A minimally-invasive closed chest myocardial occlusion-reperfusion model in rhesus monkeys (<Emphasis Type="Italic">Macaca mulatta</Emphasis>): monitoring by contrast-enhanced ultrasound imaging

Myocardial infarction is frequently developed in canine and porcine models but exceptionally in non-human primates. The aim of this study was to develop a minimally invasive myocardial ischemic/reperfusion model in the monkey intended to be combined with imaging techniques, in particular myocardial contrast echocardiography (MCE). A balloon-tipped catheter was advanced via the femoral artery into the left anterior descending artery (LAD) under fluoroscopic guidance in ten anaesthetized male rhesus monkeys (Macaca mulatta). The balloon was inflated to completely occlude the vessel. Coronary angiography (CA) was performed to control the reality of the LAD occlusion/reperfusion. The ischemia period was followed by 3–6 h of reperfusion. Myocardial perfusion was evaluated during ischemia and at reperfusion by MCE using a novel ultrasound contrast agent (BR38). Occlusion was successfully induced during 18–50 min in nine out of the ten evaluated monkeys. ST segment elevation indicated myocardial ischemia. MCE showed complete transmural arrest of myocardial blood flow during the ischemia period and no persistent microvascular perfusion defects during reperfusion. A minimally invasive closed-chest model was successfully developed for creating myocardial ischemia in the rhesus monkey (Macaca mulatta). This technique could have an important role in mimicking acute coronary syndrome under physiologically and ethically-acceptable conditions. MCE provides non-invasively information on myocardial perfusion status, information not available from CA.     

速度向量成像技术评价犬心肌缺血与梗死状态下左心室节段性旋转特征

目的应用速度向量成像(VVI)技术评价心肌缺血及心肌梗死状态下犬心肌旋转运动特征。方法选用杂种犬12只,在超声实时引导下结扎前降支定量制备前降支轻度狭窄(狭窄率:50%～75%)与完全闭塞模型,应用VVI技术分析前降支结扎前、轻度狭窄与完全闭塞状态下左心室旋转特征的改变。结果 12只杂种犬成功制备前降支轻度狭窄与完全闭塞模型,应用VVI技术对缺血与梗死状态下心肌旋转运动分析结果显示:(1)前降支部分结扎状态下室间隔的旋转角度与圆周应变较正常显著降低(P<0.05);径向应变与应变率较正常差异有统计学意义(P<0.05);(2)前降支完全结扎状态下:前间隔、室间隔、前壁的旋转角度与旋转速度、圆周应变与圆周应变率较正常及部分结扎状态下均显著减低(P<0.05);径向应变与应变率较正常状态下显著降低(P<0.05),与部分结扎状态下比较,差异无统计学意义。结论 VVI技术可以无创、敏感地评价心脏旋转运动。前降支部分结扎状态下心脏的旋转在个别节段已经出现减低,前降支完全结扎后,旋转角度与旋转速度较结扎前、部分结扎后均显著降低,心脏旋转可以更加敏感的反映心脏收缩功能。     

自体心包膜移植后受体心电活动的变化

背景：自体心包膜移植治疗已广泛应用于临床,主要涉及心血管修补重建、眼表疾病的治疗等领域;但其对心脏本身在缺血损伤下的保护作用却研究甚少。探索自体心包膜带瓣移植的安全性及其对缺血损伤后心肌的保护作用具有重要意义。 目的：观察心脏接受自体心包膜移植后对心电活动的影响及其对缺血心肌的保护作用。 方法：以荣昌肉猪和SD大鼠为研究对象,2种动物分别分为3组：移植组、心肌梗死组及心肌梗死＋移植组,心肌梗死组及心肌梗死＋移植组动物结扎冠状动脉前降支建立心肌梗死模型,移植组及心肌梗死＋移植组动物以自体心包膜组织带瓣移植建立移植模型。 结果与结论：①猪心电图监测室上性早搏常见;移植组室性早搏偶见,监测过程中未见室性心动过速和室性颤动。与心肌梗死组相比,心肌梗死＋移植组室性早搏减少,超声心动图检查示心功能改善（P 〈0.05）。②移植组大鼠心电图监测未见室性颤动;心肌梗死组、心肌梗死＋移植组均见非致死性室性颤动。与心肌梗死组相比,心肌梗死＋移植组心功能改善,心肌凋亡指数降低,Bcl-2蛋白表达升高,Caspase-3蛋白表达降低（P 〈0.05）。提示自体心包膜带瓣移植未诱发恶性室性心律失常,其安全性相对较高;并在一定程度上减少缺血损伤后室性早搏个数、促进心功能恢复,其可能与抑制缺血区域细胞凋亡有关。     

