Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion.

BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

[Development of an Active Mechanical Lung for Simulating Human Pulmonary Ventilation].

At present, the passive simulated lung including the splint lung is an important device for hospitals and manufacturers in testing the functions of a respirator. However, the human respiration simulated by this passive simulated lung is quite different from the actual respiration. And it is not able to simulate the spontaneous breathing. Therefore, including" the device simulating respiratory muscle work "," the simulated thorax" and" the simulated airway", an active mechanical lung to simulate human pulmonary ventilation was designed:3D printed human respiratory tract was developed and connected the left and right air bags at the end of the respiratory tract to simulate the left and right lungs of the human body. By controlling a motor running to drive the crank and rod to move a piston back and forth, and to deliver an alternating pressure in the simulated pleural, and so as to generate an active respiratory airflow in airway. The experimental respiratory airflow and pressure from the active mechanical lung developed in this study are consistent with the target airflow and pressure which collected from the normal adult. The developed active mechanical lung function will be conducive to improve the quality of the respirator.

Accuracy of the estimations of respiratory mechanics using an expiratory time constant in passive and active breathing conditions: a bench study.

BACKGROUND: Respiratory mechanics monitoring provides useful information for guiding mechanical ventilation, but many measuring methods are inappropriate for awake patients. This study aimed to evaluate the accuracy of dynamic mechanics estimation using expiratory time constant (RCexp) calculation during noninvasive pressure support ventilation (PSV) with air leak in different lung models. METHODS: A Respironics V60 ventilator was connected to an active breathing simulator for modeling five profiles: normal adult, restrictive, mildly and severely obstructive, and mixed obstructive/restrictive. Inspiratory pressure support was adjusted to maintain tidal volumes (VT), achieving 5.0, 7.0, and 10.0 ml/kg body weight. PEEP was set at 5 cmH2O, and the back-up rate was 10 bpm. Measurements were conducted at system leaks of 25-28 L/min. RCexp was estimated from the ratio at 75% exhaled VT and flow rate, which was then used to determine respiratory system compliance (Crs) and airway resistance (Raw). RESULTS: In non-obstructive conditions (Raw ≤ 10 cmH2O/L/s), the Crs was overestimated in the PSV mode. Peak inspiratory and expiratory flow and VT increased with PS levels, as calculated Crs decreased. In passive breathing, the difference of Crs between different VT was no significant. Underestimations of inspiratory resistance and expiratory resistance were observed at VT of 5.0 ml/kg. The difference was minimal at VT of 7.0 ml/kg. During non-invasive PSV, the estimation of airway resistance with the RCexp method was accurately at VT of 7.0 ml/kg. CONCLUSIONS: The difference between the calculated Crs and the preset value was influenced by the volume, status and inspiratory effort in spontaneously breathing.

[Modeling the noninvasive bi-level positive airway pressure ventilation therapy system and simulated application].

Without artificial airway though oral, nasal or airway incision, the bi-level positive airway pressure (Bi-PAP) has been widely employed for respiratory patients. In an effort to investigate the therapeutic effects and measures for the respiratory patients under the noninvasive Bi-PAP ventilation, a therapy system model was designed for virtual ventilation experiments. In this system model, it includes a sub-model of noninvasive Bi-PAP respirator, a sub-model of respiratory patient, and a sub-model of the breath circuit and mask. And based on the Matlab Simulink, a simulation platform for the noninvasive Bi-PAP therapy system was developed to conduct the virtual experiments in simulated respiratory patient with no spontaneous breathing (NSB), chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). The simulated outputs such as the respiratory flows, pressures, volumes, etc, were collected and compared to the outputs which were obtained in the physical experiments with the active servo lung. By statistically analyzed with SPSS, the results demonstrated that there was no significant difference ( P > 0.1) and was in high similarity ( R > 0.7) between the data collected in simulations and physical experiments. The therapy system model of noninvasive Bi-PAP is probably applied for simulating the practical clinical experiment, and maybe conveniently applied to study the technology of noninvasive Bi-PAP for clinicians.

Modeling the therapy system of noninvasive pressure support ventilation with the respiratory patient in COPD and ARDS.

