dedicated to it. Optimization of the therapy, definition of new therapeutic strategies, and ECMO interaction with the cardiorespiratory system require numerous specific skills and preclinical models for patient successful management. The aim of the present work is to develop and validate a computational model of ECMO and connect it to an already existing lumped parameter model of the cardiorespiratory system. The ECMO model was connected between the right atrium and the aorta of the cardiorespiratory simulator. It includes a hydraulic module that is a representation of the tubing, oxygenator, and pump. The resulting pressures and flows within the ECMO circuit were compared to the measurements conducted in vitro on a real ECMO. Additionally, the hemodynamic effects the ECMO model elicited on the cardiorespiratory simulator were compared with experimental data taken from the literature. The comparison between the hydraulic module and the in vitro measurements evidenced a good agreement in terms of flow, pressure drops across the pump, across the oxygenator and the tubing (maximal percentage error recorded was 17.6%). The hemodynamic effects of the ECMO model on the cardiovascular system were in agreement with what observed experimentally in terms of cardiac output, systemic pressure, pulmonary arterial pressure, and left atrial pressure. The ECMO model we developed and embedded into the cardiorespiratory simulator, is a useful tool for the investigation of basic physiological mechanisms and principles of ECMO therapy. The model was sided by a user interface dedicated to training applications. As such, the resulting simulator can be used for the education of students, medical and paramedical personnel.

Pleural Pressure Pulse in Patients with Pleural Effusion: A New Phenomenon Registered during Thoracentesis with Pleural Manometry.

Pleural manometry enables the assessment of physiological abnormalities of lung mechanics associated with pleural effusion. Applying pleural manometry, we found small pleural pressure curve oscillations resembling the pulse tracing line. The aim of our study was to characterize the oscillations of pleural pressure curve (termed here as the pleural pressure pulse, PPP) and to establish their origin and potential significance. This was an observational cross-sectional study in adult patients with pleural effusion who underwent thoracentesis with pleural manometry. The pleural pressure curves recorded prior to and during fluid withdrawal were analyzed. The presence of PPP was assessed in relation to the withdrawn pleural fluid volume, lung expandability, vital and echocardiographic parameters, and pulmonary function testing. A dedicated device was developed to compare the PPP to the pulse rate. Fifty-four patients (32 women) median age 66.5 (IQR 58.5-78.7) years were included. Well visible and poorly visible pressure waves were detected in 48% and 35% of the patients, respectively. The frequency of PPP was fully concordant with the pulse rate and the peaks of the oscillations reflected the period of heart diastole. PPP was more visible in patients with a slower respiratory rate (p = 0.008), a larger amount of pleural effusion, and was associated with a better heart systolic function assessed by echocardiography (p < 0.05). This study describes a PPP, a new pleural phenomenon related to the cyclic changes in the heart chambers volume. Although the importance of PPP remains largely unknown, we hypothesize that it could be related to lung atelectasis or lower lung and visceral pleura compliance.

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.

The use of a virtual patient to follow changes in arterial blood gases associated with therapeutic thoracentesis.

PURPOSES:: Some controversies exist on the effect of therapeutic thoracentesis (TT) on arterial blood oxygen tension. The aim of this study was to evaluate this issue using a previously developed virtual patient. METHODS:: The analysis was based and supported by clinical data collected during 36 TT. Pleural pressure and transcutaneous oxygen and carbon dioxide pressures (PtcO2 and PtcCO2) were measured during pleural fluid withdrawal. Arterial blood oxygen tension and arterial CO2 tension (PaO2 and PaCO2) were analysed in simulations that mimicked TT. Minute ventilation was adjusted to maintain arterial CO2 tension at a constant level unless arterial blood oxygen tension fell below 8 kPa. Specifically, the influence of hypoxic pulmonary vasoconstriction efficiency was tested. RESULTS:: In patients, PtcCO2 remained at an approximately constant level (average amplitude: 0.63 ± 0.29 kPa), while some fluctuations of PtcO2 were observed (amplitude: (1.65 ± 1.18 kPa) were observed. In 42% of patients, TT was associated with decrease in PtcCO2. Simulations showed the following: (a) there were similar PaO2 fluctuations in the virtual patient; (b) the lower the hypoxic pulmonary vasoconstriction efficiency, the more pronounced the PaO2 fall during fluid withdrawal; and (c) the lower the atelectatic lung areas recruitment rate, the slower the PaO2 normalization. The decrease in PaO2 was caused by an increase of pulmonary shunt. CONCLUSION:: Therapeutic thoracentesis may cause both an increase and a decrease in PaO2 during the procedure. Pleural pressure decrease, caused by pleural fluid withdrawal, improves the perfusion of atelectatic lung areas. If the rate of recruitment of these areas is low, a lack of ventilation causes the arterial blood oxygen tension to fall. Effective hypoxic pulmonary vasoconstriction may protect against the pulmonary shunt.

