In-vivo measurements of wall shear stress in human coronary arteries

BACKGROUND: Wall shear stress (WSS) is closely associated with arteriosclerosis. WSS values for various vessels and species are available, but fully in-vivo measurements in human coronary arteries have not yet been reported. OBJECTIVE: To measure WSS in undiseased coronary arteries of adult patients at rest. METHODS: We recorded the temporal average value (APV) of the instantaneous maximal blood velocity in the three vessel segments of angiographically normal coronary artery bifurcations in 21 patients undergoing cardiac catheterization to treat various diseases by means of a 0.036 cm Doppler wire (FloWire). In total, 36 bifurcations were examined. The 36 x 3 cross-sectional areas (CSA) were determined by means of a three-dimensional angiographic technique. The three flows, Q1 (inflow), Q2, and Q3 of each bifurcation were calculated according to Q=0.5 x APV x CSA. For each segment, WSS was calculated as WSS=32 eta Q/(pi D3) (where blood viscosity eta=3.5 mPa s and D is vessel diameter). Only the 54 WSS values obtained from the 18 flow triplets which satisfied the equation Q1/(Q2+Q3)=1 better than did the 18 other ones were retained. RESULTS: The 54 WSS values ranged from 0.33 to 1.24 Pa (mean 0.68 Pa, SEM, 0.027 Pa). They did not depend significantly on Q (r=0.07; P=0.60) and the CSA (r=0.24, P=0.08) but the second relationship approached significance. CONCLUSION: The obtained mean WSS value (0.68 Pa) is half the value predicted for coronary arteries from optimality principles. It is also smaller than many values reported for human carotid, renal, and femoral arteries.     

Determination of in vivo velocity and endothelial shear stress patterns with phasic flow in human coronary arteries: a methodology to predict progression of coronary atherosclerosis

Background Although the coronary arteries are equally exposed to systemic risk factors, coronary atherosclerosis is focal and eccentric, and each lesion evolves in an independent manner. Variations in shear stress elicit markedly different humoral, metabolic, and structural responses in endothelial cells. Areas of low shear stress promote atherosclerosis, whereas areas of high shear stress prevent atherosclerosis. Characterization of the shear stresses affecting coronary arteries in humans in vivo may permit prediction of progression of coronary disease, prediction of which plaques might become vulnerable to rupture, and prediction of sites of restenosis after percutaneous coronary intervention. Methods To determine endothelial shear stress, the 3-dimensional anatomy of a segment of the right coronary artery was determined immediately after directional atherectomy by use of a combination of intracoronary ultrasound and biplane coronary angiography. The geometry of the segment was represented in curvilinear coordinates and a computational fluid dynamics technique was used to investigate the detailed phasic velocity profile and shear stress distribution. The results were analyzed with several conventional indicators and one novel indicator of disturbed flow. Results Our methodology identified areas of minor flow reversals, significant swirling, and large variations of local velocity and shear stress—temporally, axially, and cirumferentially—within the artery, even in the absence of significant luminal obstruction. Conclusions We have described a system that permits, for the first time, the in vivo determination of pulsatile local velocity patterns and endothelial shear stress in the human coronary arteries. The flow phenomena exhibit characteristics consistent with the focal nature of atherogenesis and restenosis. (Am Heart J 2002;143:931-9.)     

Association of coronary shear stress with endothelial function and vascular remodeling in patients with normal or mildly diseased coronary arteries

BACKGROUND: The relationship between coronary remodeling, shear stress and endothelial function remains unclear. OBJECTIVE: The present study investigated the effects of mechanical factors on structure and function of epicardial coronary arteries. METHODS: Patients (group 1: %area stenosis<40%, n=55; or group 2: %area stenosis>or=40%, n=17) with a discrete mildly stenotic lesion (%diameter stenosis<30%) underwent intravascular ultrasound examination of the left anterior descending coronary artery for determination of vessel area, lumen area, plaque area, cross-sectional areas at reference segments, and remodeling index (the ratio of vessel area at the culprit lesion to vessel area at the proximal reference site). Further, vascular reactivity was examined using intracoronary administration of acetylcholine, papaverine, and nitroglycerin. RESULTS: Vessel area significantly correlated with plaque area in both groups (r=0.65, P<0.0001 and r=0.85, P<0.0001). Group 1 showed significantly greater acetylcholine-induced percentage changes in coronary blood flow (67+/-70 vs. 16+/-75%, P<0.05) and coronary artery diameter (-7+/-18 vs.-32+/-31%, P<0.01) and also significantly smaller coronary wall shear stress (65+/-27 vs. 81+/-32 dynes/cm, P<0.05) than group 2. The percentage increase in coronary blood flow induced by acetylcholine was significantly and positively correlated with remodeling index in group 1 (r=0.64, P<0.0001) but not in group 2 (r=-0.03, P=0.90) and was also significantly and positively correlated with coronary wall shear stress in group 1 (r=0.46, P<0.001) but not in group 2 (r=-0.33, P=0.19). CONCLUSIONS: Endothelium-dependent vasodilation in the resistance coronary artery correlates with remodeling via increased wall shear stress when target lesions %area stenosis is <40%.     