The noninvasive pressure support ventilation (NPSV) has been one of mechanical ventilation widely applied for the respiratory patients in chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), etc. To investigate and develop the technologies in NPSV conveniently and in low-cost, in this article, a therapy system model of NPSV was designed with developing the mathematical submodels of NPSV respirator and respiratory patient in COPD and ARDS. By simulating the respirator, breath circuit, mask and respiratory patients, a MATLAB-based virtual experimental platform was developed for virtual ventilations. And in order to test the authenticity and practicability of the therapy system model of NPSV, a lot of ASL5000-based physical experiments were carried out for comparative analysis with the simulated outputs: pressures, flows and volumes. The statistical conclusions demonstrate that the simulated results are consist with the results from the physical experiments (TTEST P > 0.39). The experimental results tell that the therapy system model of NPSV is effective and workable. The developed therapy system model of NPSV will be beneficial for clinician and researcher to explore the therapeutic methods and some potential measures in NPSV for saving the respiratory patient's health and life.

Bistable insulin response: The win-win solution for glycemic control.

To satisfy both the safety and rapidity of glycemic control, muscles' insulin response must be bistable, as theoretically predicted. Here, we test the bistability hypothesis by combining cellular experiments (to measure the threshold values in vitro) with mathematical modeling (to test the relevance of bistability in vivo). We examine bistability in C2C12 myotubes by both single-cell analysis (FÓ§rster resonance energy transfer) and cultured cells analysis (immunoblot). These technologies demonstrate bistable insulin response, with typical switch-on and switch-off thresholds of approximately 300 and 100 pM, respectively. Our mathematical model demonstrates the indispensability of bistability in interpreting experimental data, reveals fine details of plasma glucose-insulin dynamics, and explains unclear phenomena. These results suggest that the body's ability to simultaneously avoid both hypoglycemia and hyperglycemia is mediated by bistability. The switch-on threshold is a promising biomarker for metabolic complications due to its deep quantitative connection with body composition, which is easy to measure.

Gas Exchange Mechanism of High Frequency Ventilation: A Brief Narrative Review and Prospect.

The high frequency ventilation (HFV) can well support the breathing of respiratory patient with 20%-40% of normal tidal volume. Now as a therapy of rescue ventilation when conversional ventilation failed, the HFV has been applied in the treatments of severe patients with acute respiratory failure (ARF), acute respiratory distress syndrome (ARDS), etc. However, the gas exchange mechanism (GEM) of HFV is still not fully understood by researchers. In this paper, the GEM of HFV is reviewed to track the studies in last decades and prospect for the next likely studies. And inspired by previous studies, the GEM of HFV is suggested to be continually developed with various hypotheses which will be testified in simulation, experiment and clinic trail. One of the significant measures is to study the GEM of HFV under the cross-disciplinary integration of medicine and engineering. Fully understanding the GEM can theoretically support and expand the applications of HFV, and is helpful in investigating the potential indications and contraindications of HFV.

[Circuit Designed for Driving Blower in Non-invasive Positive Airway Pressure Respirator].

One of critical technologies in a non-invasive positive airway pressure respirator is to output the airflow for meeting the requirement of respiratory patient in breath. In order to develop a safe and reliable blower driving system, a circuit based on the special chips MC33035 and MC33039 was designed. The linear relationship between the input control voltage and the output air flow was achieved. This designed circuit will be embedded in the non-invasive ventilator system as a module. And based on this circuit, the secure and controllable ventilation flow can be performed.

Continuous estimation of airway resistance in non-invasive ventilation.

BACKGROUND: This study aimed to evaluate the accuracy of expiratory time constant (RCexp) to continuously calculate the airway resistance (Raw). MATERIAL AND METHODS: A Respironics V60 ventilator was connected to a lung simulator for modeling different profiles of respiratory mechanics. RESULTS: During assisted ventilation, the respiratory system compliance (Crs) calculation was always overestimated in most lung models. The Raw estimation using the expiratory resistance (Rexp) method was close to the calculated value with the occlusion method during volume-controlled ventilation (VCV). In expiratory flow limitation (EFL) lung models, similar results were obtained in the estimation of inspiratory resistance (Rinsp), but different variations were observed in the calculation of the Rexp. The results estimated with RCexp and with dynamic signal analysis had significant variation and accuracy (p < 0.001). CONCLUSION: The RCexp method is a robust approach to provide real-time assessments of Rinsp and Rexp in spontaneously breathing patients during noninvasive ventilation. An underestimation of Rexp was observed in EFL lung models.

