Impact of plaques in the left coronary artery on wall shear stress and pressure gradient in coronary side branches

In this study, we investigate plaques located at the left coronary bifurcation. We focus on the effect that the resulting changes in wall shear stress (WSS) and wall pressure stress gradient (WPSG) have on atherosclerotic progress in coronary artery disease. Coronary plaques were simulated and placed at the left main stem and the left anterior descending to produce >50% narrowing of the coronary lumen. Computational fluid dynamics analysis was carried out, simulating realistic physiological conditions that show the in vivo cardiac haemodynamic. WSS and WPSG in the left coronary artery were calculated and compared in the left coronary models, with and without the presence of plaques during cardiac cycles. Our results showed that WSS decreased while WPSG was increased in coronary side branches due to the presence of plaques. There is a direct correlation between coronary plaques and subsequent WSS and WPSG variations based on the bifurcation plaques simulated in the realistic coronary models.     

Fluid–structure interaction analysis of the left coronary artery with variable angulation

The aim of this study is to elucidate the correlation between coronary artery branch angulation, local mechanical and haemodynamic forces at the vicinity of bifurcation. Using a coupled fluid–structure interaction (FSI) modelling approach, five idealized left coronary artery models with various angles ranging from 70° to 110° were developed to investigate the influence of branch angulations. In addition, one CT image-based model was reconstructed to further demonstrate the medical application potential of the proposed FSI coupling method. The results show that the angulation strongly alters its mechanical stress distribution, and the instantaneous wall shear stress distributions are substantially moderated by the arterial wall compliance. As high tensile stress is hypothesized to cause stenosis, the left circumflex side bifurcation shoulder is indicated to induce atherosclerotic changes with a high tendency for wide-angled models.     

Components of flow-induced dilation in rat perfused coronary artery

This study was undertaken to determine the endothelial factors involved in the flow-induced dilation of a rat perfused coronary artery. Segments of the right interventricular coronary artery were taken from 10–15-week-old male Wistar rats. Vessels were mounted in an arteriograph where internal diameter was continuously monitored while intraluminal pressure was controlled. Vessels were preconstricted with serotonin (10 mol/L), and the dilation induced by flow (0–800 l/min) was quantified. This dilator effect was measured in control conditions, after incubation with L-NAME (100 mol/L), with indomethacin (100µmol/L), and after mechanical destruction of the endothelium (–E). Dilations were expressed as percentage of the serotonin-induced constriction, and wall shear stress due to the physical forces exerted on the wall of the vessel was calculated and expressed in dyn/cm².In control conditions, raising the flow up to 800 l/min led to an increase in dilation (maximal dilation 63% ± 4%) and in sheer stress (maximal shear stress 76 ±4dyn/cm²). With indomethacin, maximal dilation was 69% ± 4% and maximal shear stress was 81 ± 6 dyn/cm². With L-NAME or after destruction of endothelium, dilation was greatly reduced (39% ± 3% and 40% ± 2%, respectively) whereas shear stress values were greatly increased (173 ± 14 and 150 ± 13 dyn/cm², respectively).These results confirm the viability of this model for the study of flow-dependent dilation. This dilation seems to be greatly dependent on NO release. In contrast, results do not favor a significant involvement of prostanoid vasodilating substance. Without endothelium, a dilation was still observed and showed the persistence of an endothelium-independent component of flow-induced dilation in this preparation that remains to be determined.Abbreviations Ach acetylcholine - BSA bovine serum albumin - EDRF endothelium-derived relaxing factor - EDHF endothelium-derived hyperpolarizing factor - L-NAME N -nitro-L-arginine-methyl ester - NO nitric oxide - PSS physiological salt solution - PGI₂ prostacyclin - 5-HT serotonin - SNP sodium nitroprusside - TXA₂ thromboxane A₂     

Haemodynamic assessment of human coronary arteries is affected by degree of freedom of artery movement

Abnormal haemodynamic parameters are associated with atheroma plaque progression and instability in coronary arteries. Flow recirculation, shear stress and pressure gradient are understood to be important pathogenic mediators in coronary disease. The effect of freedom of coronary artery movement on these parameters is still unknown. Fluid–structure interaction (FSI) simulations were carried out in 25 coronary artery models derived from authentic human coronaries in order to investigate the effect of degree of freedom of movement of the coronary arteries on flow recirculation, wall shear stress (WSS) and wall pressure gradient (WPG). Each FSI model had distinctive supports placed upon it. The quantitative and qualitative differences in flow recirculation, maximum wall shear stress (MWSS), areas of low wall shear stress (ALWSS) and maximum wall pressure gradient (MWPG) for each model were determined. The results showed that greater freedom of movement was associated with lower MWSS, smaller ALWSS, smaller flow recirculation zones and lower MWPG. With increasing percentage diameter stenosis (%DS), the effect of degree of freedom on flow recirculation and WSS diminished. Freedom of movement is an important variable to be considered for computational modelling of human coronary arteries, especially in the setting of mild to moderate stenosis.