Usefulness of shear stress pattern in predicting neointima distribution in sirolimus-eluting stents in coronary arteries

The true 3-dimensional neointimal thickness distribution in sirolimus-eluting stents was investigated in relation to the shear stress distribution, which was obtained from computational fluid dynamics calculations. Small pits were observed between the stent struts in all patients, and a significant inverse relation between neointimal thickness and shear stress was found, indicating that deeper pits were present in the outside curve of the stented segments.     

急性冠脉综合征氧化应激损伤及与低密度脂蛋白的相关性

目的:通过检测急性冠脉综合征(ACS)患者体内晚期蛋白氧化产物(AOPP)、低密度脂蛋白(LDL)、丙二醛(MDA)的水平来探讨氧化应激损伤与急性冠脉综合症发生发展的关系。方法:入选73例急性心肌梗塞(AMI)(含46例择期PCl和27例急诊PCI)、49例不稳定性心绞痛(UAP)及21例非冠心病患者,均经造影证实。于入院即刻、24 h和48 h采集外周静脉血标本。紫外荧光光度法测定AOPP浓度;硫代巴比妥酸(TBA法)光度法测定MDA浓度等,进行Pearson相关分析。结果:AOPP浓度在AMI组(AMI择期组较急诊PCI组更高),UAP组明显升高(P<0.05);UAP组入院48 h与入院即刻比较AOPP浓度明显下降(P<0.05);AMI择期PCI组AOPP浓度与LDL-C呈正相关,r=0.370(入院即刻)、r=0.422(入院24 h)、r=0.559(入院48 h)。MDA浓度:与非冠心病组对应各时间点比较,AMI择期PCI组、AMI急诊PCI组的均升高(P<0.05~<0.01),而UAP组无显著改变(P>0.05)。结论:ACS患者血浆中AOPP、MDA浓度显著升高;AMI患者中AOPP水平与LDL呈止相关。氧化应激可能是AS发生发展过程中的重要环节,并与脂代谢失调有一定的相关性。     

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)     

Thrombolysis in myocardial infarction frame count with angiographically normal coronary arteries and its relationship to ST-segment depression

BACKGROUND: The thrombolysis in myocardial infarction frame count (TFC) has been proposed as a simple, reproducible, objective and quantitative method to assess coronary blood flow. However, the TFC in normal coronary arteries has not been investigated in detail. The aim of this study was to determine normal TFC values and investigate their correlation with ST-segment depression during exercise testing (ET). METHODS AND RESULTS: The TFC was measured in 116 cases with normal coronary arteries who underwent ET. The ST segment was evaluated on 12-lead electrocardiograms at 60 ms after the J-point. Horizontal or downsloping ST-segment depression of > or = 0.5 mm was recorded and the sum of the depressions was calculated. When ST-segment depression > or = 1 mm compared to the level of PR segment on two or more leads was detected, the test was accepted as positive. The TFC for the left anterior descending coronary artery (LAD) was significantly higher than those for the left circumflex coronary artery (LCx) and the right coronary artery (RCA). The TFC of coronary arteries was significantly higher in patients with ET positive (for LAD, 39.5 +/- 10.7 compared with 30.1 +/- 7.6 frames; for LCx, 29.2 +/- 9.3 compared with 23.6 +/- 6.5 frames; and for RCA, 30.7 +/- 11 compared with 23.7 +/- 7 frames; P < 0.001 for overall comparisons). Women had a lower TFC than men in the LAD. Moreover, it was determined that the TFC values for the LAD, LCx and RCA significantly correlated with the sum of ST-segment depression (r = 0.57, r = 0.46 and r = 0.41, respectively, P < 0.001 for overall correlations). It was also determined that the TFC was affected by the proximal diameter of the coronary arteries. CONCLUSIONS: The results of this study highlight the differences of the TFC in normal LAD, LCx and RCA. In patients with normal coronary arteries, the fact that the TFC is higher in ET-positive than in ET-negative patients may explain false positive results of ET. Sex and coronary artery diameter should be taken into consideration in evaluating the TFC.     

