Wall Cross-sectional Area Research Articles

Non-Invasive Biomechanical Evaluation of Implanted Human Cryopreserved Arterial Homografts

Native vessels-grafts biomechanical mismatch (BM) is related to graft failure. The BM could be reduced using human cryopreserved/defrosted arteries (cryografts), but post-thaw cryografts' recovery could be associated with an impaired biomechanical behavior. In vitro, we demonstrated that our cryopreservation methods do not affect arteries' biomechanics, but only post-implant studies would allow determining the cryografts' biomechanical performance. To characterize the biomechanical properties of implanted cryografts, and to compare them with cryografts pre-implant, recipients' native arteries, and arteries from subjects with characteristics similar to those of the recipients and multiorgan donors (MOD) whose arteries were cryopreserved. Native femoral arteries anastomosed to cryografts, implanted cryografts, and arteries from subjects, recipient-like and MOD-like, were studied. In vitro (pre-implant cryografts) and in vivo non-invasive studies were performed. Arterial pressure, diameter, and wall thickness were obtained to quantify local and regional biomechanical parameters, and to evaluate the arterial remodeling. Implanted cryografts were remodeled, with an increased wall thickness, wall-to-lumen ratio, and wall cross-sectional area. The proximal-distal gradual transition in stiffness remained unchanged. Implanted cryografts were stiffer than MOD-like arteries, but more compliant than recipients' arteries. The cryografts-native arteries biomechanical differences were lesser than those described for venous grafts or expanded polytetrafluoroethylene.

Wall-to-Lumen Ratio of Retinal Arterioles and Arteriole-to-Venule Ratio of Retinal Vessels in Patients with Cerebrovascular Damage

There is evidence that generalized retinal arteriolar narrowing, which can be measured by the arteriole-to-venule ratio (AVR) of retinal vessels, predicts cerebrovascular events. The wall-to-lumen ratio (WLR) and wall cross-sectional area (WCSA) of retinal arterioles reflect structural arteriolar parameters. The primary objective was to test the association between WLR and AVR in a distinct cohort of patients with cerebrovascular damage. In this cross-sectional study, 23 patients (57.5 +/- 9.4 years) with acute transitory ischemic attack or lacunar cerebral infarct were compared with two age-matched control groups: 83 subjects with essential hypertension (53.7 +/- 5.5 years) and 16 normotensive subjects (52.2 +/- 8.3 years). Retinal arteriolar parameters (WLR, WTH, and WCSA) were assessed in vivo with scanning laser Doppler flowmetry (SLDF). AVR and a qualitative evaluation of retinal vessels were obtained from digital retinal color photographs. The intima-media thickness (IMT) of the carotid artery was measured. WLR (0.44 +/- 0.1 vs. 0.34 +/- 0.1 vs. 0.30 +/- 0.1, P < 0.001) and carotid IMT (P < 0.05) were significantly greater in the cerebrovascular event group compared with normotensive subjects. WLR and WCSA were significantly higher in the cerebrovascular event group compared with subjects with mild arterial hypertension. AVR was similar in all three study groups (0.75 +/- 0.07 vs. 0.74 +/- 0.07 vs. 0.78 +/- 0.1, P = 0.18). The increase in WLR and WCSA of retinal arterioles, as well as in IMT in patients with cerebrovascular damage suggests vascular hypertrophy in the microvascular and macrovascular bed. The lack of association between AVR of retinal vessels and WLR of retinal arterioles may point to different stages of cerebrovascular disease and/or different pathophysiological changes in the arteriolar wall.

Possible functional consequences of structural adaptation along single arterioles

Arterioles are normally thought of as having a constant structural diameter between branch points. In unbranched rat cremaster arterioles, however, structural diameter increases downstream along the vessel (upstream tapering) without change in cross‐sectional area of the vascular wall (1). We addressed the possible functional consequence of this configuration by flow‐simulations comparing myogenically active vessels of uniform structural radius with those having an upstream tapering shape. In our model cross‐sectional area of the vascular wall remains invariant along the vessel and the flow is the same in all cases.ResultsThe vascular wall material can be arranged in an upstream tapering configuration such that circumferential wall stress is uniform along the vessel. The stress remains uniform during flow‐autoregulation when perfusion pressure is changed. In contrast, when the structural radius is uniform along the vessel wall stress is much higher upstream than downstream, and this difference is maintained under variations in perfusion pressure.ConclusionIn a myogenically active vessel upstream tapering of the inner radius allows the circumferential wall stress, and hence possibly the contractile state of the wall smooth muscle cells, to remain constant along the vessel at a given pressure. This is not the case for a vessel with a uniform radius. The upstream tapering shape is consistent with the vascular wall cells having a uniform point of operation as regards stress‐induced myogenic contraction.

