Hemodynamic Environment Research Articles

Studying the efficacy of antiplatelet drugs on atherosclerosis by optofluidic imaging on a chip.

Vascular stenosis caused by atherosclerosis instigates activation and aggregation of platelets, eventually resulting in thrombus formation. Although antiplatelet drugs are commonly used to inhibit platelet activation and aggregation, they unfortunately cannot prevent recurrent thrombotic events in patients with atherosclerosis. This is partially due to the limited understanding of the efficacy of antiplatelet drugs in the complex hemodynamic environment of vascular stenosis. Conventional methods for evaluating the efficacy of antiplatelet drugs under stenosis either fail to simulate the hemodynamic environment of vascular stenosis characterized by high shear stress and recirculatory flow or lack spatial resolution in their analytical techniques to statistically identify and characterize platelet aggregates. Here we propose and experimentally demonstrate a method comprising an in vitro 3D stenosis microfluidic chip and an optical time-stretch quantitative phase imaging system for studying the efficacy of antiplatelet drugs under stenosis. Our method simulates the atherogenic flow environment of vascular stenosis while enabling high-resolution and statistical analysis of platelet aggregates. Using our method, we distinguished the efficacy of three antiplatelet drugs, acetylsalicylic acid (ASA), cangrelor, and eptifibatide, for inhibiting platelet aggregation induced by stenosis. Specifically, ASA failed to inhibit stenosis-induced platelet aggregation, while eptifibatide and cangrelor showed high and moderate efficacy, respectively. Furthermore, we demonstrated that the drugs tested also differed in their efficacy for inhibiting platelet aggregation synergistically induced by stenosis and agonists (e.g., adenosine diphosphate, and collagen). Taken together, our method is an effective tool for investigating the efficacy of antiplatelet drugs under vascular stenosis, which could assist the development of optimal pharmacologic strategies for patients with atherosclerosis.

Nitric Oxide Generation and Endothelial Progenitor Cells Recruitment for Improving Hemocompatibility and Accelerating Endothelialization of Tissue Engineering Heart Valve

AbstractTissue engineering heart valve (TEHV) offers great potential to overcome the limitations of commercial artificial valves used in clinical practice as a permanent prosthetic valve. Currently, decellularized heart valve (DHV) is the most widely used scaffold for TEHV, but showed suboptimal performance due to difficulty of endothelialization. Facilitating endothelialization of DHV is indispensable for better valve performance, and excellent hemocompatibility guarantees enough time windows for endothelialization process. Herein, a dual‐functional TEHV scaffold with improving hemocompatibility and accelerating endothelialization is constructed by modifying DHV with copper ions (Cu) and growth differentiation factor 11 (GDF11). Results show the newly‐constructed scaffold successfully generates endogenous nitric oxide (NO) through catalysis of Cu, and possesses improved hemocompatibility by down‐regulating platelets activation and adhesion. Furthermore, GDF11 immobilization significantly accelerates scaffold endothelialization through facilitating recruitment, supporting growth, and alleviating apoptosis of endothelial progenitor cells . This TEHV scaffold shows favorable performance under in vivo hemodynamic environment with intact endothelial coverage and adaptive ECM remodeling, and without thrombus or calcification formation. This newly‐constructed TEHV scaffold is expected to make up for the shortcomings of currently available prosthetic valves in clinical practice and has the potential possibility of rapid translation to the clinic as a better prosthetic valve.

The effect of subbranch for the quantification of local hemodynamic environment in the coronary artery: a computed tomography angiography–based computational fluid dynamic analysis

