Dietary supplementation with copper nanoparticles influences the markers of oxidative stress and modulates vasodilation of thoracic arteries in young Wistar rats.

We aimed to study the physiological effects of diet supplemented with copper (Cu) nanoparticles (NPs). During the eight weeks of the experiment, young Wistar rats (at seven weeks of age, n = 9) were supplemented with 6.5 mg of Cu either as NPs or carbonate salt (Cu6.5). A diet that was not supplemented with Cu served as a negative control (Cu0). The impact of nano Cu supplementation on lipid (reflected as thiobarbituric acid reactive substances-TBARS) and protein peroxidation (thiol and carbonyl groups) in blood plasma as well as the influence on the vasodilatory mechanism(s) of isolated rat thoracic arteries were studied. Supplementation with Cu enhanced lipid peroxidation (TBARS) in NP6.5 (x2.4) and in Cu6.5 (x1.9) compared to the negative control. Significant increase in TBARS was also observed in NP6.5 (x1.3) compared to the Cu6.5 group. The level of thiol groups increased in NP6.5 (x1.6) compared to Cu6.5. Meanwhile, significant (x0.6) decrease was observed in the Cu6.5 group compared to the negative control. Another marker of protein oxidation, carbonyl groups increased in NP6.5 (x1.4) and Cu6.5 (x2.3) compared to the negative control. However significant difference (x0.6) was observed between NP6.5 and Cu6.5. Arteries from Cu supplemented rats exhibited an enhanced vasodilation to gasotransmitters: nitric oxide (NO) and carbon monoxide (CO). An enhanced vasodilation to NO was reflected in the increased response to acetylcholine (ACh) and calcium ionophore A23187. The observed responses to ACh and CO releasing molecule (CORM-2) were more pronounced in NP6.5. The activator of cGMP-dependent protein kinases (8-bromo-cGMP) induced similar vasodilation of thoracic arteries in NP6.5 and Cu0 groups, while an increased response was observed in the Cu6.5 group. Preincubation with the inducible nitric oxide (iNOS) synthase inhibitor- 1400W, decreased the ACh-induced vasodilation in NP6.5, exclusively. Meanwhile the eicosanoid metabolite of arachidonic acid (20-HETE) synthesis inhibitor-HET0016, enhanced vasodilation of arteries from Cu0 group. In conclusion, this study demonstrates that supplementation with nano Cu influences oxidative stress, which further has modified the vascular response.

Resveratrol modulates the blood plasma levels of Cu and Zn, the antioxidant status and the vascular response of thoracic arteries in copper deficient Wistar rats.

Copper (Cu) deficiency plays an important role in the development of cardiovascular disorders. Resveratrol (RSV) possesses pleiotropic cardiovascular benefits; however, the mechanism(s) by which RSV exerts protective effects are not completely understood. Male Wistar rats at 6 weeks of age were fed for 8 weeks with a Cu deficient diet (no added Cu, Cu = 0). In addition, Cu deficient rats were supplemented with RSV (500 mg/kg of diet, n = 9). Blood and intestinal samples were taken for further analysis together with internal organs and thoracic arteries. RSV supplementation resulted in elevated blood plasma levels of Cu (x2.1) and Zn (x1.1), in an increased activity of superoxide dismutase (SOD, x1.5) and ferric reducing antioxidant power (FRAP, x1.2). Meanwhile, markers of lipid peroxidation expressed as malondialdehyde (MDA, x1.5) and lipid hydroperoxides (LOOH, x1.1) were also increased in a significant way. Food intake, body weight, blood glucose, catalase, ceruloplasmin, lipid profile and intestinal samples were not modified. RSV enhanced the vasoconstriction of isolated thoracic arteries to noradrenaline (x1.4), potentiated the vasodilation to acetylcholine (ACh, x1.4) and increased the sensitivity to sodium nitroprusside (SNP). In addition, preincubation with the cyclooxygenase (COX)-inhibitor, indomethacin, potentiated the ACh-induced vasodilation, which was more pronounced in animals not supplemented with RSV. The KATP channel opener, pinacidil, induced a similar response in both studied groups. In conclusion, this study demonstrates that RSV supplementation influences oxidative stress and the antioxidant status, which may modify the vascular response in Cu deficiency.

