Change In Mean Pressure Research Articles

Acute hemodynamic effects of the Marshall-Plan ablation on left and right atrial pressure: does 'respecting atrial physiology' prevent stiff left atria? A retrospective single- center analysis

Abstract Introduction Stiff left atrium (STILA)-syndrome is a relevant concern after extensive ablation in the left atrium (LA) e.g. in persistent atrial fibrillation (AF). STILA often causes disabling heart failure symptoms worse than the initial arrhythmia symptoms. Therefore preventing adverse ablation-induced hemodynamic effects is of utmost concern. Methods This single-center study retrospectively analyzed data from 89 consecutive patients who underwent biatrial ablation for AF following the Marshall-Plan between February 2022 and November 2023. The procedures included ablation of the CTI and PVI where necessary followed by ablation of a LA roof line and ablation of the lateral mitral isthmus after previously performed ethanol ablation of the vein of Marshall. This lesion set is considered to maintain physiological activation of the LA. This study evaluates acute hemodynamic changes following the Marshall-Plan. Invasive hemodynamic measurements of mean left and right atrial pressure, as well as A- and V-waves were performed in all patients before and after the ablation. We assessed the acute changes of atrial hemodynamics in these procedures. Continuous data are given as mean ± standard deviation, categorical data are expressed as number and percentages. Differences between groups were determined by Student’s t-test, chisquare-test, and Fisher’s exact test using SPSS software. A p-value of <0.05 was deemed significant. Results The patients' mean age was 70.1 ± 7.5 years and 39.0% were female. Mean BMI was 28.9 ± 5.2 kg/m². Procedures were performed under general anesthesia (with a PEEP of 5.5cmH2O (2-10 cmH2O)) and took 181 minutes on average. Left atrial mean pressure averaged at 15.7mmHg before the procedure. The overall average change of left atrial mean pressure was +1,8mmHg. The average change in left atrial A- and V-Wave amounted to -1.9mmHg and -0.9mmHg respectively. The pre-procedural average right atrial mean pressure was 12.1mmHg. Right atrial mean pressure inclined by +1.6mmHg. The average change in right atrial A- and V-Wave was +0.6mmHg and +1.1mmHg respectively. The i.v. administered volume averaged 1900 ± 285ml. 3.3% of patients showed an increase of mean LA-pressure >9mmHg. Those patients tended to be older (74.3years), were all male (100%) and had a higher BMI (31.5 kg/m²) as well as higher amount of i.v. administered volume (2333ml) and a longer procedure (213min). Discussion Complex and extensive biatrial ablation following the Marshall-Plan does not lead to acute significant increases in left or right atrial pressures. The administered i.v. volume might explain the slight increases observed. In our observation, the rate of significant increases in LA-pressure is low. This suggests that disrupting the (left) atrial activation pattern might play a role in the development of diastolic dysfunction and thereby STILA-syndrome. Respecting atrial physiology may be beneficial for preventing adverse hemodyamic changes after ablation.

The influence of upright posture on craniospinal, arteriovenous, and abdominal pressures in a chronic ovine in-vivo trial

IntroductionMost investigations into postural influences on craniospinal and adjacent physiology have been performed in anesthetized animals. A comprehensive study evaluating these physiologies while awake has yet been completed.MethodsSix awake sheep had telemetric pressure sensors (100 Hz) implanted to measure intracranial, intrathecal, arterial, central venous, cranial, caudal, dorsal, and ventral intra-abdominal pressure (ICP, ITP, ABP, CVP, IAPcr, IAPcd, IAPds, IAPve, respectively). They were maneuvered upright by placing in a chair for two minutes; repeated 25 times over one month. Changes in mean and pulse pressure were calculated by comparing pre-chair, P0, with three phases during the maneuver: P1, chair entrance; P2, chair halftime; P3, prior to chair exit. Statistical significance (p ≤ .05) was assessed using repeated measures ANOVA.ResultsSignificant mean pressure changes of (P1 − P0) and (P3 − P0) were measured at − 12.1 ± 3.1 and − 14.2 ± 3.0(p < .001), 40.8 ± 10.5 and 37.7 ± 3.5(p = .019), 9.7 ± 8.3 and 6.2 ± 5.3(p = .012), 22.3 ± 29.8 and 12.5 ± 12.1(p = .042), and 11.7 ± 3.9 and 9.0 ± 5.2(p = .014) mmHg, for ICP, ITP, IAPds, IAPcr, IAPca, respectively. For pulse pressures, significant changes of (P1 − P0) and (P3 − P0) were measured at − 1.3 ± 0.7 and − 2.0 ± 1.1(p < .001), 4.7 ± 2.3 and 1.4 ± 1.4(p < .001), 15.0 ± 10.2 and 7.3 ± 5.5(p < .001), − 0.7 ± 1.8 and − 1.7 ± 1.7(p < .001), − 1.3 ± 4.2 and − 1.4 ± 4.7(p = .006), and 0.3 ± 3.9 and − 1.0 ± 1.3(p < .001) mmHg, for ICP, ITP, ABP, IAPds, IAPcr, IAPca, respectively.ConclusionsPressures changed posture-dependently to differing extents. Changes were most pronounced immediately after entering upright posture (P1) and became less prominent over the chair duration (P2-to-P3), suggesting increased physiologic compensation. Dynamic changes in IAP varied across abdominal locations, motivating the abdominal cavity not to be considered as a unified entity, but sub-compartments with individual dynamics.

