Vascular Loading Research Articles

The effects of an IV fluid bolus on mitral annular velocity and the assessment of diastolic function: a prospective non-randomized study

BackgroundAbnormal diastolic function is an independent predictor of adverse postoperative outcomes. Mitral annular tissue Doppler velocity (e’) is a key parameter for assessing diastolic function. The purpose of this study was to confirm that an acute increase in preload did not significantly impact the intraoperative measurement of e’ and secondarily evaluate the impact of this acute intravascular volume increase on the clinical assessment of diastolic function using a previously described simplified algorithm.MethodsThis was a prospective, non-randomized study in adult patients undergoing elective cardiac surgeries requiring transesophageal echocardiographic monitoring, arterial pressure and Swan-Ganz catheter placements as part of the surgical procedure. Following baseline echocardiographic and hemodynamic measurements, 500 ml of crystalloid solution was infused over 10 min. Hemodynamic and echocardiographic measurements were repeated 5 min after fluid administration.ResultsComplete data sets were available from 84 of the 100 patients who were enrolled in this study. There was no significant change in the values of e’. The average baseline was 7.8 ± 2.0 cm/s (95%CI: 7.4, 8.2) and 8.1 ± 2.4 (95%CI: 7.6, 8.6) following the fluid bolus (p = 0.10). All hemodynamic variables associated with increased intravascular volume (central venous pressure, pulmonary arterial pressures and stroke volume variation) changed significantly. The overall distribution of diastolic function grades did not change following fluid administration (p = 0.69). However, there were many individual patient differences. When using this simplified algorithm, functional grading changed in 35 patients. Thirty of these 35 changes were only a single grade shift. 22 patients had worse functional grading after fluid administration while 13 had improved grading. Nine patients with normal diastolic function at baseline demonstrated diastolic dysfunction after fluid administration while 6 patients with baseline dysfunction normalized following the fluid bolus.ConclusionWe confirmed that e’ is a robust measurement that is reproducible in the intraoperative setting despite variable vascular volume loading conditions, however, the clinical assessment of diastolic function was still altered in 42% of the patients following an intravenous fluid bolus.

Exercise and pulsatile pulmonary vascular loading in chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty-five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p < 0.001). ExABN patients had lower PA compliance and higher pulmonary vascular resistance at rest and exercise and prolonged resistance-compliance time product at rest. The physiological relationship between changes in PA pressures relative to PAWP was disrupted in the ExABN group. In CTEPD without PH, exercise RHC revealed latent pulmonary vascular afterload elevations in 58% of patients with more frequent augmentation of pulsatile than resistive pulmonary vascular afterload.

State-of-the-art methodologies used in preclinical studies to assess left ventricular diastolic and systolic function in mice, pitfalls and troubleshooting.

Cardiovascular diseases (CVD) are still the leading cause of death worldwide. The improved survival of patients with comorbidities such as type 2 diabetes, hypertension, obesity together with the extension of life expectancy contributes to raise the prevalence of CVD in the increasingly aged society. Therefore, a translational research platform that enables precise evaluation of cardiovascular function in healthy and disease condition and assess the efficacy of novel pharmacological treatments, could implement basic science and contribute to reduce CVD burden. Heart failure is a deadly syndrome characterized by the inability of the heart to meet the oxygen demands of the body (unless there is a compensatory increased of filling pressure) and can manifest either with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). The development and progression of HFrEF is mostly attributable to impaired contractile performance (systole), while in HFpEF the main problem resides in decreased ability of left ventricle to relax and allow the blood filling (diastole). Murine preclinical models have been broadly used in research to understand pathophysiologic mechanisms of heart failure and test the efficacy of novel therapies. Several methods have been employed to characterise cardiac systolic and diastolic function including Pressure Volume (PV) loop hemodynamic analysis, echocardiography and Magnetic Resonance Imaging (MRI). The choice of one methodology or another depends on many aspects including budget available, skills of the operator and design of the study. The aim of this review is to discuss the importance of several methodologies that are commonly used to characterise the cardiovascular phenotype of preclinical models of heart failure highlighting advantages and limitation of each procedure. Although it requires highly skilled operators for execution, PV loop analysis represents the "gold standard" methodology that enables the assessment of left ventricular performance also independently of vascular loading conditions and heart rate, which conferee a really high physiologic importance to this procedure.

