Association between wall shear stress and flow-mediated vasodilation in healthy men

Wall shear stress contributes to the endothelial production of vasoactive mediators, like nitric oxide (NO). Brachial artery vasodilation that follows increased blood flow is regulated by NO release. Aim of the present study was to investigate whether resting wall shear stress of the brachial artery is related to flow-mediated vasodilation (FMD) induced by forearm ischemia. Wall shear stress was calculated according to the following formula: Wall shear stress=Blood viscosity x Blood velocity/Internal diameter. FMD was calculated as percentage change of brachial artery diameter following forearm ischemia. Twenty-seven healthy male subjects were investigated. Peak wall shear stress and FMD were 37.3+/-12.8 dynes/cm(2) and 110.7+/-5.6%, respectively (mean+/-S.D.). In simple regression analyses, age was inversely associated with wall shear stress (r=48, P<0.01) and, marginally, with FMD (r=0.33, P=0.08). Wall shear stress and FMD were directly related (r=0.60, P<0.001). In multiple regression analysis, including wall shear stress, age, blood pressure, lipids, glucose and Body Mass Index as independent variables, wall shear stress was the only variable independently associated with FMD (standardized beta coefficient=0.690, P相似文献   

Endothelium dependent control of arterial diameter by blood viscosity

The local control of arterial diameter by blood flow rate has been attributed to the ability of the endothelial cells to sense the shear stress exerted on them by flowing blood. Since shear stress is proportional to the product of flow rate and fluid viscosity, an increase in the latter will augment shear stress and lead to arterial dilatation as well. We therefore designed experiments to reveal the control of the arterial lumen by blood viscosity and to compare it with the control by blood flow rate. Changes in external diameter of a segment of feline femoral artery caused by variations in blood viscosity and/or flow rate were recorded during the perfusion in situ under stabilised transmural pressure. Decrease in blood viscosity evoked by haemodilution at a constant flow rate led to arterial constriction whereas an increase in viscosity due to haemoconcentration caused arterial dilatation. These viscosity induced changes in arterial diameter depended on intact endothelium. Responses to the changes in blood viscosity and flow rate of the same magnitude were practically identical. These results show that blood viscosity is a factor affecting vascular smooth muscle tone and confirm the suggestion that shear stress is the key signal in the endothelium dependent control of the arterial lumen by blood flow rate.     

Non-invasive evaluation of segmental pressure drop and resistance in large arteries in humans based on a Poiseuille model of intra-arterial velocity distribution

STUDY OBJECTIVE--The aim of the study was to evaluate in hypertensive subjects the longitudinal pressure drop and segmental resistance in a large artery in relation to shearing forces of the circulating blood column at the arterial wall. DESIGN--Arterial diameter, blood velocity, and flow were measured in the brachial artery using pulsed Doppler apparatus. Blood viscosity was measured at 96 s-1 with a low shear viscometer. Segmental resistance per unit arterial length was calculated using the basic Poiseuille resistance expression from the ratio between blood viscosity and the fourth power of arterial diameter. Longitudinal pressure drop was deduced as the product between segmental resistance and blood flow. The Poiseuille model of velocity distribution also enabled wall shear rate and stress to be calculated from the ratio between blood velocity and arterial diameter and from the product between shear rate and blood viscosity respectively. PATIENTS--19 ambulatory male patients with mild to moderate hypertension and 11 normotensive male controls of similar age were studied. RESULTS--Compared to controls, hypertensive patients had higher arterial diameter (p less than 0.001) lower blood velocity (p less than 0.05), higher blood viscosity (p less than 0.01), lower segmental resistance and pressure drop (p less than 0.001, p less than 0.01) and lower shear rate and stress (p less than 0.01, p less than 0.05). A negative correlation existed in the overall normotensive and hypertensive population between pressure drop and mean blood pressure (r = -0.55, p less than 0.01). CONCLUSION--The hypertensive state is associated with a clear reduction in large artery segmental resistance and longitudinal pressure drop concomitantly with a decrease in shear conditions at the arterial wall. The mechanisms of reduced resistance and pressure drop are related to decreased wall shear and increased diameter of the artery, both of which reduce the frictional forces at the blood-arterial wall interface.     