PPARδ agonist prevents endothelial dysfunction via induction of dihydrofolate reductase gene and activation of tetrahydrobiopterin salvage pathway.

BACKGROUND AND PURPOSE: Impaired endothelium-dependent relaxation (EDR) is a hallmark of endothelial dysfunction. A deficiency of tetrahydrobiopterin (BH4 ) causes endothelial NOS to produce ROS rather than NO. PPARδ is an emerging target for pharmacological intervention of endothelial dysfunction. Thus, the present study examined the role of PPARδ in the regulation of dihydrofolate reductase (DHFR), a key enzyme in the BH4 salvage pathway. EXPERIMENTAL APPROACH: Gene expression was measured by using qRT-PCR and western blotting. Biopterins and ROS were determined by using HPLC. NO was measured with fluorescent dye and electron paramagnetic resonance spectroscopy. Vasorelaxation was measured by Multi Myograph System. KEY RESULTS: The PPARδ agonist GW501516 increased DHFR and BH4 levels in endothelial cells (ECs). The effect was blocked by PPARδ antagonist GSK0660. Chromatin immunoprecipitation identified PPAR-responsive elements within the 5'-flanking region of the human DHFR gene. The promoter activity was examined with luciferase assays using deletion reporters. Importantly, DHFR expression was suppressed by palmitic acid (PA, a saturated fatty acid) but increased by docosahexaenoic acid (DHA, a polyunsaturated fatty acid). GSK0660 prevented DHA-induced increased DHFR expression. Conversely, the suppressive effect of PA was mitigated by GW501516. In mouse aortae, GW501516 ameliorated the PA-impaired EDR. However, this vasoprotective effect was attenuated by DHFR siRNA or methotrexate. In EC-specific Ppard knockout mice, GW501516 failed to improve vasorelaxation. CONCLUSION AND IMPLICATIONS: PPARδ prevented endothelial dysfunction by increasing DHFR and activating the BH4 salvage pathway. These results provide a novel mechanism for the protective roles of PPARδ against vascular diseases.

Histomorphometric analysis of the human internal thoracic artery and relationship with cardiovascular risk factors.

In this study, we aimed at performing a histomorphometric analysis of human left internal thoracic artery (ITA) samples as well as at correlating the histomorphometric findings with the clinical profile, including risk factors and medication. Distal segments of ITA were obtained from 54 patients undergoing coronary artery bypass grafting. Histological observation was performed in paraffin-embedded transverse sections of ITA through four staining protocols: hematoxylin-eosin, van Gieson, Masson's trichrome and von Kossa. Morphometric analysis included the intimal width (IW), medial width (MW) and intima/media ratio (IMR). No overt atherosclerotic lesions were observed. Mild calcifications were observed across the vascular wall layers in almost all samples. Multivariable linear regression analysis showed associations between IW and IMR and the following clinical variables: age, gender, kidney function expressed as eGFR and myocardial infarction history. Age (odds ratio = 1.16, P = 0.004), female gender (odds ratio = 11.34, P = 0.011), eGFR (odds ratio = 1.03, P = 0.059) and myocardial infarction history (odds ratio = 4.81, P = 0.040) were identified as the main clinical predictors for intimal hyperplasia. Preatherosclerotic lesions in ITA samples from patients undergoing coronary revascularization were associated not only with classical cardiovascular risk factors such as age and gender, but also with other clinical variables, namely kidney function and myocardial infarction history.

Effect of Low-Intensity Cavitation on the Isolated Human Thoracic Artery In Vitro.