Pulmonary Hypertension Phenotype Can Be Identified in Heart Failure With Reduced Ejection Fraction Using Echocardiographic Assessment of Pulmonary Artery Pressure With Supportive Use of Pressure Reflection Variables

Pulmonary hypertension (PH) is frequent in patients with heart failure and reduced ejection fraction (HFrEF) with 2 different phenotypes: isolated postcapillary PH (IpcPH) and, with the worst prognosis, combined pre- and postcapillary PH (CpcPH). The aims of the present echocardiography study were to investigate (1) the ability to identify PH phenotype in patients with HFrEF using the newly adopted definition of PH (mean pulmonary artery pressure >20mm Hg) and (2) the relationship between PH phenotype and right ventricular (RV) function. One hundred twenty-four patients with HFrEF consecutively referred for heart transplant or heart failure workup were included with echocardiography and right heart catheterization within 48hours. We estimated systolic pulmonary artery pressure (sPAPDoppler) and used a method to detect increased pulmonary vascular resistance (>3 Wood units) based on predefined thresholds of 3 pressure reflection (PRefl) variables (the acceleration time in the RV outflow tract [RVOT], the interval between peak RVOT and peak tricuspid regurgitant velocity, and the RV pressure augmentation following peak RVOT velocity). Using receiver operator characteristic analysis in a derivation group (n=62), we identified sPAPDoppler ≥35mm Hg as a cutoff that in a test group (n=62) increased the likelihood of PH 6.6-fold. The presence of sPAPDoppler >40mm Hg and 2 or 3 positive PRefl variables increased the probability of CpcPH 6- to 8-fold. A 2-step approach with primarily assessment of sPAPDoppler and the supportive use of PRefl variables in patients with mild/moderate PH (sPAPDoppler 41-59mm Hg) showed 76% observer agreement and a weighted kappa of 0.63. The steady-state (pulmonary vascular resistance) and pulsatile (compliance, elastance) vascular loading are increased in both IpcPH and CpcPH with a comparable degree of RV dysfunction. The PH phenotype can be identified in HFrEF using standard echocardiographic assessment of pulmonary artery pressure with supportive use of PRefl variables in patients with mild to moderate PH.

Multifunctional fish gelatin hydrogel inverse opal films for wound healing

BackgroundWound healing has become a worldwide healthcare issue. Attempts in the area focus on developing patches with the capabilities of avoiding wound infection, promoting tissue remolding, and reporting treatment status that are of great value for wound treatment.ResultsIn this paper, we present a novel inverse opal film (IOF) patch based on a photo-crosslinking fish gelatin hydrogel with the desired features for wound healing and dynamic monitoring. The film with vibrant structure colors was constructed by using the mixture of fish gelatin methacryloyl, chitosan, and polyacrylic acid (PAA) to replicate colloidal crystal templates. As the structures of these natural biomolecules are well-retained during the fabrication, the resultant IOF was with brilliant biocompatibility, low immunogenicity, antibacterial property, as well as with the functions of promoting tissue growth and wound healing. In addition, the IOF presented interconnected nanopores and high specific surface areas for vascular endothelial growth factor loading, which could further improve its angiogenesis capability. More attractively, as the pH-responsive PAA was incorporated, the IOF patch could report the wound healing status through its real-time structural colors or reflectance spectra.ConclusionsThese features implied the practical value of the multifunctional fish gelatin hydrogel IOFs in clinical wound management.Graphical

A numerical bone regeneration model incorporating angiogenesis, considering oxygen-induced secretion of vascular endothelial growth factor and vascular remodeling

Angiogenesis is considered playing an important role in bone regeneration. Studies have shown that angiogenesis is affected by biological factors, oxygen tension, and blood flow. In this paper, we propose a bone regeneration model with angiogenesis based on the theories of mechanobiology regulation, vascular network modeling, oxygen-induced secretion of vascular endothelial growth factor (VEGF), and vascular remodeling. The results showed that this model can describe the distribution and concentration of vascular endothelial growth factor induced by oxygen tension during bone regeneration, the growth and remodeling of vascular tissue under the influence of vascular endothelial growth factor and mechanical loading, and the correspondence between vascular tissue and bone regeneration.

