Pressure Rate Changes Research Articles

Association between rate of change in PaCO2 and functional outcome for patients with hypercapnia after out-of-hospital cardiac arrest: Secondary analysis of a randomized clinical trial

BackgroundNormocapnia is suggested for post resuscitation care. For patients with hypercapnia after cardiac arrest, the relationship between rate of change in partial pressure of carbon dioxide (PaCO2) and functional outcome was unknown. MethodsThis was the secondary analysis of Resuscitation Outcomes Consortium (ROC) amiodarone, lidocaine, and placebo (ALPS) trial. Patients with at least 2 PaCO2 recorded and the first indicating hypercapnia (PaCO2 > 45 mmHg) after return of spontaneous circulation (ROSC) were included. The rate of change in PaCO2 was calculated as the ratio of the difference between the second and first PaCO2 to the time interval. The primary outcome was modified Rankin Score (mRS), dichotomized to good (mRS 0–3) and poor (mRS 4–6) outcomes at hospital discharge. The independent relationship between rate of change in PaCO2 and outcome was investigated with multivariable logistic regression model. ResultsA total of 746 patients with hypercapnia were included for analysis, of which 264 (35.4%) patients had good functional outcome. The median rate of change in PaCO2 was 4.7 (interquartile range [IQR] 1.7–12) mmHg per hour. After adjusting for confounders, the rate of change in PaCO2 (odds ratio [OR] 0.994, confidence interval [CI] 0.985–1.004, p = 0.230) was not associated the functional outcome. However, rate of change in PaCO2 (OR 1.010, CI 1.001–1.019, p = 0.029) was independently associated with hospital mortality. ConclusionsFor OHCA patients with hypercapnia on admission, the rate of change in PaCO2 was not independently associated with functional outcome; however, there was a significant trend that higher decreased rate was associated with increased hospital mortality.

Short-term effects of transcatheter aortic valve replacement on blood pressure and cardiac function in elderly patients with severe aortic stenosis.

Transcatheter aortic valve replacement (TAVR) is a standard treatment for elderly and high-risk patients with aortic valve stenosis (AS); however, its short-term effects on blood pressure (BP) and cardiac function are not clear. Therefore, we aimed to determine the short-term effects of TAVR in elderly patients (>75 years), who reflect the clinical situation in Japan. Twenty-eight consecutive elderly patients with severe AS and hypertension who underwent TAVR under general anesthesia were retrospectively investigated. All patients had hypertension that was well controlled with antihypertensive drugs. Serum brain natriuretic peptide level and peak velocity in the aortic valve were significantly reduced. TAVR induces an increase in BP that requires additional antihypertensive agents. There was no correlation between the change rate of SBP and stroke volume index (SVI), but there was a positive correlation between the rate of change in pulse pressure (PP) and SVI. This tendency was particularly observed in patients with low brachial-ankle pulse wave velocity (baPWV). We observed post-TAVR hypertension and required additional antihypertensive drugs. The increases in SVI and PP after TAVR resulted in post-TAVR hypertension. Moreover, post-TAVR hypertension is less likely to occur in elderly patients with a high baPWV, which indicates advanced arteriosclerosis.

Research on the Effect of the Outlet Throttle Diameter Deviation on the Pressure Relief Rate of the Injector Control Valve

Common rail injector response characteristics depend on the control chamber pressure change rate, the outlet throttle diameter by manufacturing errors, or wear-induced deviations that affect the rate of pressure change in the control chamber, so the accuracy of the outlet throttle diameter directly affects the control valve response consistency. This paper presents a computational fluid dynamics (CFD) simulation of the effect of the deviation of the outlet throttle diameter on the average mass flow rate of the outlet throttle during the opening of the spherical valve in order to reduce this difference and ensure uniform injection characteristics. The results illustrate that with the increase in outlet throttle diameter deviation, the volume of gas phase in the control valve increases and the rate of pressure reduction in the control chamber accelerates, and the sensitivity coefficient of the average mass flow rate of the outlet throttle to the outlet throttle diameter deviation remains unchanged at 24.77. Cavitation occurs in the area of the outlet throttle when the spherical valve lift is 0.045 mm. The increase in rail pressure not only leads to an increase in the low-pressure area on the inner wall of the outlet throttle, an increase in the volume share of the gas phase, and an increase in the hydraulic impact on the sealing wall but also makes the average mass flow rate of the outlet throttle and the rate of change of the control chamber pressure during the opening of the spherical valve more sensitive to the deviation of the outlet throttle diameter.