Brugada Syndrome: A Case Report of an Unusual Association with Vasospastic Angina and Coronary Myocardial Bridging

IMAZIO, M., et al. : Brugada Syndrome: A Case Report of an Unusual Association with Vasospastic Angina and Coronary Myocardial Bridging. This report describes a case of an unusual association between vasospastic angina, coronary myocardial bridging, and Brugada syndrome. The patient complained of chest pain followed by rhythmic palpitation and syncope. Brugada syndrome ECG markers were documented with transient ST-segment elevation in lateral leads. A coronary angiogram showed a myocardial bridging in the left anterior descending artery and coronary vasospasm was reproduced after intracoronary ergonovine injection in the circumflex coronary artery. Ventricular fibrillation was induced by programmed electrical stimulation. The described association can be important because interaction between ischemia and Brugada syndrome electrophysiological substrate could modulate individual susceptibility to life-threatening ventricular tachyarrhythmias.     

Myocardial bridging: light in the tunnel

Myocardial bridging is a congenital anomaly in which a segment of a coronary artery runs intramuscularly. Although traditionally considered as a benign condition, myocardial bridging may be associated with clinically important complications such as myocardial ischemia, acute coronary syndromes and sudden death. We report the case of a highly symptomatic 36 years old patient with a myocardial bridge in left anterior descending coronary artery in which surgical treatment was proposed. Previous to surgery a non invasive coronariography with Cardiac CT was practised in order to define the anatomy.     

Prognostic value of combined magnetic resonance myocardial perfusion imaging and late gadolinium enhancement

Late gadolinium enhancement (LGE) and myocardial perfusion study by cardiac magnetic resonance (CMR) have a diagnostic and prognostic value in patients with suspected coronary artery disease (CAD). The purpose of this study was to determine the prognostic value of combined myocardial perfusion CMR and LGE in patients with known or suspected CAD. We studied patients with known or suspected CAD. All patients underwent CMR for functional study, myocardial perfusion and LGE. Myocardial ischemia by CMR was defined as a perfusion defect in patients without LGE or a perfusion defect beyond the LGE area. Patients were followed up for cardiovascular outcomes including hard cardiac events (cardiac death or non-fatal myocardial infarction) and major adverse cardiac events (MACE) which included cardiac death, non-fatal myocardial infarction, hospitalization for unstable angina, and heart failure. There were a total of 587 men and 645 women. Average age was 64.6 ± 11.1 years. LGE was detected in 326 patients (26.5%). Myocardial ischemia by CMR was detected in 423 patients (34.3%). Average follow-up duration was 34.9 ± 15.6 months. Univariate analysis showed that age, diabetes, use of beta blocker, left ventricular ejection fraction, left ventricular mass, wall motion abnormality, LGE, and myocardial ischemia are predictors for hard cardiac events and MACE. Multivariable analysis revealed that myocardial ischemia was the strongest predictor for hard cardiac events and MACE. Other independent predictors were age, use of beta blocker, and left ventricular mass. Myocardial ischemia by CMR has an incremental prognostic value for cardiac events in patients with known or suspected CAD.     