Reported here are the results of an experimental study on the response to low-intensity cavitation induced by low-frequency (4-6 W/cm2, 20 kHz and 32.6 kHz) ultrasound of isolated human arterial samples taken during conventional myocardial revascularization operations. Studies have found that low-frequency ultrasound results in a significant (48%-54%) increase in isometric contraction force and does not depend on the number of exposures (10 or 20) or the time passed since the start of ultrasound (0, 10 and 20 min), but does depend on the frequency and location (internal or external) of the blood vessels for the application of ultrasound. Diltiazem (an inhibitor of slow calcium channels) and carbachol (an agonist of muscarinic receptors) used in a concentration-dependent manner did not modify the relaxation dynamics of smooth muscle affected by ultrasound. Thus, ultrasound conditioned to the augmentation of the isometric contraction force the smooth muscle of blood vessels and did not improve endothelial- and calcium channel blocker-dependent relaxation.

Quantitative Assessment of Iron-Labeled Stem-Cell Adhesion at the Vessel Wall in a Vascular Flow Model: Correlation of T2*-Weighted Imaging at 3 T and Histology.

PURPOSE: To evaluate the distribution of superparamagnetic iron oxide (SPIO)-labeled cells in a perfused segment of a porcine artery and to estimate the number of adherent cells by means of magnetic resonance (MR) imaging. MATERIALS AND METHODS: Six vessel specimens (diameters between 0.8 and 1.2 cm) were placed in a bioreactor system, and 2 × 10(4) to 1 × 10(6) SPIO-labeled endothelial colony-forming cells were injected into the artery within the perfused reactor. The area of resulting signal extinctions at the inner wall of the vessels was quantified on MR images by using a high-resolution T2*-weighted sequence with a slice-by-slice approach. After imaging, the labeled cells were quantified histologically. RESULTS: The total iron load of each cell was 56.5 pg ± 14.4. In the applied range of 2 × 10(4) to 1 × 10(6) cells per vessel, the area of iron-induced signal extinction at the vessel wall on T2*-weighted imaging corresponded to the histologically detected cell number (r = 0.98, P < .001). CONCLUSIONS: A correlation between the area of signal extinction and the number of labeled cells at the vessel wall was found. This might help to evaluate dose rates in further clinical applications of intravascular cell-based therapies.

Hox control of Drosophila larval anatomy; The Alary and Thoracic Alary-Related Muscles.

The body plan of arthropods and vertebrates involves the formation of repetitive segments, which subsequently diversify to give rise to different body parts along the antero-posterior/rostro-caudal body axis. Anatomical variations between body segments are crucial for organ function and organismal fitness. Pioneering work in Drosophila has established that Hox transcription factors play key roles both in endowing initially identical segments with distinct identities and organogenesis. The focus of this review is on Alary Muscles (AMs) and the newly discovered Thoracic Alary-Related Muscles (TARMs). AMs and TARMs are thin muscles which together connect the circulatory system and different midgut regions to the exoskeleton, while intertwining with the respiratory tubular network. They were hypothesized to represent a new type of muscles with spring-like properties, maintaining internal organs in proper anatomical positions during larval locomotion. Both the morphology of TARMs relative to AMs, and morphogenesis of connected tissues is under Hox control, emphasizing the key role of Hox proteins in coordinating the anatomical development of the larva.

Clinical analysis of 33 flow-through latissimus dorsi flaps.