[Prospects and developments in the technologies of high frequency oscillatory ventilation].

The high frequency oscillatory ventilation (HFOV) is characterized with low tidal volume and low mean airway pressure, and can well support the breathing of the patients with respiratory diseases. Since the HFOV was proposed, it has been widely concerned by medical and scientific researchers. About the HFOV, this paper discussed its current research status and prospected its future development in technologies. The research status of ventilation model, mechanisms and ventilation mode were introduced in detail. In the next years, the technologies in developing HFOV will be focused on: to develop the branched high-order nonlinear or volume-depended resistance-inertance-compliance (RIC) ventilation model, to fully understand the mechanisms of HFOV and to achieve the noninvasive HFOV. The development in technologies of HFOV will be beneficial to the patients with respiratory diseases who failed with conventional mechanical ventilation as one of considerable ventilation methods.

Accuracy of the dynamic signal analysis approach in respiratory mechanics during noninvasive pressure support ventilation: a bench study.

OBJECTIVE: To evaluate the accuracy of respiratory mechanics using dynamic signal analysis during noninvasive pressure support ventilation (PSV). METHODS: A Respironics V60 ventilator was connected to an active lung simulator to model normal, restrictive, obstructive, and mixed obstructive and restrictive profiles. The PSV was adjusted to maintain tidal volumes (VT) that achieved 5.0, 7.0, and 10.0 mL/kg body weight, and the positive end-expiration pressure (PEEP) was set to 5 cmH2O. Ventilator performance was evaluated by measuring the flow, airway pressure, and volume. The system compliance (Crs) and airway resistance (inspiratory and expiratory resistance, Rinsp and Rexp, respectively) were calculated. RESULTS: Under active breathing conditions, the Crs was overestimated in the normal and restrictive models, and it decreased with an increasing pressure support (PS) level. The Rinsp calculated error was approximately 10% at 10.0 mL/kg of VT, and similar results were obtained for the calculated Rexp at 7.0 mL/kg of VT. CONCLUSION: Using dynamic signal analysis, appropriate tidal volume was beneficial for Rrs, especially for estimating Rexp during assisted ventilation. The Crs measurement was also relatively accurate in obstructive conditions.

Comparison of Inspiratory Effort, Workload and Cycling Synchronization Between Non-Invasive Proportional-Assist Ventilation and Pressure-Support Ventilation Using Different Models of Respiratory Mechanics.

BACKGROUND This study assessed lung models for the influence of respiratory mechanics and inspiratory effort on breathing pattern and simulator-ventilator cycling synchronization in non-invasive ventilation. MATERIAL AND METHODS A Respironics V60 ventilator was connected to an active lung simulator modeling mildly restrictive, severely restrictive, obstructive and mixed obstructive/restrictive profiles. Pressure-support ventilation (PSV) and proportional-assist ventilation (PAV) were set to obtain similar tidal volume (VT). PAV was applied at flow assist (FA) 40-90% of resistance (Rrs) and volume assist (VA) 40-90% of elastance (Ers). Measurements were performed with system air leak of 25-28 L/minute. Ventilator performance and simulator-ventilator asynchrony were evaluated. RESULTS At comparable VT, PAV had slightly lower peak inspiratory flow and higher driving pressure compared with PSV. Premature cycling occurred in the obstructive, severely restrictive and mildly restrictive models. During PAV, time for airway pressure to achieve 90% of maximum during inspiration (T90) in the severely restrictive model was shorter than those of the obstructive and mixed obstructive/restrictive models and close to that measured in the PSV mode. Increasing FA level reduced inspiratory trigger workload (PTP300) in obstructive and mixed obstructive/restrictive models. Increasing FA level decreased inspiratory time (TI) and tended to aggravate premature cycling, whereas increasing VA level attenuated this effect. CONCLUSIONS PAV with an appropriate combination of FA and VA decreases work of breathing during the inspiratory phase and improves simulator-ventilator cycling synchrony. FA has greater impact than VA in the adaptation to inspiratory effort demand. High VA level might help improve cycling synchrony.

