Measurement of In-Vivo Pulmonary Vascular Impedance in Two Animal Models of Pulmonary Hypertension

2007 ◽  
Author(s):  
Kendall S. Hunter ◽  
Craig J. Lanning ◽  
Joseph A. Albietz ◽  
Masahiko Oka ◽  
Karen A. Fagan ◽  
...  
Keyword(s):  
Vascular Stiffness ◽  
Resistive Load ◽  
Total Load ◽  
Vascular Impedance ◽  
Disease Outcomes ◽  
Pulmonary Arterial ◽  
The Mean ◽  
The Right ◽  
The Impact

Pulmonary vascular input impedance has been increasingly promoted as an important diagnostic for pulmonary arterial hypertension (PAH) [1,2]. The gold-standard clinical diagnostic for the disease, pulmonary vascular resistance (PVR), quantifies only the mean resistance to flow but ignores the impact of vascular stiffness and flow pulsatility, which in PAH can represent up to 40% of the total load presented to the right ventricle. PVR has also been found to be only a moderate predictor of PAH outcomes [3]. The first of these deficiencies is not present in impedance; clinical studies have found the sum of its 1st and 2nd harmonic moduli to have good correlation (r2 = 0.812) with global pulmonary vascular stiffness (PVS) [2], a hemodynamically-measured quantifier of vascular stiffness. Additionally, the 0th harmonic modulus of impedance has excellent correlation to PVR (r2 = 0.974); thus, it also quantifies the resistive load. Moreover, because PVS has recently been found as a valuable determinant of mortality in PAH [4], we believe that impedance, as a combined measure of PVR and PVS, might be an excellent predictor of disease outcomes.

Effect of Vascular Stiffness on Pulmonary Flow in Normotensive and Hypertensive States: Numerical Study With Fluid Structure Interaction

2008 ◽  
Author(s):  
Zhenbi Su ◽  
Kendall Hunter ◽  
Robin Shandas
Keyword(s):  
Numerical Study ◽  
Vascular Stiffness ◽  
Mean Flow ◽  
Pulmonary Flow ◽  
Vascular Flow ◽  
Primary Determinant ◽  
Mean Pressure ◽  
Pulmonary Arterial ◽  
The Mean ◽  
The Right

Invasive measurement of pulmonary vascular flow and pressure provides the hemodynamic status of the pulmonary circulation for children with pulmonary arterial hypertension (PAH). Clinicians are primarily interested in pulmonary vascular resistance, which is the mean pressure of the circuit divided by the mean flow through it [1], in that it is believed to well-quantify the right ventricular (RV) afterload, the primary determinant of mortality. However, previous and current investigations on the pulmonary vascular stiffness (PVS), input impedance and RV power [2–4] have found PVS to be an important contributor to power, and thus, afterload. These previous and current investigations focus on the analysis of clinical data, which is limited by the clinical equipment and techniques.

scholarly journals The striated muscles in pulmonary arterial hypertension: adaptations beyond the right ventricle

2015 ◽  
Vol 46 (3) ◽  
pp. 832-842 ◽  
Author(s):  
Emmy Manders ◽  
Silvia Rain ◽  
Harm-Jan Bogaard ◽  
M. Louis Handoko ◽  
Ger J.M. Stienen ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Exercise Intolerance ◽  
Muscle Dysfunction ◽  
Striated Muscles ◽  
Pulmonary Arterial ◽  
The Right ◽  
The Impact

Pulmonary arterial hypertension (PAH) is a fatal lung disease characterised by progressive remodelling of the small pulmonary vessels. The daily-life activities of patients with PAH are severely limited by exertional fatigue and dyspnoea. Typically, these symptoms have been explained by right heart failure. However, an increasing number of studies reveal that the impact of the PAH reaches further than the pulmonary circulation. Striated muscles other than the right ventricle are affected in PAH, such as the left ventricle, the diaphragm and peripheral skeletal muscles. Alterations in these striated muscles are associated with exercise intolerance and reduced quality of life. In this Back to Basics article on striated muscle function in PAH, we provide insight into the pathophysiological mechanisms causing muscle dysfunction in PAH and discuss potential new therapeutic strategies to restore muscle dysfunction.

scholarly journals Comparison of branded rugby headguards on their effectiveness in reducing impact on the head

2018 ◽  
Vol 4 (1) ◽  
pp. e000361 ◽  
Author(s):  
Erin R A Frizzell ◽  
Graham P Arnold ◽  
Weijie Wang ◽  
Rami J Abboud ◽  
Tim S Drew
Keyword(s):  
Impact Force ◽  
Linear Acceleration ◽  
Baseline Measurement ◽  
Peak Acceleration ◽  
Impact Forces ◽  
Impact Attenuation ◽  
The Mean ◽  
Force Reduction ◽  
The Right ◽  
The Impact