Temporal Patterns of Pulmonary Vascular Loading during Exercise in Patients with Pre versus Post Capillary Pulmonary Hypertension

<h3>Purpose</h3> In healthy humans, pulmonary artery pressures (PAP) increase modestly and equilibrate rapidly in response to constant intensity exercise. PAP increase markedly in pre- or post-capillary pulmonary hypertension (pre-cap or post-cap PH), but the time course is unclear. We studied pulse (PP) and diastolic (PADP) PAP as indices of pulsatile load and pulmonary vascular outflow pressure, respectively, and explored whether the magnitude and time course of their response to exercise differs in pre-cap or post-cap PH. <h3>Methods</h3> Patients underwent right heart catheterization with cycle-ergometry (25/40W, F/M), and were classified by their exercise hemodynamic responses: 1) Normal 2) pre-cap PH and 3) post-cap PH. PAP were recorded continuously and analyzed offline. Changes from Control, 2 min, and 7 min were examined. <h3>Results</h3> We studied 76 patients (47% F; 59±15 years); groups comprised 32 Normal, 22 pre-cap PH, and 22 post-cap PH. After exercise onset in the Normal group, PADP increased at 2 min (∆5±3mmHg). This increase was less than both pre-cap PH (∆9±4mmHg, p<0.01) and post-cap PH (∆8±6mmHg, p=0.1), which did not differ (p=0.99). While PADP did not increase further at 7 min in Normal and post-cap PH groups, it did in the pre-cap PH group (∆3±5mmHg, p=0.04, Fig. 1). In the Normal group, PP increased at 2 min (∆5±4mmHg). PP increases at 2 min were greater in pre-cap PH (∆13±8mmHg) than post-cap PH (∆7±4mmHg, p<0.01) and Normal (p<0.01). Although PP increased further at 7 min in the Normal group (∆2±3mmHg, p<0.01), the increases in pre-cap PH (∆6±5mmHg, p<0.01) and post-cap PH (∆6±6mmHg, p<0.01) were both greater compared to Normal (pre-cap PH: p<0.01 post-cap PH: p=0.02, Fig. 1). <h3>Conclusion</h3> During exercise, patients with pre-cap or post-cap PH demonstrate differences in both the magnitude and temporality of change in PAP. Despite constant work-rate, the pulmonary vascular load continues to increase in both pre-cap and post-cap PH.

Aortic Vessel Wall Properties during 60 Days Strict Head down Tilt Bedrest

BackgroundChanges in large artery properties including increased arterial compliance and increased carotid artery stiffness have been described after space flight. Altered vascular structure, which heralds cardiovascular risk, and reversible changes in vascular function could contribute to the response. Compared with previous bedrest studies, which did not reproduce these findings, the artificial gravity bedrest study (AGBRESA) applied strict ‐6° head‐down tilt bedrest (HDT) for 60 days mimicking chronic cephalad fluid shifts in space. We assessed aortic vessel wall properties using state‐of‐the art imaging methods and pulse wave analysis and tested for possible protective effects of artificial gravity training.Material and MethodsThe AGBRESA Study is a joint project between NASA, ESA and DLR and is conducted in line with the declaration of Helsinki and the federal regulations of the U.S. Government. After the first of two AGBRESA campaigns, we present data from 12 healthy subjects (8 men, 4 women) obtained during baseline data collection 9–6 days before bedrest (BDC, supine position) and towards the end of two months head down tilt bedrest (MRI on day 56 and echocardiography on day 60 of HDT). Subjects were assigned to 30 minutes per day continuous short arm centrifugation (cAG), 6 times for 5 minutes interval short arm centrifugation, iAG), or a control group (ctr). We assessed aortic pulse wave velocity (PWV) using oscillometric upper arm and thigh cuffs (PWV‐2C, CardioCube, AIT, Vienna, Austria) and 4D‐flow cardiac velocity encoded phase contrast magnetic resonance imaging (PWV‐4D‐MRI). We also measured area, area changes, and distensibility (AoD) of the ascending aorta by 2D‐phase contrast cardiac MRI and arterial compliance (Ca) using transthoracic echocardiography.ResultsMean aortic area increased in all subjects after 60 days head down tilt bedrest (5.3±0.7 vs. 5.8±0.7 cm2, p&lt;0.05). Stroke volume decreased from 94±13 to 84±10 ml (p&lt;0.05) and pulse pressure from 56±11 to 46±9 mmHg (p&lt;0.05) in part through reductions in stroke volume. The figure illustrates individual data on aortic properties: Differences (end of HDT – BDC) in PWV measured with 2 cuffs (A) and with 4D‐Flow MRI (B), changes in AoD (C) and Ca (D) from BDC to the end of HDT (red diamonds = women). In contrast to the more consistent changes in aortic area, stroke volume, and pulse pressure, aortic distensibility, arterial compliance, and PWV responses show substantial inter‐individual variability.ConclusionThe important finding of our study is that 60 days strict head down bedrest elicit consistent changes in ascending aortic area, pulse pressure, and stroke volume. The resulting changes in vascular loading conditions likely confound vascular function measurements, both, in head down tilt bedrest studies and in space.Support or Funding InformationThe study was funded by the German Aerospace Center, the European Space Agency (contract number 4000113871/15/NL/PG) and the National Aeronautics and Space Administration (contract number 80JSC018P0078).Figure 1