Abbreviations: 3D: Three-dimensional; 3DR: Three-dimensional Reconstruction; 3D-QCA: Three-dimensional quantitative coronary angiography; ALWSS: Areas of low wall shear stress; CAD: Coronary artery disease; CFD: Computational fluid dynamics; %DS: Diameter stenosis percentage; EPCS: End point of counter-rotating streamlines; FSI: Fluid–structure interaction; IVUS: Intravascular ultrasound; LAD: Left anterior descending; MWSS: Maximum wall shear stress; SST: Shear stress transport; TAWSS: Time-averaged wall shear stress; WSS: wall shear stress; WPG: Wall pressure gradient; MWPG: Maximum wall pressure gradient; FFR: Fractional flow reserve; iFR: Instantaneous wave-free ratio     

Effect of temporary reductions in feeding on protein synthesis and energy storage of juvenile Atlantic salmon

Biochemical and tissue-composition indices were used to determine the impacts of temporary feeding reductions on juvenile Atlantic salmon (4.2g initial weight). Three levels of food reduction (fasting, 20% of control, 50% of control) lasting for 2, 4 or 8 days were compared to a control group (constant feeding at 2.75% of body weight day⁻¹). Ornithine decarboxylase (ODC) activity and RNA concentrations were used to measure changes in protein synthesis; condition factor ( K) , liver-somatic index (LSI), visceral-somatic index (VSI), and gut index (GI)were used to provide information on stored energy levels. Results showed that physiological adjustments to decreases or increases in feeding occur very quickly. The most rapid responses were changes in ODC activity (within 2 days) and LSI (2–4 days). Changes in RNA concentrations and K required 4–8 days. There was no apparent effect of the treatments on VSI or GI. Temporary reductions of feeding lasting 2 days or less would not be detected by any index except ODC activity. Changes in the indices are discussed with respect to short-term changes in rates of protein synthesis and energy storage.     

The influence of aortic dimensions on calculated wall shear stress in the mouse aortic arch

In this paper, the influence of the aortic dimensions of an investigated mouse on its resulting wall shear stress (WSS) was studied. A numerical model of a mouse aortic arch was created based on a micro-CT scan of a vascular corrosion cast of an 8-week-old wild type mouse. This model was then rescaled to obtain five models with aortic root diameters corresponding to five different stages in the mouse life cycle varying from late fetal (0.7 mm) to old adult (1.5 mm). Consistent with literature, WSS values much higher than those normally encountered in humans were found. WSS was found to decrease rapidly in early life stages and to reach a plateau in adulthood, thus supporting a mediating role for WSS in arterial growth. Our results show that WSS values for mice should be interpreted very cautiously, and if possible an animal-specific geometry with animal-specific boundary conditions should be used.     

Differences in the responses of stem diameter and pod thickness to drought stress during the grain filling stage in soybean plants

This study investigated the factor of the physiological characteristics causing the reduction of yield of soybean plants (Glycine max (L.) Merr.) by drought stress, by monitoring changes in stem diameter and pod thickness, and photosynthetic activity, partitioning of ¹³C-labeled photosynthate. Drought stress reduced the whole plant dry weight due to the decrease in leaf and pod dry matter accumulation; however, this stress did not have a significant effect on stem growth. Leaf photosynthesis was also severely decreased by drought stress in the early stage of stress treatment as leaf water potential decreased. Imposition of stress decreased pod thickness, but stem diameter increased. The adverse effect of drought stress on pod thickness was more evident at night than during the day. The stem diameter also shrank during the day and expanded at night, but the nocturnal increase in stem diameter during drought stress treatment was greater for stressed plants compared with well-watered controls. Drought stress significantly promoted ¹³C partitioning from the fed leaf to other parts of the plant; the stem was the largest beneficiary. Soluble carbohydrates accumulated in various plant parts under the influence of the stress, but starch concentration declined in all organs except the stem. These results indicated that stem growth was promoted by drought stress compared to pod growth at the early grain-filling stage.     