Patterns of pleural pressure amplitude and respiratory rate changes during therapeutic thoracentesis.

BACKGROUND: Although the impact of therapeutic thoracentesis on lung function and blood gases has been evaluated in several studies, some physiological aspects of pleural fluid withdrawal remain unknown. The aim of the study was to assess the changes in pleural pressure amplitude (Pplampl) during the respiratory cycle and respiratory rate (RR) in patients undergoing pleural fluid withdrawal. METHODS: The study included 23 patients with symptomatic pleural effusion. Baseline pleural pressure curves were registered with a digital electronic manometer. Then, the registrations were repeated after the withdrawal of consecutive portions of pleural fluid (200 ml up to 1000 ml and 100 ml above 1000 ml). In all patients the pleural pressure curves were analyzed in five points, at 0, 25%, 50%, 75% and 100% of the relative volume of pleural effusion withdrawn in particular patients. RESULTS: There were 11 and 12 patients with right sided and left sided pleural effusion, respectively (14 M, 9F, median age 68, range 46-85 years). The most common cause of pleural effusion were malignancies (20 pts., 87%). The median total volume of withdrawn pleural fluid was 1800 (IQR 1500-2400) ml. After termination of pleural fluid withdrawal Pplampl increased in 22/23 patients compared to baseline. The median Pplampl increased from 3.4 (2.4-5.9) cmH2O to 10.7 (8.1-15.6) cmH2O (p < 0.0001). Three patterns of Pplampl changes were identified. Although the patterns of RR changes were more diversified, a significant increase between RR at baseline and the last measurement point was found (p = 0.0097). CONCLUSIONS: In conclusion, therapeutic thoracentesis is associated with significant changes in Pplampl during the respiratory cycle. In the vast majority of patients Pplampl increased steadily during pleural fluid withdrawal. There was also an increase in RR. The significance of these changes should be elucidated in further studies. TRIAL REGISTRATION: ClinicalTrial.gov, registration number: NCT02192138 , registration date: July 1st, 2014.

[The number of intraepithelial lymphocytes in digestive tract in patients with IgG-dependent intolerance of cereal products]. / Liczba limfocytów sródnablonkowych w przewodzie pokarmowym u osób z IgG-zalezna nietolerancja pokarmowa.

Abnormal reaction of food antigens cause a variety disorders of gastrointestinal tract. It is not clear why exactly the same products provoke diarrhea or constipation. AIM: The aim of this study was to assess the number of intraepithelial lymphocytes (IEL) in different parts of gastrointestinal tract in patients with specific IgG antibodies against wheat and secale products. MATERIALS AND METHODS: The study was performed in 36 healthy subjects(group I) and in 70 patients with diarrhea predominant (group II, n=38) or with constipation (group III, n=32). The level of specific IgG antibodies in blood were determined using Food Detective tests (Cambridge Diagnostics). The biopsy material obtained from duodenum, jejunum as well as from right and left colon was used for routine hematoxylin-eosin staining. RESULTS: In group II compared to control group the number of IEL was statistical higher in all part of gastrointestinal tract. Furthermore, in 9 patients (23.6%) in duodenum exceed 30/100 enterocytes, and in colon mucosa exceed 25/100 (21.0%) enterocytes. In patients with constipation (group III) the number of IEL was similar to healthy subjects. CONCLUSIONS: Food intolerance of cereal products may cause immuneinflammatory changes in digestive tract comparable to celiakia and lymphocytic colitis.

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.