AimTo compare the available brands of rugby headguards and evaluate their impact attenuation properties at various locations on the cranium, with regard to concussion prevention.MethodsSeven different branded headguards were fitted onto a rigid headform and drop-tested in three different positions. An accelerometer measured the linear acceleration the headform experienced on impact with the ground. Each test involved dropping the headform from a height that generated 103.8 g on average when bare, which is the closest acceleration to the upper limit of the concussion threshold of 100 g. A mean peak acceleration for each drop position was calculated and compared with the bare baseline measurement.ResultsEach headguard demonstrated a significant decrease in the mean peak acceleration from the baseline value (all p≤0.01). Overall the Canterbury Ventilator was the most effective headguard, decreasing the impact force on average by 47%. The least effective was the XBlades Elite headguard, averaging a force reduction of 27%. In five of the seven headguards, the right side of the headwear was the most effective at reducing impact force.ConclusionOverall, the results indicate that it would be beneficial to wear a headguard during rugby in order to reduce the impact forces involved in head collisions. There was also a clear difference in performance between the tested brands, establishing the Canterbury headguard as the most effective. However, only one model of headguard from each brand was tested, so further research evaluating all other models should be considered.

scholarly journals Relative Rates of Gluten Digestion by Nine Commercial Dietary Digestive Supplements

2021 ◽  
Vol 8 ◽  
Author(s):  
Gregory John Tanner
Keyword(s):  
Amino Acids ◽  
Celiac Disease ◽  
Initial Rate ◽  
Relative Rate ◽  
Elisa Method ◽  
Fasting Stomach ◽  
The Mean ◽  
Stomach Volume ◽  
The Impact

Endopeptidases containing supplements may digest gluten and reduce the impact on celiac and gluten-sensitive subjects who inadvertently consume gluten. We investigated the relative rate of disappearance of coeliac relevant epitopes in extracts of nine commercial supplements, using two competitive enzyme-linked immunosorbent assays (ELISAs)—Ridascreen (detects QQPFP, QQQFP, LQPFP, and QLPFP) and Gluten-Tec (detects Glia-α20 and PFRPQQPYPQ). All epitopes are destroyed by cleavage after P and Q amino acids. Rates at pH 3.5 and pH 7.0 were measured. These experiments were designed to measure relative rates of epitope digestion not to mimic in vivo digestion. The supplements were: 1 GluteGuard, 2 GlutenBlock, 3 GliadinX, 4 GlutnGo, 5 GlutenRescue, 6 Eat E-Z Gluten+, 7 Glutenease, 8 Glutezyme, and 9 Gluten Digest. The mean initial rate and half-lives of epitope digestion were deduced and extrapolated to rates at the recommended dose of one supplement in a fasting stomach volume. At pH 7, supplement 1 was the fastest acting of the supplements, with Ridascreen ELISA, more than twice as fast as the next fastest supplements, 5, 6, 7, and 8. Supplements 2, 3, and 4 showed little activity at pH 7.0. Supplement 1 was also the fastest acting at pH 7 with Gluten-Tec ELISA, more than three times the rate for supplements 2 and 3, with supplements 4–9 showing minimal activity. At pH 3.5, supplement 1 acted more than five times as fast as the next fastest supplements, 2 and 3, when measured by Ridascreen, but supplements 2 and 3 were over two times faster than supplement 1 when measured by Gluten-Tec. Supplements 4–9 demonstrated minimal activity at pH 3.5 with either ELISA. Supplement 1 most rapidly digested the key immuno-reactive gluten epitopes identified by the R5 antibody in the Codex-approved competitive Ridascreen ELISA method and associated with the pathology of celiac disease.

scholarly journals Impact of Wind Veer and the Coriolis Force for an Idealized Farm to Farm Interaction Case

2019 ◽  
Vol 9 (5) ◽  
pp. 922 ◽  
Author(s):  
Ola Eriksson ◽  
Simon-Philippe Breton ◽  
Karl Nilsson ◽  
Stefan Ivanell
Keyword(s):  
Coriolis Force ◽  
Wind Shear ◽  
Source Term ◽  
Wind Farms ◽  
Long Distance ◽  
Large Eddy ◽  
Relative Production ◽  
The Mean ◽  
The Right ◽  
The Impact