Abstract Background Hemodynamic parameters derived from computed tomography angiography–based computational fluid dynamics (CFD) analysis have been widely used for clinical decision-making and researches to assess the vulnerability of atherosclerotic plaques and explain the initialization and development of atherosclerosis. Subbranches in the CFD model might affect the accuracy of hemodynamic parameters, but the effectiveness has been least quantified. Methods A coronary artery baseline model was generated with focal stenosis at the proximal left anterior descending artery. Nineteen comparing models were created by systematically removing various subbranches to examine the changes in hemodynamic parameters, including time-averaged pressure (TAP), time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and particle relative residence time (RRT). Changes in these parameters were assessed quantitatively around the stenosis and near the region where subbranches were removed. Results The removal of subbranches caused a significant change in outflow rate, and there was generally a decrease in all CFD parameters in the regions of interest with a decrease in outflow rate. The subbranch removal had a significant impact on the calculation of TAWSS, OSI, and RRT, whereas TAP was insensitive to the removal with approximately 0.25% variation in all 19 models. The local effect from removing branch segments generally became negligible after 5 diameters away from the cutting-off position, but the decrease could be affected by other factors, such as a large curvature. Conclusion The outflow rate is a dominant factor for the calculation of TAP, TAWSS, OSI, and RRT. Removal of subbranches has a minor effect on the TAP calculation, but its effect is considerable on the TAWSS, OSI, and RRT. The effect of subbranch removal is limited in a region with 5 local diameters.

Electrohydraulic Vascular Compression Device (e‐VaC) with Integrated Sensing and Controls

AbstractRight ventricular (RV) failure remains a significant clinical burden particularly during the perioperative period surrounding major cardiac surgeries, such as implantation of left ventricular assist devices (LVADs), bypass procedures or valvular surgeries. Device solutions designed to support the function of the RV do not keep up with the pace of development of left‐sided solutions, leaving the RV vulnerable to acute failure in the challenging hemodynamic environments of the perioperative setting. This work describes the design of a biomimetic, soft, conformable sleeve that can be prophylactically implanted on the pulmonary artery to support RV ventricular function during major cardiac surgeries, through afterload reduction and augmentation of flow. Leveraging electrohydraulic principles, a technology is proposed that is non‐blood contacting and obviates the necessity for drivelines by virtue of being electrically powered. In addition, the integration of an adjacent is demonstrate, continuous pressure sensing module to support physiologically adaptive control schemes based on a real‐time biological signal. In vitro experiments conducted in a pulsatile flow‐loop replicating physiological flow and pressure conditions show a reduction of mean pulmonary arterial pressure of 8 mmHg (25% reduction), a reduction in peak systolic arterial pressure of up to 10 mmHg (20% reduction), and a concomitant 19% increase in diastolic pulmonary flow. Computational simulations further predict substantial augmentation of cardiac output as a result of reduced RV ventricular stress and RV dilatation.

Effect of lower extremity amputation on cardiovascular hemodynamic environment: An in vitro study

Lower extremity amputation (LEA) was associated with a greater risk of cardiovascular disease, but its hemodynamic mechanisms have not been fully studied. Therefore, to clarify the interrelationship between them, and figure out the potential pathogenesis, the exploration of the hemodynamic environment change of patients after LEA was premeditatedly executed. A near-physiological mock circulatory system (MCS) was employed in the present work to replicate the cardiovascular circulation after LEA in a short time and the unsteady-state numerical simulation was utilized as an auxiliary method to observe the changes of the hemodynamic environment inside the blood vessel. Higher severity of LEA leads to higher peripheral vascular impedance, higher blood pressure, and more obvious redistribution of blood perfusion volume. In addition, higher severity of LEA leads to lower wall shear stress (WSS), higher oscillatory shear index (OSI), and higher relative residence time (RRT) appeared in the infrarenal abdominal aorta and the iliac artery, while these changes are closely related to the higher probability of cardiovascular diseases. Results showed that different degrees of LEA (varying heights, unilateral/bilateral) have diverse effects on the patient's hemodynamic environment. This study explained the potential pathogenesis of cardiovascular diseases after LEA from a hemodynamic perspective and provided a certain reference value for the improvement of the cardiovascular hemodynamic environment and the prevention of cardiovascular diseases in lower extremity amputees.

Hemodynamic evaluation of endarterectomy and stenting treatments for carotid web.

