高分辨力超声评价川崎病急性期肱动脉内皮功能及维生素C的作用

目的研究川崎病(KD)急性期肱动脉内皮依赖性血管舒张(EDD)功能及快速经静脉输注维生素C的作用。方法应用高分辨力超声分别测定KD急性期患者及对照组反应性充血介导的肱动脉内径百分变化率,并测定快速经静脉输注维生素C后反应性充血介导的肱动脉内径百分变化率。结果KD急性期组反应性充血介导肱动脉内径百分变化率明显低于对照组(P<0.01),其中并发冠状动脉扩张者与未并发冠状动脉扩张者间差异无统计学意义(P>0.05)。KD急性期患者快速经静脉输注维生素C后反应性充血介导肱动脉内径百分变化率较前明显增加(P<0.01)。结论KD急性期外周动脉内皮功能减低,经静脉快速输注大剂量维生素C可以改善KD急性期外周动脉内皮功能。     

Evaluation of endothelial function in hypertensive elderly patients by high-resolution ultrasonography.

BACKGROUND: Multiple investigations, both in experimental models and in middle-aged patients with essential hypertension, demonstrate impaired endothelium-dependent vasodilatation. HYPOTHESIS: We attempted to determine whether hypertension still exerts additional negative effect on endothelial function of large arteries in hypertensive elderly patients who may already be affected by endothelial dysfunction due to aging. METHODS: We compared 13 elderly patients with hypertension [69 +/- 9 years, (mean +/- standard deviation)] with 13 matched healthy elderly subjects (72 +/- 6 years) as controls. Using high-resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilatation) and sublingual nitroglycerin (causing endothelium-independent dilatation). RESULTS: Flow-mediated dilatation correlated inversely with age (r = -0.60, p = 0.03) in the controls. Flow-mediated dilatation was significantly impaired in hypertensive elderly patients (6.7 +/- 3.3 vs. 13.3 +/- 1.8% in controls, p < 0.0001). No significant difference could found in nitroglycerin-induced dilatation between controls (12.1 +/- 4.9%) and hypertensive elderly patients (10.2 +/- 6.8%, p = 0.5). On multivariate analysis, flow-mediated dilatation in hypertensive elderly patients was inversely related to aging (r = -0.37, p = 0.04) and mean blood pressure (r = -0.57, p = 0.03). CONCLUSIONS: Our study showed decreased flow-mediated dilatation with aging even in the healthy controls, and further decline in flow-mediated dilatation in hypertensive elderly patients compared with controls. This impairment of flow-mediated dilatation in hypertensive elderly patients was related to age and mean blood pressure, indicating that aging and hypertension may independently impair endothelial function in the brachial artery of these patients.     

Impaired endothelium-dependent vasodilation in the brachial artery in variant angina pectoris and the effect of intravenous administration of vitamin C

Endothelial dysfunction in the coronary artery contributes to the pathogenesis of variant angina, and endothelial dysfunction in variant angina may be associated with increased oxidant stress in the systemic arteries. We investigated whether endothelial dysfunction exists in the peripheral artery in patients with variant angina, and also examined the effect of vitamin C, an antioxidant, on endothelium-dependent vasodilation. Using high-resolution ultrasound, both the flow-mediated vasodilation (FMD, endothelium-dependent vasodilation) and sublingual nitroglycerin-induced vasodilation (NTG-D, endothelium-independent vasodilation) in the brachial artery were measured in 28 patients with variant angina and 24 control subjects who had normal coronary arteries. FMD was significantly impaired in patients with variant angina compared with control subjects (1.8 +/- 2.2% vs 6.4 +/- 4.9%, p <0.001). FMD and NTG-D before and after intravenous administration of either vitamin C or placebo were measured in 17 patients with variant angina. FMD significantly improved after the administration of vitamin C (from 2.2 +/- 2.4% to 4.5 +/- 1.6%, p <0.01), but not after administration of the placebo (from 2.0 +/- 2.6% to 1.7 +/- 1.9%). The improved FMD due to vitamin C in patients with variant angina, however, was not significantly different from that in the control subjects. NTG-D was not significantly different between patients with variant angina and control subjects (14.0 +/- 7.8% vs 13.6 +/- 5.0%) and it was also not affected by vitamin C. In conclusion: (1) FMD in the brachial artery is impaired in patients with variant angina, and (2) the acute administration of the antioxidant, vitamin C, was observed to reverse this endothelial dysfunction. These findings support the theory that the systemic inactivation of nitric oxide due to oxidative stress might exist in patients with variant angina.     