前壁合并下壁心肌梗死的临床特点及罪犯血管

目的探讨前壁合并下壁心肌梗死的临床特点及其与冠状动脉造影结果的关系。方法对22例前壁合并下壁心肌梗死患者进行回顾性研究分析。结果本组患者22例,男21例,女1例。合并高血压病、高脂血症及糖尿病分别为72.7%、31.8%和18.2%。有吸烟史占22.7%。典型胸痛、不典型胸痛及无胸痛分别为54.5%、22.7%和22.7%。胸片、心脏超声、心电图及肾功能异常分别为72.7%、100%、100%和18.2%。冠状动脉造影显示:冠脉为右优势分布14例,占63.6%,左优势分布3例,占13.6%;均衡型分布5例,占22.7%。病变累及冠脉66支共76处,单支病变22.7%、二支病变27.3%、多支病变50.0%,受累的前降支(LAD)、右冠状动脉(RCA)、左回旋支(LCX)及左主干(LM)分别为100%、54.5%、72.7%和9.1%。A型病变累及冠脉17支22处(25.8%)、B型病变累及冠脉26支30处(39.4%)、C型病变累及冠脉23支24处(34.8%),重度以上狭窄占80.3%。16例(72.7%)有不同程度的侧支循环。3例AAMI+AIMI中,2例罪犯血管为单支病变,均为LAD,1例为多支病变,累及LAD、LCX及RCA。结论前壁合并下壁心肌梗死患者,多合并危险因素,临床表现复杂,临床检查多有异常,冠脉分布以右优势型居多,冠脉病变以二支及多支病变为主,B型及C型病变占大多数、冠脉狭窄程度较严重,多数患者有不同程度的侧支循环。AAMI+AIMI中,罪犯血管多为LAD,且预后良好。     

Echocardiographic visualization of acute myocardial ischemia--in vitro study

To evaluate whether myocardial texture changes resulting from acute ischemia can be visualized with satisfactory spatial resolution, short axis compound echo images (CEI) (B-scan) were obtained from 12 excised canine hearts in vitro. Seven had myocardial ischemia produced by open chest ligation of the left anterior descending coronary artery (LAD) for 15-30 min prior to excision. The CEI were constructed by compounding 60 simple linear B-scans. Hearts were sectioned after scanning, and gross morphological changes were recorded. Microscopic comparison between grossly abnormal and normal regions were recorded. The CEI from the ischemic group revealed altered myocardial texture seen as bright coarsely granular echoes in the regions normally perfused by the ligated LAD artery. Corresponding anatomic sections revealed increased redness in these regions. Microscopically these regions revealed interstitial and intercellular edema as compared to the normal regions. Acute myocardial ischemia can be visualized in CEI and these regions have significantly increased backscatter, decreased attenuation, and decreased speed of ultrasound relative to normal regions in the same hearts. Myocardial edema is probably responsible for these changes.     

Cardiac fibrinolytic capacity is markedly increased after brief periods of local myocardial ischemia, but declines following successive periods in anesthetized pigs

BACKGROUND: Fibrinolysis in blood is mainly reflected by the activities of tissue plasminogen activator (tPA) and of plasminogen activator inhibitor-1 (PAI-1). The effect of myocardial ischemia on their activities in the coronary circulation is, however, not established. OBJECTIVES: With an improved experimental model, we therefore examined the effect of a brief period of myocardial ischemia on their activities. Furthermore, the consequences of repeated periods of ischemia, mimicking the situations in patients with unstable angina, were investigated. METHODS: In six anesthetized pigs, we occluded the distal left anterior descending coronary artery (LAD) four times for 10 min with 40 min intervals and determined the activities of tPA and PAI-1 in arterial and coronary venous blood. By simultaneously recording LAD flow, we could estimate cardiac release of these factors at baseline conditions and during reperfusion. RESULTS: Neither net cardiac release of PAI-1 nor alterations in plasma PAI-1 levels were demonstrated during the experiment. However, a significant net release of tPA activity of 10.4 +/- 3.2 IU mL(-1) (P < 0.005) was recorded during baseline conditions. During reperfusion following the first period of ischemia, the cardiac release of tPA activity increased to a peak of 103 +/- 30-fold baseline release, but declined progressively after repeated periods of ischemia. After the fourth period, tPA release did not exceed an estimated baseline accumulation during ischemia and early reperfusion. CONCLUSIONS: In this porcine model, a substantial local increase in fibrinolytic capacity was observed after brief periods of ischemia, but declined subsequently by repeated periods of ischemia.     