Labial and Palatal Pressure Changes in Extraction Cases Before and After Maxillary Incisor Retraction: A Quasi-Experimental Study.

To evaluate the changes in lip and tongue pressure before and after incisor retraction in patients undergoing orthodontic treatment with premolar extraction and incisor retraction. A Quasi-experimental study Place and Duration of the Study: Orthodontic Department at Dow University of Health Sciences, Pakistan, from January 2018 to November 2019. The study included 64 patients who were divided into two groups, (32 patients of class I and 32 patients of class II malocclusion). The lip and tongue pressures were recorded before and after incisor retraction with the help of Flexiforce sensor. The collected data were statistically analysed using the SPSS V-24 software. Shapiro-Wilk test was used to test the normality of data. The mean difference between lip and tongue pressure before and after incisor retraction was analyzed by Wilcoxon Signed Ranks Test. The difference in soft tissue pressures between class I and class II treatment groups was carried out using the Mann Whitney test. The mean pressure on the labial surface of incisors was significantly reduced after premolar extraction and incisor retraction (p ≤0.001). On the other hand tongue pressure on the palatal side of incisors was enhanced after incisor retraction (p=0.008) Comparing the differences between Angle's class I and class II malocclusion in mean pressure changes before and after incisor retraction revealed that the difference was not statistically significant on labial (p=0.58) or palatal side (p=0.28) of maxillary incisors. Reduced lip pressure and increased tongue pressure were observed after incisor retraction, whereas no significant change was seen in between the class I and class II cases. This signifies that orthodontic extraction affects the pressure changes on incisors and teeth do not remain in balance equilibrium at rest. Lip pressure, Tongue pressure, Orthodontic treatment, Flexiforce resistive sensor, Extraction, neutral zone.

A pilot study to evaluate changes in pelvic floor muscle tone following pelvic organ prolapse surgery using a novel intra-vaginal pressure sensor device

Introduction and hypothesisPelvic floor muscle weakness is a common cause of pelvic organ prolapse and urinary incontinence. Surgical repair of prolapse is commonly undertaken; however, the impact on pelvic floor muscle tone is unknown. The aim of this study was to compare the effect of anterior and posterior colporrhaphy on pelvic floor activation.MethodsPatients aged under 70 undergoing primary anterior or posterior colporrhaphy were recruited. Intra-vaginal pressure was measured at rest and during pelvic floor contraction using the Femfit® device (an intra-vaginal pressure sensor device [IVPSD]). Peak pressure and mean pressure over 3 s were measured in millimetres of mercury. The pre- and post-operative measurements were compared. The difference between the means was assessed using Cohen’s D test, with significance set at p<0.05ResultsA total of 37 patients completed pre- and post-operative analysis, 25 in the anterior colporrhaphy group and 12 in the posterior colporrhaphy group. Anterior colporrhaphy showed no significant change in pelvic floor tone. Change in peak pressure was −1.71mmHg (−5.75 to 2.33; p=0.16) and change in mean pressure was −0.86 mmHg (−4.38 to 2.66; p=0.31). Posterior colporrhaphy showed a significant increase in peak pelvic floor muscle tone of 7.2 mmHg (0.82 to 13.58; p=0.005) and mean pressure of 4.19 mmHg (−0.09 to 8.47; p=0.016).ConclusionsPosterior colporrhaphy significantly improves pelvic floor muscle tone, whereas anterior colporrhaphy does not. Improved understanding of the impact of pelvic floor surgery may guide future management options for other pelvic floor disorders. Further work is needed to confirm the association of this improvement in pelvic floor disorders.

Estimation of Changes in Intracardiac Hemodynamics Using Wearable Seismocardiography and Machine Learning in Patients With Heart Failure: A Feasibility Study.