Spatial Patterns of Transforming Growth Factor Beta Signaling in Mgr‐/‐ Mouse Model of Marfan Syndrome

The balance between wall stress and structure of a blood vessel is crucial for its optimal function and is maintained by remodeling. Marfan patients, harboring mutations of fibrillin1 (FBN1) gene, exhibit aberrant vascular remodeling, formation of aortic aneurysms and dissections. This is associated with altered signaling through transforming growth factor beta (TGFβ) pathway. Non‐invasive imaging and computational modeling of blood flow predict complex pattern of wall stress in the ascending aorta and arch. We hypothesized that these regions of aorta exhibit altered morphology and signaling patterns. Aortas from 15 wild type and 15 FBN1 deficient (FBN1‐/‐) mice were isolated and divided into 4 segments: ascending aorta, arch, proximal and distal thoracic aorta. VVG staining of aortic cross‐sections showed that aortas of FBN1‐/‐ mice have diffuse fragmentation of elastic lamella and decreased elastic lamellar thickness (p=0.005). Increased wall thickness (p=0.002), inner radius (p=0.000), and wall cross‐sectional area (p=0.000) was present in the ascending aorta and arch of FBN1‐/‐ mice. The same area was associated with increased levels of pSMAD3 protein and decreased relative expression of SMAD3 mRNA. More research is needed to determine relationships between TGFβ signaling, distributions of wall stresses, and increased wall stiffness due to elastin fragmentation in aortas of Marfan patients.

NOX2 deficiency prevents angiotensin II‐induced hypertrophy and inward remodeling in cerebral arterioles

We examined the role of NAD(P)H oxidase subunit NOX2 on structural alterations in cerebral arterioles induced by angiotensin II (Ang II). NOX2‐deficient (NOX2‐/‐) and wild‐type (WT) mice were infused with a pressor or a sub‐pressor dose of Ang II (1000 or 200 ng/kg/day) or saline via osmotic minipumps for 4 weeks. Systolic arterial pressure (SAP) was measured by a tail‐cuff method. Pressure and diameter of cerebral arterioles were measured via an open cranial window in anesthetized mice. In WT and NOX2‐/‐ mice, the pressor, but not the sub‐pressor, dose of Ang II increased SAP (135±5 vs 106±3 mmHg). Superoxide levels in cerebral arterioles (hydroethidine staining) were increased by both doses of Ang II in WT (staining density: 41±5 and 32±2 vs 18±5 %), but not in NOX2‐/‐ mice. The sub‐pressor, as well as the pressor, dose of Ang II significantly reduced external diameter of maximally dilated cerebral arterioles in WT mice (51±3 and 52±3 vs 58±2 μm at 30 mmHg), but not in NOX2‐/‐ mice. Cross‐sectional area (CSA) of the arteriolar wall was significantly increased in WT mice (497±58 vs 388±50 μm2) by the pressor, but not the sub‐pressor, dose of Ang II. In contrast, the pressor dose of Ang II did not increase CSA in NOX2‐/‐ mice. These findings suggest that generation of superoxide may play an important role in Ang II‐induced hypertrophy and inward remodeling in cerebral arterioles.

Effect of chronic nNOS inhibition on blood pressure, vasoactivity, and arterial wall structure in Wistar rats

