Flow inhibits inward remodeling in cannulated porcine small coronary arteries

2005 ◽  
Vol 289 (6) ◽  
pp. H2632-H2640 ◽  
Author(s):  
Adrian Pistea ◽  
Erik N. T. P. Bakker ◽  
Jos A. E. Spaan ◽  
Ed VanBavel
Keyword(s):  
Coronary Arteries ◽  
Vascular Remodeling ◽  
Culture Period ◽  
Control Group ◽  
Shear Stresses ◽  
No Production ◽  
Flow Conditions ◽  
Resistance Arteries ◽  
Organoid Culture ◽  
Flow Through

The mechanisms of flow-induced vascular remodeling are poorly understood, especially in the coronary microcirculation. We hypothesized that application of flow in small coronary arteries in organoid culture would cause a nitric oxide (NO)-mediated dilation and inhibit inward remodeling. We developed an organoid culture setup to drive a flow through cannulated arterioles at constant luminal pressure via a pressure gradient between the pipettes. Subepicardial porcine coronary arterioles with diameter at full dilation and 60 mmHg ( D0) of 168 ± 10 (SE) μm were cannulated. Vessels treated with Nω-nitro-l-arginine (l-NNA) to block NO production and untreated vessels were pressurized at 60 mmHg for 3 days with and without flow. Endothelium-dependent dilation to 10−7 M bradykinin was preserved in all groups. Tone was significantly less in vessels cultured under flow conditions in the last half of the culture period. Untreated and l-NNA-treated vessels regulated their diameter to yield shear stresses of 10.3 ± 2.1 and 14.0 ± 2.4 (SE) dyn/cm2, respectively (not significantly different). Without l-NNA, passive pressure-diameter curves at the end of the culture period revealed inward remodeling in the control group [to 92.3 ± 1.3% of D0 (SE)] and no remodeling in the vessels cultured under flow conditions (100.2 ± 1.3% of D0); with l-NNA, the group subjected to flow showed inward remodeling (92.1 ± 2.5% of D0). We conclude that pressurized coronary resistance arteries could be maintained in culture for several days with flow. Vessels cultured under flow conditions remained more dilated when NO synthesis was blocked. Inward remodeling occurred in vessels cultured under no-flow conditions and was inhibited by flow-dependent NO synthesis.

Abstract MP10: Early Functional and Structural Alterations of Resistance Arteries in Mice Treated with an Inhibitor of the Vascular Endothelial Growth Factor Receptor

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
CARMINE SAVOIA ◽  
Emanuele Arrabito ◽  
Augusto C Montezano ◽  
Carmine Nicoletti ◽  
Heather Y Small ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Remodeling ◽  
Growth Factor Receptor ◽  
Mesenteric Arteries ◽  
No Production ◽  
Vascular Endothelial ◽  
Resistance Arteries ◽  
Structural Alterations ◽  
Endothelial Growth Factor

Background: Inhibition of tyrosine kinases receptors such as vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) improves outcomes in patients with cancers. Only VEGFR inhibitors, however, induce severe hypertension whose mechanisms remain unclear. We hypothesized that VEGFR inhibitors may induce early vascular functional and structural alterations, that may precede the development of hypertension. Methods and results: Normotensive SV-129 mice (8 weeks old, 5 for each group) were treated or not with the VEGFR inhibitor Vatalanib (VAT, 100 mg/Kg/day) or the EGFR inhibitor Gefitinib (GEF, 100 mg/Kg/day). Vehicle-treated control mice were also studied. Blood pressure (BP) was measured by tail-cuff method. Endothelium-dependent and -independent relaxations were assessed by concentration-response curves to acetylcholine (1 nM to 100 μM) ± L-NAME (100 μM) and sodium nitroprusside (10 nM to 1 mM) respectively, in mesenteric arteries pre-contracted with norepinephrine (10 μM). Media-to-lumen ratio (M/L, an index of early vascular remodeling), and cross sectional area (CSA) were evaluated on pressurized preparations. After two weeks, BP was similarly preserved in both VAT- and GEF-treated mice as compared to vehicle-treated mice (89.8±1.5 mmHg and 87.2±2.8 mmHg vs 92.2±2.2 mmHg, respectively, NS). Endothelium-dependent relaxation was similarly preserved in vehicle-treated and GEF-treated mice, whereas it was reduced in VAT-treated mice (-17% vs vehicle-treated mice, P<0.05). L-NAME blunted acetylcholine-induced relaxation in all groups except in VAT-treated mice, suggesting an impairment of NO production only in this group. Endothelium-independent relaxation was similar in all groups. Only VAT-treated mice presented increased M/L as compared to vehicle-treated mice (6.3±0.1% vs 5.4±0.1%, P<0.05). M/L resulted similar in GEF-treated and vehicle-treated mice. CSA was similar in all groups. Conclusion: In normotensive mice, only VAT promoted early vascular alterations such as endothelial dysfunction and vascular remodeling in resistance arteries. Those changes in the vasculature are distinctive of hypertension and might precede and sustain the development of the hypertensive disease.