INTRODUCTION: Indications for flow-through latissimus dorsi (LD) flaps have been limited for reconstructing distal extremities. In addition, there has been little discussion in regard to the question of which branch is most suitable as a distal runoff of the flow-through anastomosis. The aims of this study were to investigate the feasibility of flow-through LD flaps in various areas in the body and the rationale for branch selection for the distal runoff vessel. METHODS: This retrospective study included 33 patients who underwent reconstruction of an oncology-related defect with a free flow-through LD flap. Defect locations, branches used for the distal runoff, and postoperative complications were investigated. RESULTS: The defect location was in the lower extremity in 13 patients, the scalp in seven, the upper extremity in six, the pelvis in six, and the chest in one. In 19 of the 33 patients, the defects were located in areas other than the distal extremities. The circumflex scapular artery (CSA) was most frequently used as the distal runoff vessel (24 patients) followed by the serratus anterior branch (SAB) (five patients). All flaps were transferred successfully without anastomotic failure. CONCLUSIONS: The flow-through LD flap is a reliable option for reconstruction in many areas of the body. It can provide high success rates not only for extremity reconstruction but also for scalp and pelvic reconstruction. The CSA matches well with the workhorse recipient vessels. The SAB is suitable when there is a vascular defect of the recipient artery.

The role of external Ca²âº in the action of Ca²âº-channel agonists and antagonists on isolated human thoracic arteries.

In systemic atherosclerosis develops the abnormal vascular tone which is associated with elevated calcium influx into smooth muscle cells and their calcification that may be proportional to the extent and severity of atherosclerotic disease. The goal of the present study was to investigate the responses of isolated human arterial samples to Ca²âº-channel agonists and antagonists by varying the external Ca²âº concentration. Two dihydropyridine type calcium-channel blockers, amlodipine and cerebrocrast, were used in this study. The benzodiazepine-type calcium-channel blocker diltiazem, the benzimidazole derivative 1-acetyl-5,6-dimethoxy-2-methylthiobenzimidazole and 3,4'-bipyridine derivative milrinone were also used. Experiments were carried out on isolated human thoracic artery samples obtained from 74 patients, aged 38-88 years, during conventional myocardial revascularisation operations. The contraction of artery samples was recorded using an iFOT10 force transducer. Cumulative concentration-contraction curves of the tested agents (10⁻7 to 10⁻4 M) were established by varying the external Ca²âº concentration from 0.9 mM to 2.7 mM. Cerebrocrast, regardless of the Ca²âº concentration significantly increased arterial contraction, particularly at the lower Ca²âº (≈77%). Diltiazem, the benzimidazole derivative and milrinone caused the artery samples to relax at 10⁻4 M concentrations by 55%, 55% and 44%, respectively, when the external Ca²âº corresponded to the physiological standard. Shifting to lower or higher Ca²âº concentrations significantly altered the response of vessel samples by increasing their contraction. In conclusion, the present study shows that the response of isolated human thoracic artery samples to both the slow calcium channel suppressant diltiazem and to agonists of that channel (milrinone and the benzimidazole derivative) is regulated by the amount of calcium present in the physiological solution. Treatment with a slow calcium channel inhibitor, the 1,4-dihydropyridine derivative cerebrocrast, resulted in a response that was independent of the external Ca²âº concentration.

Intraoperative hemodynamic evaluation of the latissimus dorsi muscle flap: a prospective study.

The aim of this study was to assess intraoperatively the hemodynamic changes in the donor vessel of free latissimus dorsi (LD) flap before and after denervation and to analyze flow changes after flap transfer. Twenty-seven patients underwent LD muscle microvascular reconstruction for lower-limb soft tissue defects. Measurements of blood flow were performed intraoperatively by using a 2- to 5-mm probe ultrasonic transit-time flowmeter around the dissected vessels. Registrations were made in the thoracodorsal artery before and after harvesting the flap, after compressing and cutting the motor nerve, and after anastomosis. Mean blood flow of in situ harvested thoracodorsal artery as measured intraoperatively by transit-time flowmeter was (mean ± standard deviation) 16.6 ± 11 mL/min and was significantly increased after raising the flap to 24.0 ± 22 mL/min (p <0.05); it was 25.6 ± 23 mL/min after compressing the motor nerve and was significantly increased after cutting the motor nerve to 32.5 ± 26 mL/min (p <0.05). A significant increase of blood flow to 28.1 ± 19 mL/min was also detected in the thoracodorsal artery after flap transplantation with end-to-side anastomosis (p <0.05). Vascular resistance in the thoracodorsal artery significantly decreased after flap raising and anastomosis (from 7.5 ± 3.4 to 4.0 ± 1.9 and to 4.5 ± 2.4, respectively, p <0.05). LD flap harvesting increases blood flow and decreases resistance in the thoracodorsal artery, especially after denervation.