Tracking changes in hemodynamic congestion and the consequent proactive readjustment of treatment has shown efficacy in reducing hospitalizations for patients with heart failure (HF). However, the cost-prohibitive nature of these invasive sensing systems precludes their usage in the large patient population affected by HF. The objective of this research is to estimate the changes in pulmonary artery mean pressure (PAM) and pulmonary capillary wedge pressure (PCWP) following vasodilator infusion during right heart catheterization (RHC), using changes in simultaneously recorded wearable seismocardiogram (SCG) signals captured with a small wearable patch. A total of 20 patients with HF (20% women, median age 55 (interquartile range (IQR), 44-64) years, ejection fraction 24 (IQR, 16-43)) were fitted with a wearable sensing patch and underwent RHC with vasodilator challenge. We divided the dataset randomly into a training-testing set (n = 15) and a separate validation set (n = 5). We developed globalized (population) regression models to estimate changes in PAM and PCWP from the changes in simultaneously recorded SCG. The regression model estimated both pressures with good accuracies: root-mean-square-error (RMSE) of 2.5 mmHg and R2 of 0.83 for estimating changes in PAM, and RMSE of 1.9 mmHg and R2 of 0.93 for estimating changes in PCWP for the training-testing set, and RMSE of 2.7 mmHg and R2 of 0.81 for estimating changes in PAM, and RMSE of 2.9 mmHg and R2 of 0.95 for estimating changes in PCWP for the validation set respectively. Changes in wearable SCG signals may be used to track acute changes in intracardiac hemodynamics in patients with HF. This method holds promise in tracking longitudinal changes in hemodynamic congestion in hemodynamically-guided remote home monitoring and treatment for patients with HF.

Association of changes in NT-proBNP, hsTnT and uric acid levels with haemodynamic changes after targeted medical therapies in patients with idiopathic pulmonary arterial hypertension.

During pulmonary arterial hypertension (PAH)-targeted therapies for patients with idiopathic pulmonary arterial hypertension (IPAH), regular follow up to evaluate treatment efficacy is essential. Serum biomarkers can reflect various pathobiological processes in IPAH and have the advantages of being non-invasive, simple to carry out and low cost. The aim of our study was to evaluate whether serum biomarkers could serve as non-invasive markers to reflect haemodynamic changes after PAH-targeted therapies in patients with IPAH. A total of 31 eligible patients aged 38.1 ± 12.1 years (25 were female) were included in this study. Changes in haemodynamic parameters and several serum biomarkers (cardiac markers, serum uric acid, high-sensitivity C-reactive protein, hepatic and kidney function markers) were compared before and after at least six months of PAH-targeted therapies. The time interval between the blood assays and right heart catheterisation was within five days. After at least six months of PAH-targeted therapies, the N-terminal pro-brain natriuretic peptide (NT-proBNP) level decreased from 579 (191-905) to 135 pg/ml (60-395) (p < 0.01), high-sensitivity cardiac troponin T (hsTnT) level decreased from 0.009 (0.006-0.012) to 0.007 ng/ml (0.005-0.01) (p < 0.01), and serum uric acid level decreased from 381.5 ± 131.4 to 327.2 ± 110.0 µmol7sol;l (p = 0.011). The change in NT-proBNP level was positively correlated with changes in pulmonary vascular resistance (r = 0.538, p < 0.01) and mean pulmonary arterial pressure (r = 0.440, p = 0.013). The change in hsTnT level was positively correlated with the change in mean right atrium pressure (r = 0.504, p < 0.01). The change in serum uric acid level was negatively correlated with that of cardiac index (r = -0.471, p < 0.01). NT-proBNP, hsTnT and serum uric acid levels can be used as non-invasive tools for evaluating the efficacy of PAH-targeted medications for IPAH patients. The role of these biomarkers in the follow up should be emphasised.

Contact Pressures Change According to Displacement Shape in Isolated Medial Malleolar Fracture: Cadaver Study

Category:Trauma; Basic Sciences/BiologicsIntroduction/Purpose:Ankle fractures, representing 9% of all fractures, are among the most common types of fractures worldwide. 1 of 5 ankle fractures is an isolated medial malleolar fracture (IMMF). IMMF were treated surgically, but recently it was concluded that all IMMF(<=2mm) should be treated conservatively. The indication for surgery or conservative treatment of IMMF remains unclear. The purpose of the present study is to check the change of pressure in the ankle joint according to the shape and the displacement in the medial malleolus fractures.Methods:Twenty pairs of fresh-frozen cadaveric lower legs, disarticulated at the knee, will be used. Specimen pairs were assigned at random into 1 of 2 groups. This study measures the pressure change in the ankle joint according to Muller type C and D. The specimen was mounted in the materials testing machine with the plantar aspect of the foot in contact with the foot-plate. Load was applied with the ankle in the neutral position. Contact area and contact pressure were quantitated with low-grade pressure-sensitive film (Prescale film; Fuji Photo Film, Tokyo, Japan). The color densities were converted to measurements of pressure. After osteotomy the medial malleolus in Muller type C and D, displace each 2mm and fix it with diameter 4.0mm and length 45 mm cortical bone screws. Pressure measurement is done in the same way as above.Results:The median value and wilconxon singed rank test was used for the results. The median value of normal ankle contact area was 3.15cm2 [2.61.;3.51], the mean pressure was 2.18 Mpa(Megapascal) [2.00.;2.43], and the median value of contact area after transverse osteotomy was 2.89cm2 [2.41.;3.24], mean pressure was 2.37Mpa [2.14.;2.75], and the median value of contact area after oblique osteotomy was 2.72cm2 [2.50.;3.16], mean pressure was 2.50Mpa [2.33.;2.74]. P value of the mean area and mean pressure change after transverse and oblique was <0.05.Conclusion:At 2mm transverse and oblique displacement, ankle contact area and pressure decreased significantly.