Human common carotid wall shear stress as a function of age and gender: a 12-year follow-up study

Hemodynamic forces play a role in the development of atherosclerosis. Their variations with age have been assessed in cross-sectional, but not longitudinal, studies. The aim of the present study was to investigate in both sexes the age-dependent change in wall shear stress and arterial stiffness in subjects studied twice 12 years apart. Forty-eight subjects (15 women and 33 men) were studied twice 12 years apart. Subjects underwent blood viscosity measurement and echo-Doppler of carotid arteries, from which the intima–media thickness (IMT) was measured and the wall shear stress and Peterson’s elastic modulus were calculated. Blood viscosity increased in both sexes, more markedly in women (+13.2%) than men (+7.2%). Common carotid diameter increased in both sexes, but in men (+7.4%) more than in women (+5.5%). Peak and mean velocity decreased at follow-up by 10.7% and 18.9% in women and by 14.2% and 18.1% in men. Peak and mean shear stress significantly decreased in men by 13.0% and 17.5%, respectively, while in women only the mean shear stress was reduced (−11.8%). The IMT of the common carotid artery increased by 29% in women and 20% in men. Arterial stiffness significantly increased (+74.5% in women and +28.0% in men). The percent change in mean shear stress was significantly and inversely associated with the percent change in IMT. The data of this study show that, in a middle-aged population observed for almost 12 years, the mean shear stress decreases significantly in both sexes, while peak shear stress decreases significantly only in men. The change in mean shear stress is inversely associated with changes in IMT. Arterial stiffness, on the other hand, increases with aging.     

Contribution of blood viscosity in the assessment of flow-mediated dilation and arterial stiffness

Flow-mediated dilation (FMD) is a non-invasive index of endothelial function. In an attempt to standardize FMD for shear stimulus, shear rate (velocity/diameter), rather than shear stress (viscosity*velocity/diameter), is commonly used as a surrogate measure, although it is limited by individual differences in blood viscosity. The purpose of this study was to determine the contribution of whole blood viscosity to FMD and other key measures of vascular function. Blood viscosity, FMD, carotid artery compliance, and carotid-femoral pulse wave velocity (cfPWV) were measured in 98 apparently healthy adults varying widely in age (18-63 years). Whole blood viscosity was not significantly correlated with FMD, cfPWV, or carotid artery compliance. Shear rate was a stronger correlate with FMD than shear stress that takes blood viscosity into account (r = 0.43 vs 0.28). No significant differences were observed between whole blood viscosity and traditional risk factors for cardiovascular disease. Age was positively correlated with cfPWV (r = 0.65, p < 0.001) and negatively correlated with FMD (r = -0.24, p < 0.05) and carotid artery compliance (r = -0.45, p < 0.01). Controlling for viscosity did not reduce the strength of these relations. These results indicate that whole blood viscosity does not significantly impact measures of vascular function and suggests that the common practice to use shear rate, rather than shear stress, in the adjustment of FMD is valid.     

Haemoconcentration, shear-stress increase and carotid artery diameter regulation after furosemide administration in older hypertensives

The aim of the present study was to determine whether changes of carotid wall shear stress induced by changes in blood viscosity after diuretic administration cause carotid arterial dilatation in elderly hypertensives, as reported in the cat. Arterial wall shear rate (ultrasound technique, profilmeter FRP III), the systo-diastolic diameter (echotracking technique) and the mean blood flow velocity and volume of the common carotid artery, the blood viscosity (rotational viscometer) and the finger arterial blood pressure (Finapress Ohmeda) were measured in 12 young volunteers (aged 25+/-2 years) and in 12 elderly hypertensives (aged 80+/-4 years) treated with short-acting calcium antagonists up to 24h before the study, both at baseline and after intravenous furosemide infusion (0.5mg/min), when the haematocrit had increased by at least two percentage points.After furosemide administration the mean arterial blood pressure decreased and blood viscosity and carotid systolic shear stress increased in both groups. However, common carotid artery diameter increased only in the young controls but not in the elderly hypertensives. These data show that an increase in carotid shear stress caused by haemoconcentration induces carotid vasodilatation only in young healthy subjects, and not in elderly hypertensives. This effect may be related to impaired endothelium function and/or arterial wall mechanics.     