Effect of treadmill exercise testing on P wave duration and dispersion in patients with isolated myocardial bridging

Several previous studies suggest that myocardial bridging (MB) is associated with ischemia and rhythm disturbances. We sought to examine exercise-induced changes in P wave duration and dispersion (PWD), the markers of atrial conduction abnormalities in patients with isolated MB of left anterior descending artery (LAD) and control subjects. Eighteen patients with MB of LAD (group-I) and 22 subjects with angiographically demonstrated normal coronary arteries (group-II) underwent treadmill exercise testing. Before and after exercise ECG was recorded at a paper speed of 50 mm/s. The change in maximum and minimum P wave duration was measured manually and difference between two values was defined as PWD. There was no difference between two groups in terms of demographic properties. Baseline maximum and minimum P wave duration and PWD durations were similar in both groups and they did not change after exercise. (Group-I: before and after test; 114 ± 10 vs. 114 ± 9, 66 ± 13 vs. 67 ± 10, and 47 ± 9 vs. 45 ± 13 ms, P > 0.05, group-II; 113 ± 9 vs. 115 ± 8, 68 ± 11 vs. 68 ± 11, 45 ± 11 vs. 48 ± 15 ms for each, respectively). In addition there was no significant correlation between PWD and P wave duration and echocardiographic variables. In patients with MB of LAD, PWD and P wave duration were not different than healthy subjects and treadmill exercise testing did not induce atrial conduction abnormalities in both groups.     

Angiographic correlations of patients with small vessel disease diagnosed by adenosine-stress cardiac magnetic resonance imaging

Cardiac magnetic resonance imaging (CMR) with adenosine-stress myocardial perfusion is gaining importance for the detection and quantification of coronary artery disease (CAD). However, there is little knowledge about patients with CMR-detected ischemia, but having no relevant stenosis as seen on coronary angiography (CA). The aims of our study were to characterize these patients by CMR and CA and evaluate correlations and potential reasons for the ischemic findings. 73 patients with an indication for CA were first scanned on a 1.5T whole-body CMR-scanner including adenosine-stress first-pass perfusion. The images were analyzed by two independent investigators for myocardial perfusion which was classified as subendocardial ischemia (n = 22), no perfusion deficit (n = 27, control 1), or more than subendocardial ischemia (n = 24, control 2). All patients underwent CA, and a highly significant correlation between the classification of CMR perfusion deficit and the degree of coronary luminal narrowing was found. For quantification of coronary blood flow, corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) was evaluated for the left anterior descending (LAD), circumflex (LCX) and right coronary artery (RCA). The main result was that corrected TFC in all coronaries was significantly increased in study patients compared to both control 1 and to control 2 patients. Study patients had hypertension or diabetes more often than control 1 patients. In conclusion, patients with CMR detected subendocardial ischemia have prolonged coronary blood flow. In connection with normal resting flow values in CAD, this supports the hypothesis of underlying coronary microvascular impairment. CMR stress perfusion differentiates non-invasively between this entity and relevant CAD.     

T-wave changes in patients with Wellens syndrome are associated with increased myocardial mechanical and electrical dispersion

Some patients with unstable angina and critical stenosis of the left anterior descending coronary artery (LAD) present with Wellens syndrome (WS), i.e., inverted or biphasic T-waves in the anterior precordial leads. We assessed clinical, angiographic, electro- and echocardiographic characteristic of patients with WS. In this retrospective study, clinical, angiographic, electro- and echocardiographic characteristic of 35 patients with WS were compared to 57 patients with critical LAD stenosis and normal resting electrocardiogram (ECG), and 45 subjects with normal coronary angiogram. QTc dispersion was measured from the 12-lead ECG as the difference between longest and shortest QTc intervals. Mechanical dispersion was defined as the time difference between the longest and shortest contraction durations which were measured as the time from the first deflection of the QRS complex to maximum myocardial shortening of each 18 segmental longitudinal strain curves derived by speckle tracking echocardiography. There were no significant differences in the complexity and location of the LAD lesion, anterograde and collateral flow in LAD and coronary artery dominance between patients with WS and normal ECG (P?>?0.05, for all). Patients with WS had lower global longitudinal strain (GLS) and more pronounced both QTc and myocardial mechanical dispersion than patients with critical LAD stenosis and normal ECG, and control subjects (P?<?0.05). T-wave changes in patients with WS are associated with more profound regional myocardial dysfunction and increased QTc and myocardial mechanical dispersion. Similar angiographic characteristics of the LAD lesion were seen in patients with WS and normal ECG.     