Heparin/poly-l-lysine nanoplatform with growth factor delivery for surface modification of cardiovascular stents: The influence of vascular endothelial growth factor loading.

The rapid re-endothelialization of the vascular stent surface is desirable for preventing thrombosis or reducing restenosis. Many biological factors that promote the biological behavior of endothelial cells have been used for the surface modification of stents. Vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, induces strong vascular growth. In this study, we investigated different VEGF concentrations (50 to 500 ng/ml) to determine the optimum concentration for biocompatibility. First, VEGF-loaded heparin/poly-l-lysine (Hep-PLL) nanoparticles were created by electrostatic interactions. Then, the VEGF-loaded nanoparticles were immobilized on dopamine-coated 316 L stainless steel (SS) surfaces. The physical and chemical properties of the modified surface were characterized and the biocompatibility was evaluated in vitro. The results indicated that the VEGF-loaded nanoparticles were immobilized successfully on the 316LSS surface, as evidenced by the results of Alcian Blue staining and water contact angle (WCA) measurements. The low platelet adhesion and activation indicated that the modified surfaces had good blood compatibility. The modified surfaces showed a good inhibitory effect on smooth muscle cells, indicating that they inhibited tissue hyperplasia. In addition, the modified surfaces significantly promoted endothelial cell adhesion, proliferation, migration, and biological activity, especially VEGF concentration was 350 ng/ml (NPV350). The optical VEGF concentration of the surface modified Hep-PLL nanoparticles was 350 ng/ml. The proposed method shows promise for potential applications for cardiovascular devices.

Small, Long Blood Half-Life Iodine Nanoparticle for Vascular and Tumor Imaging

Standard clinical X-ray contrast agents are small iodine-containing molecules that are rapidly cleared by the kidneys and provide robust imaging for only a few seconds, thereby limiting more extensive vascular and tissue biodistribution imaging as well as optimal tumor uptake. They are also not generally useful for preclinical microCT imaging where longer scan times are required for high resolution image acquisition. We here describe a new iodine nanoparticle contrast agent that has a unique combination of properties: 20 nm hydrodynamic diameter, covalent PEG coating, 40 hour blood half-life, 50% liver clearance after six months, accumulation in tumors, and well-tolerated to at least 4 g iodine/kg body weight after intravenous administration in mice. These characteristics are unique among the other iodine nanoparticles that have been previously reported and provide extended-time high contrast vascular imaging and tumor loading. As such, it is useful for preclinical MicroCT animal studies. Potential human applications might include X-ray radiation dose enhancement for cancer therapy and vascular imaging for life-threatening situations where high levels of contrast are needed for extended periods of time.

Abscisic acid enhances lead translocation from the roots to the leaves and alleviates its toxicity in Populus × canescens.