An Implantable Electronic Device for Monitoring Fetal Lung Pressure in a Lamb Model of Congenital Diaphragmatic Hernia

Tracheal occlusion (TO) is a fetal treatment option for congenital diaphragmatic hernia. It aims to reduce lung hypoplasia and hypertension by occluding the trachea with a subsequent increase in pulmonary pressure. However, how TO affects lung pressure is unknown, and no devices are available for its measurement. We developed an implantable device for real-time wireless monitoring and long-term logging of lung pressure in ovine fetuses. The device comprised a microcontroller unit, two pressure sensors, an inertial measurement unit (IMU), a radio frequency unit, and an antenna. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">In vitro</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> tests were performed to evaluate device performances. A diaphragmatic hernia was created in ovine fetuses via hysterotomy. Nine devices were implanted at 100 days of gestation and remained until delivery (~142 d). One pressure sensor measured pressure in the amniotic sac and the other in the fetal trachea. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">In vitro</i> pressure accuracy was median (interquartile range) 0.31% (0.1%). <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">In vitro</i> device lifetime was ~60 days. The <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> device recording time was 26.0 (3.9) days and it was well tolerated by the fetus and the ewe. Data telemetry operated throughout the device lifetime. At delivery, amniotic fluid, device encapsulation, and lamb skin did not present evidence of damages. Pressure data in four lambs were analyzed. Fast pressure changes due to the spontaneous fetal activity and long-term mean pressure changes resulting from TO were detected. The IMU allowed for the assessment of changes in fetal position. This device allows long-term monitoring of mean lung pressure, spontaneous breathing activity, and movements in physiological and pathological ovine fetal models.

Comparison of hemostatic effect and safety between epinephrine and tramazoline during nasotracheal intubation: a double-blind randomized trial

BackgroundNasal bleeding is the most common complication during nasotracheal intubation (NTI). To reduce nasal bleeding, the nasal mucosa is treated with vasoconstrictors (epinephrine [E] or tramazoline [T]) prior to NTI. This study aimed to determine whether E or T is more effective and safe for reducing nasal bleeding during NTI.MethodsThis study was preregistered on UMIN-CTR after being approved by the IRB of the School of Dentistry at Aichi Gakuin University. Written consent was received from all the patients. Total 206 patients aged 20–70 years and classified as 1–2 on American Society of Anesthesiologists-physical status were scheduled to undergo general anesthesia with NTI. At last, 197 patients were randomly divided into two groups and treated with either E (n = 99; 3 patients were discontinued) or T (n = 98; 2 patient were discontinued). After induction of general anesthesia, each patient’s nasal mucosa was treated using either E or T. The E used in this study was BOSMIN® SOLUTION 0.1% (Daiichi-Sankyo Co., Ltd., Tokyo), and the T used in this study was TRAMAZOLIN Nasal Solution 0.118% AFP, (Alfresa Pharma Corporation, Osaka). E was diluted five times according to the package insert (final concentration of E = 0.02%), and T was used in its original solution. After 2 min, NTI was performed via the right nostril. Primary outcome were the presence of nasal bleeding (if bleeding was recognized at the posterior pharyngeal wall via nasal cavity during intubation, it was defined as bleeding) and the degree of bleeding (classified as none, mild, moderate, or severe). Secondary outcomes were arrhythmia, and hemodynamic (mean atrial pressure and heart rate) changes associated with vasoconstrictors.ResultsThe presence of bleeding was comparable in both groups (12.5%, E; 14.5%, T; P = 0.63). No significant difference between the groups regarding the degree of bleeding (P = 0.78) was observed, with most patients having no bleeding (n = 84, E; n = 82, T). No severe bleeding and no arrhythmias induced by vasoconstrictor were observed in the two groups.ConclusionsNasal treatment with E or T shows no difference in nasal bleeding during NTI. Although no arrhythmia associated with E was observed in this study, it has been reported in literature. Therefore, as frequency and degree of nasal bleeding were comparable, nasal treatment with T could reduce the risk of NTI.Trial registrationUMIN-CTR (Registration No. UMIN000037907). Registered (05/09/2019).

Observations of DC shift and chugging in a pressurized rotating detonation combustor

Rotating detonation combustors are prone to a wide range of off-design behaviors during both atmospheric and pressurized operation. The current manuscript deals with the transient mean pressure change seen in back-pressurized combustors after ignition. Using experimental high-speed pressure data acquired during this transience, we report two distinct, but overlapping, mechanisms that are well-known in deflagrative rocket combustors, but are not currently considered in rotating detonation combustors: DC shift and chugging. The former is characterized by sudden and seemingly random alterations of the time-averaged chamber pressure during operation, not unlike the same behavior observed in conventional rockets during instability onset. The latter is a low frequency instability that is inherently coupled to the reactants feed, causing significant oscillations of the mean chamber pressure. We show that these phenomena are strongly linked, where onset of chugging oscillations alter the frequency and pressure of the operating mode, which in turn produces a DC shift of the mean chamber pressure. To discern this complex interaction, we use multivariate polynomial curve-fitting, considering all the appropriate parameters to arrive at an empirical formulation that is seen to reasonably match the observed pressure transience after ignition.