Abnormal wall shear conditions in the brachial artery of hypertensive patients

Brachial artery wall shear phenomena were studied in 20 untreated essential hypertensive patients and in 11 normotensive controls of similar age. A pulsed-Doppler velocimeter was used to measure brachial artery internal diameter and mean cross-sectional and systolic centreline blood velocities. A coaxial-cylinder viscometer was used to measure blood viscosity at a shear rate of 96 s-1. A Poiseuille model of velocity distribution across the arterial lumen was used to determine wall shear rate and stress from, respectively, the ratio of blood velocity to arterial diameter and the product of shear rate and blood viscosity. Mean and systolic shear rates and stresses were calculated using, respectively, mean cross-sectional and systolic centreline blood velocities. Hypertensive patients had larger brachial artery diameters (P less than 0.001), lower systolic centreline and mean cross-sectional blood velocities (P less than 0.001, P less than 0.05), higher blood viscosity (P less than 0.001), lower mean and systolic wall shear rates (P less than 0.01, P less than 0.001) and lower systolic wall shear stress (P less than 0.05) than normotensive controls. In all subjects, mean blood pressure was negatively correlated both with mean and systolic shear rates (r = -0.38, P less than 0.05;r = -0.45, P less than 0.01). Thus the hypertensive state was associated with decreases in both mean and systolic wall shear rates, and in systolic wall shear stress. These shear abnormalities merit attention because of the atherogenic effect of low-shear conditions.     

Non invasive evaluation of endothelial shearing phenomena in human arteries. Application to essential hypertension

Pulsatile wall shear conditions close to the brachial artery were evaluated in 11 normotensive and in 19 hypertensive patients of similar age by determining arterial diameter and centerline blood velocity with a pulsed Doppler and blood viscosity at 96 sec-1 with a coaxial cylinder viscometer. A Womersley model of intraluminal distribution of blood velocities enabled to determine from unsteadiness parameter alpha of Womersley, arterial diameter and maximal minimal and pulse (maximal-minimal) values of centerline velocity, the maximal minimal and pulse shear rate and shear stress (product between shear rate and viscosity) close to the endothelium. Compared to normotensives hypertenvises had higher arterial diameter (p less than 0.001), lower maximal minimal and pulse centerline velocities (p less than 0.001, p less than 0.01, p less than 0.001) higher blood viscosity (p less than 0.001), lower maximal, minimal and pulse wall shear rate (p less than 0.001, p less than 0.05, p less than 0.001) and lower maximal minimal and pulse shear stress (p less than 0.01). In the overall normotensive and hypertensive group, mean blood pressure negatively correlated to maximal minimal and pulse shear rates (r = -0.65; r = -0.45, r = -0.63) and to maximal, minimal and pulse shear stress (r = -0.46; r = -0.37, r = -0.48). Thus, hypertension is associated with a reduction of oscillating shear conditions in the viscosity of the brachial artery wall which might in long term influence structural and/or functional response to the endothelium.     

Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation

Interactions between the endothelium and erythrocytes may contribute to the vascular complications of sickle cell disease (SCD). Endothelium-derived nitric oxide (NO) plays a major role in the regulation of vasomotor tone in response to wall shear stress (WSS) variations and pharmacologic stimuli. However, little is known about endothelial NO production in patients with steady-state SCD. We investigated endothelial NO production in response to flow or vasoactive agonists in 16 homozygous patients with steady-state SCD and 15 controls. Flow-mediated dilation (FMD), arterial diameter changes in response to 100% oxygen inhalation, blood viscosity, and calculated WSS were determined in all patients and controls. At baseline, WSS was higher in SCD patients than in controls, whereas arterial diameter was similar. In patients with SCD, FMD was impaired (1.73% +/- 0.44% vs 3.97% +/- 0.24% in the controls, P <.001) and vasoconstriction in response to 100% oxygen was abolished. Using venous occlusion plethysmography, forearm blood flow (FBF) was evaluated in response to acetylcholine, nitro-monomethyl-L-arginine (L-NMMA), and sodium nitroprusside (SNP) in subgroups of 9 controls and 7 patients with SCD. Acetylcholine induced a significantly greater FBF increase in the patients (9.7 +/- 2.9 mL/min/100 mL of forearm volume vs 2.5 +/- 1.5 mL/min/100 mL in the controls, P <.001), whereas responses to L-NMMA and SNP were similar. These results suggest that endothelial dysfunction may prevent the arterial diameter of patients with SCD from adapting to chronic or acute shear stress elevations. This may contribute to the pathophysiology of vaso-occlusive crisis in patients with SCD.     

Paradoxal diminution of resistance of the large arteries in human essential hypertension

Segmental pressure drop and longitudinal resistance of brachial artery were evaluated in 11 normotensive (NT) and 19 hypertensive (HT) subjects of similar age by measuring arterial diameter (D), blood velocity (V) and flow (Q) with pulsed Doppler and blood viscosity (mu) at 96 sec-1 with a coaxial cylinder viscometer. Mean pressure drop (delta P) per unit of length of artery was calculated according to the relation delta P = 4 tau/D, where tau is the mean wall shear stress evaluated on the basis of a Poiseuille velocity profile by the formula: r = vV/D. Brachial artery resistance per unit of length was deduced as the (delta P/Q) ratio. (table; see text) In the overall normotensive and hypertensive group, (n = 30), pressure drop (delta P) was negatively correlated with mean blood pressure (r = -0.55, P less than 0.01). Despite increased viscosity hypertensive patients have a decreased resistance of large arteries whose mechanisms include a reduction in shear stress close to the endothelium and a dilation of the conduit artery; these two abnormalities contribute to decrease the viscous force of the circulating blood column against the arterial wall.     

Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo: relevance to endothelial dysfunction in hypercholesterolemia

Flow-mediated dilatation (FMD) of conduit arteries is dependent on an intact endothelium, although the mechanisms are not fully understood. Using high-resolution ultrasound, we examined the role of endothelial mediators in radial artery dilatation in response to transient (short period of reactive hyperemia) and sustained (prolonged period of reactive hyperemia, hand warming, or an incremental infusion of acetylcholine into the distal radial artery) hyperemia. After short episodes of reactive hyperemia, FMD was abolished by local infusion of the nitric oxide synthesis inhibitor N:(G)monomethyl-L-arginine (5.3+/-1.2% versus 0.7+/-0.7%, P:<0.001). In contrast, basal vessel diameter and dilatation after prolonged episodes of reactive hyperemia, hand warming, and distal infusion of acetylcholine were not attenuated by nitric oxide synthesis inhibition. Inhibition of cyclooxygenase or local autonomic nervous system blockade also had no effect on FMD. Patients with hypercholesterolemia exhibited reduced FMD in response to transient hyperemia, but the response to sustained hyperemia was normal. These data suggest heterogeneity of endothelial responses to blood flow that are dependent on the characteristics of the flow stimulus. Dilatation after brief episodes of hyperemia is mediated by release of nitric oxide, whereas dilatation during sustained hyperemia is unaffected by NO synthesis inhibition. Hypercholesterolemia seems to differentially affect these pathways with impairment of the nitric oxide-dependent pathway and preservation of non nitric oxide-mediated dilatation to sustained flow stimuli.     

Endothelial function in chronic congestive heart failure.