Remodeling of resistance arteries in organoid culture is modulated by pressure and pressure pulsation and depends on vasomotion

2004 ◽  
Vol 286 (6) ◽  
pp. H2052-H2056 ◽  
Author(s):  
Erik N. T. P. Bakker ◽  
Oana Sorop ◽  
Jos A. E. Spaan ◽  
Ed VanBavel
Keyword(s):  
High Pressure ◽  
Vascular Remodeling ◽  
Pressure Pulsation ◽  
Progressive Increase ◽  
Pressure Level ◽  
Lumen Diameter ◽  
Myogenic Tone ◽  
Cremaster Muscle ◽  
Resistance Arteries ◽  
Organoid Culture

The hypothesis was tested that pressure and pressure pulsation modulate vascular remodeling. Arterioles (∼200 μm lumen diameter) were dissected from rat cremaster muscle and studied in organoid culture. In the first series, arterioles were kept at a stable pressure level of either 50 or 100 mmHg for 3 days. Both groups showed a progressive increase in myogenic tone during the experiment. Arterioles kept at 50 mmHg showed larger endothelium-dependent dilation, compared with vessels kept at 100 mmHg on day 3. Remodeling, as indicated by the reduction in maximally dilated diameter at 100 mmHg, was larger in arterioles kept at 50 mmHg compared with 100 mmHg: 34 ± 4.5 versus 10 ± 4.8 μm ( P < 0.05). In the second series, arterioles were subjected to a stable pressure of 60 mmHg or oscillating pressure of 60 ± 10 mmHg (1.5 Hz) for 4 days. Pressure pulsation induced partial dilation and was associated with less remodeling: 34 ± 4.0 versus 19 ± 4.5 μm ( P < 0.01) for stable pressure versus oscillating pressure. Vasomotion was frequently observed in all groups, and inward remodeling was larger in vessels with vasomotion: 30 ± 2.5 μm compared with vessels that did not exhibit vasomotion: 8.0 ± 5.0 μm ( P < 0.01). In conclusion, these results indicate that remodeling is not enhanced by high pressure. Pressure pulsation causes partial dilation and reduces inward remodeling. The appearance of vasomotion is associated with enhanced inward remodeling.

scholarly journals Comparative analysis of prothrombotic activity in patients with myocardial infarction with non-obstructive and obstructive atherosclerotic lesions of the coronary arteries