The Simulation of the Nonlinear Consolidation of Porous Media

In this paper, the general formulation of the problem of coupled deformation of a porous deformable medium with a fluid flowing through the pores is formulated, mathematically investigated and numerically implemented within the framework of physical and geometric nonlinearity. We present the formulation of the problem in velocities of solid phase displacements and the rate of pore pressure change in differential and variational forms. A phenomenological approach was used to formulate the mechanical model. The equations of the coupled consolidation model were derived from the general conservation laws of continuum mechanics using spatial averaging over a representative volume element. The consolidation model took into account the change in the porosity and permeability of the medium during deformation. The equations of filtration and porosity change, originally presented in Euler approach, were reformulated in Lagrangian coordinates of the solid phase using the relative fluid velocity according to ALE (Arbitrary Lagrangian - Eulerian) approach. The Gâteaux differentiation technique was used to linearize the variational equilibrium equations. For spatial discretization of the saddle system of equations, the finite element method (FEM) was used: quadratic serendipity elements for approximating the equilibrium equations and Brick type elements for approximating the filtration equation. To solve the system of equilibrium and filtration equations, a generalization of the implicit scheme with internal iterations at each time step by the Uzawa method was used. The results of numerical simulation of elastoplastic deformation of a water-saturated soil under load with fluid outflow are presented. To simulate the constitutive relations of elastoplastic deformation of soil under short-term loads, a generalization of S.S. Grigoryan's model to large deformations is proposed. The calculations were carried out in our own program code. The developed consolidation model can be used to simulate the formation of tracking ruts and unevenness of natural roads, as well as to calculate the uneven settlement of engineering structures.

Abstract 10050: Omecamtiv Mecarbil and Its Effects on Cardiac Parameters in Heart Failure With Reduced Ejection Fraction (HFrEF). A Meta-Analysis of Randomized Controlled Trials

Introduction: Omecamtiv mecarbil (OM) is a novel selective cardiac myosin activator that has been shown to improve cardiac function in patients with HFrEF. Proposed mechanism of action suggests that it increases myocardial systolic function and systolic ejection time without associated increases in intracellular concentrations of calcium or the rate of change in left ventricular pressure or any direct effects on vascular tissue, cardiovascular receptors, or ion channels. Methods: Systematic review identified phase II/III randomized controlled trials (RCTs) evaluating OM versus placebo. Mean Difference (MD) of different echocardiographic parameters from baseline and Odds Ratios (OR) of cardiovascular (CV) death (along with 95% confidence intervals; CI) were extracted to compute pooled MD and OR using RevMan v.5.3. Random effects model was employed when there was significant heterogeneity (>40%, as assessed by I-squared). Results: Four RCTs were finalized (n=9331; OM: 4722, placebo: 4609). Majority of the patients were males (n=7359; 79%), of white ethnicity (n=7345; 78.7%), and had ischemic heart failure (n=5109; 54.7%). All patients had EF <40% and were on guideline-directed therapy. When patients were pooled for stroke volume; OM increased mean SV to 4.34 ml from baseline as compared to placebo (MD 4.34, 95% CI 2.03-6.65; p=0.0002; I 2 =0%). Mean LV ejection time increased to 32 milliseconds (ms) (MD 32.60, 27.34-37.87; p<0.00001; I 2 =84%). OM resulted in 1.68 mm reduction in mean LV end-systolic diameter (MD -1.68; -2.73 to -0.62; p=0.002; I 2 =0%)). However, reduction in mean end-diastolic diameter (MD -1.05; -1.98 to -0.12; p=0.34; I 2 =42%) was statistically non-significant. Mean LV Fractional Shortening improved to 2% with OM but was statistically insignificant (MD 2.18; 0.54-3.82; p=0.09; I 2 =42%). OM resulted in slightly decreased heart rate (MD -1.77 beats/min; -2.29 to -1.24; p<0.00001; I 2 =0%) with no effect on mean systolic BP (MD -0.05; -0.73 to 0.64; p=0.89; I 2 =0%). In terms of CV mortality, OM decreased the odds for mortality but results were statistically non-significant (OR 0.93, 95% CI 0.80 to 1.08; p=0.34; I 2 = 0%). Conclusion: Omecamtiv mecarbil improved the echocardiographic parameters in patients with HFrEF.