There is evidence that the endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide. The hypothesis that an impairment of this mechanism is involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure (CHF) was tested. Acetylcholine and N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis from L-arginine, were infused in the brachial artery of healthy volunteer subjects (controls) and patients with severe CHF. The radial artery diameter was determined by a high-precision A-mode ultrasound device, using a 10 MHz probe. Forearm blood flow was calculated from vessel diameter and blood flow velocity measured simultaneously by Doppler. The blood flow response to acetylcholine was blunted in patients with CHF compared with that in control subjects. In contrast, the decrease in blood flow induced by L-NMMA was exaggerated in CHF, and the blood flow response to nitroglycerin was preserved. The changes in radial artery diameter induced by acetylcholine and L-NMMA were not significant in control subjects and CHF patients, but dilation of the radial artery by nitroglycerin was significantly reduced in CHF. The results demonstrate an impaired endothelium-dependent dilation of forearm resistance vessels in CHF, suggesting a reduced release of nitric oxide on stimulation. In contrast, the basal release of nitric oxide from endothelium of forearm resistance vessels is preserved or may even be enhanced, and may play an important compensatory role in chronic CHF by antagonizing neurohumoral vasoconstrictor forces in CHF.     

Effect of smoking on blood viscosity and arterial rigidity in normal and hypertensive subjects

The purpose of the study was to assess whether cigarettes smoking could induce blood hyperviscosity and arterial rigidity in 30 normotensive and 70 hypertensive men aged from 24 to 65 years. Of those, 20 normotensive and 20 hypertensive were cigarettes smokers, while the remaining subjects were non smokers. Age and weight were similar in the 4 groups of subjects. A couette viscometer with coaxial cylinders allowed the measurements of blood viscosity over a wide range of shear rates (0.033 to 241 sec-1) mimicking the flow condition of the circulation, and two strain gauge transducers permitted the measurements of the brachial to radial pulse wave velocity as an index of arterial wall distensibility. In normotensive subjects cigarettes smoking increased pulse wave velocity from 7.1 + 1 to 9.2 + 0.6 m/sec. (P less than 0.05) as well as blood viscosity, which increased both at higher shear rates (+10% from 52 to 241 sec-1, P less than 0.05) and lower shear rates (+20% from 11.2 to 0.2 sec-1, P less than 0.02). In hypertensives, cigarettes smoking increased pulse wave velocity (9.8 + 0.3 to 11.3 + 0.4; P less than 0.05) and blood viscosity (4% at higher shear rate P less than 0.05 and 10% at lower shear rates P less than 0.02). Although hypertensive patients had increased pulse wave velocity and blood viscosity compared to normotensive controls, these variables were not significantly different when hypertensive non smokers were compared to normotensive. The present study demonstrated that cigarettes smoking produced in normotensive and hypertensive men significant rheological disturbances of flow and wall arteries.2     

Exercise training in coronary artery disease and coronary vasomotion

Exercise training has assumed a major role in cardiac rehabilitation, mostly because of its positive effects on myocardial perfusion in patients with coronary artery disease. The mechanisms involved in mediating this key effect have long been debated: both regression of coronary artery stenosis and improvement of collateralization have been suggested as potential adaptations. However, the comparatively minute changes in luminal diameter and myocardial contrast staining do not fully explain the significant changes in myocardial perfusion. During the last decade, endothelial dysfunction was identified as a trigger of myocardial ischemia. The impaired production of endothelium-derived nitric oxide (NO) in response to acetylcholine and flow leads to paradoxic vasoconstriction and exercise-induced ischemia. Recently, it was confirmed in humans that training attenuates paradoxic vasoconstriction in coronary artery disease and increases coronary blood flow in response to acetylcholine. Data from cell-culture and animal experiments suggest that shear stress acts as a stimulus for the endothelium to increase the transport capacity for L-arginine (the precursor molecule for NO), to enhance NO synthase activity and expression, and to increase the production of extracellular superoxide dismutase, which prevents premature breakdown of NO. Exercise also affects the microcirculation, where it sensitizes resistance arteries for the vasodilatory effects of adenosine. These novel findings provide a pathophysiological framework to explain the improvement of myocardial perfusion in the absence of changes in baseline coronary artery diameter. Because endothelial dysfunction has been identified as a predictor of coronary events, exercise may contribute to the long-term reduction of cardiovascular morbidity and mortality.     