To shed light on physiological mechanisms underlying abscisic-acid (ABA)-mediated lead (Pb) uptake, translocation and detoxification, we exposed Populus × canescens saplings to either 0 or 3 mM Pb2+ in combination with either 0 or 10 μM exogenous ABA. Pb was taken up by the roots and accumulated mainly in the cortex. A fraction of the Pb in the roots was translocated to the leaves, thereby resulting in decreased photosynthesis and biomass. Pb accumulation caused a burst of reactive oxygen species (ROS), with higher concentrations of total thiols, glutathione, and ascorbate in the roots and/or leaves. Exogenous ABA stimulated Pb uptake, decreased Pb deposition in the cortex, and enhanced Pb vascular loading in the roots. Exogenous ABA alleviated the Pb-induced reductions in photosynthesis and root biomass, and decreased Pb-triggered ROS overproduction in the roots and/or leaves. Correspondingly, exogenous ABA stimulated the mRNA levels of a few genes involved in Pb uptake, transport, and detoxification, including NRAMP1.4, ABCG40, FRD3.1, PCS1.1, and ABCC1.1. These results suggest that exogenous ABA enhances Pb uptake and translocation, and alleviates Pb toxicity in poplars through the ABA-induced movement of Pb from the root cortex to the vascular stele, and transcriptionally regulated key genes involved in Pb tolerance.

Intraosseous pressure during loading and with vascular occlusion in an animal model.

ObjectivesWe studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection.Materials and MethodsNeedles were placed in the femoral condyle and proximal tibia of five anaesthetized rabbits and connected to pressure recorders. The limb was loaded with and without proximal vascular occlusion. An additional subject had simultaneous triple recordings at the femoral head, femoral condyle and proximal tibia. In a further subject, saline injections at three sites were carried out in turn.ResultsLoading alone caused a rise in subchondral IOP from 11.7 mmHg (sd 7.1) to 17.9 mmHg (sd 8.1; p < 0.0002). During arterial occlusion, IOP fell to 5.3 mmHg (sd 4.1), then with loading there was a small rise to 7.6 mmHg (sd 4.5; p < 0.002). During venous occlusion, IOP rose to 20.2 mmHg (sd 5.8), and with loading there was a further rise to 26.3 mmHg (sd 6.3; p < 0.003). The effects were present at three different sites along the limb simultaneously. Saline injections showed pressure transmitted throughout the length of the femur but not across the knee joint.ConclusionThis is the first study to report changes in IOP in vivo during loading and with combinations of vascular occlusion and loading. Intraosseous pressure is not a constant. It is reduced during proximal arterial occlusion and increased with proximal venous occlusion. Whatever the perfusion state, in vivo load is transferred partly by hydraulic pressure. We propose that joints act as hydraulic pressure barriers. An understanding of subchondral physiology may be important in understanding osteoarthritis and other bone diseases.Cite this article: M. Beverly, S. Mellon, J. A. Kennedy, D. W. Murray. Intraosseous pressure during loading and with vascular occlusion in an animal model. Bone Joint Res 2018;7:511–516. DOI: 10.1302/2046-3758.78.BJR-2017-0343.R2.

A Novel Theory: Measuring the Real-Time-Based Arterial Properties via Vascular Loading Decoupling Technique

This paper presents a decoupling theory named as Vascular Loading Decoupling Technique (VLDT), extended from the beat-based Tissue Control Method (TCM), for noninvasive measurement of real-time-based intra-arterial blood pressure and dynamic compliance of blood vessel. Both VLDT and TCM are based upon the decoupling theory to cause the arterial pulsation without the influence from surrounding tissues and measure the variations of the vascular diameter at critical depth. Meanwhile, the AC part of blood pressure is lost, that is, the reference pressure for AC controller is absent as well. To remedy this problem, VLDT employs Step-Hold control rules and cubic spline curve fitting technique to estimate the reference pressure, identify the impedance of blood vessel, and calculate the AC control gain at Hold stage, then track the AC part of blood pressure and compute the real-time arterial blood pressure at Step stage by turns, which makes the real time measurement feasible; moreover, the dynamic compliance of blood vessel can be extracted from real-time impedances of blood vessel. Since the compliance of blood vessel is decoupled from surrounding tissues, it is valuable for diagnosing the severity of vascular sclerosis. The simulation results showed that the VLDT approach is superiority over TCM. This could provide new prospective to circulatory medicine research.