Study on the importance of bed shape in combined DEM-CFD simulation of fixed-bed Biomass gasifiers

The extensive utilization of fossil fuels is limited by the environmental problems related to carbon dioxide and other greenhouse gas emissions. As a result, the generation of energy and heat from biomass has become increasingly economically and ecologically important in recent decades. In existing numerical studies, the effect of slope form on airflow within the biomass gasifier was not systematically investigated. To explore the potential impact of the real shape of a fuel bed on local gasification conditions, a small-scale updraft fixed-bed gasifier was modeled in this study with a default lateral feeding position and air supply from below. The discrete element method (DEM) was combined with computational fluid dynamics (CFD) by using two open-source software: LIGGGHTS® and OpenFOAM®. The particle models of two biomasses (olive stone and almond shells) were calibrated and used to investigate qualitatively and quantitatively the airflow patterns, including the resulting uneven pressure and temperature distribution at/over the slope surface. Besides, the effects of operating parameters of the feeding system on slope form were highlighted. Therefore, the real fuel heap shape should be taken into consideration for future simulation studies on side-fed, fixed bed gasifiers. • Material models for DEM simulation are calibrated and validated. • The influences of heap shape and inlet air velocity are explored comprehensively. • Quantitative discussion on the rates of temperature and pressure change. • Suggests that different screw feeding speeds can realize dynamic combustion optimization. • Limitations of a particular DEM-CFD co-simulation model are addressed.

A lightweight flexible semi-cylindrical valve for seamless integration in soft robots based on the giant electrorheological fluid

Complete compliance of soft robots is a trending research topic. One significant aspect is the control element. In the current work, a flexible electro-rheological (ER) valve development is chosen due to the advantage of its dynamic power density, convenient electronic control mode, and no mechanical moving parts. These properties enable the ER valve to be miniaturized and easily integrated into a fluid-driven soft robot. However, the integration effect of the existing flexible ER valve configuration in soft robots is not ideal. In this study, a novel concentric semi-cylindrical flexible giant ER (GER) valve with a dual flowing direction is proposed for a soft robot to enable a larger deformation bending motion with multiple motion modes. The resulting valve has an overall volume of 50 mm3, a mass of 0.88 g, and a maximum controlling pressure of 84 kPa with a pressure change rate of 13.9, which is suitable for most soft robot applications. The pressure difference calculation method for the concentric semi-cylindrical GER valve is discussed. The effects of size, voltages, and flow rates on the valve’s static and dynamic performances, as well as the characteristics of the two pressure regulation modes, are investigated through simulations and experiments. The seamless integration and flexibility of the proposed valve are demonstrated by controlling a typical network actuator with six motion modes. Finally, a soft robot composed of two actuators is fabricated and realized the grasping of multiple everyday objects using different motion modes.

Influence of pressure and dilution gas on the explosion behavior of methane-oxygen mixtures

This study investigates the influence of initial pressure (P0) and dilution gas (N2, CO2, He, or Ar) on the explosion behavior of CH4-O2 mixtures. Spherical premixed flames in a 20 L spherical vessel are recorded by high-speed schlieren photography. The explosion parameters, explosion duration (τe), maximum explosion pressure (Pmax), maximum explosion pressure change rate ((dP/dt)max), flame speed, burning velocity, and Markstein length, are experimentally investigated at various pressures up to 250 kPa and at room temperature (280 ± 3 K). The experimental results show that Pmax and (dP/dt)max increase linearly with P0. The influence on the explosion intensities, (dP/dt)max, and flame speed, from high to low with the dilution is in the order of CO2, N2, Ar, and He, which indicates that CO2 and N2 more significantly inhibit CH4-O2 explosion. The results suggest that CO2 not only has a strong endothermic ability and reacts with H, but also changes the active free radicals to molecules due to three-element collision. The experimental phenomena are explained and validated by the results from the Chemkin package using two detailed mechanisms, indicating that (dP/dt)max is closely related to the content of H, O, OH, and CH3. The cellular instability is analyzed by the flame thickness and Markstein length, and it becomes more obvious as the flame thickness and Markstein length decrease. The buoyancy instability, Rayleigh-Taylor instability, and a series of phenomena due to the dilution of CO2 are analyzed. The maximum explosion pressure and flame speed decrease significantly with the addition of CO2 into CH4-air mixtures, and CO2 affects the generation of flame. The buoyancy instability of CH4-air mixtures with CO2 addition is examined. The experimental results contribute to a deeper understanding of the explosion behavior of CH4-O2 mixtures and the dilution effect of other gases on it.