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
VV Ryabov ◽  
D Vorobyeva ◽  
YUG Lugacheva ◽  
IV Kulagina
Keyword(s):  
Myocardial Infarction ◽  
Coronary Arteries ◽  
Von Willebrand Factor ◽  
Protein C ◽  
Control Group ◽  
Moderate Correlation ◽  
Blood Tests ◽  
Group A ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The reported study was funded by RFBR, project number №19-315-90106 Aim To compare indicators of blood prothrombotic activity in patients with myocardial infarction with and without coronary arteries obstruction Material and methods. The study included 40 patients with AMI (19 patients in the main group and 21 patients in the control group). Three patients (15.7%) with acute myocarditis were excluded from the analysis. Hemostasiological and hematological blood tests were studied upon admission, on the 2nd, 4th, 7th days from hospitalization. Blood samples for protein C, antithrombin, von Willebrand factor (WF), plasminogen, homocysteine were performed on 4th ± 1 day from hospitalization. To determine the IgG / IgM antibodies to cardiolipin and β2-glycoprotein for the diagnosis of APS, the ORGENTEC Anti-β2-Glycoprotein I IgG / IgM ELISA enzyme immunoassay was used. Blood tests for lupus anticoagulant were performed using an ACL-Top 700 analyzer (Werfen) with HemosIL SynthASil dRVVT screen reagents / dRVVT confirm  and with a SCT screen / SCT confirm quartz activator. Results In patients with MINOCA a statistically higher level of homocysteine (p = 0.03) and a lower level of plasminogen (p = 0.007) are determined. Protein C, antithrombin, WF the presence of lupus anticoagulant, antibodies to cardiolipin and β2-glycoprotein no differences between the groups were detected, p &gt;0.05. MINOCA patients have a statistically higher platelet level on the 2nd and 4th day of AMI (p = 0.046 and p = 0.01 ) however the level of hemoglobin and hematocrit was statistically lower on the 4th day of AMI, (p = 0.008). In the main group, a moderate correlation was found between protein C and antithrombin (r = 0.65, p = 0.0001), antithrombin and von Willebrand factor (r = 0.54, p = 0.0001), between protein C and platelet level by 4th day (r = - 0.49, p = 0.04). In MINOCA patients a moderate negative correlation was found between homocysteine and plasminogen (r = -0.69, p = 0.002). In the control group, a high correlation was found between protein C and antithrombin (r = 0.96, p = 0.0001), a moderate correlation between protein C and plasminogen (r = 0.47, p = 0.03). In addition, a relationship was revealed between the presence of thrombosis according to ICAG data and the level of ejection fraction (r = 0.46, p = 0.04) in the control group, as well as between the presence of thrombosis and the level of fibrinogen upon admission (r = 0.55, p = 0.008). Conclusions Patients with MINOCA have a higher level of homocysteine and a lower level of plasminogen. For such indicators as protein C, antithrombin III, WF the presence of antibodies on the APS is not defined differences between groups. According to laboratory data patients with MINOCA showed higher levels of platelets but lower levels of hemoglobin and hematocrit in the early post-infarction period.

Point-of-Care Diagnostic Assays and Novel Preclinical Technologies for Hemostasis and Thrombosis

2021 ◽  
Vol 47 (02) ◽  
pp. 120-128
Author(s):  
Christina Caruso ◽  
Wilbur A. Lam
Keyword(s):  
Point Of Care ◽  
Healing Process ◽  
Coagulation Factors ◽  
Wound Healing Process ◽  
Shear Stresses ◽  
Flow Conditions ◽  
Novel Technologies ◽  
Clinical Consequences ◽  
Complex Wound ◽  
Reproducible Analysis

AbstractHemostasis is a complex wound-healing process involving numerous mechanical and biochemical mechanisms and influenced by many factors including platelets, coagulation factors, and endothelial components. Slight alterations in these mechanisms can lead to either prothrombotic or bleeding consequences, and such hemostatic imbalances can lead to significant clinical consequences with resultant morbidity and mortality. An ideal hemostasis assay would not only address all the unique processes involved in clot formation and resolution but also take place under flow conditions to account for endothelial involvement. Global assays do exist; however, these assays are not flow based. Flow-based assays have been limited secondary to their large blood volume requirements and low throughput, limiting potential clinical applications. Microfluidic-based assays address the aforementioned limitations of both global and flow-based assays by utilizing standardized devices that require low blood volumes, offer reproducible analysis, and have functionality under a range of shear stresses and flow conditions. While still largely confined to the preclinical space, here we aim to discuss these novel technologies and potential clinical implications, particularly in comparison to the current, commercially available point-of-care assays.