Increased chalcone synthase (CHS) expression is associated with dicamba resistance in Kochia scoparia.

Resistance to the synthetic auxin herbicide dicamba is increasingly problematic in Kochia scoparia. The resistance mechanism in an inbred dicamba-resistant K. scoparia line (9425R) was investigated using physiological and transcriptomics (RNA-Seq) approaches. No differences were found in dicamba absorption or metabolism between 9425R and a dicamba-susceptible line, but 9425R was found to have significantly reduced dicamba translocation. Known auxin-responsive genes ACC synthase (ACS) and indole-3-acetic acid amino synthetase (GH3) were transcriptionally induced following dicamba treatment in dicamba-susceptible K. scoparia but not in 9425R. Chalcone synthase (CHS), the gene regulating synthesis of the flavonols quertecin and kaemperfol, was found to have twofold higher transcription in 9425R both without and 12 h after dicamba treatment. Increased CHS transcription co-segregated with dicamba resistance in a forward genetics screen using an F2 population. Prior work has shown that the flavonols quertecin and kaemperfol compete with auxin for intercellular movement and vascular loading via ATP-binding cassette subfamily B (ABCB) membrane transporters. The results of this study support a model in which constitutively increased CHS expression in the meristem produces more flavonols that would compete with dicamba for intercellular transport by ABCB transporters, resulting in reduced dicamba translocation. © 2017 Society of Chemical Industry.

PRISE EN CHARGE INITIALE DES BRULURES GRAVES EN REANIMATION EN MILIEU TROPICAL

Introduction: Severe burn is the destruction of the skin that engages the vital and functional prognosis. They constitute a real problem, due to their heavy management and their consequences with invalidating sequellea. Our objective was to evaluate the management of severe burn in our African tropical environment. Methodology: A retrospective study was conducted at the intensive care unit of A. Le Dantec University teaching hospital in Dakar, over 10 years (May 1999 to April 2009), involving all patients admitted in the intensive care unit for severe burn. Data on: age, sex, time lapse before admission, clinical and paraclinical evaluation, management and outcome were collected. Results: 72 patients were selected over a total of 101 patients admitted for burn. We noted a male predominance with a sex ratio of 1.4. The average age was 21.8 years. The average time before admission was 11.3 hours. Domestic accidents accounted for 75 %, accidents at work accounted for 18.1% and suicide accounted for 5.6% of cases. Thermal burns accounted for 80.6 % and electric burns accounted for 19.4 %. The depth was mostly of second degree, with an average width of 34.9%. The average score of BAUX was 56.7% and the ABSI average score was 6. The vascular loading was adequate in 75 % of cases, and vasopressors were used in 41.7 % of cases. Mechanical ventilation after tracheal intubation was performed in 41.7 % of cases. Surgery was performed in 54.2 % of cases. No graff was performed in any case. A multi organ failure was noted in 22.2% of cases, a septic shock was noted in 30.6 % of cases and an hypovolemic shock was noted in 5.6 % of cases. The average time of stay in the ICU was 3.8 days with a mortality rate of 62.5%. Keywords: severe burn, tropical environment, intensive care unit.

Multiscale and Multiaxial Mechanics of Vascular Smooth Muscle

Mathematical models can facilitate an integrative understanding of the complexity underlying biological structure and function, but they must be informed and validated by empirical data. Uniaxial contraction of an arterial ring is a well-used in vitro approach for studying characteristics of smooth muscle contractility even though this experimental arrangement does not mimic the in vivo vascular geometry or loading. In contrast, biaxial contraction of an inflated and axially extended excised vessel provides broader information, both passive and active, under more realistic conditions. Few investigations have compared these two in vitro approaches directly, namely how their results overlap, how they differ, or if each provides unique complementary information. Toward this end, we present, to our knowledge, a new multiscale mathematical model of arterial contractility accounting for structural and functional constituents at molecular, cellular, and tissue levels. The artery is assumed to be a thick-walled incompressible cylinder described by an anisotropic model of the extracellular matrix and, to our knowledge, novel model of smooth muscle contractility. The latter includes a 3D structural sensitivity to deformation, including microscale muscle filament overlap and filament lattice spacing. The overall model captures uniaxial and biaxial experimental contraction data, which was not possible when accounting for filament overlap alone. The model also enables parameter sensitivity studies, which confirmed that uniaxial contraction tests are not as efficient as biaxial tests for identifying changes in vascular smooth muscle function.