Combining Knowledge and a Data Driven Method for Identifying the Gas Kick Type in a Fractured Formation

The main forms of gas kicks into the wellbore during drilling in fractured carbonate reservoirs are underbalanced pressure and gravity displacement. These two forms of gas kicks have different mechanisms of gas entry into the wellbore and different well control measures, which require the timely identification of the type of gas kick when it occurs. A two-phase flow model with a wellbore-formation coupling was developed, based on the gas kick rate models. The variation characteristics of the bottomhole gas influx rate, the wellbore free gas, the bottomhole pressure, the bottomhole pressure change rate, the pit gain and the outlet flow rate during an underbalanced pressure gas kick and a gravity displacement gas kick, were compared and analyzed. Combining the dynamic time warping (DTW) and the wellbore-formation, coupled with a two-phase flow model, an identification method of the gas kick type, based on the DTW was proposed. Following the detection of the gas kick, the identification is performed by calculating the DTW distance between the surface parameter time series, obtained from the two-phase flow simulation and the surface parameter time series, measured in real time. The field example results show that the method can identify the type of gas kick, based on the real-time surface measurement parameters and provide a basis for taking targeted well control measures.

Dapagliflozin attenuates residual cardiac remodeling after surgical ventricular reconstruction in mice with an enlarged heart after myocardial infarction

BackgroundSevere heart failure refractory to conventional therapy requires alternative treatment modalities. Surgical ventricular reconstruction (SVR) has been used to reverse cardiac remodeling in post-myocardial infarction (MI) patients with large left ventricular (LV) aneurysm, however, residual LV remodeling and dysfunction remain postoperatively. It is unclear whether SVR recovers response to drug treatment and whether the sodium-glucose co-transporter 2 inhibitor dapagliflozin (DAPA) reverses residual LV remodeling after SVR. MethodsAdult male C57 mice were subjected to MI or sham surgery. Four-week later, MI mice with LV aneurysm underwent modified SVR or second open-chest sham operation and were randomized to DAPA or vehicle for four-week. Cardiac remodeling, LV function, and the underlying mechanisms were evaluated by echocardiography, invasive LV hemodynamic measurements, mRNA sequencing, and bioinformatics analysis. ResultsSVR significantly decreased LV volume; increased myocardial strain, LV pressure change rates and end-systolic elastance; and decreased heart-to-body weight ratio and myocardial fibrosis. However, significant residual cardiac remodeling remained. DAPA significantly attenuated residual cardiac remodeling and improved LV function in SVR mice but did not have curative effects in non-SVR mice. Of the 1532 genes differentially expressed in SVR and MI mice, 1037 were associated with cardiac metabolism; Src, Crebbp, Fn1, Grb2, and Mapk14 were the top 5 hub genes. Unlike sham surgery, MI upregulated those 5 genes, and treatment with SVR + DAPA normalized their expression. ConclusionsSVR restores therapeutic response in the post-MI heart with large LV aneurysm, and DAPA attenuates residual cardiac remodeling after SVR by normalizing some cardiac metabolism-related hub genes.