The impact of the Coriolis force on the long distance wake behind wind farms is investigated using Large Eddy Simulations (LES) combined with a Forced Boundary Layer (FBL) technique. When using the FBL technique any mean wind shear and turbulent fluctuations can be added with body forces. The wind shear can also include the mean wind veer due to the Coriolis force. The variation of the Coriolis force due to local deviations from the mean profile, e.g., from wakes, is not taken into account in the FBL. This can be corrected for with an extra source term in the equations, hereon defined as the Coriolis correction. For a row of 4 turbines it is shown that the inclusion of the wind veer turns the wake to the right, while including the Coriolis correction turns it to the left. When including both wind veer and Coriolis correction the impact of wind veer dominates. For an idealized farm to farm interaction case, two farms of 4 ∗ 4 turbines with 6 km in between, it can be seen that when including wind veer and the Coriolis correction a approximately 3% increase in the relative production for a full wake direction can be seen and only a slightly smaller increase can be seen when including only wind veer. The results indicate that FBL can be used for studies of long distance wakes without including a Coriolis correction but efforts need to be taken to use a wind shear with a correct mean wind veer.

scholarly journals Cellular crowding guides and debundles the microtubule cytoskeleton

2019 ◽  
Author(s):  
A. Z. Płochocka ◽  
N. A. Bulgakova ◽  
L. Chumakova
Keyword(s):  
Mathematical Modelling ◽  
Biological Systems ◽  
Follicular Epithelium ◽  
Microtubule Cytoskeleton ◽  
Cytoskeleton Organization ◽  
Cell Organization ◽  
The Mean ◽  
Cellular Components ◽  
The Impact

Cytoplasm is densely packed with macromolecules causing cellular crowding, which alters interactions inside cells and differs between biological systems. Here we investigate the impact of crowding on microtubule cytoskeleton organization. Using mathematical modelling, we find that only anisotropic crowding affects the mean microtubule direction, but any crowding reduces the number of microtubules that form bundles. We validate these predictions in vivo using Drosophila follicular epithelium. Since cellular components are transported along microtubules, our results identify cellular crowding as a novel regulator of this transport and cell organization.

scholarly journals Endothelial BMPR2 Loss Drives a Proliferative Response to BMP (Bone Morphogenetic Protein) 9 via Prolonged Canonical Signaling

2020 ◽  
Vol 40 (11) ◽  
pp. 2605-2618
Author(s):  
Anne L. Theilmann ◽  
Lindsey G. Hawke ◽  
L. Rhiannon Hilton ◽  
Mara K.M. Whitford ◽  
Devon V. Cole ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Morphogenetic Protein ◽  
Pulmonary Arterial ◽  
The Impact

Objective: Pulmonary arterial hypertension is a disease of proliferative vascular occlusion that is strongly linked to mutations in BMPR2 —the gene encoding the BMPR-II (BMP [bone morphogenetic protein] type II receptor). The endothelial-selective BMPR-II ligand, BMP9, reverses disease in animal models of pulmonary arterial hypertension and suppresses the proliferation of healthy endothelial cells. However, the impact of BMPR2 loss on the antiproliferative actions of BMP9 has yet to be assessed. Approach and Results: BMP9 suppressed proliferation in blood outgrowth endothelial cells from healthy control subjects but increased proliferation in blood outgrowth endothelial cells from pulmonary arterial hypertension patients with BMPR2 mutations. This shift from growth suppression to enhanced proliferation was recapitulated in control human pulmonary artery endothelial cells following siRNA-mediated BMPR2 silencing, as well as in mouse pulmonary endothelial cells isolated from endothelial-conditional Bmpr2 knockout mice ( Bmpr2 EC −/− ). BMP9-induced proliferation was not attributable to altered metabolic activity or elevated TGFβ (transforming growth factor beta) signaling but was linked to the prolonged induction of the canonical BMP target ID1 in the context of BMPR2 loss. In vivo, daily BMP9 administration to neonatal mice impaired both retinal and lung vascular patterning in control mice ( Bmpr2 EC+/+ ) but had no measurable effect on mice bearing a heterozygous endothelial Bmpr2 deletion ( Bmpr2 EC +/− ) and caused excessive angiogenesis in both vascular beds for Bmpr2 EC −/− mice. Conclusions: BMPR2 loss reverses the endothelial response to BMP9, causing enhanced proliferation. This finding has potential implications for the proposed translation of BMP9 as a treatment for pulmonary arterial hypertension and suggests the need for focused patient selection in clinical trials.

scholarly journals Decreased Fast Ripples in the Hippocampus of Rats with Spontaneous Recurrent Seizures Treated with Carbenoxolone and Quinine

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Consuelo Ventura-Mejía ◽  
Laura Medina-Ceja
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
High Frequency Oscillations ◽  
The Mean ◽  
Eeg Recordings ◽  
The Right ◽  
Spontaneous Recurrent Seizures

