endothelin-1 and Chest-Pain

Endothelial microparticles (EMPs) are vehicles released from activated or apoptotic endothelium. The aim of this study was to establish a new cytometric bead assay for EMPs and investigate the prognostic value of EMPs in chest pain patients.. We invented and verified the cytometric bead assay to quantify EMP level in vitro. A total of 80 healthy volunteers and 350 chest pain patients were recruited and the EMPs measured. The major adverse cardiovascular events (MACE) of documented coronary artery disease patients were recorded in the follow-up period. The level of EMPs statistically correlated with those of endothelin-1 (ET-1) and intercellular adhesion molecule-1 (ICAM-1) in vitro. The EMP level in healthy subjects was <300.10. The patients had a remarkably higher EMP level than healthy subjects. Diabetes mellitus, EMP, and ET-1 levels were significantly associated with future cardiovascular events in chest pain patients. There was a significantly higher event incidence in the top tertile EMP level than in the lower tertile in the acute coronary syndrome (ACS) patient group.. A novel EMP quantification assay has been successfully established. The EMPs in vitro and in patients were significantly correlated with ET-1 and ICAM-1 level. The patients with a higher EMP level had a higher risk of MACE. EMP level is a predictor for MACE in ACS patients.

Topics: Aged; Cell-Derived Microparticles; Chest Pain; Coronary Artery Disease; Diabetes Mellitus; Endothelial Cells; Endothelin-1; Female; Flow Cytometry; Follow-Up Studies; Humans; Intercellular Adhesion Molecule-1; Male; Middle Aged; Prognosis

We have demonstrated that estrogen can reduce myocardial injury in ischemia-reperfusion via activation of ATP-sensitive potassium (K(ATP)) channels. We sought to determine whether the protective effect of estrogen extends to epicardial coronary artery with attenuated vasoconstriction in patients after angioplasty by activation of such channels.. The study was designed to prospectively investigate 41 consecutive patients scheduled for elective coronary angioplasty. Pretreatment with estrogen limited myocardial ischemia during coronary occlusion and attenuated postangioplasty coronary vasoconstriction at the dilated and distal segments. An inhibitor of K(ATP) channels, glibenclamide, did not affect coronary vasomotor response, although it abolished the beneficial effect of estrogen on myocardial ischemia. Patients to whom estrogen was administered after the second balloon deflation experienced a similar magnitude of myocardial ischemia as controls but showed significantly attenuated vasoconstriction compared with controls (P=0.0001). Endothelin-1 levels from the great cardiac vein rose significantly from 1.9+/-0.4 to 3.1+/-0.6 pg/mL (P=0.001) 15 minutes after angioplasty in the control group; this was attenuated after estrogen was administered. Significant correlation was found between the changes in coronary vasomotion of the dilated segment and endothelin-1 levels (r=0.65, P<0.0001).. These results demonstrate that estrogen is protective against both myocardial ischemia and coronary vasoconstriction through different mechanisms. The myocardial effect of estrogen was abolished by glibenclamide, which suggests that the cardioprotective effect of estrogen may result from activation of K(ATP) channels. In contrast, estrogen-induced attenuated vasoconstriction is associated with an attenuated release of endothelin-1, independent of K(ATP) activation.

Topics: Adenosine Triphosphate; Angioplasty, Balloon, Coronary; Cardiotonic Agents; Chest Pain; Coronary Disease; Electrocardiography; Endothelin-1; Estrogens, Conjugated (USP); Female; Glyburide; Heart; Hemodynamics; Humans; Lactic Acid; Male; Middle Aged; Myocardial Ischemia; Myocardium; Potassium Channel Blockers; Potassium Channels; Vasoconstriction