While the unequivocal pattern of endothelial nitric oxide (NO) synthase (eNOS) inhibition in cardiovascular control has been recognised, the role of NO produced by neuronal NOS (nNOS) remains unclear. The purpose of the present study was to describe the cardiovascular effects of NO production interference by inhibition of nNOS with 7-nitroindazole (7-NI). Wistar rats (10 weeks old) were used: control and experimental rats were administered 7-NI 10 mg/kg b.w./day in drinking water for 6 weeks. Systolic blood pressure (BP) was measured by the tail-cuff plethysmographic method. Isolated thoracic aortas (TAs) were used to study vasomotor activity of the conduit artery in vitro. The BP response of anaesthetised animals was used to follow the cardiovascular-integrated response in vivo. Geometry of the TA was measured after perfusion fixation (120 mm Hg) by light microscopy. Expression of eNOS was measured in the TA by immunoblot analysis. Although 6 weeks of nNOS inhibition did not alter systolic BP, the heart/body weight ratio was decreased. Relaxation of the TA in response to acetylcholine (10 −9–10 −5 mol/L) was moderately inhibited. However, no difference in the BP hypotensive response after acetylcholine (0.1, 1, 10 μg) was observed. The contraction of TA in response to noradrenaline (10 −10–10 −5 mol/L), and the BP pressor response to noradrenaline (0.1, 1 μg) was attenuated. The inner diameter of the TA was increased, and the wall thickness, wall cross-sectional area, and wall thickness/inner diameter ratio were decreased. The expression of eNOS in the TA was increased. In summary, cardiac and TA wall hypotrophy, underlined by decreased contractile efficiency, were observed. The results suggested that two constitutive forms of NOS (nNOS, eNOS) likely participate in regulation of cardiovascular tone by different mechanisms.

Biomechanical changes in oxazolone-induced colitis in BALB/C mice

Ulcerative colitis (UC) is associated with intestinal and extra intestinal clinical manifestations. The profound organic changes in UC indicate that the colonic mechanical and mechanosensory functions are affected. The aim was to study acute morphological and biomechanical properties of the distal colon in oxazolone-induced UC in BALB/C mice. Six normal male BALB/C mice and 10 oxazolone-induced UC mice were studied. UC was induced by epicutaneous and intrarectal administration of oxazolone. The mechanical test was done as a distension experiment where the colon was distended up to 20 cmH 2O. The pressure, outer diameter and length were recorded simultaneously. Circumferential and longitudinal stresses and strains were computed. The intestinal specimens were processed for histology. The mucosa was infiltrated with acute and chronic inflammatory cells. Mucosal bleeding, irregular ulcers crypt abscess, and destruction of the epithelial border were observed. Although, the mucosa in ulcers was much thinner than in the normal controls, the mucosa and submucosa around the ulcer were thicker than in the normal controls ( P<0.05). Oxazolone-induced colitis increased the circumferences and wall cross-sectional area ( P<0.01), the opening angle and residual strain at the serosa increased ( P<0.01). Furthermore, the circumferential and longitudinal stiffness increased in the UC wall and was most pronounced in longitudinal direction. The opening angle and residual strain was linearly correlated to the wall thickness, area and inflammation degree. In conclusion, morphological and biomechanical changes of the colon occurred during the development of UC. The increased stiffness may contribute to the abnormal function in patients with UC.

I033 Celiprolol increases the elasticity of the radial artery in vascular Ehlers-Danlos syndrome : a randomized controlled clinical trial

Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant inherited disorder of connective tissue. This syndrome results from mutations in the gene encoding type III procollagen. The patients can present with spontaneous arterial rupture or dissection. We had previously described that celiprolol stiffened large-sized elastic artery (common carotid artery) in vEDS. We tested the effects of celiprolol, a beta1-adrenoceptor antagonist with a beta2-adrenoceptor agonist action in small-sized muscular artery (radial artery) in vEDS. 47 vEDS patients with no previous beta-blocker were randomized to 5 years treatment. According to a PROBE design, they were allocated either to celiprolol (50 to 200 mg once a day, n=23) or no treatment (n=24). Radial internal diameter, intimamedia thickness (IMT) and distension were measured on the right arm with a 10-MHz ultrasound system analyzing the radiofrequency signal. Radial blood pressures were obtained with applanation tonometry. Other radial parameters (wall cross-sectional area, wall-to-lumen ratio, distensibility, Young's elastic modulus and circumferential wall stress) were calculated from radial internal diameter, IMT, distension, mean blood pressure and pulse pressure. We used MIXED procedure of the SAS® System through the repeated statements to compare serial changes in blood pressure and arterial parameters in two groups. After 12 months, heart rate, radial systolic and mean blood pressure, pulse pressure, IMT, Young's elastic modulus and circumferential wall stress did not change in both groups. Radial diastolic blood pressure decreased significantly (p=0.03) and to the same extent in both groups (−5 % in the celiprolol group and −6 % in the control group) (period effect). Radial internal diameter, wall cross-sectional area increased significantly (+5 %, p=0.04 and +12 %, p=0.04 respectively) and wall-to-lumen ratio decreased significantly (−2 %, p=0.04) in celiprolol group but not in control group (periodby-group interaction). Significant increase in distensibility was observed in celiprolol group (+18 %, p=0.04) but not in control group (group effect). compared to no treatment, celiprolol induced a moderate dilation and an important augmentation of elasticity of the radial artery with no change in radial blood pressure. The results proposed the pleiotropic effect of celiprolol in small-sized muscular artery.