A carotid web is a thin, shelf-like luminal protrusion in the internal carotid artery that might cause carotid stenosis and stroke by inducing disturbed flow patterns, thrombosis, and abnormal biomechanical stimulus to the endothelial cells. This study simulated and evaluated how the two main treatments (endarterectomy and stenting) influence hemodynamic environments in the carotid artery and distal carotid siphon arteries, aiming to provide more references for the selection of clinical treatment. The carotid web, endarterectomy, and stenting models were reconstructed based on CT images. The blood flow simulations were conducted, and critical parameters related to thrombosis formation and artery remodeling, including swirling strength, wall shear stress (WSS), vortex Q-criterion, and oscillating shear index (OSI), were analyzed. In the model of the carotid web, obvious recirculation formed distal to the web, accompanied by lower velocity, lower WSS, higher relative resident time (RRT), and higher Q value. While in both two treatment models, the velocity increased and the Q value and RRT decreased at the carotid bifurcation. In addition, both treatments provide more kinetic energy to the distal carotid siphon artery, especially the stenting model. The carotid web can significantly influence the flow environments in the carotid artery. Both endarterectomy and stenting treatments could significantly diminish the side effects of the web and are feasible choices for web patients in terms of hemodynamics. Besides, the treatments for the carotid web would also influence the flow patterns at the distal carotid siphon, especially for the stenting treatment. But more innovational designs are needed to make the minimally invasive stenting treatment more beneficial.

Predicting the growth of middle cerebral artery bifurcation aneurysms using differences in the bifurcation angle and inflow coefficient.

Growing intracranial aneurysms (IAs) are prone to rupture. Previous cross-sectional studies using postrupture morphology have shown the morphological or hemodynamic features related to IA rupture. Yet, which morphological or hemodynamic differences of the prerupture status can predict the growth and rupture of smaller IAs remains unknown. The purpose of this longitudinal study was to investigate the effects of morphological features and the hemodynamic environment on the growth of IAs at middle cerebral artery (MCA) bifurcations during the follow-up period. One hundred two patients with MCA M1-2 bifurcation saccular IAs who underwent follow-up for more than 2 years at the authors' institutions between 2011 and 2019 were retrospectively identified. During the follow-up period, cases involving growth of MCA IAs were assigned to the event group, and those with MCA IAs unchanged in size were assigned to the control group. The morphological parameters examined were aneurysmal neck length, dome height, aspect ratio and volume, M1 and M2 diameters and their ratio, and angle configurations among M1, M2, and the aneurysm. Hemodynamic parameters were flow rate and wall shear stress in M1, M2, and the aneurysm, including the aneurysmal inflow rate coefficient (AIRC), defined as the ratio of the aneurysmal inflow rate to the M1 flow rate. Those parameters were compared statistically between the two groups. Correlations between morphological and hemodynamic parameters were also examined. Eighty-three of 102 patients were included: 25 with growing MCA IAs (event group) and 58 with stable MCA IAs (control group). The median patient age at initial diagnosis was 66.9 (IQR 59.8-72.3) years. The median follow-up period was 48.5 (IQR 36.5-65.6) months. Both patient age and the AIRC were significant independent predictors of the growth of MCA IAs. Moreover, the AIRC was strongly correlated with sharper bifurcation and inflow angles, as well as wider inclination angles between the M1 and M2 arteries. The AIRC was a significant independent predictor of the growth of MCA IAs. Sharper bifurcation and inflow angles and wider inclination angles between the M1 and M2 arteries were correlated with the AIRC. MCA IAs with such a bifurcation configuration are more prone to grow and rupture.

The Role of Endothelial Cells in the Onset, Development and Modulation of Vein Graft Disease.

Endothelial cells comprise the intimal layer of the vasculature, playing a crucial role in facilitating and regulating aspects such nutrient transport, vascular homeostasis, and inflammatory response. Given the importance of these cells in maintaining a healthy haemodynamic environment, dysfunction of the endothelium is central to a host of vascular diseases and is a key predictor of cardiovascular risk. Of note, endothelial dysfunction is believed to be a key driver for vein graft disease—a pathology in which vein grafts utilised in coronary artery bypass graft surgery develop intimal hyperplasia and accelerated atherosclerosis, resulting in poor long-term patency rates. Activation and denudation of the endothelium following surgical trauma and implantation of the graft encourage a host of immune, inflammatory, and cellular differentiation responses that risk driving the graft to failure. This review aims to provide an overview of the current working knowledge regarding the role of endothelial cells in the onset, development, and modulation of vein graft disease, as well as addressing current surgical and medical management approaches which aim to beneficially modulate endothelial function and improve patient outcomes.