Rapamycin modulates the eNOS vs. shear stress relationship

AIMS: Studies in animals and patients indicate that rapamycin affects vasodilatation differently in outer and inner curvatures of blood vessels. We evaluated in this study whether rapamycin affects endothelial nitric oxide synthase (eNOS) responsiveness to shear stress under normo- and hypercholesteraemic conditions to explain these findings. METHODS AND RESULTS: Shear stress levels were varied over a large range of values in carotid arteries of transgenic mice expressing human eNOS fused to enhanced green fluorescence protein. The mice were divided into control, low-dose rapamycin (3 microg/kg/day), and high-dose rapamycin (3 mg/kg/day) groups and into normocholesteraemic and hypercholesteraemic (ApoE-/- on high cholesterol diet for 3-4 weeks) groups. The effect of rapamycin treatment on eNOS was evaluated by quantification of eNOS expression and of intracellular protein levels by en face confocal microscopy. A sigmoid curve fit was used to described these data. The efficacy of treatment was confirmed by measurement of rapamycin serum levels (2.0 +/- 0.5 ng/mL), and of p27kip1 expression in vascular tissue (increased by 2.4 +/- 0.5-fold). In control carotid arteries, eNOS expression increased by 1.8 +/- 0.3-fold in response to rapamycin. In the treated vessels, rapamycin reduced maximal eNOS expression at high shear stress levels (>5 Pa) in a dose-dependent way and shifted the sigmoid curve to the right. Hypercholesteraemia had a tendency to increase the leftward shift and the reduction in maximal eNOS expression (P = 0.07). CONCLUSION: Rapamycin is associated with high eNOS in low shear regions, i.e. in atherogenic regions, protecting these regions against atherosclerosis, and is associated with a reduction of eNOS at high shear stress affecting vasomotion in these regions.     

Low wall shear stress in carotid arteries in subjects with left ventricular hypertrophy

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular complications including atherosclerosis. The close linkage between LVH and carotid atherosclerosis has been the focus of much research. However, the underlying mechanism linking the two conditions is not fully understood. Low wall shear stress contributes to intimal thickening and atherosclerosis development as a local mechanism. In the present study, we investigated the relationship between wall shear stress and LVH in subjects with risk factors for atherosclerosis. Eighty subjects with at least one risk factor for atherosclerosis; ie, hypertension, diabetes mellitus, hyperlipidemia, or smoking, were enrolled. Intimal-medial thickness (IMT), number of plaques, internal dimensions, and blood flow velocity in the common carotid artery were evaluated. Wall shear stress was calculated using a Poiseuillean parabolic model of velocity distribution: shear stress = 4 x blood viscosity x central flow velocity/internal dimension. Subjects were divided into two groups; LVH(-) (n = 36) and LVH(+) (n = 44), according to their left ventricular mass index (LVMI). Mean shear stress and systolic peak shear stress were significantly lower in subjects with LVH compared with subjects without LVH. Furthermore, mean shear stress (r = -0.42, P < .0001) and peak shear stress (r = -0.31, P < 0.01) were significantly inversely related to LVMI. Stepwise regression analysis revealed that wall shear stress independently correlated with LVMI as well as IMT. These results indicate that low shear stress could function as a local factor in the development of atherosclerosis in subjects with LVH.     

Variable patterns of ST-T abnormalities in patients with left ventricular hypertrophy and normal coronary arteries.