Small Vessel Remodeling and Impaired Endothelial-Dependent Dilatation in Subcutaneous Resistance Arteries from Patients with Acromegaly

Patients with acromegaly have increased morbidity and mortality, predominantly from cardiovascular disease. Hypertension and diabetes are more prevalent, and both cause small vessel remodeling and endothelial dysfunction. To understand the structure and function of small arteries in acromegaly, sc blood vessels from gluteal fat biopsies were harvested from 18 patients with active disease (AD; age, 56 +/- 15 yr; 14 males), 23 patients in remission (CD; age, 55 +/- 12 yr; 15 males), and 20 healthy controls (age, 55 +/- 11 yr; 10 males) and examined in vitro using pressure myography. Contractile responses to cumulative noradrenaline concentrations were recorded and followed by dose-dependent dilator responses to acetylcholine. The acetylcholine protocol was repeated after incubation with a nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester) and cyclooxygenase inhibitor (indomethacin). After perfusion with Ca(2+)-free physiological saline solution, structural measurements were recorded at varying intraluminal pressures (3-180 mm Hg). Wall thickness and wall:lumen ratio were increased in AD, reduced with treatment but remained greater in CD than controls. Wall cross-sectional area was increased in AD vs. controls (P < 0.001), decreased with treatment (AD vs. CD, P < 0.001), but remained higher than controls (CD vs. controls, P = 0.015). Growth index was increased in AD (20%) compared to controls (CD, 9%). Contractility was similar in all groups. Endothelial-dependent dysfunction was evident in AD compared with CD (P < 0.001) and controls (P < 0.01). Dilation did not change after N-nitro-L-arginine methyl ester but was impaired after indomethacin incubation. Active acromegaly is associated with hypertrophic remodeling of the vascular wall and embarrassed endothelial function due to reduced nitric oxide and endothelium-derived hyperpolarizing factor bioavailability, both of which may contribute to the early mortality from cardiovascular disease.

Some Engineering Properties of Barley Straw

This research was carried out to determine the effects of moisture content and internode position on physical and mechanical properties of barley straw. The experiments were conducted at four moisture contents of 10.8%, 14.3%, 18.5%, and 22.5% w.b. and at three internode positions down from the ear. Based on the results obtained, the moisture content did not have significant effect on physical properties of barley straw. There was a significant increase in the stem's major and minor diameters, thickness, wall cross-sectional area, second moment of area, and mass per unit length towards the third internode position. At the different moisture contents studied, the values of the shear strength were within the ranges of 3.90 to 5.27 MPa, 4.31 to 5.96 MPa, and 4.49 to 6.18 MPa for the first, second, and third internode positions, respectively. The maximum specific shearing energy was 32.53 mJ mm-2, occurred at the third internode position with the moisture content of 22.5% w.b. The bending stress and Young's Modulus decreased with an increase in moisture content. Their values also decreased towards the third internode position.

Comparison of Linear Methods for the Determination of Propagation Coefficient in Arterials Systems: Numerical Investigation

To get a deeper insight into the factors affecting the vascular hemodynamic, the propagation coefficient (γ) should be calculated. However, results from estimated method of this quantity are conflicting. Using numerical tools, three methods permitting an estimation of this complex number were investigated. We studied the influence of peripheral resistance, fluid and wall viscosities, stiffness, cross-sectional area, vessel length and measurements errors on the accuracy of these methods. Results obtained from this analysis demonstrated that the three methods provide exact value of propagation coefficient when analysing accurate flow velocity and diameter data. Conversely, in realistic condition (i.e. inaccurate data) significant errors related to the degrees of inaccuracy within the data arise. These errors are systematically larger on the values of propagation coefficient obtained by the three-point method than the error on the values calculated by two-point methods. Hence, we believe that difference in sensitivity of each method to the measurements errors may be the main source of the disparity of results reported in literature. In addition, the small value of attenuation and time lag seem to be the sources of the large difference between calculated and theoretical values of this parameter. Our finding doesn't support previous works which attributed the disparity of results to the high reflection or/and to the failure of the methods themselves. In realistic condition, it seems that two-point methods are more reliable than the three-point method for the estimation of the true propagation coefficient.