The effects of high-intensity interval training and moderate-intensity continuous training on visceral fat and carotid hemodynamics parameters in obese adults

Background/ObjectivesThe present study aimed to examine the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on visceral fat and hemodynamic parameters in obese adults. MethodsFifty-two males were included in this study and divided into three groups: HIIT group (n = 21, age = 20.86 ± 1.62 years, BF (%) = 30.10 ± 5.02), MICT group (n = 22, age = 20.76 ± 1.14 years, BF (%) = 30.19 ± 5.76), and control group (CON) (n = 9, age = 21.38 ± 1.77 years, BF (%) = 30.40 ± 5.10). The HIIT and MICT groups received the exercise intervention three to four times per week for eight weeks (HIIT: exercise intensity 80–95% HRmax, circuit; MICT: exercise intensity 60–70% HRmax, running), and the control (CON) group received health education and guidance without exercise intervention. The body compositions and serum lipid indexes were tested to calculated LAP and VAI. The color doppler ultrasound diagnostic technology was used to test the artery diameter and blood velocity before and after the intervention. Based on the test data, MATLAB software and Womersley theory were used to calculate the hemodynamic parameters of the common carotid artery, including wall shear stress, flow rate, blood pressure, oscillatory shear index, elasticity modulus, dynamic resistance, artery diameter, arterial stiffness, circumferential strain and pulsatility index. ResultsWe found that lipid accumulation product (LAP) was significantly decreased in both the HIIT group (p < 0.01) and MICT (p < 0.05) group but not in the CON group (p > 0.05). In contrast, visceral adiposity index (VAI) decreased in both the HIIT and MICT groups and increased in the CON group, although the difference among groups was not significant (p > 0.05). After 8 weeks of intervention, the blood velocity and wall shear stress were greater after HIIT and MICT intervention (p < 0.01). Artery diameter, oscillatory shear index, arterial stiffness, and pulsatility index decreased significantly, and circumferential strain increased significantly in the HIIT group (all, p < 0.01, p < 0.05) but not in the MICT group (p > 0.05). Dynamic resistance was significantly decreased in the MICT group. There was no difference in the CON group after the period of intervention (all, p > 0.05). LAP was positively related to artery diameter (r = 0.48, p = 0.011), blood pressure (r = 0.46, p = 0.002), flow rate (r = 0.31, p = 0.04), oscillatory shear index (r = 0.44, p = 0.03), and elasticity modulus (r = 0.33, p = 0.029) but inversely related to circumferential strain (r = −0.36, p = 0.028). The VAI was also positively associated with artery diameter (r = 0.33, p = 0.03), elasticity modulus (r = 0.38, p = 0.009), and arterial stiffness (r = 0.39, p = 0.012). In addition, the VAI was negatively correlated with the circumferential strain (r = −0.33, p = 0.04). ConclusionThe present study demonstrated that both HIIT and MICT exercises for 8 weeks could effectively enhance visceral fat indices and partial hemodynamic parameters. Therefore, HIIT and MICT exert important effects on reducing fat content and improving hemodynamic environment. But HIIT on oscillatory shear index, arterial stiffness, circumferential strain, and pulsatility index was superior to MICT. In addition, there are close correlations between visceral fat and partial hemodynamic parameters of the common carotid artery.