Biomechanical behaviour of cerebral aneurysm and its relation with the formation of intraluminal thrombus: a patient-specific modelling study

Cerebral aneurysm is an irreversible dilatation causing intracranial haemorrhage with severe complications. It is assumed that the biomechanical factor plays a significant role in the development of cerebral aneurysm. However, reports on the correlations between the formation of intraluminal thrombus and the flow pattern, wall shear stress (WSS) distribution of the cerebral aneurysm as well as wall compliance are still limited. In this research, patient-specific numerical simulation was carried out for three cerebral aneurysms based on magnetic resonance imaging (MRI) data-sets. The interaction between pulsatile blood and aneurysm wall was taken into account. The biomechanical behaviour of cerebral aneurysm and its relation with the formation of intraluminal thrombus was studied systematically. The results of the numerical simulation indicated that the region of low blood flow velocity and the region of swirling recirculation were nearly coincident with each other. Besides, there was a significant correlation between the slow swirling flow and the location of thrombus deposition. Excessively low WSS was also found to have strong association with the regions of thrombus formation. Moreover, the relationship between cerebral aneurysm compliance and thrombus deposition was discovered. The patient-specific modelling study based on fluid–structure interaction) may provide a basis for future investigation on the prediction of thrombus formation in cerebral aneurysm.     

Dynamic response of wall shear stress on the stenosed artery

The present study deals with an appropriate mathematical model of an artery in the presence of constriction in which the generated wall shear stress due to blood flow is analysed. The geometry of the stenosed arterial segment in the diseased state, causing malfunction of the cardiovascular system, is formed mathematically. The flowing blood contained in the stenosed artery is treated as non-Newtonian and the flow is considered to be two-dimensional. The motion of the arterial wall and its effect on local fluid mechanics is not ruled out from the present pursuit. The flow analysis applies the time-dependent, two-dimensional incompressible nonlinear Navier–Stokes equations for non-Newtonian fluids. The flow-field can be obtained primarily following the radial coordinate transformation, using the appropriate boundary conditions and finally adopting a suitable finite difference scheme numerically. The influences of flow unsteadiness, the arterial wall distensibility and the presence of stenosis on the flow-field and the wall shear stresses are quantified in order to indicate the susceptibility to atherosclerotic lesions and thereby to validate the applicability of the present theoretical model.     

Polyamine metabolism and gene regulation during the transition of autonomous sugar beet cells in suspension culture from quiescence to division

Sugar beet cells grown in batch suspension culture have been used to study the regulation of polyamine levels during the transition from a quiescent to a proliferating state. The quiescent state was achieved by maintenance of the phytohormone autonomous cells in the stationary phase of the batch culture cycle. After subculture into fresh medium there was an increase in DNA synthesis which was accompanied by a dramatic increase in cellular polyamine levels. The levels of both free and bound cellular putrescine and spermidine within the cells reached a peak before the onset of the first synchronous division. The levels of putrescine, spermidine and to some extent spermine in the culture medium also increased dramatically shortly after subculture. The increase in polyamines was preceded by a rapid but transient increase in omithine decarboxylase (EC 4.1.1.17) and S -adenosylmethionine decarboxylase (EC 4.1.1.50). Arginine decarboxylase (EC 4.1.1.19) and S -adenosylmethionine synthetase (EC 2.5.1.6) activity did not show the same pattern of cell division-related variation. Inhibition of S -adenosylmethionine biosynthesis with methylglyoxal bis-(guanylhydra-zone) (MGBG) reduced cell division in the suspension culture. Inhibitors of ornithine decarboxylase and arginine decarboxylase individually had little effect on cell division, but in combination led to a reduction in cell division. Addition of polyamines and their precursors to cells in the stationary phase of a batch culture cycle led to the induction of expression of a mitotic cyclin sequence ( Bvcycll ).     