The effect of an NO donor, pentaerythrityl tetranitrate, on biochemical, functional, and morphological attributes of cardiovascular system of spontaneously hypertensive rats

The status of nitric oxide (NO) in spontaneously hypertensive rats (SHR) is unclear and its bioavailability may be affected by imbalance with reactive oxygen species. We studied cardiovascular effects of an NO donor, pentaerythrityl tetranitrate (PETN) in SHR. We used Wistar rats, SHR and SHR treated with PETN (200 mg/kg/day). After six weeks, myocardium and aorta from each group were taken for biochemical and iliac artery for functional and morphological study. Long-term administration of PETN to SHR increased cGMP level in platelets and did not affect blood pressure. In myocardium, the therapy resulted in a decrease in cardiac hypertrophy and MDA level, and the increased antioxidant enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). In aorta, PETN decreased the NO-synthase activity and had no affect on the enzyme activities of SOD and GPx or on MDA level. In the iliac artery, the endothelium-dependent relaxation to acetylcholine was slightly improved and the maximum vasoconstriction to noradrenaline was decreased. Wall thickness, cross-sectional area, inner diameter, and wall thickness/ inner diameter measured after perfusion fixation (120 mmHg) were not affected. The small effect of PETN on cardiovascular system suggests that NO deficiency is probably not the main cause of pathological alterations in SHR.

Effect of electrical stimulation of the cervical spinal cord on blood flow following subarachnoid hemorrhage

Cervical spinal cord stimulation (SCS) increases global cerebral blood flow (CBF) and ameliorates cerebral ischemia according to a number of experimental models as well as some anecdotal reports in humans. Nonetheless, such stimulation has not been systematically applied for use in cerebral vasospasm. In the present study the authors examined the effect of cervical SCS on cerebral vasoconstriction in a double-hemorrhage model in rats. Subarachnoid hemorrhage (SAH) was induced with 2 blood injections through an indwelling catheter in the cisterna magna. Spinal cord stimulation was applied 90 minutes after induction of the second SAH (Day 0) or on Day 5 post-SAH. Measurements of the basilar artery (BA) diameter and cross-sectional area and regional CBF (using laser Doppler flowmetry and (14)C-radiolabeled N-isopropyl-p-iodoamphetamine hydrochloride) were obtained and compared between SAH and sham-operated control rats that did not receive SCS. At Day 0 after SAH, there were slight nonsignificant decreases in BA diameter and cross-sectional area (89 +/- 3% and 81 +/- 4%, respectively, of that in controls) in no-SCS rats. At this time point, BA diameter and crosssectional area were slightly increased (116 +/- 6% and 132 +/- 9%, respectively, compared with controls, p < 0.001) in SCS-treated rats. On Day 5 after SAH, no-SCS rats had marked decreases in BA diameter and cross-sectional area (64 +/- 3% and 39 +/- 4%, respectively, compared with controls, p < 0.001) and corrugation of the vessel wall. These changes were reversed in rats that had received SCS (diameter, 110 +/- 9% of controls; area, 106 +/- 4% of controls; p < 0.001). Subarachnoid hemorrhage reduced CBF at Days 0 and 5 post-SAH, and SCS increased flows at both time points, particularly in regions supplied by the middle cerebral artery. Data in this study showed that SCS can reverse BA constriction and improve global CBF in this SAH model. Spinal cord stimulation may represent a useful adjunct in the treatment of vasospasm.

Biomechanical and Histomorphometric Colon Remodelling in STZ-Induced Diabetic Rats

The histomorphologic and passive biomechanical properties were studied in the mid-colon of 16 non-diabetic and 20 streptozotocin (STZ)-induced diabetic rats (50 mg/kg STZ, ip). The diabetic rats were divided into groups living 4 and 8 weeks after the induction of diabetes (n = 10 for each group). The mechanical test was a ramp distension of fluid into the colon in vitro. The colon diameter and length were obtained from digitized images of the segments at pre-selected pressures and at the no-load and zero-stress states. Circumferential and longitudinal stresses and strains were computed from the length, diameter, and pressure data and from the zero-stress state geometry. The blood glucose level increased 3-4-fold in the diabetic rats compared with the controls (P < 0.001). Diabetes generated pronounced increases in the colon weight per length, wall thickness, and wall cross-sectional area (P < 0.001). Histologically, the thickness of all layers was increased during diabetes (P < 0.05), especially the mucosa layer. The opening angle, and absolute values of residual strain increased in the diabetic group (P < 0.05 and P < 0.01, respectively). Furthermore, diabetes increased the circumferential and longitudinal stiffness of the colon wall (P < 0.001). The observed changes in residual strain, opening angle, and stress-strain relation may be contributing factors to colonic dysfunction and abdominal pain in diabetic patients.