BACKGROUND--Classically, the ST-T configuration in the electrocardiogram of patients with left ventricular hypertrophy is said to have a typical pattern of ST depression together with asymmetrical T wave inversion (the so-called left ventricular strain pattern). However, many patients with left ventricular hypertrophy may also have ischaemic heart disease. To revise the electrocardiographic criteria for left ventricular hypertrophy the ST-T configuration in patients with left ventricular hypertrophy documented by echocardiography and with normal coronary arteries was assessed. METHODS--24 patients were selected for this study. All had left ventricular hypertrophy documented by echocardiography, normal coronary arteries by cardiac catheterisation, and ST and/or T wave abnormalities in the lateral leads of their electrocardiogram. There were eight patients with aortic valve disease and 16 with hypertension who had coronary angiography as part of an investigation into the risk factors of sudden cardiac death caused by hypertensive left ventricular hypertrophy. No patient was receiving digitalis preparations or had electrolyte disturbances, and none had a previous myocardial infarction or ventricular conduction defect. RESULTS--Typical electrocardiographic evidence of left ventricular strain was found in approximately two thirds (63%) of patients and 95% of this subgroup had asymmetrical T wave inversion. Flat ST segment depression, with or without T wave inversion or isolated T wave inversion (symmetrical or asymmetrical) in the anterolateral leads, was seen in the remaining 37% of patients. CONCLUSIONS--These findings indicate that left ventricular hypertrophy without coronary artery disease can cause variable types of ST-T abnormalities in the anterolateral leads including the typical left ventricular strain pattern and non-specific ST-T changes. Non-specific abnormalities could not be distinguished from those of coronary artery disease and may adversely affect the accuracy of the electrocardiographic criteria for the diagnosis of left ventricular hypertrophy because they do not accord with the criteria for left ventricular strain.     

Plaque morphology and pathologic changes in arteries from patients dying after coronary balloon angioplasty

Morphologic correlates of pathologic success or failure were studied at autopsy in 28 patients with 40 coronary arteries that had been subjected to balloon angioplasty. The presence of the following histologic features was evaluated: plaque concentricity or eccentricity, calcification, fibrous or fibropultaceous plaque, medial disruption, luminal thrombus and inflammation. Angioplasty was considered successful (residual cross-sectional luminal area greater than 25%) on pathologic examination in 14 arteries and unsuccessful in 26 arteries. Eccentric plaques were more likely to be successfully dilated than were concentric lesions (p less than 0.05). Six (50%) of 12 fibropultaceous plaques were successfully dilated compared with only 8 (29%) of 28 fibrous plaques. Moderate to severe calcification did not preclude morphologic success. Medial stretching or dissection, or both, was more often associated with a successful result. Thus, plaque morphology may be an important determinant of pathologic outcome after coronary angioplasty.     

Clinical, psychological and thallium stress studies in patients with chest pain and normal coronary arteries.

The clinical and psychological profiles of 36 consecutive patients with chest pain and normal coronary arteries (study group) were compared to those of 34 patients with chest pain and significant coronary arterial disease (control group). All 70 patients were hospitalized for chest pain at least once prior to coronary angiography. The features of a typical episode of chest pain were similar in the normal coronary arteries and coronary arterial disease groups, but the female patients with normal coronary arteries had a shorter duration of a typical episode of chest pain, and the male patients with normal coronary arteries had a lower frequency of positive effort tests. Psychological testing showed the women with normal coronary arteries to have a tendency to increased somatization, anxiety, and a lower ability to identify origin of difficulties. The patients in the normal coronary and coronary arterial disease groups had psychological profiles typical of patients with chronic somatic disease. A psychiatric interview demonstrated an increased frequency of depressive trait (score 0-2) in the normal women (0.6 +/- 0.8 vs 0, P less than 0.05), and a tendency to increased somatization, anxiety, and sleeping disorders. Increased somatization was found in the normal coronary men (1.1 +/- 0.7 vs 0.5 +/- 0.7, P less than 0.05). Twenty-five patients of the normal coronary group underwent quantitative thallium stress studies, and 13 patients (52%) had evidence of stress-induced myocardial perfusion defect. There were no differences in the clinical and psychological profiles of the patients with normal and those with pathological thallium stress tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischaemia and outcome with normal coronary arteries.

Despite attempts to optimize patient selection for coronaryangiography based on the clinical history and results of stresstesting, the rate of normal coronary angiography in most laboratoriesranges from 10 to 20%, more in women than in men.¹ These patientsgenerally have a good outcome, although many continue to complainof chest pain and some suffer cardiac events.² Although traditionallyconsidered a failing of clinical evaluation or stress test interpretation,these ‘false positive’ stress results may be dueto one or more pathophysiological entities that do not encroach