Evaluation of subjective discomfort of the seated human body exposed to vertical vibration using dynamic body pressure

Pressure distribution has been regarded as a crucial parameter for static comfort evaluation of the seated human body. However, the association between the pressure distribution and subjective rating, exposed to vertical vibration, is still unclear. This study devotes to characterizing the vibration discomfort of the seated human body on a foam seat using dynamic body pressure distribution and investigating the associations between them. First, the dynamic body pressure of twelve subjects seated on a foam seat exposed to vertical random excitation was measured at frequencies from 0.5 to 20 Hz with six magnitudes (0.2, 0.4, 0.6, 0.8, 1.0, and 1.2 m/s2 r.m.s.). Meanwhile, the subjective discomfort rating of the foam seat was evaluated with the relative magnitude estimation method. Then, the influence of vibration magnitude on subjective discomfort ratings and dynamic body pressure indicators was investigated. The results show that with the increase of vibration magnitude, the mean average dynamic pressure, the mean peak dynamic pressure, the mean dynamic contact area, and the normal dynamic force had no significant change. On the contrary, the subjective discomfort ratings, normal dynamic force change rate root-mean-square, and the indicators related to pressure change rate root-mean-square increased significantly. Finally, the relation between the subjective discomfort ratings and dynamic body pressure indicators was analyzed using Stevens’ power law. The linear regression fitting accuracy of the average dynamic pressure change rate root-mean-square, peak dynamic pressure change rate root-mean-square, area pressure change rate root-mean-square, and normal dynamic force change rate root-mean-square with discomfort ratings were above 95%. The four dynamic body pressure indicators are highly correlated with the subjective discomfort ratings, which can be used as objective indicators for vibration discomfort evaluation.

Analysis and reduction of the pressure and shear damage probability of fish in a Francis turbine

The fish mortality rate for a Francis turbine mainly depends on the runner. To reduce fish injury and mortality caused by Francis runners, the effects of the number and wrap angle of runner blade on the pressure and shear damage probability are investigated in this paper. The pressure and shear damage probability of different runner schemes are evaluated quantitatively by the computational fluid dynamics (CFD) simulation, and the accuracy of CFD simulation has been verified. The results show that both the pressure and shear damage probability induced by runner have a positive correlation with the discharge. But the shear damage probability is much less than the pressure damage probability. Pressure damage probability should be the main factor to be considered in the design of fish-friendly Francis runner. Reducing the blade number and increasing the warp angle of the runner blade could effectively reduce the damage probability caused by low pressure and high shear stress. But it has little effect on the damage probability caused by high pressure change rate and also results in slight decrease in hydraulic efficiency. This work is beneficial to the fish-friendly turbine design and optimization.

Predicting the annular pressure behavior during water injection in offshore wells with a transient, multiphysics model

Predicting the pressure behavior of annular fluids during production and injection operations in oil wells became a major research topic in the exploration of deep-water reservoirs. Although pseudo-steady-state models can predict annular pressure buildup in most production scenarios, more robust transient approaches are required in injection operations due to the short time scales involved. This paper presents a new transient thermo-structural model that calculates temperature and pressure profiles during a recycled saltwater injection operation in a well with three concentric annuli. The model was compared with field data acquired uninterruptedly for a seven-day period containing two consecutive well shutdowns. The maximum relative deviation between the numerical results and the field down-hole pressure was lower than 4%. Absolute down-hole temperature deviations were smaller than 5 °C. Furthermore, simulations based on a newly proposed dimensionless inter-annular pressure difference parameter facilitated identifying the risk of thermally-induced casing collapse due to contrasting rates of pressure change between neighboring annuli. The effectiveness of mitigating such risks using rupture disks was evaluated numerically, and the most favorable scenario consisted of rupture disks installed in the two casings connecting the three annuli.

Discrimination Method of Gas Pressure Measurement in Coal Seams: Physical Experiment and Model Development.

Coal seam gas pressure is a key parameter of gas accident control and gas drainage. At present, there are some problems in field pressure measurement, such as long period, and there is often a need to drill more holes to ensure the reliability of pressure measurement. In this research, a physical gas pressure measurement experiment in a coal sample borehole was carried out, and a mathematical model of gas pressure evolution with time was constructed. Based on the OpenFOAM platform and C++ language, a numerical solver was developed, and the mathematical model was verified by the data of gas pressure in coal seam boreholes. The results show that the evolution process of gas pressure in coal seam boreholes can be divided into two stages. In the first stage, the gas pressure increases rapidly, and the pressure change rate decreases continuously. In the second stage, the gas pressure is slow and stable, and the pressure change rate tends to 0. The correlation coefficients between the mathematical model and the field-measured data are more than 0.94, and the calculation and prediction accuracy are high. Therefore, the model can be used to verify the field data during pressure measurement, which has better field significance and application value.