Heart rate in ischemic heart disease. The innovation of ivabradine: More than pure heart rate reduction

A wealth of data suggests that heart rate (HR) is an independent predictor of cardiovascular and all-cause mortality in men and women of all ages with and without cardiovascular disease. Data gathered from clinical trials suggest that HR reduction is an important mechanism of benefit of HR-lowering drugs. A high HR has direct detrimental effects not only on myocardial ischemia but also on the progression of atherosclerosis, ventricular arrhythmias, and on left ventricular function. The risk increases with HR >60 b.p.m. Ivabradine, a drug that slows HR though an effect on the If channels, has been approved for the control of myocardial ischemia in patients with coronary artery disease intolerant to beta-blockers. More recently, the indication of ivabradine has been extended for use in association with beta-blockers in patients with coronary artery disease. The effects of ivabradine on myocardial ischemia are greater than those predicted by pure HR reduction with beta-blockers, suggesting additional mechanisms of action.     

99mTc-MIBI心肌断层显像多巴酚丁胺试验对冠心病诊断的临床价值

目的 为了证实多巴酚丁胺^99mTc-MIBI 心肌断层显像诊断冠心病的价值,临床104 例患者进入本试 验。方法 多巴酚丁胺用生理盐水稀释后分级经静脉滴入,待达到预定最大剂量后,静脉推注^99m Tc-MIBI 740MBq ,维持多巴酚丁胺液2 分钟,60 分钟后行心肌断层显像,隔日以同等条件再次行静态心肌断层显像。结果 36 例非心肌梗塞阳性34 例,敏感性94.4 % ,48 例心肌梗塞45 例阳性,敏感性93.8 %。单支,双支和三支病变的敏感性分别为86.8 % ,95.8 %和100 %。检出RCA ,LAD ,LCX 的敏感性与特异性分别为91.7 %和75.8 % ,86.8 %和81.6 % ,70 %和81.6 %。介入性治疗3～6 个月内。多巴酚丁胺-ECT 的116 个室壁节段异常中,心肌缺血消失和改善79 个节段,总有效率68.1 %。32 个节段心肌梗塞,术后43.8 %的室壁节段缺血消失或改善。84 个节段ECT 呈心梗伴缺血或单纯缺血,术后7714 %的异常室壁节段缺血得到改善。心肌有明显缺血者疗效明显高于心梗者( P < 0.01) 。结论 多巴酚丁胺2ECT 对诊断冠心病心肌缺血与潘生丁和运动-ECT 一样有较高的灵敏性和特异性。     

Multifocal coronary artery myocardial bridging involving the right coronary and left anterior descending arteries detected by ECG-gated 64 slice multidetector CT coronary angiography

Myocardial bridging is a congenital condition in which a segment of a major epicardial coronary artery has an intramyocardial course. Myocardial bridging is usually confined to a single vessel (typically the mid segment of the left anterior descending artery) and is usually asymptomatic, however, bridging may be associated with chest pain, myocardial infarction, or sudden cardiac death. While more commonly identified at autopsy, myocardial bridging is occasionally diagnosed by coronary angiography with identification of concomitant myocardial bridging involving both the left and right coronary arteries appearing to be uncommon. We present three patients presenting with atypical chest pain symptoms in whom concomitant right coronary artery and left anterior descending artery myocardial bridging was identified by ECG gated multidetector computed tomography (MDCT).     

Neutrophil-Derived Oxidative Stress After Myocardial Ischemia Induced by Incremental Atrial Pacing

We studied the effect of atrial pacing-induced myocardial ischemia on the generation of oxygen free radicals (OFR) in 8 patients with verified coronary artery disease (CAD) and in a control group of 4 patients without coronary atherosclerosis. Myocardial ischemia was measured metabolically by simultaneous lactate sampling from coronary sinus (CS) and arterial blood. Generation of OFR from purified viable polymorphonuclear neutrophils (PMN) was assessed by means of the chemiluminescence (CL) method. At peak pacing, 7 of 8 patients with CAD exhibited transient myocardial ischemia (mean lactate extraction ratio at rest: 23.6 ± 7.7 vs 5.21 ± 5.1 % at peak pacing, p= 0.012). In these patients, unstimulated PMN harvested from the CS depicted a significant increase of luminol-enhanced CL (from 1.06 ± 0.54 to 2.15 ± 1.28 cpm x 10⁵, p= 0.012) after atrial pacing. There was no additional effect from further ex vivo stimulation with phorbol myristate acetate.
This finding underscores the role of myocardial ischemia as a potent endogenous activator of PMN function and may have implications in the pathogenesis and progression of atherosclerosis.     