Paricalcitol Treatment and Arterial Tone in Experimental Renal Insufficiency

Aim: To examine whether treatment of secondary hyperparathyroidism with paricalcitol provides benefits to arteries in uremic rats. Methods: 5/6-nephrectomized rats were treated (NX+Pari) or not treated (NX) with paricalcitol (200 ng/kg, thrice weekly) for 12 weeks. Aortic histology and isolated segments of the main and 2nd-order mesenteric arterial branches were studied. Results: Creatinine clearance was reduced by 54–61%, plasma phosphate increased 2.1- to 2.5-fold, and blood pressure by 40 mm Hg in both NX groups. PTH increased 13-fold in NX and 5-fold in NX+Pari rats. Calcification in aortic cross-sections increased from 2.1 to 7.1% after paricalcitol. In the large mesenteric artery, vasoconstriction to noradrenaline was reduced in NX+Pari rats. In the large and small arteries, vasorelaxation to acetylcholine was impaired in NX rats and unaffected by paricalcitol. In the small artery, paricalcitol increased nitric oxide synthase inhibition-resistant relaxation to acetylcholine, and maximal relaxation to levcromakalim. The small arteries of NX rats featured increased wall cross-sectional area, while paricalcitol further increased wall thickness and the wall:lumen ratio. Conclusion: Paricalcitol treatment showed both benefits and harmful effects in uremic rats: in the large artery vasoconstriction was reduced but calcification increased, while in the small artery vasorelaxation via potassium channels was moderately improved but hypertrophic remodeling was aggravated.

Genetic deficiency of heme oxygenase-1 impairs functionality and form of an arteriovenous fistula in the mouse

Vascular access dysfunction contributes to patient morbidity during maintenance hemodialysis. In this study we determined if knockout of heme oxygenase-1 predisposed to malfunction of arteriovenous fistulas. After three weeks, all fistulas in wild type mice were patent whereas a third of the fistulas in knockout mice were occluded and these exhibited increased neointimal hyperplasia and venous wall thickening. Heme oxygenase-1 mRNA and protein were robustly induced in the fistulas of the wild type mice. In the knockout mice there was increased PAI-1 and MCP-1 expression, marked induction of MMP-2 and MMP-9, but similar expression of PDGF alpha, IGF-1, TGF-beta1, VEGF, and osteopontin compared to wild type mice. We conclude that heme oxygenase-1 deficiency promotes vasculopathic gene expression, accelerates neointimal hyperplasia and impairs the function of arteriovenous fistulas.

Analysis of retinal arteriolar structure in never-treated patients with essential hypertension

Increased wall-to-lumen ratio of small arteries is a predictor of adverse cardiovascular prognosis. We aimed to analyze retinal arteriolar structure in never-treated patients with essential hypertension and to test whether elevated blood pressure is associated with an increased wall-to-lumen ratio of retinal arterioles. The study cohort comprised 21 untreated male patients with essential hypertension (mean age 39.1 +/- 5.4 years) and 29 untreated normotensive men (mean age 36.7 +/- 5.9 years). Wall-to-lumen ratio of retinal arterioles was assessed in vivo using scanning laser Doppler flowmetry. Patients with essential hypertension had a higher wall-to-lumen ratio of retinal arterioles than normotensive individuals (0.36 +/- 0.1 vs. 0.28 +/- 0.1, P = 0.028). Wall cross-sectional area of retinal arterioles did not differ between the study groups. The growth index, indicating the percentage of difference in average wall cross-sectional area of retinal arterioles between both groups, was 18%. Both systolic (r = 0.360, P = 0.010) and diastolic (r = 0.536, P < 0.001) blood pressures were related to wall-to-lumen ratio of retinal arterioles. Multiple regression analysis including a variety of known cardiovascular risk factors revealed that blood pressure is independently associated with an increased wall-to-lumen ratio of retinal arterioles (systolic blood pressure: beta = 0.417, P = 0.012; diastolic blood pressure: beta = 0.548, P = 0.001). The changes in arteriolar structure of retinal vessels in our study cohort revealed a similar pattern to that observed previously by other investigators in subcutaneous small arteries in essential hypertension. Blood pressure emerged as an important and independent determinant of wall-to-lumen ratio of retinal arterioles.