Time to Lung Volume Stability After Pressure Change During High-Frequency Oscillatory Ventilation.

Prospective observational study. Regional quaternary teaching hospital neonatal ICU. Thirteen term or near-term infants receiving high-frequency oscillatory ventilation and muscle relaxants. One to two cm H2O mean airway pressure changes every 10 minutes as part of an open lung strategy based on oxygen response. Continuous lung volume measurements (respiratory inductive plethysmography) were made during the mean airway pressure changes. Volume signals were analyzed with a biexponential model to calculate the time to stable lung volume if the model R 2 was greater than 0.6. If volume stability did not occur within 10 minutes, the model was extrapolated to maximum 3,600 s. One-hundred ninety-six mean airway pressure changes were made, with no volume change in 33 occurrences (17%). One-hundred twenty-five volume signals met modeling criteria for inclusion; median (interquartile range) R 2, 0.96 (0.91-0.98). The time to stable lung volume was 1,131 seconds (718-1,959 s) (mean airway pressure increases) and 647 seconds (439-1,309 s) (mean airway pressure decreases), with only 17 (14%) occurring within 10 minutes and time to stability being longer when the lung was atelectatic. During high-frequency oscillatory ventilation, the time to stable lung volume after a mean airway pressure change is variable, often requires more than 10 minutes, and is dependent on the preceding volume state.

Impact of acute changes in blood pressure and arterial stiffness on cerebral pulsatile haemodynamics in young and middle-aged adults.

What is the central question of this study? Does cerebrovascular pulsatility respond differently to acute increases in arterial stiffness in middle-aged compared with young adults? What is the main finding and its importance? Compared with young adults, middle-aged adults exhibited similar changes in cerebral pulsatile damping despite attenuated changes in carotid diameter and cerebrovascular pulsatility during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness. Acute manipulation of arterial stiffness through interventions that increase sympathetic activity might provoke cerebral pulsatility and damping and reveal whether cerebrovascular haemodynamics respond differently to transient elevations in arterial stiffness in middle-aged compared with young adults. We compared cerebral pulsatility and damping in middle-aged versus young adults during two different sympathetic interventions [cold pressor test (CP) and lower-body negative pressure (LBNP)] that increase arterial stiffness acutely. Cerebrovascular haemodynamics were assessed in 15 middle-aged (54 ± 7years old; 11 female) and 15 sex-matched young adults (25 ± 4years old) at rest and during the CP test (4min, 6.4 ± 0.8°C) and LBNP (6min, -20mmHg). Mean blood pressure was measured continuously via finger photoplethysmography. Carotid-femoral pulse wave velocity (cfPWV) and carotid stiffness were measured via tonometry and ultrasound. Blood velocity pulsatility index (PI) was measured at the middle cerebral (MCA) and common carotid artery (CCA) using Doppler, with pulsatile damping calculated as CCA PI divided by MCA PI. Increases in cfPWV were driven by changes in mean pressure during CP but not during LBNP in both groups (P<0.05). Pulsatile damping decreased in both groups (P<0.05) despite reductions in MCA PI and greater carotid dilatation during CP in young compared with middle-aged adults (P<0.05). Pressure-independent increases in cfPWV during LBNP did not alter pulsatile damping but decreased MCA PI in both young and middle-aged adults (P<0.05). These data suggest that changes in carotid diameter and cerebrovascular pulsatility differ between young and middle-aged adults despite similar changes in cerebral pulsatile damping during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness.

Intracisternal administration of tanshinone IIA-loaded nanoparticles leads to reduced tissue injury and functional deficits in a porcine model of ischemic stroke.