Contrary effects of hypertension and cigarette smoking on the conditions of wall shear in large arteries

Systolic wall shear conditions were studied in the brachial artery of 4 groups of subjects including 11 non-smokers normotensives (NSNT), 25 non smokers hypertensives (NSHT), 21 smokers normotensives (SNT) and 10 smokers hypertensives (SHT). Brachial artery diameter (D) and systolic centerline blood velocity (VCLS) were measured with a pulsed Doppler device and blood viscosity at 96 sec-1 was measured with a coaxial cylinder viscometer. The wall shear rate (gamma S) corresponding to systolic velocity was calculated using a Womersley model of pulsatile flow according to the formula: alpha = (D/2) (omega/mu) 1/2, omega being the angular pulse frequency and mu the kinematic viscosity. The wall shear stress was then calculated as the product between wall shear rate and viscosity. The analysis of results in the 4 groups showed that both hypertension and smoking increased blood viscosity bu their effects on wall shear were opposite since hypertension decreased shear and stress while smoking did not change it. However, in hypertensive patients, smoking induced a clear elevation in wall shear rate and stress, whereas in smokers hypertension did not change shear conditions. Thus, opposite and interactive effects of hypertension and smokers exist on large artery wall shear phenomena which could induce differences in response of functional and structural endothelial cells to these two vascular risk factors.     

Comparison of 99mTc-teboroxime with thallium for myocardial imaging in the presence of a coronary artery stenosis

BACKGROUND. This study tested the hypotheses in the setting of a coronary artery stenosis that 1) planar 99mTc-teboroxime myocardial scans are capable of providing a good estimate of relative coronary flow reserve, and 2) delayed washout of the tracer from the myocardium is a marker of reduced myocardial blood flow and, in certain cases, myocardial ischemia. METHODS AND RESULTS. Experiments were conducted in eight closed-chest domestic swine prepared with an artificial stenosis that reduced diameter of the left anterior descending coronary artery by 80%. Measurements of hemodynamics, regional myocardial blood flow, oxygen, and lactate metabolism were made 1) at baseline, 2) after 5 minutes of intravenous infusion of adenosine and neosynephrine ("stress"), and 3) at recovery 2 hours after discontinuing the adenosine/neosynephrine infusion. Simultaneous intravenous injection of teboroxime (approximately 9 mCi) and thallium (approximately 3.5 mCi) was made at peak stress, and serial planar teboroxime imaging began 1-2 minutes later. Scans were made in dynamic mode for 30 seconds each for 7 minutes after which a stress thallium scan (7 minutes acquisition) was obtained. A redistribution thallium scan was made 2 hours later after which a repeat teboroxime injection followed by serial imaging for 7 minutes was performed. The animal was then killed, and the heart removed for determination of microsphere activity. Under baseline conditions, transmural myocardial blood flow (ml/min/g) distal to the stenosis (1.06 +/- 0.17) was reduced (p less than 0.01) compared with the normally perfused circumflex zone (1.50 +/- 0.31). In response to intravenous infusion of adenosine/neosynephrine, flow increased (p less than 0.01) compared with baseline in both distal (2.00 +/- 0.84) and circumflex (4.67 +/- 1.55) zones. However, the distal : circumflex flow declined (0.45 +/- 0.17) compared with baseline (0.73 +/- 0.17; p less than 0.01). Two hours later flow had returned to baseline levels in both zones, and lactate production during stress (-41.7 +/- 37.5 mumol/min/100 g) had reverted to consumption (13.6 +/- 7.7; p less than 0.05). Analysis of stress teboroxime scans demonstrated 1) an increase (p less than 0.01) in the ischemic : normal zone (IZ:NZ) count between 30-second (0.50 +/- 0.14) and 7-minute scans (0.61 +/- 0.11); 2) a good correlation between the 30-second scan IZ:NZ count and the stress distal : circumflex flow (0.45 +/- 0.17; r = 0.74; p less than 0.05; slope = 0.90; intercept = 0); and 3) a close correlation between the IZ:NZ count of the 7-minute scan (0.61 +/- 0.11) and the recovery distal : circumflex flow (0.69 +/- 0.21; r = 0.89; p less than 0.01). The IZ:NZ count also increased (p less than 0.01) between 30-second (0.65 +/- 0.15) and 7-minute (0.72 +/- 0.14) scans following rest injection of teboroxime. As anticipated, serial thallium scans demonstrated evidence of redistribution between stress (IZ:NZ count = 0.62 +/- 0.08) and recovery (IZ:NZ count = 0.75 +/- 0.06; p less than 0.01) time points. The stress thallium scan IZ:NZ, however, was greater than that of the 30-second teboroxime scan as well as that of the stress distal : circumflex flow. CONCLUSIONS. Accordingly, the data indicate that 1) myocardial imaging with 99mTc-teboroxime is valuable in the noninvasive assessment of relative coronary flow reserve and that 2) delayed washout of the tracer from the myocardium reflects reduced myocardial blood flow and, under conditions comparable to those of the present study, may be a marker of myocardial ischemia.     