The Stability of Flow Through Porous Screens

1960 ◽  
Vol 64 (594) ◽  
pp. 359-362 ◽  
Author(s):  
P. G. Morgan
Keyword(s):  
Pressure Drop ◽  
Sufficient Information ◽  
Flow Conditions ◽  
Flow Through ◽  
The Stability

In many cases of the flow through porous screens, one may consider it to be made up of a number of jets passing through the openings of the screen. These jets are separated by a series of wakes behind the solid parts of the screen. The majority of investigations on the flow through such screens have been concerned with the measurement of pressure drop and its variation with different flow conditions; it has been assumed that the pressure is discontinuous at the screen itself and that the pressure drop coefficient Δp/½ρυ2 provides sufficient information, where Δp is the pressure drop across the screen, ρ the density of the fluid, and υ the velocity of approach to the screen.

Renal and pressor effects of aminoguanidine in cirrhotic rats with ascites.

1996 ◽  
Vol 7 (12) ◽  
pp. 2694-2699
Author(s):  
M C Ortíz ◽  
L A Fortepiani ◽  
C Martínez ◽  
N M Atucha ◽  
J García-Estañ
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Liver Cirrhosis ◽  
Experimental Model ◽  
Systemic Blood Pressure ◽  
Arterial Hypotension ◽  
Control Group ◽  
No Production ◽  
Water Excretion ◽  
Excretory Function

Recent work indicates that nitric oxide (NO) plays an important role in the systemic and renal alterations of liver cirrhosis. This study used aminoguanidine (AG), a preferential inhibitor of inducible nitric oxide synthase (iNOS), to evaluate the role of this NOS isoform in the systemic and renal alterations of an experimental model of liver cirrhosis with ascites (carbon tetrachloride/ phenobarbital). Experiments have been performed in anesthetized cirrhotic rats and their respective control rats prepared for clearance studies. Administration of AG (10 to 100 mg/kg, iv) elevated dose-dependent mean arterial pressure (MAP, in mm Hg) in the cirrhotic rats from a basal level of 79.3 +/- 3.6 to 115.0 +/- 4.7, whereas in the control animals, MAP increased only with the highest dose of the inhibitor (from 121.8 +/- 3.6 to 133.3 +/- 1.4). In the cirrhotic group, AG also significantly increased sodium and water excretion, whereas these effects were very modest in the control group. Plasma concentration of nitrates+nitrites, measured as an index of NO production, were significantly increased in the cirrhotic animals in the basal period and decreased with AG to levels not significantly different from the control animals. Similar experiments performed with the nonspecific NOS inhibitor N omega-nitro-L-arginine (NNA) also demonstrated an increased pressor sensitivity of the cirrhotic rats, but the arterial hypotension was completely corrected. These results, in an experimental model of liver cirrhosis with ascites, show that AG exerts a beneficial effect as a result of inhibition of NO production, increasing blood pressure and improving the reduced excretory function. Because NNA, but not AG, completely normalized the arterial hypotension, it is suggested that the constitutive NOS isoform is also contributing in an important degree. It is concluded that the activation of both inducible and constitutive NOS isoforms plays an important role in the lower systemic blood pressure and associated abnormalities that characterize liver cirrhosis.

Gender influences coronary L-type Ca2+current and adaptation to exercise training in miniature swine

2001 ◽  
Vol 91 (6) ◽  
pp. 2503-2510 ◽  
Author(s):  
D. K. Bowles
Keyword(s):  
Smooth Muscle ◽  
Exercise Training ◽  
Endurance Training ◽  
Coronary Arteries ◽  
Current Density ◽  
Adaptive Response ◽  
Heart Weight ◽  
Internal Diameter ◽  
Resistance Arteries ◽  
Miniature Swine