BackgroundThe absolute number of new stroke patients is annually increasing and there still remains only a few Food and Drug Administration (FDA) approved treatments with significant limitations available to patients. Tanshinone IIA (Tan IIA) is a promising potential therapeutic for ischemic stroke that has shown success in pre-clinical rodent studies but lead to inconsistent efficacy results in human patients. The physical properties of Tan-IIA, including short half-life and low solubility, suggests that Poly (lactic-co-glycolic acid) (PLGA) nanoparticle-assisted delivery may lead to improve bioavailability and therapeutic efficacy. The objective of this study was to develop Tan IIA-loaded nanoparticles (Tan IIA-NPs) and to evaluate their therapeutic effects on cerebral pathological changes and consequent motor function deficits in a pig ischemic stroke model.ResultsTan IIA-NP treated neural stem cells showed a reduction in SOD activity in in vitro assays demonstrating antioxidative effects. Ischemic stroke pigs treated with Tan IIA-NPs showed reduced hemispheric swelling when compared to vehicle only treated pigs (7.85 ± 1.41 vs. 16.83 ± 0.62%), consequent midline shift (MLS) (1.72 ± 0.07 vs. 2.91 ± 0.36 mm), and ischemic lesion volumes (9.54 ± 5.06 vs. 12.01 ± 0.17 cm3) when compared to vehicle-only treated pigs. Treatment also lead to lower reductions in diffusivity (−37.30 ± 3.67 vs. −46.33 ± 0.73%) and white matter integrity (−19.66 ± 5.58 vs. −30.11 ± 1.19%) as well as reduced hemorrhage (0.85 ± 0.15 vs 2.91 ± 0.84 cm3) 24 h post-ischemic stroke. In addition, Tan IIA-NPs led to a reduced percentage of circulating band neutrophils at 12 (7.75 ± 1.93 vs. 14.00 ± 1.73%) and 24 (4.25 ± 0.48 vs 5.75 ± 0.85%) hours post-stroke suggesting a mitigated inflammatory response. Moreover, spatiotemporal gait deficits including cadence, cycle time, step time, swing percent of cycle, stride length, and changes in relative mean pressure were less severe post-stroke in Tan IIA-NP treated pigs relative to control pigs.ConclusionThe findings of this proof of concept study strongly suggest that administration of Tan IIA-NPs in the acute phase post-stroke mitigates neural injury likely through limiting free radical formation, thus leading to less severe gait deficits in a translational pig ischemic stroke model. With stroke as one of the leading causes of functional disability in the United States, and gait deficits being a major component, these promising results suggest that acute Tan IIA-NP administration may improve functional outcomes and the quality of life of many future stroke patients.

Hemodynamic Effects of Ultrasound-Assisted, Catheter-Directed, Very Low-Dose, Short-Time Duration Thrombolysis in Acute Intermediate–High Risk Pulmonary Embolism (from the EKOS-PL Study)

Ultrasound-assisted, catheter-directed, low-dose thrombolysis (USAT) at an average alteplase dose of 20 mg infused over 12 to 24 hours reversed right ventricular disfunction and improved pulmonary hemodynamics in intermediate-high-risk pulmonary embolism patients. As bleeding risk increases with the thrombolytic dose, establishing a minimal effective USAT dosing regimen is of clinical importance. We aimed to investigate hemodynamic effects and safety of a very low-alteplase-dose USAT of 10 mg administered within 5 hours. We included 12 consecutive intermediate-high-risk pulmonary embolism patients with symptoms duration of <14 days and proximal thrombi location in pulmonary arteries. Pulmonary Embolism Response Team decision-based fixed, bilateral ultrasound-assisted alteplase infusions at the rate of 1mg/hour/catheter for 5 hours through EKOS system catheters were made. The primary efficacy measure was the change in invasive systolic and mean pulmonary arteries pressure, and in cardiac index from USAT start to termination. Safety measures were 180-day all-cause death or cardiopulmonary decompensation and bleeding complications. The systolic pulmonary arteries pressure and mean pulmonary arteries pressure decreased from 53 (45.5 to 59) to 37.5 (27.5 to 40.5) mm Hg (p = 0.02) and from 29.5 (27.5 to 32) to 21.5 (15.5 to 25) mm Hg (p = 0.02), respectively. The cardiac index increased from 1.6 (1.5 to 1.8) to 2.2 (1.9 to 2.4) l/min/m2, (p = 0.02). No deaths, decompensations, or need for therapy intensification occurred. There was 1 episode of access-site bleeding, which subsided after conservative management. No intracranial hemorrhages appeared. In conclusion, reduced dose and duration USAT improved pulmonary hemodynamics and cardiac function leading to cardiopulmonary stabilization in intermediate-high risk pulmonary embolism patients at a low periprocedural risk.

Hemodynamic Effects of Sacubitril-Valsartan in Heart Failure with Reduced-Ejection Fraction: Are All Doses Created Equal?