Polyamine metabolism and gene regulation during the transition of autonomous sugar beet cells in suspension culture from quiescence to division

Sugar beet cells grown in batch suspension culture have been used to study the regulation of polyamine levels during the transition from a quiescent to a proliferating state. The quiescent state was achieved by maintenance of the phytohormone autonomous cells in the stationary phase of the batch culture cycle. After subculture into fresh medium there was an increase in DNA synthesis which was accompanied by a dramatic increase in cellular polyamine levels. The levels of both free and bound cellular putrescine and spermidine within the cells reached a peak before the onset of the first synchronous division. The levels of putrescine, spermidine and to some extent spermine in the culture medium also increased dramatically shortly after subculture. The increase in polyamines was preceded by a rapid but transient increase in omithine decarboxylase (EC 4.1.1.17) and S -adenosylmethionine decarboxylase (EC 4.1.1.50). Arginine decarboxylase (EC 4.1.1.19) and S -adenosylmethionine synthetase (EC 2.5.1.6) activity did not show the same pattern of cell division-related variation. Inhibition of S -adenosylmethionine biosynthesis with methylglyoxal bis-(guanylhydra-zone) (MGBG) reduced cell division in the suspension culture. Inhibitors of ornithine decarboxylase and arginine decarboxylase individually had little effect on cell division, but in combination led to a reduction in cell division. Addition of polyamines and their precursors to cells in the stationary phase of a batch culture cycle led to the induction of expression of a mitotic cyclin sequence ( BvcycII ).     

Numerical investigations of the haemodynamic changes associated with stent malapposition in an idealised coronary artery

The deployment of a coronary stent near complex lesions can sometimes lead to incomplete stent apposition (ISA), an undesirable side effect of coronary stent implantation. Three-dimensional computational fluid dynamics (CFD) calculations are performed on simplified stent models (with either square or circular cross-section struts) inside an idealised coronary artery to analyse the effect of different levels of ISA to the change in haemodynamics inside the artery. The clinical significance of ISA is reported using haemodynamic metrics like wall shear stress (WSS) and wall shear stress gradient (WSSG). A coronary stent with square cross-sectional strut shows different levels of reverse flow for malapposition distance (MD) between 0 mm and 0.12 mm. Chaotic blood flow is usually observed at late diastole and early systole for MD=0 mm and 0.12 mm but are suppressed for MD=0.06 mm. The struts with circular cross section delay the flow chaotic process as compared to square cross-sectional struts at the same MD and also reduce the level of fluctuations found in the flow field. However, further increase in MD can lead to chaotic flow not only at late diastole and early systole, but it also leads to chaotic flow at the end of systole. In all cases, WSS increases above the threshold value (0.5 Pa) as MD increases due to the diminishing reverse flow near the artery wall. Increasing MD also results in an elevated WSSG as flow becomes more chaotic, except for square struts at MD=0.06 mm.     

Novel insights into interactions between mitochondria and xanthine oxidase in acute cardiac volume overload

Xanthine oxidoreductase (XOR) is increased in the left ventricle (LV) of humans with volume overload (VO), and mitochondrial inhibition of the respiratory chain occurs in animal models of VO. Because mitochondria are both a source and a target of reactive oxygen and nitrogen species, we hypothesized that activation of XOR and mitochondrial dysfunction are interdependent. To test this we used the aortocaval fistula (ACF) rat model of VO and a simulation of the stretch response in isolated adult cardiomyocytes with and without the inhibitor of XOR, allopurinol, or the mitochondrially targeted antioxidant MitoQ. Xanthine oxidase (XO) activity was increased in cardiomyocytes from ACF vs sham rats (24h) without an increase in XO protein. A twofold increase in LV end-diastolic pressure/wall stress and a decrease in LV systolic elastance with ACF were improved when allopurinol treatment (100mg/kg) was started at ACF induction. Subsarcolemmal State 3 mitochondrial respiration was significantly decreased in ACF and normalized by allopurinol. Cardiomyocytes subjected to 3h cyclical stretch resulted in an increase in XO activity and mitochondrial swelling, which was prevented by allopurinol or MitoQ pretreatment. These studies establish an early interplay between cardiomyocyte XO activation and bioenergetic dysfunction that may provide a new target that prevents progression to heart failure in VO.     

Thioredoxin-interacting protein promotes activation and inflammation of monocytes with DNA demethylation in coronary artery disease