Impaired endothelial function in patients with rapidly stabilized unstable angina: assessment by noninvasive brachial artery ultrasonography.

BACKGROUND: Endothelial dysfunction may contribute to symptoms of instability in patients with acute coronary syndromes. High-resolution external ultrasound assessment of the brachial artery responses allows noninvasive determination of endothelial function. HYPOTHESIS: This study was conducted to assess endothelial function in patients with unstable angina using a noninvasive technique. METHODS: We studied 189 patients who were subdivided into three groups. Group 1: 60 apparently healthy subjects with no cardiovascular risk factors or symptoms of coronary artery disease; Group 2: 105 subjects with cardiovascular risk factors--arterial hypertension, hypercholesterolemia, cigarette smoking, diabetes, and obesity, but no evidence of coronary artery disease; and Group 3: 24 patients with unstable angina (chest pain at rest within the 24 h preceding study entry). All patients underwent pre- and postischemic brachial artery test evaluation with measurements of internal arterial diameters and blood flow. RESULTS: Results are expressed as percentage change from basal values. Subjects in Groups 1 and 2 showed a diameter increase of 19.1 and 11.9%, respectively, whereas patients in Group 3 showed a diameter change of 1.2% (p < 0.002 and < 0.0001, respectively). Calculated blood flow did not differ significantly in Groups 1 or 2 (74.4 and 56.4%), but was notably lower in Group 3 (18.4%, p < 0.005 vs. Groups 1 and 2). In nine patients of Group 3, the brachial studies were repeated 4 weeks after symptom stabilization and showed values comparable with those in Group 2. CONCLUSIONS: Patients with unstable angina showed endothelial dysfunction compared with control individuals. It is of interest that in patients whose symptoms were stabilized by medical therapy, endothelial function was restored 4 weeks after hospital discharge.     

高血压合并冠状动脉狭窄患者肱动脉内皮功能研究

目的:观察高血压合并冠心病患者血流介导的肱动脉扩张(FMD)的程度,探讨冠心病患者冠脉病变支数与FMD的关系。方法:选取在我科行冠脉造影检查的高血压患者160例。依据冠脉造影结果分为1、高血压合并冠心病组(冠心病组,98例),并依据冠脉造影(冠脉狭窄≥50%)再分为:①单支病变组(35例);②双支病变组(47例);③多支病变组(16例);2、高血压组(对照组,62例)。通过超声检测肱动脉基础状态,去压30秒、60秒的内径变化(FMD)。以Logistic回归分析:冠脉病变支数与FMD的关系。结果:冠心病组的FMD(7.41±0.73)显著小于高血压组的(10.51±0.68,P0.05)。冠心病单支、双支、多支病变组的FMD组间比较均有显著差异(P均0.05)病变支数越多,FMD越小,去压60秒的FMD为[单支病变组(7.01±0.29)、双支病变组(6.82±0.35)、多支病变组(6.09±0.29)。多元Logistic回归分析显示,与FMD关系密切的依次为冠状动脉多支病变去压后60秒(OR=3.158,P=0.000)、双支病变去压后30秒(OR=1.163,P=0.003)、单支病变去压后30秒(OR=1.076,P=0.004)。结论:高血压合并冠心病患者随着冠脉病变程度增加,动脉内皮功能损害就越重,呈负相关。检测血流介导的肱动脉扩张有助判断冠脉病变程度。     