Mechanisms of Arterial Remodeling in Hypertension

Diverse data collected over the past 4 decades suggest the existence of a mechanical homeostasis across multiple length and time scales in the vasculature. For example,1 stress fibers within endothelial and vascular smooth muscle cells appear to disassemble and then reassemble in a mechanically preferred manner when perturbed from a normal value of mechanical stress or strain; focal adhesions in smooth muscle cells and fibroblasts tend to increase in area in response to local increases in mechanical loading so as to maintain the stress constant at a preferred value; fibroblasts tend to increase the tractions that they exert on the extracellular matrix when external loads are decreased from a preferred value, thus suggesting an attempt to enforce a “tensional homeostasis”; vascular smooth muscle cells tend to relengthen to their normal, preferred values when an arteriole is forced into a vasoconstricted state for an extended period; and arteries tend to decrease in caliber in response to sustained decreases in flow-induced wall shear stress, to increase in thickness in response to sustained increases in pressure-induced circumferential stress, and to lengthen in response to extension-induced increases in axial stress. Although changes in the cytoskeleton and integrins occur within minutes, changes at the cell-cell and cell-matrix levels occur over hours, and those at the vessel level occur over days to weeks or months. Hence, despite marked differences in length scales (dimensions from nanometers to centimeters) and time scales (durations from minutes to months), mechanobiological control mechanisms in the vasculature tend to restore values of stress or strain toward preferred (homeostatic) values in response to diverse perturbations from normal.2–5 Biomechanics and mechanobiology thus play key roles in vascular development, tissue maintenance in maturity, normal adaptations, aging, disease progression, and responses to injury or clinical interventions. A current challenge in hypertension research is to …

Modal Analysis for Externally Driven Micropump and Additional Mass Effect of Water

The externally driven micropump is common means of transporting liquid on the microscale. It is usually difficult to evaluate the oscillation characteristics with the influence of the liquid inside the micropump taken into account. In this study, modal analysis with an additional mass effect of liquid is carried out for the evaluation of the influences of miniaturization and internal liquid. Analyses under three typical conditions of microfluidics devices were carried out: (1) cantilever-type actuator vibrates a flexible microchannel, (2) film-type actuator vibrates a microchannel, and (3) oscillation of single microchannel. The results indicate that the liquid inside the microchannel and the microchannel shape greatly influence the oscillation characteristics. The microchannel should be designed to have a small aspect ratio, a large cross-sectional area of the upper wall, and a cross-sectional area of channel smaller than that of the upper wall. These effects should be taken into account in the design of the externally driven micropunp.

Neointimal formation is exacerbated following vascular injury in p22phox overexpressing transgenic mice

These studies tested the hypothesis that transgenic mice overexpressing the p22phox subunit of the NAD(P)H oxidase selectively in smooth muscle (Tgp22smc) would exhibit exacerbated neointimal formation following mechanically induced transluminal vascular injury compared to wild‐type control mice. Tgp22smc mice have a two‐fold increase in p22phox expression and H2O2 production; thus providing a model to examine the effects of elevated vascular ROS production on VSMC function in vivo. To induce vascular injury, a 0.36 mm steel catheter was guided 4–5 mm into the left common carotid via the external carotid. Following one minute the catheter was removed and reperfusion verified. The degree of neointimal formation was assessed by morphological analysis of wall thickness (WT) and cross‐sectional wall area (CSWA) in male Tgp22smc mice and littermate controls 14 days following injury. WT following injury indicated significantly greater neoinitimal formation in Tgp22smc mice (54.3 ± 7.3 vs. 43.7 ± 4.1 μm), while non‐injured contralateral carotids were similar between groups (28.5 ± 3.3 vs. 33.8 ± 2.8 μm). Moreover, the increase in carotid artery CSWA following injury was approximately four‐fold greater in Tgp22smc mice compared to control animals. Findings from these in vivo studies strongly support in vitro data which has implicated ROS as a crucial mediator of both VSMC proliferation and migration. AHA 03300119N