Comparison of two doses of hypobaric bupivacaine in unilateral spinal anesthesia for hip fracture surgery: 5 mg versus 7.5 mg

IntroductionHip fracture is a frequent and severe disease. Its prognosis depends on the perioperative hemodynamic stability which can be preserved by the unilateral spinal anesthesia especially with low doses of local anesthetics. This study aims to compare the efficacy and hemodynamic stability of two doses of hypobaric bupivacaine (7.5 mg vs 5 mg) in unilateral spinal anesthesia.MethodsIn this prospective, randomized, double-blind study, 108 patients scheduled for hip fracture surgery under unilateral spinal anesthesia were enrolled to receive either 5 mg (group 1) or 7.5 mg (group 2) of hypobaric bupivacaine. Spinal anesthesia was performed in lateral position. Patients’ socio-demographic characteristics, hemodynamic profile, sensory and motor blocks parameters were recorded.ResultsBoth groups were comparable regarding to demographic data. Two cases of failure occurred in group 1 and one case in group 2 corresponding to a comparable efficiency rates (96.29% and 98.14% respectively; p = 0.5). A higher mean onset and lower mean regression times of sensory block were significantly noted in group 1 (7.79±3.76 min vs 5.75±2.35 min, p < 0.001 and 91.29±31.55 min vs 112.77±18.77 min, p <0.001 respectively). Incidence of bilateralization (29.62% vs 87.03%, p < 0.001), incidence of hypotensive episodes (59.25% vs 92.59%, p < 0.001) and vascular loading (1481.48±411.65 ml vs 2111.11±596.10 ml, p < 0.001) were significantly higher in group 2.ConclusionThe dosage of 5mg of hypobaric bupivacaine in unilateral spinal anesthesia is as effective as the dosage of 7.5 mg with lower bilateralization incidence and better hemodynamic stability.

Cardiac remodeling following reperfused acute myocardial infarction is linked to the concomitant evolution of vascular function as assessed by cardiovascular magnetic resonance

BackgroundLeft ventricular (LV) remodeling following acute myocardial infarction (MI) is difficult to predict at an individual level although a possible interfering role of vascular function has yet to be considered to date. This study aimed to determine the extent to which this LV remodeling is influenced by the concomitant evolution of vascular function and LV loading conditions, as assessed by phase-contrast Cardiovascular Magnetic Resonance (CMR) of the ascending aorta.MethodsCMR was performed in 121 patients, 2–4 days after reperfusion of a first ST-segment elevation myocardial infarction and 6 months thereafter. LV remodeling was: (i) assessed by the 6-month increase in end-diastolic volume (EDV) and/or ejection fraction (EF) and (ii) correlated with the indexed aortic stroke volume (mL.m−2), determined by a CMR phase-contrast sequence, along with derived functional vascular parameters (total peripheral vascular resistance (TPVR), total arterial compliance index, effective arterial elastance).ResultsAt 6 months, most patients were under angiotensin enzyme converting inhibitors (86%) and beta-blockers (84%) and, on average, all functional vascular parameters were improved whereas blood pressure levels were not. An increase in EDV only (EDV+/EF-) was documented in 17% of patients at 6 months, in EF only (EDV-/EF+) in 31%, in both EDV and EF (EDV+/EF+) in 12% and neither EDV nor EF (EDV-/EF-) in 40%. The increase in EF was mainly and independently linked to a concomitant decline in TPVR (6-month change in mmHg.min.m2.L−1, EDV-/EF-: +1 ± 8, EDV+/EF-: +3 ± 9, EDV-/EF+: -7 ± 6, EDV+/EF+: -15 ± 20, p < 0.001) while the absence of any EF improvement was associated with high persisting rates of abnormally high TPVR at 6 months (EDV-/EF-: 31%, EDV+/EF-: 38%, EDV-/EF+: 5%, EDV+/EF+: 13%, p = 0.007). By contrast, the 6–month increase in EDV was mainly dependent on cardiac as opposed to vascular parameters and particularly on the presence of microvascular obstruction at baseline (EDV-/EF-: 37%, EDV+/EF-: 76%, EDV-/EF+: 38%, EDV+/EF+: 73%, p = 0.003).ConclusionLV remodeling following reperfused MI is strongly influenced by the variable decrease in systemic vascular resistance under standard care vasodilating medication. The CMR monitoring of vascular resistance may help to tailor these medications for improving vascular resistance and consequently, LV ejection fraction.Trial registrationNCT01109225 on ClinicalTrials.gov site (April, 2010).