Soluble L-selectin and neutrophil derived oxidative stress after pacing induced myocardial ischemia in chronic stable coronary artery disease

We studied the effect of atrial pacing induced myocardial ischemia on levels of soluble L-selectin (sL-selectin) and generation of neutrophil derived reactive oxygen species (ROS) in 10 patients with coronary artery disease (CAD) and stable angina and in six individuals without CAD. Myocardial ischemia was measured metabolically by lactate sampling from the coronary sinus (CS) and arterial blood at each pacing step. Before each pacing step, at peak pacing and shortly after cessation, plasma concentrations of sL-selectin and generation of ROS using the chemiluminescence method were measured in CS and femoral artery blood. Baseline sL-selectin levels in CS samples were significantly lower in the CAD compared to the control group (547 +/- 80 vs 836 +/- 82 ng/mL, P = 0.03). At peak pacing, nine of ten patients with CAD developed myocardial ischemia (lactate extraction ratio at rest 28% +/- 7%, at peak pacing -16% +/- 6%). In these patients, luminol-enhanced chemiluminescence (CL, 0.88 +/- 0.45 vs 1.9 +/- 0.9 cpm x 10(5), P = 0.09) and levels of sL-selectin (547 +/- 80 vs 764 +/- 86 ng/mL, P = 0.03) from naive neutrophils increased significantly in CS blood suggesting a potent in vivo activation of neutrophils. In control patients, incremental pacing caused neither myocardial ischemia nor a significant change of chemiluminescence or of sL-selectin levels. In conclusion, myocardial ischemia induced by pacing tachycardia is able to activate neutrophils in patients with chronic stable coronary artery disease leading to increased generation of ROS and shedding of L-selectin into the coronary circulation.     

电针对心肌缺血再灌注损伤家兔心肌细胞凋亡的影响

目的:研究电针对心肌缺血再灌注损伤家兔心肌细胞凋亡的影响.方法:将结扎左冠状动脉前降支30 min,再灌注60 min,成功制作为心肌缺血再灌注损伤模型的家兔24只,随机分为模型组、电针1及2组各8只.另仅开胸未结扎冠状动脉的8只为假手术组作为正常对照.电针1、2组术后30 min分别采用电针针刺内关穴与列缺穴60 min,仅1次,应用原位末端标记法观察4组家兔心肌细胞凋亡情况.结果:心肌凋亡细胞数量,模型组显著高于假手术组(P＜0.01),电针1组与电针2组、模型组比较显著降低(P＜0.05,P＜0.01),但仍高于假手术组(P＜0.01).结论:细胞凋亡参与心肌缺血再灌注损伤的病理过程,电针内关穴可以减少缺血再灌注损伤心肌细胞凋亡的数量,从而达到抗缺血再灌注损伤的作用.     

The instantaneous impedance frequency curve of the ventricle with the regional ischemia

We studied the feasibility of using the impedance frequency curve method (IFM) to detect the myocardial physical heterogeneity of a cross-circulated isolated canine left ventricle with regional ischemia. The curve changed from a single-peak configuration to a double-peak configuration after the LAD coronary flow cessation and returned to the single-peak configuration with the reperfusion of LAD coronary flow. We concluded that IFM can be a useful tool to describe the physical heterogeneity of the ventricular muscle under the regional ischemia.     

心肌声学造影和背向散射组织定征对犬顿抑心肌的研究

目的：研究犬顿抑心肌模型的血流灌注图像和背向散射组织定征信号的变化。方法：对9条健康杂种犬通过结扎左冠状动脉前降支（LAD）制作顿抑心肌模型,检测LAD结扎前、结扎后不同时间顿抑心肌图像的平均强度（AⅡ）及背向散射积分周期变化幅度（CVIB）。观察心肌血流灌注显像。结果：LAD供血区域心肌的AⅡ值、CVIB值及心肌血流灌注图像在LAD结扎前、结扎时,恢复再灌注后不同时间内发生了一系列变化。结论：心肌声学造影可清楚显示心肌的血流灌注状态,帮助判断冠脉支的走行和分布;背向散射心肌组织定征在评价不同血供状态、心动周期不同时相心肌内微小散射体的超声信号变化及其几何形态的变化方面有较大价值。