Paradigm HF trial showed that Sacubitril/Valsartan (LCZ696) 97/103 mg bid reduces the risk of death and hospitalizations for heart failure (HF). We tested the hypothesis that this clinical benefit is reflected by changes in hemodynamic profile in a population of patients (pts) affected by advanced HF. Among pts included in our prospective HF Registry, we enrolled those who underwent two right heart catheterizations (RHC) and started LCZ696 in between, from May 2017 to April 2019. Baseline and follow-up RHC were compared in a matched paired fashion. We collected hemodynamic, clinical and echocardiographic data at both RHC. The dose of LCZ696 was expressed as a percentage of the target dose (TD,97/103 mg bid). The endpoint were hemodynamic changes between the two RHC. Changes in symptoms, echo parameters and medical therapy were also assessed. 44 pts (88% males; 54±8 yrs; 50% DCM; systolic blood pressure 108±17 mmHg; LVEF: 27±5%; NYHA III-IV: 46%) underwent a baseline RHC, started LCZ696 few days after, then repeated a RHC 178±59 days after the beginning of LCZ696. All pts were on diuretics (including MRAs), ACE-i/ARBs and beta-blockers at baseline. By comparing the two RHC, we observed a significant reduction in right atrial (from 7.5±2.5 to 5.6±2.5 mmHg), mean pulmonary artery (from 31.0±10.4 to 26.5±10.2 mmHg), pulmonary capillary wedge pressures (from 19.8±7.7 to 17.9±8.5 mmHg), transpulmonary gradient (from 10.4±4.6 to 8.6±3.8 mmHg) and pulmonary vascular resistances (from 2.7±1.5 to 2.2±1.3 WU), (p ≤ 0.01 for all), without significant change in systolic and mean systemic pressure. 50% of pts were taking ≤ 37.5% % of the TD; the hemodynamic changes were not influenced by LCZ696 dose. NYHA class improved (III-IV: 40.4 vs 16.7%, p<0.01) and mitral regurgitation greater than moderate was numerically reduced (40.4 vs 28.5%, p=0.09). Diuretics and beta-blockers doses did not change significantly after starting LCZ696. LCZ696 was not interrupted due to hypotension or side effects during the study period. Our study shows that LCZ696 improves hemodynamic profile and symptoms in pts with advanced HF by reducing pulmonary and left ventricular filling pressures. This effect seems to be dose-independent. Our results suggest that LCZ696 can lead to a significant clinical and hemodynamic improvement even at low doses.

Measurement of Outlet Pressures Favors Rib Resection for Decompression of Thoracic Outlet Syndrome

When conservative therapy for thoracic outlet syndrome fails, scalenectomy with or without first-rib resection (FRR) is the treatment of choice. We measured pressure in the costoclavicular space before and after FRR at time of neurogenic thoracic outlet syndrome release to evaluate whether FRR is required to completely decompress the costoclavicular space. Using a supraclavicular exposure for anterior-middle scalenectomy with FRR, costoclavicular space pressures were measured using a balloon catheter with the patient's arm in neutral anatomic position, secondarily, the arm abducted and externally rotated. Pressures were recorded in both arm positions before scalenectomy, after scalenectomy, and after FRR. Paired Student's t test was used to compare differences in group means for paired samples. Patient-reported outcomes were reported using the Derkash classification and quick disabilities of the arm, shoulder, and hand (qDASH) questionnaire. Fifteen patients (16 cases) surgically treated for neurogenic thoracic outlet syndrome were included in this retrospective study. There was no significant difference in pressure change between arm positions before scalenectomy (161.56 ± 71.65 mm Hg difference) or after scalenectomy (148.5 ± 80.24 mm Hg difference). There was a significant difference in pressure change between post-scalenectomy and post-FRR arm positions; mean pressure change between arm positions after FRR was 50.56 ± 40.28 mm Hg. Mean postoperative qDASH score was 20 ± 23.2. All patients reported improvement in symptoms and functional status. Supraclavicular first rib resection for management of neurogenic thoracic outlet syndrome can be safely performed with favorable outcomes. The pressure increase in the costoclavicular space caused by arm abduction and external rotation was significantly reduced only after FRR, raising concerns about potential incomplete costoclavicular space decompression with scalenectomy alone for neurogenic thoracic outlet syndrome management.

Cerebrospinal Fluid Removal for Idiopathic Intracranial Hypertension: Less Cerebrospinal Fluid Is Best.

Although lumbar punctures (LPs) are used for diagnostic evaluation in idiopathic intracranial hypertension (IIH), they can also provide relief from IIH-associated headache. Conversely, low-pressure headache secondary to LP can be debilitating. Low-volume cerebrospinal fluid (CSF) removal to a "high-normal" closing pressure (CP), approximately 18-20 cm H2O, may result in relief of IIH-associated headache with a lowered frequency of post-LP headache. We conducted a single-center retrospective analysis from 2011 to 2016 of patients who underwent fluoroscopic LPs aiming for high-normal CPs. Inclusion criteria were as follows: 1) pre-existing diagnosis of IIH, or opening pressure (OP) and clinical findings diagnostic for IIH; 2) height and weight recorded within 1 year; 3) documented LP data parameters; and 4) one week post-LP follow-up documenting whether headache was worse, unchanged, or better. One hundred forty-six patients met the inclusion criteria. Mean age was 34.9 years ± 11.0, and mean body mass index was 39.2 kg/m ± 10.5. Mean volume removed was 9.7 mL ± 4.6. The mean CP was 17.9 cm H2O ±2.7. The mean pressure change (OP-CP) per volume removed was 1.50 cm H2O/mL ±0.6. Headache symptoms at follow-up were improved in 64% (80/125) of patients, worse in 26% (33/125), and unchanged in 10% (12/125). Eleven patients were headache-free, and 11 patients required hospital care for post-LP headache. Low-volume CSF removal to approximately 18 cm H2O resulted in relief of IIH-associated headache in most patients and a low incidence of post-LP headache. Although clinically variable, these data suggest that for every 1 mL of CSF removed, the CP decreases approximately 1.5 cm H2O.