Background. In models of temporal lobe epilepsy and in patients with this pathology, high frequency oscillations called fast ripples (FRs, 250–600 Hz) can be observed. FRs are considered potential biomarkers for epilepsy and, in the light of manyin vitroandin silicostudies, we thought that electrical synapses mediated by gap junctions might possibly modulate FRsin vivo.Methods. Animals with spontaneous recurrent seizures induced by pilocarpine administration were implanted with movable microelectrodes in the right anterior and posterior hippocampus to evaluate the effects of gap junction blockers administered in the entorhinal cortex. The effects of carbenoxolone (50 nmoles) and quinine (35 pmoles) on the mean number of spontaneous FR events (occurrence of FRs), as well as on the mean number of oscillation cycles per FR event and their frequency, were assessed using a specific algorithm to analyze FRs in intracranial EEG recordings.Results. We found that these gap junction blockers decreased the mean number of FRs and the mean number of oscillation cycles per FR event in the hippocampus, both during and at different times after carbenoxolone and quinine administration.Conclusion. These data suggest that FRs may be modulated by gap junctions, although additional experimentsin vivowill be necessary to determine the precise role of gap junctions in this pathological activity associated with epileptogenesis.

scholarly journals Increased Red Blood Cell Stiffness Increases Pulmonary Vascular Resistance and Pulmonary Arterial Pressure

2016 ◽  
Vol 138 (2) ◽  
Author(s):  
David A. Schreier ◽  
Omid Forouzan ◽  
Timothy A. Hacker ◽  
John Sheehan ◽  
Naomi Chesler
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Arterial Compliance ◽  
Cell Stiffness ◽  
The Third ◽  
Vascular Impedance ◽  
Increased Risk ◽  
Before And After ◽  
Pulmonary Arterial ◽  
The Impact

Patients with sickle cell anemia (SCD) and pulmonary hypertension (PH) have a significantly increased risk of sudden death compared to patients with SCD alone. Sickled red blood cells (RBCs) are stiffer, more dense, more frequently undergo hemolysis, and have a sixfold shorter lifespan compared to normal RBCs. Here, we sought to investigate the impact of increased RBC stiffness, independent of other SCD-related biological and mechanical RBC abnormalities, on the hemodynamic changes that ultimately cause PH and increase mortality in SCD. To do so, pulmonary vascular impedance (PVZ) measures were recorded in control C57BL6 mice before and after ∼50 μl of blood (Hct = 45%) was extracted and replaced with an equal volume of blood containing either untreated RBCs or RBCs chemically stiffened with glutaraldehyde (Hct = 45%). Chemically stiffened RBCs increased mean pulmonary artery pressure (mPAP) (13.5 ± 0.6 mmHg at baseline to 23.2 ± 0.7 mmHg after the third injection), pulmonary vascular resistance (PVR) (1.23 ± 0.11 mmHg*min/ml at baseline to 2.24 ± 0.14 mmHg*min/ml after the third injection), and wave reflections (0.31 ± 0.02 at baseline to 0.43 ± 0.03 after the third injection). Chemically stiffened RBCs also decreased cardiac output, but did not change hematocrit, blood viscosity, pulmonary arterial compliance, or heart rate. The main finding of this study is that increased RBC stiffness alone affects pulmonary pulsatile hemodynamics, which suggests that RBC stiffness plays an important role in the development of PH in patients with SCD.

scholarly journals Chagas Disease Drug Discovery

2014 ◽  
Vol 20 (1) ◽  
pp. 22-35 ◽  
Author(s):  
Eric Chatelain
Keyword(s):  
Chagas Disease ◽  
New Technologies ◽  
Low Cost ◽  
Screening Strategy ◽  
New Drugs ◽  
In Vivo Models ◽  
The Right ◽  
The Impact

American trypanosomiasis, or Chagas disease, is the result of infection by the Trypanosoma cruzi parasite. Endemic in Latin America where it is the major cause of death from cardiomyopathy, the impact of the disease is reaching global proportions through migrating populations. New drugs that are safe, efficacious, low cost, and adapted to the field are critically needed. Over the past five years, there has been increased interest in the disease and a surge in activities within various organizations. However, recent clinical trials with azoles, specifically posaconazole and the ravuconazole prodrug E1224, were disappointing, with treatment failure in Chagas patients reaching 70% to 90%, as opposed to 6% to 30% failure for benznidazole-treated patients. The lack of translation from in vitro and in vivo models to the clinic observed for the azoles raises several questions. There is a scientific requirement to review and challenge whether we are indeed using the right tools and decision-making processes to progress compounds forward for the treatment of this disease. New developments in the Chagas field, including new technologies and tools now available, will be discussed, and a redesign of the current screening strategy during the discovery process is proposed.

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