停用辛伐他汀对冠心病及冠心病危险因素患者血管内皮功能的影响

目的 观察在冠心病及冠心病危险因素患者中,停用辛伐他汀治疗对血管内皮功能的影响,并探讨相应作用机制。方法 入选33例血清胆固醇（Tc）水平未达标的冠心病及冠心病危险因素患者,分别于基线水平、停药前（即辛伐他汀20mg治疗4周后）及停用辛伐他汀1周时,采用高分辨超声技术检测肱动脉血流介导性扩张（FMD）评估血管内皮依赖性舒张功能,并测定一氧化氮（NO）、血浆内皮素（ET）、6-酮-前列腺素F1α（6-keto-PGF1α）和血栓素B2（TXB2）的水平及主要血脂参数的变化。结果 辛伐他汀治疗4周后可有效降低冠心病及冠心病危险因素患者TC、低密度脂蛋白胆固醇（LDL-C）水平,并明显改善患者肱动脉内皮依赖性舒张功能（FMD）。然而,停用辛伐他汀治疗1周后,所有患者肱动脉内皮依赖性舒张功能均较停药前明显下降（4．82士0．71）％与11．51±0．87％,P〈0．01）,甚至低于未服用辛伐他汀时的基线水平（4．82±0．71％与5．89±0．65％,P〈0．01）,其中冠心病患者停药后FMD下降幅度较仅有冠心病危险因素患者更显著（65．6％与56．3％,P〈0．01）。停药1周后,患者血清NO水平较停药前及基础值均明显降低,而血浆ET水平升高。血浆TXB,水平在停药前后无明显变化。此外,停药后患者血清LDL-C水平虽较治疗4周时有所升高,但仍未恢复至基线水平。停药后肱动脉FMD的变化仅与血清NO降低幅度呈正相关关系（r=0．674。P=0．004）,而与血清LDL-C水平变化无明显相关性（r=-0．414,P=0．083）。结论 在TC水平未达标的冠心病及冠心病危险因素患者中突然终止辛伐他汀治疗可在1周内完全逆转该药对血管内皮功能的改善作用,甚至还可能导致血管内皮功能进一步恶化。并且这种撤药反应随基础疾病的严重性增加。停药所致血管内皮功能损害可能与血管内皮源性的NO减少有关,是非胆固醇依赖性作用。     

Prognostic value of brachial artery endothelial function and wall thickness.

OBJECTIVES: We sought to examine the prognostic value of brachial artery (BA) flow-mediated vasodilation (FMD) and intima-media thickness (IMT) in patients admitted for invasive evaluation of chest pain. BACKGROUND: Both FMD and IMT of the BA have been associated with coronary risk factors and the presence of coronary artery disease (CAD). Recent studies on the prognostic value of FMD have been conflicting. METHODS: In 398 consecutive patients (age 54 +/- 9 years) undergoing coronary angiography, FMD and IMT of the BA were measured using high-resolution ultrasound (13 MHz). Patients were divided into two groups according to the FMD median (7.6%). After a mean follow-up of 39 +/- 12 months, cardiovascular events were documented. RESULTS: No difference was found in the number of cardiovascular events between groups. On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of CAD, FMD, and IMT, only the presence of CAD and IMT remained significantly associated with cardiovascular events. CONCLUSIONS: Intima-media thickness predicted late (up to 4 years) cardiovascular events in a large population admitted for evaluation of chest pain. In contrast, the long-term prognostic value of a single baseline measure of BA-FMD seems to be limited.     

肱动脉内皮功能对老年冠心病患者的预测价值

目的 探讨肱动脉内皮功能对老年冠心病患者的预测价值.方法 测定98例冠心病患者及37例对照者肱动脉内皮依赖血管舒张功能(FMD)及非内皮依赖血管舒张功能(NMD),根据冠脉造影结果将患者分为冠脉病变＜50%,50%～75%,＞75%病变组和冠脉病变0、1、2、3支病变组,以比较老年冠心病患者冠脉病变程度、范围与肱动脉F...     