Effects of a brief Valsalva manoeuvre on hemodynamic response to strength exercises.

Strength training is a recommended measure against loss of strength and muscle mass because of age- or illness-induced inactivity. Strength exercises may impose heavy cardiovascular load by increasing heart rate and blood pressure. To increase strength efficiently, a heavy load has to be applied; this, however, leads to a spontaneous Valsalva manoeuvre, which additionally raises blood pressure. Avoidance of this manoeuvre is recommended. If the additional rise in arterial blood pressure caused by Valsalva manoeuvre is smaller than intrathoracic or intracranial pressures during this manoeuvre, Valsalva manoeuvre may actually protect arteries located in the thorax and in the brain by diminishing transmural pressure acting across these vessels. Effect of controlled breathing or brief Valsalva manoeuvre on arterial pressure at rest and during knee extension against 15-repetition maximum resistance was evaluated. In 12 healthy young men blood pressure was measured continuously and non-invasively, knee angle, speed of respiratory air or mouth pressure (MP) were continuously registered. Each combination of respiratory and exercise manoeuvres was repeated six times, for every of last three repetitions peak and trough systolic and diastolic pressure were determined. Strength exercises elevated peak pressures more than trough pressures, systolic more than diastolic. Valsalva manoeuvre increased only peak systolic and peak diastolic pressure. This increase was in average lesser than MP, thus rendering an argument in favour of protective role of brief Valsalva manoeuvre because of decline in transmural pressure acting on thoracic and possibly cerebral arteries. However, there was strong individual variability, and in few instances, arterial pressure increased because of brief Valsalva manoeuvre more than MP; thus in some subjects, the manoeuvre might enhance transmural pressure acting on thorax arteries.

Effects of thoracic epidural anesthesia on flow and endothelium of internal thoracic artery in coronary artery bypass graft surgery.

OBJECTIVES: The internal thoracic artery (ITA) is the preferred conduit for coronary artery bypass graft (CABG) surgery. The authors investigated whether thoracic epidural anesthesia (TEA) as an adjunct to general anesthesia (GA) can increase the blood flow of the ITA. DESIGN: A prospective randomized study. SETTING: A university hospital. PARTICIPANTS: Patients with ischemic heart disease. INTERVENTIONS: Thirty patients scheduled for elective CABG surgery were randomized to receive either GA (n = 15) or GA + TEA (n = 15) after receiving institutional review board approval. Demographics showed similarity between the groups. The epidural catheter was inserted in the thoracic region between T1 and T5 levels. In the GA + TEA group, the patients received a 20-mg bolus of 0.25% bupivacaine through epidural catheters 1 hour before surgery, and this was followed by the infusion (20 mg/h) of 0.25% bupivacaine. In all patients, ITA free blood flow was measured before cardiopulmonary bypass and without the administration of any vasodilatory agent. A short segment of ITA was excised for histologic examination; immunocytochemistry analysis was performed using antirabbit polyclonal VEGF antibody, rabbit polyclonal inducible nitric oxide synthase (i-NOS) antibody, and adenosine anti-A2B receptor antibody. The immunoreactivity rates then were evaluated. MAIN RESULTS: The mean ITA free flow in the GA + TEA group was significantly higher than in the GA group (56.0 ± 9.0 mL/min v 39.6 ± 14 mL/min, p = 0.001). Immunostaining intensity in the sections after incubation with each primary antibody increased in the GA + TEA group compared with the GA group. CONCLUSIONS: The results of this study indicated that TEA increased ITA free blood flow significantly via increased VEGF, i-NOS, and adenosine-A2B receptor expressions. Therefore, the use of TEA as an adjunct to GA might be considered as an alternative to vasoactive agents for increasing ITA flow in CABG surgery.