Reversibility of coronary endothelial vasomotor dysfunction in idiopathic dilated cardiomyopathy: acute effects of vitamin C.

In patients with idiopathic dilated cardiomyopathy, endothelium vasomotor function is disturbed. Increased oxidative stress and the consecutive formation of oxygen free radicals have been implicated as one possibility for this observation, suggesting that nitric oxide (NO) is inactivated by oxygen free radicals. We tested the hypothesis that the antioxidant, vitamin C, may improve endothelial function in idiopathic dilated cardiomyopathy. In 11 patients, the endothelium-dependent vasomotor response of the left anterior descending coronary artery to intracoronary acetylcholine (ACh) infusion (1/2 x 10(-6) mol/L, 1/4 x 10(-5) mol/L; respectively) was determined before and immediately after intravenous infusion of 3 g of vitamin C. Coronary cross-sectional diameter was obtained by quantitative coronary angiography, average peak velocity was measured by an intracoronary Doppler flow wire, and coronary blood flow (CBF) was calculated. Maximum cross-sectional diameter was determined after administration of nitroglycerin. Dose-dependent ACh showed a decrease in cross-sectional diameter (-5% to -7%, p <0.05) and an increase in average peak velocity (+16% to +25%, p <0.05); the CBF was unchanged (+1% to -2%, p = NS). After vitamin C infusion, the cross-sectional diameter increased in a dose-dependent manner from +11% to +15%, the average peak velocity increased from +20% to + 41% (p <0.05), and the CBF increased from +38% to + 82% (p <0.01, p <0.001, respectively). Thus, patients with idiopathic dilated cardiomyopathy had endothelial dysfunction, and administration of vitamin C reversed endothelium-dependent dysfunction.     

Control of shear stress in the epicardial coronary arteries of humans: impairment by atherosclerosis

Altered arterial wall shear stress may adversely affect vascular endothelium and contribute to atherogenesis. This study examined the hypothesis that, in humans, dilation of normal coronary arteries with increased flow limits increases in shear stress and that loss of flow-mediated dilation in atherosclerosis results in failure to control shear stress. Coronary blood flow was increased by infusing adenosine (0.022 to 2.2 mg/min) through a 2.5F Doppler flow catheter positioned in the middle segment of the left anterior descending coronary artery in 8 patients with mild atherosclerosis but no flow-limiting stenosis and in 10 patients with entirely smooth coronary arteries. Quantitative angiography and coronary flow velocity were used to estimate shear stress in a proximal segment of the left anterior descending artery exposed to increased flow, but not to adenosine. The peak increase in blood flow was the same in smooth (371 +/- 65%) and irregular (377 +/- 50%) arteries. However, at peak flow, dilation was greater in smooth segments (16.3 +/- 2.7%) than in irregular segments (2.0 +/- 1.5%) (p less than 0.001). In each patient, smooth segments dilated with increasing shear stress (slope 7.4 +/- 0.9%), whereas irregular segments dilated less (slope 0.9 +/- 0.6%) and showed greater increases in shear stress (p less than 0.01). The peak increase in shear stress was less in smooth (189 +/- 23%) than in irregular (365 +/- 52%) segments (p less than 0.01). These results suggest a control mechanism in normal coronary arteries whereby increases in shear stress stimulate vasodilation and thus limit further increases in this force at the endothelial surface.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distributions of wall shear stress in venular convergences of mouse cremaster muscle