Reliability of using generic flow conditions to quantify aneurysmal haemodynamics: A comparison against simulations incorporating boundary conditions measured in vivo

Background and objectivesInitiation, growth, and rupture of intracranial aneurysms are believed to be closely related to their local haemodynamic environment. While haemodynamics can be characterised by use of computational fluid dynamics (CFD), its reliability depends heavily upon accurate assumption of the boundary conditions. Herein, we compared the simulated aneurysmal haemodynamics obtained by use of generic boundary conditions against those obtained under flow conditions measured in vivo. MethodsWe prospectively recruited 19 patients with intracranial aneurysms requiring 3-dimensional rotational angiography, during which blood pressure at the internal carotid artery was probed by catheter and flowrate measured by a dedicated software tool. Using these flow conditions measured in vivo, we quantified the aneurysmal haemodynamics for each patient by CFD, and then compared the results with those derived from a generic condition reported in the literature, in terms of the time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and percentage of the intra-aneurysmal flow (PIAF). In addition, the effects on aneurysmal haemodynamics of different outflow strategies (splitting method vs. Murray's Law) and simulation schemes (transient vs. steady-state) relative to each flow condition were also assessed. ResultsDifferences in the simulated TAWSS (−6.08 ± 10.64 Pa, p = 0.001), OSI (0.06 ± 0.13, p = 0.001), and PIAF (−0.05 ± 0.20, p = 0.012) between the patient-specific and generic boundary conditions were found to be statistically significant, in contrast to that in the RRT (49 ± 307 Pa−1, p = 0.062). Outflow strategies did not yield statistically significant differences in any of the investigated parameters (all p > 0.05); rather, the resulting parameters were found to be in good correlations (all r > 0.71, p < 0.001). Difference between the aneurysmal TAWSS and the WSS derived from cycle-averaged flowrate condition was found to be minor (0.66 ± 1.36 Pa, p = 0.000), so was that between PIAFs obtained respectively from the transient and steady-state simulations (0.02 ± 0.05, p = 0.000). ConclusionsIncorporating into simulation the patient-specific boundary conditions is critical for CFD to characterise aneurysmal haemodynamics, while outflow strategies may not introduce significant uncertainties. Steady-state simulation incorporating the cycle-averaged flow condition may produce unbiased WSS and PIAF compared to the transient analysis.

The hemodynamic effect of eccentricity in visceral branched aneurysms with multilayer stents.

It is preliminarily acknowledged that multilayer stent (MS) is a promising alternative technology in the treatment of visceral branched aneurysms, but hemodynamic consequences of eccentricity in such aneurysms with MS are less examined. In this work, we performed a time-dependent simulation of branched aneurysms of various eccentricities with different stent layers, and thrombosis-related parameters, such as time-averaged wall shear stress (TAWSS), oscillating shear index (OSI), and relative residence time (RRT), were also analyzed. Our results revealed that MS can generally restore laminar flow inside the stent, and allow proper perfusion to vital organs while also fostering a relatively secluded hemodynamic environment for thrombosis formation. Particularly, a flow in the aneurysm sac communicating between the main artery and side branch forms at early systole. However, MS fails to completely eliminate detrimental flow impingement after peak systole, which may hinder aneurysm recovery, especially in the cases of eccentric aneurysms. Therefore, saccular aneurysms should be treated with more caution than fusiform aneurysms. And further therapeutic attempts to keep both perfusion in the proximal region of the aneurysm and isolation in the distal region of the aneurysm should be considered.

Role of patient-specific blood properties in computational fluid dynamics simulation of flow diverter deployed cerebral aneurysms.

BACKGROUND: Hemodynamics and their clinical outcome of cerebral aneurysms treated with flow diverter (FD) stents have thus far been investigated using computational fluid dynamics (CFD) simulations. Although human blood is characterized as a non-Newtonian patientspecific fluid, non-patient-specific blood properties (PSBP) were applied in most extant studies.OBJECTIVE: To investigate the hemodynamic effects caused by PSBPs in aneurysms treated with FD stents.METHODS: We measured blood properties (density and viscosity) for 12 patients who underwent FD stent deployment. We conducted CFD simulations with the measured PSBPs and non-PSBPs quoted from previous studies. The average blood flow velocity and wall shear stress within the aneurysms were calculated and two simulation patterns were compared.RESULTS: The velocity and wall shear stress changed by 2.93% and 3.16% on average, respectively, without an FD stent deployed. Conversely, with the FD stents deployed, the change rates increased to 11.1% and 9.06% on average, respectively.CONCLUSIONS: The change in hemodynamic parameters if PSBPs are considered, may not be negligible when conducting CFD simulations of FD stent deployed aneurysms To obtain an adequate hemodynamic environment for cerebral aneurysms with FD stents deployed, it is recommended to use PSBPs for CFD simulations.