Endurance exercise training increases smooth muscle L-type Ca2+current density in both resistance and proximal coronary arteries of female miniature swine. The purpose of the present study was to determine 1) whether gender differences exist in coronary smooth muscle (CSM) L-type Ca2+ current density and 2) whether endurance training in males would demonstrate a similar adaptive response as females. Proximal, conduit (∼1.0 mm), and resistance [∼200 μm (internal diameter)] coronary arteries were obtained from sedentary and treadmill-trained swine of both sexes. CSM were isolated by enzymatic digestion (collagenase plus elastase), and voltage-gated Ca2+-channel current ( I Ca) was determined by using whole cell voltage clamp during superfusion with 75 mM tetraethylammonium chloride and 10 mM BaCl2. Current-voltage relationships were obtained at test potentials from −60 to 70 mV from a holding potential of −80 mV, and I Ca was normalized to cell capacitance (pA/pF). Endurance treadmill training resulted in similar increases in heart weight-to-body weight ratio, endurance time, and skeletal muscle citrate synthase activity in male and female swine. I Ca density was significantly greater in males compared with females in both conduit (−7.57 ± 0.58 vs. −4.14 ± 0.47 pA/pF) and resistance arteries (−11.25 ± 0.74 vs. −6.49 ± 0.87 pA/pF, respectively). In addition, voltage-dependent activation of I Ca in resistance arteries was shifted to more negative membrane potentials in males. Exercise training significantly increased I Ca density in both conduit and resistance arteries in females (−7.01 ± 0.47 and −9.73 ± 1.13 pA/pF, respectively) but had no effect in males (−8.61 ± 0.50 and −12.04 ± 1.07 pA/pF, respectively). Thus gender plays a significant role in determining both the magnitude and voltage dependence of I Ca in CSM and the adaptive response of I Ca to endurance training.

scholarly journals A Computational Model to Assess Poststenting Wall Stresses Dependence on Plaque Structure and Stenosis Severity in Coronary Artery

2014 ◽  
Vol 2014 ◽  
pp. 1-12
Author(s):  
Zuned Hajiali ◽  
Mahsa Dabagh ◽  
Payman Jalali
Keyword(s):  
Coronary Arteries ◽  
Computational Models ◽  
Strong Dependence ◽  
Internal Stresses ◽  
Shear Stresses ◽  
Stress Concentrations ◽  
Opening Pressure ◽  
Fibrous Cap ◽  
Stent Restenosis ◽  
Von Mises

The current study presents computational models to investigate the poststenting hemodynamic stresses and internal stresses over/within the diseased walls of coronary arteries which are in different states of atherosclerotic plaque. The finite element method is applied to build the axisymmetric models which include the plaque, arterial wall, and stent struts. The study takes into account the mechanical effects of the opening pressure and its association with the plaque severity and the morphology. The wall shear stresses and the von Mises stresses within the stented coronary arteries show their strong dependence on the plaque structure, particularly the fibrous cap thickness. Higher stresses occur in severely stenosed coronaries with a thinner fibrous cap. Large stress concentrations around the stent struts cause injury or damage to the vessel wall which is linked to the mechanism of restenosis. The in-stent restenosis rate is also highly dependent on the opening pressure, to the extent that stenosed artery is expanded, and geometry of the stent struts. The present study demonstrates, for the first time, that the restenosis is to be viewed as a consequence of biomechanical design of a stent repeating unit, the opening pressure, and the severity and morphology of the plaque.

Prediction of Fluid Flow in Artificial Cancellous Bone

2014 ◽  
Vol 695 ◽  
pp. 393-397
Author(s):  
Elsa Syuhada Abdull Yamin ◽  
Nor Azwadi Che Sidik
Keyword(s):  
Fluid Flow ◽  
Pore Size ◽  
Surface Area ◽  
Pore Diameter ◽  
Bone Surface ◽  
Flow Conditions ◽  
Morphological Aspects ◽  
Flow Through ◽  
Structure Result ◽  
Dynamics Method

The permeability of the blood in the artificial cancellous are affected by certain morphological aspects that include pore diameter, pore size, porosity and the bone surface area. In this study, computational fluid dynamics method is used to study the fluid flow through the cancellous structure. Result of the present work show that geometries with the same porosity and overall volume can have different permeability due to the differences in bone surface area. The hexahedron geometry has the highest permeability under stimulated blood flow conditions, where the cylindrical geometry has the lowest. Linear relationship is found between permeability and the two physical properties, bone surface area and the pore size.

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