川崎病致肺动脉内皮损伤和肺动脉高压的实验研究

目的 探讨川崎病(KD)对肺血管内皮功能的影响以及与肺动脉高压发生的相关性。方法 采用干酪乳杆菌细胞壁成分(LCWE)建立川崎病大鼠模型,将40只(1月龄)SD大鼠随机分为对照组和KD组,KD组大鼠腹腔注射LCWE 0.5 ml(1 mg/ml)来建造KD模型。造模2周后采用组织病理学评估冠状动脉和肺动脉的损伤情况。测定大鼠体循环压力、右心室压力和右心室肥厚指数、肺小动脉舒张功能。检测肺小动脉组织抗氧化酶锰超氧化物歧化酶(MnSOD)和过氧化氢酶(Catalase)的表达水平,以及氧化应激水平。结果 LCWE注射14 d后,与对照组比较,成功诱导KD大鼠冠状动脉损伤(P<0.05),KD组大鼠出现肺组织损伤,肺组织水肿,点、片状出血,伴中性粒细胞为主的炎性细胞浸润。肺小动脉内皮细胞肿胀,中膜层出现不规则间断性肥厚,管腔呈部分狭窄,肺动脉损伤评分升高(P<0.05)。肺小动脉组织MnSOD和Catalase的表达水平较对照组显著降低(P<0.05),髓过氧化物酶(MPO)、丙二醛(MDA)水平明显升高(P<0.05)。同时,KD组大鼠右心室压力和肥厚指数较对照组明显升高(P<0.05),离体血管灌流实验证实,KD组大鼠肺小动脉内皮依赖性的舒张作用明显减弱(P<0.01)。结论 KD可导致肺小动脉血管炎,引发肺小动脉血管内皮损伤和氧化应激损伤,可能是诱发肺动脉高压和继发性心脏损伤的重要原因之一。     

Ventricular function and coronary hemodynamics after intravenous nitroglycerin in coronary artery disease.

Left ventricular dynamics as well as systemic and coronary hemodynamics were determined in 14 patients with coronary artery disease (1) under control conditions, (2) under intravenous infusion of nitroglycerin, (3) under continued infusion of nitroglycerin with restored arterial and pulmonary artery pressures induced by the parallel infusion of dextran. Heart rate was kept constant by atrial pacing.Intravenous nitroglycerin infusion resulted in a significant reduction in left ventricular systolic (20 per cent) and end-diastolic pressure (43 per cent), peak $\text{dp}\text{dt}$ (13 per cent), cardiac index (16 per cent), stroke volume index (15 per cent), and stroke work index (30 per cent). Peak (dp/dt/total pressure) increased (15 per cent). Pulmonary vascular resistance markedly decreased (29 per cent), whereas total peripheral resistance did not change significantly (?3 per cent). Both coronary blood flow of the left ventricle (13 per cent) and myocardial oxygen consumption (15 per cent) decreased parallel to the reduction in preload and afterload. The action of nitroglycerin at restored left ventricular and pulmonary artery pressures was characterized by increase in peak $\text{dp}\text{dt}$ (12 per cent), peak ($\text{dp}\text{dt}$ total pressure) (18 per cent), cardiac index (13 per cent), stroke volume index (14 per cent), and stroke work index (10 per cent). Both coronary blood flow (28 per cent) and myocardial oxygen consumption (21 per cent) increased parallel to the enhancement of ventricular performance.The results demonstrate that intravenous nitroglycerin produces effective diastolic and systolic unloading of the heart associated with reduction in myocardial oxygen consumption and in coronary blood flow. There was marked vascular pooling which quantitatively averaged 437 ± 128 ml. This occurred concomitant with a 43 per cent decrease in left ventricular end-diastolic pressure or a 20 per cent decrease in peak systolic pressure. Significant coronary dilating properties of nitroglycerin could not be detected in these coronary patients. The increase in left ventricular contractility indices at restored pressure suggests a moderate but significant positive inotropic effect of nitroglycerin.     

停用辛伐他汀对健康男性肱动脉内皮功能的影响

目的 观察停用辛伐他汀对Tc水平正常健康男性肱动脉内皮功能的影响.方法 16例健康青年男性服用20mg辛伐他汀4周后停药,分别检测停药前后不同时间点肱动脉内皮依赖性舒张功能(FMD),并测定血管活性物质--NO、血浆内皮素和6-酮-前列腺素F1α(6-keto-PGF1α)以及血脂参数的变化.结果 健康男性服用辛伐他汀4周后,在停药第1天观察到FMD较停药前明显降低,甚至低于未服药时的基线水平(P＜0.05).停药后血清NO水平较停药前和基础值亦明显降低,其变化与FMD的变化一致.停药后血浆内皮素水平升高,6-keto-PGF1α水平降低.血清LDL-C在停药后最初2d内无明显改变,其变化与FMD无明显相关.结论 健康男性服用辛伐他汀后突然停药,不仅使该药对肱动脉内皮功能的改善作用迅速消失,而且还对血管内皮功能造成进一步损害,该不良影响可能与循环中NO水平降低有关,是非TC依赖性的.     