Minimum-incision trans-subclavian transcatheter aortic valve replacement with regional anesthesia

BackgroundMinimum-incision trans-subclavian transcatheter aortic valve replacement (MITS-TAVR) is usually performed in patients who are contraindicated for transfemoral TAVR, under regional anesthesia (RA). This study aimed to evaluate the safety and efficacy of MITS-TAVR under RA compared to MITS-TAVR under general anesthesia (GA). MethodsThis single-center observational study included 44 consecutive patients who underwent MITS-TAVR under RA (RA group, n = 19) and GA (GA group, n = 25). RA was achieved using an ultrasound-guided nerve block. ResultsThe rates of respiratory disease (RA vs. GA, 36.8 % vs. 4.0 %; p < 0.01) and dialysis (79.0 % vs. 0 %; p < 0.01) were significantly higher in the RA group. STS score was significantly higher in the RA group (RA vs. GA, 10.8 ± 1.06 % vs. 7.87 ± 0.93 %; p < 0.01). Both groups had a 100 % procedural success rate. The two groups showed comparable operation room stay times (RA vs. GA, 160 ± 6.96 min vs. 148 ± 5.90 min; p = 0.058). The mean rate of change in blood pressure, used as an index of hemodynamic stability, was significantly lower in the RA group (RA vs. GA, 19.0 ± 3.4 % vs. 35.5 ± 3.0 %; p < 0.01). No in-hospital deaths occurred in either group. One case of minor dissection occurred in the GA group (RA vs.GA, 0 % vs. 4.0 %, p = 0.378). The intensive care unit stay (RA vs. GA, 0.21 ± 0.11 days vs. 1.24 ± 0.10 days; p < 0.01) and hospital stay (RA vs. GA, 7.00 ± 1.73 days vs. 12.2 ± 1.44 days; p < 0.01) were significantly shorter in the RA group. ConclusionsMITS-TAVR under RA is safe and effective and might be a promising alternative approach. It could ensure intraoperative hemodynamic stability and shorten intensive care unit and hospital stays.

Exploring inspiratory occlusion metrics to assess respiratory drive in patients under acute intermittent hypoxia

Patients living with Amyotrophic Lateral Sclerosis (ALS) experience respiratory weakness and, eventually, failure due to inspiratory motor neuron degeneration. Routine pulmonary function tests (e.g., maximum inspiratory pressure (MIP)) are used to assess disease progression and ventilatory compromise. However, these tests are poor discriminators between respiratory drive and voluntary respiratory function at rest. To better understand ALS disease progression, we can look into compensatory strategies and how patients consciously react to the occlusion and the effort produced to meet the ventilatory challenge of the occlusion. This ventilatory challenge, especially beyond the P0.1 (200 ms and 300 ms), provides information regarding the patient’s ability to recruit additional respiratory muscles as a compensatory strategy. Utilizing a standard P0.1 protocol to assess respiratory drive, we extend the occlusion time analysis to 200 ms and 300 ms (Detected Occlusion Response (DOR)) in order to capture compensatory respiratory mechanics. Furthermore, we followed an Acute Intermittent Hypoxia (AIH) protocol known to increase phrenic nerve discharge to evaluate the compensatory strategies. Inspiratory pressure, the rate of change in pressure, and pressure generation normalized to MIP were measured at 100 ms, 200 ms, and 300 ms after an occlusion. Airway occlusions were performed three times during the experiment (i.e., baseline, 30 and 60 minutes post-AIH). Results indicated that while AIH did not elicit change in the P0.1 or MIP, the DOR increased for ALS patients. These results support the expected therapeutic role of AIH and indicate the potential of the DOR as a metric to detect compensatory changes.

Reversal of Right Ventricular Hypertrophy and Dysfunction by Prostacyclin in a Rat Model of Severe Pulmonary Arterial Hypertension.