Potential role of vasomotor effects of fibrinogen in bradykinin-induced angioedema.

BACKGROUND: Although bradykinin is known to play a major role in the pathophysiology of hereditary and angiotensin-converting enzyme inhibitor (ACEi)-induced angioedema, other factors acting as triggers or enhancers are likely important as well. OBJECTIVE: We hypothesized that fibrinogen might contribute to ACEi-induced angioedema (eg, through direct actions on vascular tone). METHODS: Plasma levels of fibrinogen were determined in 59 patients with acute angioedema. Vascular activity of human and bovine fibrinogen and its effects on bradykinin-induced vasodilation and phosphorylation of vasodilator-stimulated phosphoprotein were investigated in small (0.8-1.4 mm in diameter) porcine coronary artery and human internal thoracic artery (ITA) segments. RESULTS: In patients with ACEi-induced angioedema, fibrinogen levels (481 +/- 22 mg/dL, n = 39) were significantly higher than in patients with idiopathic angioedema (302 +/- 15 mg/dL, P < .001). Fibrinogen (1-15 mumol/L) induced a concentration-dependent vasodilation in preconstricted small porcine coronary arteries (n = 13), reaching a maximum vasodilator effect of 70% +/- 4.7%. Likewise, fibrinogen induced a 52.1% +/- 9.1% (n = 7) vasodilation in ITA rings. Fibrinogen vasorelaxations were completely inhibited by abciximab and diminished by endothelial denudation and treatment with the nitric oxide synthase inhibitor L-nitroargininemethylester and glibenclamide (P < .01). Importantly, fibrinogen increased the vasodilator potency of bradykinin by 10-fold (P < .0001) and increased bradykinin-induced vasodilator-stimulated phosphoprotein phosphorylation (P < .01). CONCLUSION: The increase of plasma fibrinogen levels, its vasodilator activity in human ITAs, and the potentiation of bradykinin-induced vasodilation suggest that fibrinogen might contribute to the pathophysiology of ACEi-induced angioedema. Thus acute-phase proteins, such as fibrinogen, might be viewed as risk factors for bradykinin-induced angioedema.

Voltage gated K+ channel expression in arteries of Wistar-Kyoto and spontaneously hypertensive rats.

BACKGROUND: We have previously demonstrated differences in the gene expression of voltage-gated K v1.X channel alpha-subunits in arteries from Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs). The purpose of this study was to test the hypothesis that these differences are also present at the protein level. METHODS: Proteins were isolated from the aorta, mesenteric (MAs) and tail arteries (TAs) of 12- to 15-week-old male WKY and SHR, and analyzed by immunoblotting. K(v) currents were recorded from MA myocytes by patch clamp methods. RESULTS: Expression of Kv1.2, Kv1.5, and Kv2.1 was higher in MAs but was not different in aortas of SHRs as compared to WKYs. In the TA, expression of Kv1.2 and Kv1.5 was higher while that of Kv2.1 was lower in SHR compared to WKY. In the MA, the larger expression of an 80 kDa species of Kv1.2 in SHRs was associated with a lower expression of a 60 kDa species. Kv2.1 gene expression was larger in MAs from SHRs but not different in TAs. K(v) currents associated with Kv1.X and Kv2.1 channels were both larger in MA myocytes from SHRs but less than expected based upon differences in K(v) alpha-subunit protein expression. CONCLUSIONS: For the MA, K(v) protein expression and current components between WKYs and SHRs were qualitatively consistent, but differences in gene and protein expression were not closely correlated. The higher expression of K(v) subunits in small mesenteric arteries (SMAs) of SHR would tend to maintain normal myogenic activity and vasoconstrictor reserve, and could be viewed as a form of homeostatic remodeling.