AECOPD对肱动脉内皮功能的影响

目的 探讨AECOPD对肱动脉内皮功能的影响.方法 78例AECOPD患者根据严重度分为COPDⅠ组(轻度和中度,共38人)及COPDⅡ组(重度和极重度,共40人),同时选取30例健康对照,测定急性加重期及稳定期肱动脉内皮功能.结果 COPD患者急性加重期FMD均减低,Ⅱ组减低更加明显,COPDⅡ组稳定期FMD仍显著减低;COPDⅠ组急性加重期及稳定期NMD正常,COPDⅡ组急性加重期及稳定期NMD均减低.结论 COPD急性加重对肱动脉内皮功能的损伤更加明显.     

Effect of smoking on endothelial function and wall thickness of brachial artery.

BACKGROUND: Impaired flow mediated dilatation (FMD) and increased wall thickness (WT) of the brachial artery have been associated with atherosclerosis and its risk factors. In this study we sought to determine brachial artery wall thickness in chronic smokers and the instantaneous effect of smoking on brachial artery endothelium dependent vasodilator function in smokers and non-smokers. METHOD AND RESULTS: Using a high-resolution ultrasound, WT of posterior brachial artery wall, the diameter of brachial artery at rest and during reactive hyperemia (FMD %), as well as after sublingual administration of nitroglycerine (nitroglycerine mediated dilatation (NMD) %) was measured in 20 smokers and 20 non-smokers. Wall thickness (WT) of the posterior brachial artery wall and the wall index (WI) were greater in smokers than non-smokers. The baseline brachial artery diameter was comparable in smokers and non-smokers. Flow mediated dilation (FMD) was found to be less in smokers than non-smokers. The NMD in smokers also did not differ significantly from that in non-smokers. Flow mediated dilation significantly reduced after smoking compared to baseline in both groups. However, NMD remained unchanged after smoking in both groups. CONCLUSIONS: Increased WT and impaired endothelium-dependent dilatation of brachial artery suggests that cigarette smoking disrupts vessel wall morphology long before atherosclerosis is manifest.     

Comparison of endothelial function evaluated by strain gauge plethysmography and brachial artery ultrasound

BACKGROUND: the cardiac Renin-Angiotensin system (RAS) plays an important role in the regulation of coronary flow and cardiac function and structure in normal and pathological conditions such as ischemia-reperfusion (I/R) injury. The aim of this study was to investigate the effects of the Angiotensin II type 1 (AT-1) receptor antagonist MK-954 (losartan potassium) on postischemic endothelial dysfunction and NOS mRNA expression (inducible nitric oxide synthase, iNOS; endothelial nitric oxide synthase, eNOS) in isolated working rat hearts. METHODS: isolated working rat hearts were subjected to 15 min global ischemia and 180 min reperfusion. MK-954 was added to perfusion buffer (a modified Krebs-Henseleit solution) at 1 microM concentration. We assessed functional parameters, creatin kinase (CK) release, heart weight changes, microvascular postischemic hyperpermeability (FITC-albumin extravasation) and morphological ultrastructural alterations. eNOS and iNOS mRNA levels were also detected by the means of multiplex RT-PCR technique using glyceraldehyde-3-phosphate dehydrogenase (G3PDH) gene as internal control; results were expressed as densitometric ratio. RESULTS: in Losartan-treated hearts we observed a significant reduction of postischemic contractile dysfunction, CK release and myocardial ultrastructural damage; postischemic FITC-albumin extravasation was significantly reduced respect to controls. Moreover, 1 microM Losartan produced a significant reduction of eNOS/G3PDH respect to untreated hearts submitted to I/R. Regarding iNOS/G3PDH ratio, no significant changes were detected in Losartan-treated hearts compared with controls. CONCLUSIONS: our study revealed that Losartan treatment before ischemia, and during reperfusion, is able to reduce the reperfusion injury of the rat heart by reducing mechanical and microcirculatory dysfunction and necrotic cell death, ameliorating cardiac ultrastructure and endothelial protection, probably inducing eNOS over-expression and reducing post-ischemic hyperpermeability of coronary microcirculation.     