Prostacyclin analogs are among the most effective and widely used therapies for pulmonary arterial hypertension (PAH). However, it is unknown whether they also confer protection through right ventricle (RV) myocardio-specific mechanisms. Moreover, the use of prostacyclin analogs in severe models of PAH has not been adequately tested. To further identify underlying responses to prostacyclin, a prostacyclin analogue, treprostinil, was used in a preclinical rat Sugen-chronic hypoxia (SuCH) model of severe PAH that closely resembles the human disease. Male Sprague–Dawley rats were implanted with osmotic pumps containing vehicle or treprostinil, injected concurrently with a bolus of Sugen (SU5416) and exposed to 3-week hypoxia followed by 3-week normoxia. RV function was assessed using pressure–volume loops and hypertrophy by weight assessed. To identify altered mechanisms within the RV, tissue samples were used to perform a custom RNA array analysis, histological staining, and protein and transcript level confirmatory analyses. Treprostinil significantly reduced SuCH-associated RV hypertrophy and decreased the rise in RV systolic pressure, mean pulmonary arterial (mPAP), and right atrial (RAP) pressure. Prostacyclin treatment was associated with improvements in RV stroke work, maximum rate of ventricular pressure change (max dP/dt) and the contractile index, and almost a complete reversal of SuCH-associated increase in RV end-systolic elastance, suggesting the involvement of load-independent improvements in intrinsic RV systolic contractility by prostacyclin treatment. An analysis of the RV tissues showed no changes in cardiac mitochondrial respiration and ATP generation. However, custom RNA array analysis revealed amelioration of SuCH-associated increases in newly identified TBX20 as well as the fibrotic markers collagen1α1 and collagen 3α1 upon treprostinil treatment. Taken together, our data support decreased afterload and load-independent improvements in RV function following prostacyclin administration in severe PAH, and these changes appear to associate with improvements in RV fibrotic responses.

Manipulation of Left Ventricular Loading Conditions is Necessary to Identify Diastolic Dysfunction in Swine with Repetitive Pressure Overload‐Induced HFpEF

ObjectiveDiagnosis of heart failure with preserved ejection fraction (HFpEF) is often complicated by the fact that many patients exhibit normal left ventricular (LV) mechanics at rest with a reduction in diastolic compliance that is only revealed when loading conditions are altered (e.g., during exercise stress). In an effort to identify parameters of diastolic function that could be utilized to detect alterations in compliance without manipulation of LV loading conditions, we utilized invasive hemodynamic analysis and speckle‐tracking echocardiography (STE) to assess diastolic strain and stiffness in swine with repetitive pressure overload (RPO)‐induced HFpEF.MethodsSwine (n=13) were subjected to 2‐weeks of RPO via daily intravenous administration of phenylephrine (PE; 400 ug/min; 1 hour/day) through an indwelling jugular vein catheter. Indices of LV relaxation as well as LV minimum and end‐diastolic pressure were obtained invasively before and after RPO at rest and during transient PE‐induced alterations in loading conditions. STE (Vivid 9; GE) was also performed throughout a single cardiac cycle to collect circumferential diastolic strain data, which were used alongside echocardiography‐derived measurements of chamber radius and wall thickness as well as catheter‐derived measurements of LV pressure to calculate regional and global circumferential subendocardial diastolic stiffness before and after RPO.ResultsCompared with baseline measurements, 2‐weeks of RPO did not significantly increase the time constant of LV relaxation (Tau; Figure A) or decrease the rate of LV pressure change during isovolumic relaxation (dP/dtmin; Figure B). Circumferential subendocardial stiffness derived via STE across a single cardiac cycle at rest was also unaffected by RPO (Figure C), despite a significant reduction in diastolic compliance that was revealed by construction of two‐point end‐diastolic pressure‐volume curves (Figure D) after manipulation of loading conditions (Figure E). Interestingly, single‐cycle STE‐derived stiffness measurements made during acute pressure overload were also similar at baseline and after RPO due to persistent elevations in LV minimum diastolic pressure during PE infusion at both timepoints.ConclusionsAlthough reductions in LV diastolic compliance are evident after chronic RPO when loading conditions are manipulated, abnormalities in LV mechanics are not exhibited at rest even when STE is used to assess diastolic stiffness throughout a single cardiac cycle. These findings highlight the challenges associated with identification of myocardial stiffening at rest in patients with HFpEF and reinforce the importance of studying LV mechanics under variable loading conditions.