Fibulin-5 functions as an endogenous angiogenesis inhibitor.

Ablation of the fibulin-5 gene (fbln5) in mice results in loose skin, emphysematous lungs and tortuous vessels. Additionally, fbln5(-/-) animals display an apparent increase in vascular sprouting from systemic and cutaneous vessels. From these observations, we hypothesized that a de-regulation of vascular sprouting occurs in the absence of endogenous fibulin-5. To test this hypothesis, vascular sprouts from the long thoracic artery were quantified and polyvinyl alcohol sponges were implanted subcutaneously in wild-type and fbln5(-/-) mice to assess fibrovascular invasion. Results showed a significant increase in in situ sprouting from vessels in fbln5(-/-) mice and a significant increase in vascular invasion, with no increase in fibroblast migration, into sponges removed from fbln5(-/-) mice compared with wild-type mice. Localization of fibulin-5 in wild-type mice showed the protein to be present subjacent to endothelial cells (ECs) in established vessels at the periphery of the sponge, and as a component of the newly formed, loose connective tissue within the sponge. These results suggest that fibulin-5 could function as an inhibitor molecule in initial sprouting and/or migration of ECs. To elucidate the molecular mechanism that drives the increased angiogenesis in the absence of fibulin-5, expression of vascular endothelial growth factor (VEGF) and the angiopoietins (Angs) was determined in sponges implanted for 12 days in wild-type and fbln5(-/-) mice. Quantitative RT-PCR showed message levels for VEGF and all three Angs to be elevated by several fold in the area of invasion of sponges from fbln5(-/-) mice compared with wild-type mice. Expression of Ang-1 was also shown to be elevated (30-fold) in vitro in aortic smooth muscle cells isolated from fbln5(-/-) mice when compared with wild-type cells, with no change in the expression of the Ang-1 mediating transcription factor, ESE-1. Taken together, these results suggest that the normal angiogenic process is enhanced in the absence of fibulin-5.

Viscoelasticity reduces the dynamic stresses and strains in the vessel wall: implications for vessel fatigue.

The mechanical behavior of blood vessels is known to be viscoelastic rather than elastic. The functional role of viscoelasticity, however, has remained largely unclear. The hypothesis of this study is that viscoelasticity reduces the stresses and strains in the vessel wall, which may have a significant impact on the fatigue life of the blood vessel wall. To verify the hypothesis, the pulsatile stress in rabbit thoracic artery at physiological loading condition was investigated with a quasi-linear viscoelastic model, where the normalized stress relaxation function is assumed to be isotropic, while the stress-strain relationship is anisotropic and nonlinear. The artery was subjected to the same boundary condition, and the mechanical equilibrium equation was solved for both the viscoelastic and an elastic (which has a constant relaxation function) model. Numerical results show that, compared with purely elastic response, the viscoelastic property of arteries reduces the magnitudes and temporal variations of circumferential stress and strain. The radial wall movement is also reduced due to viscoelasticity. These findings imply that viscoelasticity may be beneficial for the fatigue life of blood vessels, which undergo millions of cyclic mechanical loadings each year of life.

Histologic study of coronary, radial, ulnar, epigastric and internal thoracic arteries: application to coronary artery bypass grafts.