Tobacco mosaic virus-directed reprogramming of auxin/indole acetic acid protein transcriptional responses enhances virus phloem loading

Vascular phloem loading has long been recognized as an essential step in the establishment of a systemic virus infection. In this study, an interaction between the replication protein of tobacco mosaic virus (TMV) and phloem-specific auxin/indole acetic acid (Aux/IAA) transcriptional regulators was found to modulate virus phloem loading in an age-dependent manner. Promoter expression studies show that in mature tissues TMV 126/183-kDa-interacting Aux/IAAs predominantly express and accumulate within the nuclei of phloem companion cells (CCs). Furthermore, CC Aux/IAA nuclear localization is disrupted upon infection with an interacting virus. In situ analysis of virus spread shows that the inability to disrupt Aux/IAA CC nuclear localization correlates with a reduced ability to load into the vascular tissue. Subsequent systemic movement assays also demonstrate that a virus capable of disrupting Aux/IAA localization is significantly more competitive at moving out of older plant tissues than a noninteracting virus. Similarly, CC expression and overaccumulation of a degradation-resistant Aux/IAA-interacting protein was found to inhibit TMV accumulation and phloem loading selectively in flowering plants. Transcriptional expression studies demonstrate a role for Aux/IAA-interacting proteins in the regulation of salicylic and jasmonic acid host defense responses as well as virus-specific movement factors, including pectin methylesterase, that are involved in regulating plasmodesmata size-exclusion limits and promoting virus cell-to-cell movement. Combined, these findings indicate that TMV directs the reprogramming of auxin-regulated gene expression within the vascular phloem of mature tissues as a means to enhance phloem loading and systemic spread.

The synergistic effect of VEGF and biomorphic silicon carbides topography on in vivo angiogenesis and human bone marrow derived mesenchymal stem cell differentiation

Topographical features of biomaterials are able to modulate cell attachment, spreading and differentiation. The addition of growth factors to implantable biomaterials can modify these cellular responses, enhancing their therapeutic potential.The aim of this research is to establish the influence of biomorphic silicon carbide ceramics (bioSiCs) surface topography on the proliferation and osteoblastic differentiation of mesenchymal stem cells and the potential synergistic effect of the ceramic porous structure together with vascular endothelial growth factor loading (VEGF) on the surface mediated osteoblastic differentiation.Three porous bioSiCs with important differences in their microstructure were obtained from different natural precursors. Samples loaded with or without VEGF through ionic interactions were cultured with human umbilical vein endothelial cells (HUVEC) or bone marrow derived mesenchymal stem cells (hMSCs). Cell behaviour and protein activity with regard to bioSiC porous structure and surface properties were analysed. An in vivo model (Chick Chorioallantoic Membrane; CAM) was used to assess the capability of the VEGF loaded systems to promote angiogenesis.Experimental data show that loaded systems were able to control the release of VEGF for up to 15 d ensuring the activity of the protein, increasing the proliferation of HUVECs and the formation of new blood vessels in the CAM. It was found that the selection of bioSiCs with a higher pore size promoted a higher concentration of osteoblastic differentiation markers of MSCs cultured on the surface of bioSiCs. Furthermore, the addition of VEGF to the systems was able to promote a faster osteoblastic differentiation according to the qPCR results, suggesting a synergy between both the surface properties and the controlled release of the growth factor.The VEGF loaded sapelli bioSiC was found to be the most promising material for bone tissue engineering applications.