Vortex formation and associated aneurysmogenic transverse rotational shear stress near the apex of wide-angle cerebral bifurcations.

Aneurysm formation preferentially occurs at the site of wide-angle cerebral arterial bifurcations, which were recently shown to have a high longitudinal positive wall shear stress (WSS) gradient that promotes aneurysm formation. The authors sought to explore the other components of the hemodynamic environment that are altered with increasing bifurcation angle in the apical region and the effects of these components on WSS patterns on the vessel wall that may modulate aneurysm genesis and progression. Parametric models of symmetrical and asymmetrical bifurcations were created with increasing bifurcation angles (45°-240°), and 3D rotational angiography models of 13 middle cerebral artery (MCA) bifurcations (7 aneurysmal, 6 controls) were analyzed using computational fluid dynamics. For aneurysmal bifurcations, the aneurysm was digitally removed to uncover hemodynamics at the apex. WSS vectors along cross-sectional planes distal to the bifurcation apex were decomposed as orthogonal projections to the cut plane into longitudinal and transverse (tangential to the cross-sectional plane) components. Transverse rotational WSS (TRWSS) and TRWSS gradients (TRWSSGs) were sampled and evaluated at the apex and immediately distal from the apex. In parametric models, increased bifurcation angle was associated with transverse flow vortex formation with emergence of an associated apical high TRWSS with highly aneurysmogenic positive TRWSSGs. While TRWSS decayed rapidly away from the apex in narrow-angle bifurcations, it remained greatly elevated for many radii downstream in aneurysm-prone wider bifurcations. In asymmetrical bifurcations, TRWSS was higher on the aneurysm-prone daughter vessel associated with the wider angle. Patient-derived models with aneurysmal bifurcations had wider angles (149.33° ± 12.56° vs 98.17° ± 8.67°, p < 0.001), with significantly higher maximum TRWSS (1.37 ± 0.67 vs 0.48 ± 0.23 Pa, p = 0.01) and TRWSSG (1.78 ± 0.92 vs 0.76 ± 0.50 Pa/mm, p = 0.03) compared to control nonaneurysmal bifurcations. Wider vascular bifurcations are associated with a novel and to the authors' knowledge previously undescribed transverse component rotational wall shear stress associated with a positive (aneurysmogenic) spatial gradient. The resulting hemodynamic insult, demonstrated in both parametric models and patient-based anatomy, is noted to decay rapidly away from the protection of the medial pad in healthy narrow-angle bifurcations but remain elevated distally downstream of wide-angle aneurysm-prone bifurcations. This TRWSS serves as a new contribution to the hemodynamic environment favoring aneurysm formation and progression at wide cerebral bifurcations and may have clinical implications favoring interventions that reduce bifurcation angle.

Significance of aortoseptal angle anomalies to left ventricular hemodynamics and subaortic stenosis: A numerical study

Discrete subaortic stenosis (DSS) is an obstructive cardiac disease caused by a membranous lesion in the left ventricular (LV) outflow tract (LVOT). Although its etiology is unknown, the higher prevalence of DSS in LVOT anatomies featuring a steep aortoseptal angle (AoSA) suggests a potential role for hemodynamics. Therefore, the objective of this study was to quantify the impact of AoSA steepening on the LV three-dimensional (3D) hemodynamic stress environment. A 3D LV model reconstructed from cardiac cine-magnetic resonance imaging was connected to four LVOT geometrical variations spanning the clinical AoSA range (115°-160°). LV hemodynamic stresses were characterized in terms of cycle-averaged pressure, temporal shear magnitude (TSM), and oscillatory shear index. The wall shear stress (WSS) topological skeleton was further analyzed by computing the scaled divergence of the WSS vector field. AoSA steepening caused an increasingly perturbed subaortic flow marked by LVOT flow skewness and complex 3D secondary flow patterns. These disturbances generated WSS overloads (>45% increase in TSM vs. 160° model) on the inferior LVOT wall, and increased WSS contraction (>66% decrease in WSS divergence vs. 160° model) in regions prone to DSS membrane formation. AoSA steepening generated substantial hemodynamic stress abnormalities in LVOT regions prone to DSS formation. Further studies are needed to assess the possible impact of such mechanical abnormalities on the tissue and cellular responses.