Seeking mTORC1 Inhibitors Through Molecular Dynamics Simulation of Arginine Analogs Inhibiting CASTOR1.

BACKGROUND: Hyperactivity of the mechanistic target of rapamycin complex 1 (mTORC1) is implicated in a variety of diseases such as cancer and diabetes. Treatment may benefit from effective mTORC1 inhibition, which can be achieved by preventing arginine from disrupting the cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1)-GTPase-activating proteins toward RAGS subcomplex 2 (GATOR2) complex through binding with CASTOR1. An attractive idea is to determine analogues of arginine that are as competent as arginine in binding with CASTOR1, but without disrupting the CASTOR1-GATOR2 interaction. MATERIALS AND METHODS: Molecular dynamics simulations were performed for binding of arginine analogues with CASTOR1 and binding free energy, hydrogen bond formation, and root mean squared deviation and root mean square fluctuation kinetics were then calculated. RESULTS: The binding free energy calculations revealed that Nα-acetyl-arginine, citrulline, and norarginine have sufficient binding affinity with CASTOR1 to compete with arginine. The hydrogen bond analysis revealed that norarginine, Nα-acetyl-arginine and D-arginine have proficient H-bonds that can facilitate their entering the narrow binding pocket. CONCLUSION: Norarginine and Nα-acetyl-arginine are the top drug candidates for mTORC1 inhibition, with Nα-acetyl-arginine being the best choice.

[Investigating the mechanism of the high frequency ventilation for the oscillation airflow between left and right lungs].

Traditionally, adequate tidal volume is considered to be a necessary condition to support respiratory patient breathing. But the high frequency ventilation (HFV) with a small tidal volume can still support the respiratory patient breathing well. In order to further explore the mechanisms of HFV, the pendelluft ventilation between left and right lungs was proposed in this paper. And a test platform by using two fresh sheep lungs was developed for investigating the pendelluft ventilation between the left and right lungs. Furthermore, considering the viscous resistance ( R), inertance ( I) and lung compliance ( C) in the lung, a second-order lung ventilation model was designed to inspect and evaluate the pendelluft ventilation between left lung and right lungs. On referring to both results of experiments in practice and simulation in MATLAB Simulink, between the left and right lungs, the phase difference in their airflow happens during HFV at some frequencies. And the pendelluft ventilation between the left and right lungs is resulted by the phase difference, even if the total airflow entering a whole lung is 0. Under HFV, the pendelluft ventilation between left and right lungs will benefit the lungs being more adequately ventilated, and will be improve the utilization rate of oxygen in the lungs.

A noninvasive high frequency oscillation ventilator: Achieved by utilizing a blower and a valve.

After the High Frequency Oscillatory Ventilation (HFOV) has been applied in the invasive ventilator, the new technique of noninvasive High Frequency Oscillatory Ventilation (nHFOV) which does not require opening the patient's airway has attracted much attention from the field. This paper proposes the design of an experimental positive pressure-controlled nHFOV ventilator which utilizes a blower and a special valve and has three ventilation modes: spontaneous controlled ventilation combining HFOV, time-cycled ventilation combining HFOV (T-HFOV), and continuous positive airway pressure ventilation combining HFOV. Experiments on respiratory model are conducted and demonstrated the feasibility of using nHFOV through the control of fan and valve. The experimental ventilator is able to produce an air flow with small tidal volume (VT) and a large minute ventilation volume (MV) using regular breath tubes and nasal mask (e.g., under T-HFOV mode, with a maximum tidal volume of 100 ml, the minute ventilation volume reached 14,400 ml). In the process of transmission, there is only a minor loss of oscillation pressure. (Under experimental condition and with an oscillation frequency of 2-10 Hz, peak pressure loss was around 0%-50% when it reaches the mask.).