Numerous studies have demonstrated that thioredoxin-interacting protein (TXNIP) expression of peripheral blood leucocytes is increased in coronary artery disease (CAD). However, the molecular mechanism of this phenomenon remained unclear. DNA methylation plays important roles in the regulation of gene expression. Therefore, we speculated there might be a close association between the expression of TXNIP and methylation. In this study, we found that compared with controls, DNA methylation at cg19693031 was decreased in CAD, while mRNA expressions of TXNIP and inflammatory factors, NLRP3, IL-1β, IL-18, were increased. Methylation at cg19693031 was negatively associated with TXNIP expression in the cohort, THP-1 and macrophages/foam cells. Furthermore, Transwell assay and co-cultured adhesion assay were performed to investigate functions of TXNIP on the migration of THP-1 or the adhesion of THP-1 on the surface of endothelial cells, respectively. Notably, overexpressed TXNIP promoted the migration and adhesion of THP-1 cells and expressions of NLRP3, IL-18 and IL-1β. Oppositely, knock-down TXNIP inhibited the migration and adhesion of THP-1 and expressions of NLRP3, IL-18. In conclusion, increased TXNIP expression, related to cg19693031 demethylation orientates monocytes towards an inflammatory status through the NLRP3 inflammasome pathway involved in the development of CAD.     

Exercise through a cardiac rehabilitation program attenuates oxidative stress in patients submitted to coronary artery bypass grafting*

Background: Cardiovascular disease is the main cause of morbidity and mortality in the world and oxidative stress has been implicated in the pathogenesis. Cardiac rehabilitation in patients with coronary artery disease submitted to coronary artery bypass grafting may prevent cardiovascular events probably through the attenuation of oxidative stress. The aim of this study was to evaluate the benefits of a cardiac rehabilitation program in the control of the systemic oxidative stress.

Methods: The studied population consisted of 40 patients, with chronic stable coronary artery disease submitted to coronary artery bypass grafting, who attended a cardiac rehabilitation program. Biomarkers of oxidative stress were evaluated in the blood of these patients at different moments.

Results: After the onset of cardiac rehabilitation, there was a significant and progressive decrease in thiobarbituric acid reactive substances levels and protein carbonyls, an initial increase and subsequent decrease in superoxide dismutase, catalase and glutathione peroxidase activities. Also, a progressive increase of uric acid, while ferric reducing antioxidant power levels increased only at the end of the cardiac rehabilitation and a tendency to increase of glutathione contents.

Conclusions: The results suggest that regular exercise through a cardiac rehabilitation program can attenuate oxidative stress in chronic coronary artery disease patients submitted to coronary artery bypass grafting.     

Regulation of protein synthesis in root, shoot and embryonic tissues of germinating barley during salinity stress

Abstract Protein synthesis during seed germination, a stage vulnerable to salinity stress, was investigated. The responses of barley genotypes, CM72 (California Mariout 72) and Prato, toward salinity were different during seed germination. Germination of CM72 was unaffected up to 0.34 kmol m^?3 (2%) NaCl, but that of Prato was reduced 30% by 0.17 kmol m ³ NaCl and 75% by 0.34 kmol m^?3 NaCl. Therefore, the former genotype is relatively more salt-tolerant than the latter. Protein synthesis in roots, shoots, and embryos was investigated in these two genotypes before and after salinity stress. The uptake of S-methionine and its incorporation into protein were significantly reduced by salinity in both genotypes. The inhibition of global protein synthesis was significant in roots and shoots. Proteins from different tissues were resolved by single and two dimensional gels. The steady-state protein levels were maintained remarkably well during salinity stress in roots and shoots. Likewise, proteins in germinating embryos were stable except for a 42-kilodalton protein unique to the salt tolerant genotype which was apparently degraded during salinity stress. Salinity, around 0.34 kmol m^?3 NaCl, induced both quantitative and qualitative changes in the expression of some proteins labelled in vivo. The quantitative changes included repression or enhancement of synthesis of selected groups of proteins. Around 8% of the nearly 400 resolved proteins in a tissue was affected this way. Some of the proteins in this category were specific to each genotype. About 1 % of the total showed qualitative changes; these proteins were expressed only during salinity stress. In roots, two proteins (28, 41.7 kilodaltons) were detected in CM72 and five (28, 45, 60.5, 76.5, 82.5 kilodaltons) in Prato; only the 28-kilodalton protein was common to both genotypes. In shoots, four proteins (45, 60.5, 76.5, 82.5 kilodaltons) were found only in Prato and these were similar to those induced in roots. The four new proteins (32, 37.5, 89, 92 kilodaltons) in germinating embryos were apparently induced only in CM72; these were distinctly different from those detected in developed roots and shoots. The unique protein changes induced by salinity stress during germination (this study) and seedling growth studies reported earlier (Ramagopal, 1987b) are apparently different. The findings demonstrate that ontogeny plays an important role in the expression of tissue-specific proteins during salinity stress in the salt tolerant and sensitive barley genotypes.