Endovascular Repair of an Iliac Arteriovenous Fistula in a 30-Year-Old Female Patient with Suspected Severe Cardiac Insufficiency: A Case Report.

A 30-year-old female was initially diagnosed with cardiac insufficiency and severe claudication. Additional imaging revealed a large iliac arteriovenous fistula, which was treated with an endovascular technique. A custom-made, self-expanding, polytetrafluorethylene-covered stent was implanted to restore the physiologic hemodynamic environment. The patient was asymptomatic at the 12-month clinical follow-up.

Role of Rho‐associated kinase (ROCK) in the different speed of relaxation between pulmonary arteries and mesentery arteries of rats

Pulmonary arteries (PA) are exposed to hemodynamic environment and contractile stimuli different from those of systemic arteries. Previous studies reported that in situapplication of sodium nitroprusside (SNP, NO donor) lowered the PA pressure, which was less prominent than the response of systemic arteries. Here, we investigated the relaxation speed and the in vitro effects of NO‐dependent signaling modulators to compare between isolated PA and mesenteric arteries (MA) of rats. In the dual‐wire myography study, PA showed significantly slower relaxation after the response to 80 mM KCl (80K) or to pharmacological agonists (U46619 and PGF2a). Surprisingly, addition of 30 μM SNP could not prevent the 80K contraction in PA while significantly attenuated the contraction of MA. The pretreatment with soluble guanylate cyclase (sGC) inhibitor (ODQ, 10 μM) markedly further slowed the relaxation of PA after 80K or agonist‐induced contraction. Perplexingly, immunoblot assay revealed higher expression of sGC‐a with similar level of sGC‐b1 in PA than MA. The expression of RhoA‐kinase (ROCK) was higher while myosin light chain phosphatase (MYPT) appeared lower in PA than MA. The treatment with ROCK inhibitor (Y27632, 10 μM) could abolish the different of relaxation response between PA and MA. Taken together, we speculate that despite the higher expression and the functional importance of NO/sGC pathway in PA, the higher level of ROCK and relatively low MYPT in PA are responsible for the characteristic slow relaxation after removal of stimuli.

Estimation of Shear Stress Heterogeneity along Capillary Segments in Angiogenic Rat Mesenteric Microvascular Networks

Fluid shear stress has been identified as an important player in regulating endothelial cell behavior and angiogenesis, defined as the sprouting of new blood vessels from existing vessels. However, the correlative or functional linking of shear stress to vessel‐specific endothelial cell dynamics requires a better understanding of the shear stress values at the capillary level in microvascular networks. Critical questions remain unanswered. What is the shear stress experienced by endothelial cells along capillaries? Do all capillaries experience similar shear stress magnitudes? Can variations in shear stress along different capillary segments explain vessel‐specific responses? The objective of this project was to estimate shear stress values in regions of angiogenic microvascular networks. Rat mesenteric tissues were harvested from adult male Wistar rats post the stimulation of angiogenesis via 48‐80 mast cell degranulation. Microvascular networks were identified by perfusion of a 40kDa fixable dextran prior to harvesting and immunolabelling for PECAM. Dextran presence identified perfused segments along the hierarchy of microvascular networks, which were characterized by increased vessel density indicative of angiogenesis. Two representative network regions with arteriole input and venule output vessels were selected for analysis. Vessel segments were defined by nodes, branch order position, and the measurements of lengths and diameter. Assuming an inlet pressure of 75 mmHg and outlet pressure of 10 mmHg, a network segmental Newtonian flow model was used to computationally estimate vessel‐specific shear stresses and velocities. Viscosity was set to 4 cP and assumed to be constant. For region 1, shear stresses along capillaries (diameters less than 10 microns) ranged from 0.7 to 479 dyne/cm2 (average = 57± 69 dyne/cm2). For region 2, shear stresses along capillaries ranged 0.1 to 1032 dyne/cm2 (average = 75± 94 dyne/cm2). For both regions, the maximum shear stress along capillary segments was greater than the maximum shear stress in the initial arterial branches. The high variability at the capillary level in both network regions suggests the potential for vessel‐specific stimuli. The maximum shear stresses in proximal capillary segments connecting the high‐pressure arterial sides to the lower pressure venous sides in a network were increased compared to stresses for segments in more distal network regions. The results of this study highlight the heterogeneity of shear stress experienced by endothelial cells at the capillary level in angiogenic microvascular networks and motivate questions related to how vessel‐specific hemodynamic environments regulate endothelial cell function.