Acute systemic inflammation reduces both carotid and aortic wave reflection in healthy adults.

Acute inflammation increases the risk of cardiac and cerebrovascular events, possibly related to alterations in the hemodynamic load. Wave reflection at the aorta and carotid provides insight into downstream vascular changes and hemodynamic load at the heart and brain. Acute inflammation has been suggested to reduce wave reflection via downstream vasodilation; however, this is not firmly established and has only been investigated at the aorta. We sought to explore the effect of acute inflammation on aortic and carotid hemodynamics in healthy, young adults. Pressure waveforms were collected via radial and carotid applanation tonometry in 23 adults (26 ± 4 years) before and 24 h after a typhoid vaccination. Waveforms were calibrated to brachial mean and diastolic pressure, and waveform separation analyses (WSA) were performed, yielding augmentation index, reflection index, time to reflection (Tr), forward (Pf) and reflected (Pb) wave magnitude, and pulse wave velocity. Arterial diameters and carotid stiffness were measured via ultrasonography. Acute inflammation reduced wave reflection at 24 h in both the aorta and carotid (P < 0.05) without changes in mean pressure. WSA did not reveal independent changes in Pf, Pb, or Tr (P > 0.05). Arterial stiffness did not change; however, brachial and carotid artery diameters increased. Acute inflammation reduces wave reflection in the aorta and carotid artery in young adults, potentially due to downstream/peripheral vasodilation. Reduced aortic wave reflection did not disturb the cardiac workload; however, reductions in carotid wave reflection may render the brain vulnerable to pulsatile hemodynamics. These findings may have implications for cardiac and cerebrovascular risk during acute inflammation.

Comparison of clinical effects of two latanoprost 0.005% solutions (Xalatan® and Arulatan®) in primary open-angle glaucoma or ocular hypertensive patients: a randomized clinical trial.

Purpose: To evaluate the therapeutic non-inferiority between two ophthalmic latanoprost 0.005% solutions (Arulatan® [ALT] versus the reference drug Xalatan® [XLT]) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).Patients and methods: This was a 12-week Phase IV, experimental, randomized, parallel-group, double-masked clinical trial. Consecutive patients with POAG or OH from the Glaucoma Service of Instituto Paulista de Estudos e Pesquisas em Oftalmologia (São Paulo, Brazil) were enrolled between July and December 2017. The primary outcome of the study was an analysis of therapeutic non-inferiority between ALT versus XLT at 12 weeks, while secondary outcomes were mean intraocular pressure (IOP) change from baseline at 2, 6 and 12 weeks, mean IOP at 2, 6 and 12 weeks, and topical and systemic side effects. Statistical significance was set at P<0.05. Computerized analysis was performed using the R software, version 3.4.4.Results: A total of 45 patients were randomized to the two treatment groups: ALT (22) and XLT (23). A statistically significant reduction in IOP from baseline was observed in both treatment groups at all timepoints, while no statistically significant difference between groups was detected. By week 12, observed IOP reduction was −7.95 and −7.89 mmHg in the ALT and in the XLT groups, respectively (P=0.60). Treatment difference between the ALT and the XLT groups was −0.06 mm Hg (95% CI: −0.97, 0.85) and fell within the interval set for therapeutic non-inferiority. There was no statistically significant difference between the two groups in terms of safety profiles. The most commonly reported side effect was mild conjunctival/palpebral hyperemia.Conclusion: ALT was considered non-inferior to XLT in achieving a statistically significant reduction in IOP at 12 weeks in POAG and OH patients. No significant difference in the occurrence of side effects was found between both groups.

Langmuir monolayer study of phospholipid DPPC on the titanium dioxide\u2013chitosan\u2013hyaluronic acid subphases

The studies of model biological membranes consisted of phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were carried out by means of the Langmuir monolayer technique using subphases containing chitosan (Ch), titanium (IV) oxide (TiO2), hyaluronic acid (HA) or mixture of them. The aim was to determine the effect of individual components of subphase and their respective combinations on behavior of the DPPC membrane. The systems were tested at room temperature (20 °C) and at a natural pH of about 4.8, which was close to the pH of the human skin (4.7–5.6). The surface pressure–area per molecule (π–A) isotherms were obtained. Their analysis showed that all substances studied affected the phospholipid membrane which was revealed in the changes of mean molecular area, compression modulus and pressure of the liquid-expanded/liquid-condensed (LE/LC) phase transition. The results were discussed in terms of the nature and strength of mutual interactions. The more profound effect was found at low surface pressures at which the monolayers occurred in more expanded state. However, at the surface pressure corresponding to that of biological membranes, systems had very similar parameters compared to model DPPC isotherm.