The biometry and the histology of coronary, radial, ulnar, epigastric and internal thoracic arteries were studied in order to investigate the cause of their occlusions in coronary bypass grafts and to improve the results of these bypass grafts. These various arteries were removed from 40 anatomical specimens (27 males and 13 females). We found a correlation between the internal calibers of the ulnar and coronary arteries in males. Intimal changes and the presence of atheromatous plaque were observed in coronary, radial and ulnar arteries, but never in the internal thoracic artery. Like coronary arteries and their branches, radial, ulnar and epigastric arteries are muscular arteries and ageing results in thickening of the intima, which becomes fibrotic with migration of myocytes from the media and duplication of the internal elastic lamina. The media becomes fibrous, hypertrophic or atrophic. In contrast, the internal thoracic artery is an elastic artery, like the aorta. Ageing is characterized by loss, over a variable extent, of one or several elastic laminae of the media and more marked intimal thickening. Although anatomically, the caliber of radial, ulnar, and epigastric arteries remains adapted to that of coronary arteries, the long-term patency of radial, ulnar and epigastric arteries used as grafts is related to their histological characteristics.

Reliable CFD-based estimation of flow rate in haemodynamics measures.

Physically useful measures in current clinical practice refer often to the blood flow rate, that is related to the mean velocity. However, the direct measurement of the latter is currently not possible using a Doppler velocimetry technique. Therefore, the usual approach to calculate the flow rate with this technique consists in measuring the maximum velocity and in estimating the mean velocity, making the hypothesis of parabolic profile that in realistic situations results in strongly inaccurate estimates. In this paper, we propose a different way for estimating the flow rate regarded as a function of maximum velocity and Womersley number. This relation is obtained by fixing a parametrised representation and by evaluating the parameters by means of a least-square approach working on the numerical results of CFD simulations (about 200). Numerical simulations are carried out by prescribing the flow rate, not the velocity profile. In this way, no bias is implicitly induced in prescribing boundary conditions. Validation tests based on numerical simulations show that the proposed relation improves the flow rate estimation.

Compressibility of arterial wall in ring-cutting experiments.

It is common practice in the arterial wall modeling to assume material incompressibility. This assumption is driven by the observation of the global volume preservation of the artery specimens in some mechanical loading experiments. The global volume preservation, however, does not necessarily imply the local volume preservation - incompressibility. In this work, we suggest to use the arterial ring- cutting experiments for the assessment of the local incompressibility assumption. The idea is to track the local stretches of the marked segments of the arterial ring after the stress-relieving cut. In the particular case of the rabbit thoracic artery, considered in this work, the following criteria for radial stretches come from preliminary analysis. If after the radial cut the marked segments shorten at the inner surface of the wall and lengthen at the outer surface while remaining unchanged in the middle of the wall then material is locally incompressible. If, however, the marked segments remain unchanged at the surfaces while lengthening in the middle of the wall then the material is locally compressible. Any other scenario would be an indication of the improper modeling assumptions, i.e. residual stresses are not relieved or material constants are inaccurate etc. It is believed that the proposed approach can be successfully implemented in experiments shedding new light on the arterial incompressibility issue.

Vascular wall resident progenitor cells: a source for postnatal vasculogenesis.

Here, we report the existence of endothelial precursor (EPC) and stem cells in a distinct zone of the vascular wall that are capable to differentiate into mature endothelial cells, hematopoietic and local immune cells, such as macrophages. This zone has been identified to be localized between smooth muscle and adventitial layer of human adult vascular wall. It predominantly contains CD34-positive (+) but CD31-negative (-) cells, which also express VEGFR2 and TIE2. Only few cells in this zone of the vascular wall are positive for CD45. In a ring assay using the fragments of human internal thoracic artery (HITA), we show here that the CD34+ cells of the HITA-wall form capillary sprouts ex vivo and are apparently recruited for capillary formation by tumor cells. New vessels formed by these vascular wall resident EPCs express markers for angiogenically activated endothelial cells, such as CEACAM1, and also for mature endothelial cells, such as VE-cadherin or occludin. Vascular wall areas containing EPCs are found in large and middle sized arteries and veins of all organs studied here. These data suggest the existence of a ;vasculogenic zone' in the wall of adult human blood vessels, which may serve as a source for progenitor cells for postnatal vasculogenesis, contributing to tumor vascularization and local immune response.