OBJECTIVE: Wall shear stress regulates a variety of vascular functions and can be affected by variations in blood viscosity and wall shear rate independently. Therefore, the distribution of wall shear stress was characterized in converging flow regions of postcapillary venules to identify the relative contributions of shear rate and viscosity to wall shear rate and to determine whether venular branching directly affects the local shear environment. METHODS: Blood viscosity was evaluated as a function of vessel diameter and hematocrit, determined from fluorescent red blood cell (RBC) flux. Wall shear rate was measured directly from velocity profiles acquired using fluorescent RBC tracking or was estimated assuming Poiseuille flow conditions. Wall shear stress was calculated for measurements made across regions of converging flow. RESULTS: Measurements of wall shear stress showed no significant variation with location across the convergence (p < 0.9). Measures of viscosity showed little variation, for local measures of hematocrit (2.9 +/- 0.1 cp; coefficient of variation [CV]: 12%) or systemic hematocrit (3.4 +/- 0.1 centipoise [cp]; CV: 14%). Measures of wall shear rate showed greater variability for both direct measurements (61.2 +/- 8.7s; CV: 92%) and estimates assuming Poiseuille flow (122.7 +/- 15.7 s; CV: 83%). CONCLUSIONS: Variations in wall shear stress are independent of location through a venular convergence in contrast to arteriolar bifurcations. In addition, wall shear rate is significantly more variable than viscosity and, therefore, primarily accountable for wall shear stress variations in postcapillary venules.     

Mesenteric arteries responsiveness to acute variations of wall shear stress is impaired in rats with liver cirrhosis

Abstract Objective. In liver cirrhosis, excessive splanchnic vasodilation is due to abnormal synthesis of endogenous vasodilators and to decreased sensitivity to vasoconstrictors. The role of mechanical stimuli such as wall shear stress (WSS) on splanchnic circulation remains unclear. The aim of this study was to assess the vasodilation induced by wall shear stress (WSS) and acute changes in blood flow in the mesenteric arteries in an experimental model of liver cirrhosis. Materials and Methods. The effect of acute changes in intraluminal flow (0, 10, and 20 μl/min) and WSS on the diameter of the mesenteric arteries (diameters <500 μm) of control and cirrhotic rats was assessed, at baseline and after the inhibition of nitric oxide synthase, cyclooxygenase and hemeoxygenase. Concentration-response curves to phenylephrine were also obtained. Results. In controls, the increase in intraluminal flow led to a significant increase in arterial diameter (p < 0.05), while WSS remained stable; the effect was maintained in vessels pre-constricted with phenylephrine, blocked by the exposure to indomethacin and L-NAME and restored by the subsequent addition of chromium mesoporphyrin (p < 0.05). In cirrhotic arteries, arterial diameters did not change in response to acute increase in flow, neither at baseline nor after exposure to indomethacin and L-NAME, while WSS increased (p < 0.01). Responsiveness to flow was partially restored (p < 0.05) after exposure of the arteries to chromium mesoporphyrin in addition to indomethacin and L-NAME. Conclusions. Arteries from cirrhotic rats showed an abolished responsiveness to acute variations in flow, which exposes the mesenteric endothelium to sudden variations in WSS.