T18/S19 diphosphorylation of myosin regulatory Light Chain is Responsible for the impaired relaxation of pulmonary arteries in pulmonary hypertensive rats

Pulmonary arteries (PA) are exposed to hemodynamic environment and contractile stimuli different from those of systemic arteries. Previous studies reported that in situapplication of sodium nitroprusside (SNP, NO donor) lowered the PA pressure, which was less prominent than the response of systemic arteries. Here, we investigated the relaxation speed and the in vitro effects of NO‐dependent signaling modulators to compare between isolated PA and mesenteric arteries (MA) of rats. In the dual‐wire myography study, PA showed significantly slower relaxation after the response to 80 mM KCl (80K) or to pharmacological agonists (U46619 and PGF2a). Surprisingly, addition of 30 mM SNP could not prevent the 80K contraction in PA while significantly attenuated the contraction of MA. The pretreatment with soluble guanylate cyclase (sGC) inhibitor (ODQ, 10 mM) markedly further slowed the relaxation of PA after 80K or agonist‐induced contraction. Perplexingly, immunoblot assay revealed higher expression of sGC‐a with similar level of sGC‐b1 in PA than MA. The expression of RhoA‐kinase (ROCK) was higher while myosin light chain phosphatase (MYPT) appeared lower in PA than MA. The treatment with ROCK inhibitor (Y27632, 10 mM) could abolish the different of relaxation response between PA and MA. Taken together, we speculate that despite the higher expression and the functional importance of NO/sGC pathway in PA, the higher level of ROCK and relatively low MYPT in PA are responsible for the characteristic slow relaxation after removal of stimuli.

B-10 | Successful Treatment of Shock in Septic Patient with Left Ventricular Suicide-like Presentation Refractory to Medical Therapy with Impella Hemodynamic Support

B-10 | Successful Treatment of Shock in Septic Patient with Left Ventricular Suicide-like Presentation Refractory to Medical Therapy with Impella Hemodynamic Support

Spatiotemporal changes of local hemodynamics and plaque components during atherosclerotic progression in rabbit

Background and objectiveRecent evidence demonstrates that the atherogenic process is discontinuous. Our goal is to study changes of plaque components and local hemodynamics during atherosclerotic progression. MethodsThe histological and immunohistochemical staining of high-fat diet rabbit aorta were evaluated at 0, 8, 10 and 12 weeks, respectively. In addition, the blood flow and LDL transport were simulated at the above four time points. ResultsThe plaque thickness at different characteristic regions increased at different rates. The collagen continued to increase, while the elastin, fibronectin, macrophages and smooth muscle cells increased first and then decreased. The relative surface LDL concentration decreased at 8 weeks, and then it increased first and decreased slightly. Meanwhile, the hemodynamic environment became better firstly at 8 weeks, then got slightly worse and lastly improved again. ConclusionsThe local hemodynamics and plaque components vary nonlinearly during atherosclerotic progression in rabbit aorta.