Naltrindole Pretreatment Exhibits Robust Cardioprotection in an Acute In Vivo Model of Ischemia/Reperfusion

Myocardial infarctions (MI), remain prevalent in the U.S. with over one million individuals experiencing this cardiac event every year. Delta opioid receptor activation is known to mimic pharmacologic preconditioning to reduce infarct size post‐MI. Surprisingly, results from our laboratory have shown that naltrindole (NTI), a selective delta opioid receptor antagonist, elicits unexpected cardioprotective effects ex vivo when given prior to 30 min global ischemia (I) followed by 45 min reperfusion (R). Whether NTI’s cardioprotective effects can be translated in vivo with intact neurohormonal compensatory mechanisms, has not yet been elucidated. In this study, we aim to determine the cardioprotective effects of NTI in an in vivo model that more closely mimics acute MI clinically.Female Sprague‐Dawley rats (~250g) were assigned into three cohorts: non‐treated control (n=15), high dose (HD, 4.0‐8.0 mg/kg, n=5) NTI, and low dose (LD, 0.2‐1.0 mg/kg, n=18) treatment groups. All three cohorts were anesthetized with ketamine‐xylazine (90 mg/kg, 9mg/kg). Control rats received normal saline (0.9% NaCl), while treatment groups received either HD or LD NTI. NTI was infused through the jugular vein (0.4mL/min) over 5 mins before inducing regional ischemia (pretreatment). The proximal left coronary artery was occluded for 30 min followed by 3 hr reperfusion. At the end of the experiment, blue dye was administered to determine the area at risk (AR). Planimetered photographs of heart slices were then stained with 1% triphenyltetrazolium chloride to determine area of necrosis (AN) and infarct size (AN/AR). Cardiac function was measured via a pressure transducer placed into the left ventricle (LV) in a small cohort of the LD NTI (0.4‐1.0 mg/kg, n=3) and HD NTI groups (n=5). Data were analyzed via ANOVA Student Newman Keuls post‐hoc analysis (infarct size) and unpaired t‐test (cardiac function), respectively, with p&lt;0.05 considered statistically significant.HD NTI exhibited a robust ~60% reduction in infarct size (21±7 %; n=4, p&lt;0.01) compared to control (57±2 %; n=15) and LD NTI (55±4 %; n=18) hearts. HD NTI (n=5) also exerted a significant depression of the maximal and minimal rate of LV pressure change on dP/dt max (6167±489 mmHg/s vs. 3714±645 mmHg/s) and dP/dt min (‐7015±942 mmHg/s vs. ‐4034±776 mmHg/s) respectively and heart rate (261±20 BPM vs. 208±3 BPM) at the end of pretreatment compared to LD NTI (0.4‐1.0 mg/kg, n=3 all p&lt;0.05). This preconditioning effect was correlated with the robust decrease in infarct size compared to LD NTI and control groups. These results were similar to our ex‐vivo studies, although a 20x dose was needed in vivo to presumably overcome compensatory neurohormonal responses (i.e. 4mg/kg vs 0.2mg/kg). Results suggest that NTI pretreatment can protect against I/R injury. Future studies will examine the effects of drug infusion at different ischemic time points for optimal cardioprotection.

Analysis of a Measurement Method and Test System for Pressure Change Rates in Commercial Vehicle Brake Chambers.

The pressure change rate (PCR) of the brake chamber is the key control parameter and evaluation index in the pneumatic braking system for intelligent braking. The PCR threshold value of commercial vehicle brake chambers for braking comfort is analyzed. The PCR measurement method based on a laminar flow resistance tube is proposed, and the PCR test system is designed. The simulation model of a PCR test system for commercial vehicle brake chambers is presented. By analyzing the simulation and experimental results, it is validated that the PCR test system of commercial vehicle brake chambers has the function of measuring PCR in real time. Finally, according to the MSA (Measurement System Analysis) evaluation method, the performance of the PCR test system for commercial vehicle brake chambers is analyzed, and the correctness and applicability of the test system are verified.