Evaluation of the alpha and beta blocking effects of intravenous labetalol on left ventricular function in coronary artery disease

Intravenous labetalol was evaluated in 10 patients with stable angina without heart failure. Mean dose was 1.75 mg/kg (range 1.5-2 mg/kg). Measurements were taken within one minute after the injection, and at 1, 5 and 15 minutes thereafter. Labetalol significantly decreased blood pressure and increased heart rate. Peak aortic flow velocity increased only significantly at 1 minute; dP/dt+ max. was significantly decreased during all the measurements. Left ventricular end diastolic pressure did not change. Thus in patients without failure left ventricular function remained stable despite the negative inotropic effects of labetalol.     

肱动脉血流介导的舒张功能与冠状动脉病变的关系

目的:观察冠心病(CHS)患者肱动脉血流介导的舒张功能与冠状动脉(冠脉)病变之间的关系。方法:选择冠脉造影(CAG)患者107例,根据cAG结果分为冠脉正常组28例、冠脉早期病变组31例、CHD组48 例,CHD组采用Gensini评分进一步分为轻度病变(1-20分)26例,重度病变(≥20分)22例。在CAG前24 h 内应用高分辨率超声检测肱动脉血流介导的舒张功能,与CAG结果作对照分析。结果:CHD组中轻度病变与重度病变者较冠脉早期病变组及冠脉正常组的肱动脉内皮依赖的舒张功能(EDD)明显降低[(4．75±0．94)％、 (3．67±1．01)％:(5．98±0．89)％、(6．15±0．97)％,P<0．05或0．01];重度冠脉病变者EDD较轻度冠脉病变者明显下降[(3．67±1．01)％:(4．75±0．94)％,P<0．05]。而硝酸甘油介导的血管扩张功能(非EDD)在各组间差异无统计学意义(P>0．05)。肱动脉EDD与冠脉病变积分呈负相关(r=0．72,P<0．01)。结论: CHD患者常存在肱动脉EDD受损,肱动脉EDD可间接反映冠脉病变程度。     

Reproducibility of brachial ultrasonography and flow-mediated dilatation (FMD) for assessing endothelial function

Abstract Background : High-resolution brachial artery ultrasonography is used to study vasodilator response induced by physiologic reactive hyperaemia. We examined the reproducibility of measuring flow-mediated dilatation (FMD) on two occasions.
Aims : To determine the degree of variability of this technique in our vascular laboratory for the design of clinical research studies.
Methods : Nineteen subjects were studied on two separate occasions using an Acuson 128 ultrasound device and a 7.0 MHz linear array transducer. Reactive hyperaemia was induced in the brachial artery by inflation and release of a blood pressure cuff. Nitrate-induced dilatation was assessed in 11 of the 19 subjects. Measurements were made by two observers blinded to subject details.
Results : The 11 subjects given sublingual GTN during the first ultrasound study had a mean nitrate-induced dilatation of 20.7% (sd 9.6). The mean vessel diameter of 3.78 mm (sd 0.7) at rest and 3.89 mm (sd 0.7) during reactive hyperaemia yielded a mean FMD of only 3.0% (sd 2.7). The mean difference in FMD within-observers was 0.13% (sd 2.07), between-observers 0.06% (sd 2.17) and between-studies was 0.57% (sd 6.83).
Conclusions : The reproducibility of FMD measured by brachial artery ultrasound was poor and likely to render the measurements inaccurate for clinical research in our hands. Between-study variation contributed the largest proportion of total study variability. We suggest that investigators using this technique conduct their own careful reproducibility studies in order to avoid the misinterpretation of 'negative' studies.