In this study, we investigated whether increased renin angiotensin aldosterone system (RAAS) activation and endothelin-1 levels are related to coronary artery calcium (CAC) score, total plaque volume (TPV), high risk plaque, hyperemic myocardial blood flow (MBF) and coronary microvascular dysfunction (CMD).. After correction for baseline characteristics, including RAAS inhibiting therapy, renin associated positively with CAC score and TPV, but not with hyperemic MBF (p < 0.01; p = 0.02 and p = 0.23). Patients with high risk plaque displayed higher levels of renin (mean logarithmic renin 1.25 ± 0.43 vs. 1.12 ± 0.35 pg/ml; p = 0.04), but not endothelin-1. Compared to no or non-obstructive CAD patients, renin was significantly elevated in obstructive CAD patients but not in CMD patients (mean logarithmic renin 1.06 ± 0.34 vs. 1.23 ± 0.36; p < 0.01 and 1.06 ± 0.34 vs. 1.16 ± 0.41 pg/ml; p = 0.65). Endothelin-1 did not differ between the three patient groups.. Our report provides evidence that RAAS activity measured by renin concentration is elevated in patients with coronary atherosclerosis and high risk plaque but not in patients with CMD, whereas endothelin-1 is not related to either.

Topics: Aged; Chest Pain; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Endothelin-1; Female; Fractional Flow Reserve, Myocardial; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Renin; Renin-Angiotensin System

Endothelin-1 (ET-1) is a vasoconstrictor associated with cardiovascular disease, whereas adrenomedullin (ADM) is a vasorelaxant with cardioprotective properties. We sought to determine the relationship between plasma ET-1 and ADM with coronary circulatory function and long-term major adverse cardiovascular events (MACE).. Thirty-two patients undergoing coronary angiography for chest pain were recruited. Baseline plasma ET-1 and ADM levels were measured. The index of microcirculatory resistance (IMR), coronary flow mediated dilatation (cFMD) and coronary flow reserve (CFR) were measured in a non-obstructed coronary artery. Patients were assessed for MACE over a median period of 8.8 years.. Plasma ET-1 levels correlated with IMR (r = 0.57; p < 0.01) and ADM levels correlated with CFR (r = 0.50; p = 0.04) and cFMD (r = 0.62; p = 0.01). After adjustment for age, gender and cardiovascular risk factors, the association between ADM and cFMD (β = 0.79; p < 0.01) and between ET-1 and IMR (β = 5.7; p = 0.01) remained significant. IMR was higher, although not statistically significant, in patients with long-term MACE (17.9 ± 5.3 vs. 13.1 ± 6.0 units; p = 0.14). In patients free of MACE, cFMD (9.3 ± 7.6 vs. 2.8 ± 5.0%; p = 0.01) and plasma ADM levels (7.6 ± 5.3 vs. 4.0 ± 1.9 pmol/L; p = 0.07) were higher.. Plasma ET-1 and ADM were associated with measures of coronary microvascular and coronary conduit vessel function, respectively. Increased cFMD and elevated plasma ADM were associated with a cardioprotective effect.

Topics: Adrenomedullin; Aged; Biomarkers; Chest Pain; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Coronary Circulation; Endothelin-1; Female; Follow-Up Studies; Fractional Flow Reserve, Myocardial; Humans; Male; Middle Aged

A relationship between coronary artery spasm (CAS) and myocardial bridge (MB) has been noticed. This study was designed to investigate the differences of stress tests and symptoms between CAS patients with or without MB.. Two hundred and sixteen patients with atypical chest pain who underwent coronary angiography and acetylcholine provocation test were divided into MB group (n=68) and nonmyocardial bridge group (NMB, n=148). The results of acetylcholine test, treadmill exercise electrocardiography, myocardial scintigraphy, and levels of plasma endothelin-1 and nitric oxide were compared between the two groups.. Among these atypical chest pain patients, CAS was induced by acetylcholine in 85% MB patients and 53% NMB patients (P<0.001). A positive exercise electrocardiogram was identified in 71% MB patients and 8% NMB patients (P<0.001). Myocardial scintigraphy revealed ischemic changes in 67% MB patients and 9% NMB patients (P<0.001) and reverse redistribution in 87 and 69% (P<0.01), respectively. MB patients experienced exertional chest pain as well as at rest more frequently than NMB patients. Endothelin-1 levels were elevated in MB group complicated with CAS (P<0.01), whereas nitric oxide levels were reduced in the same cohort (P<0.05) compared with NMB group.. MB might predispose to CAS in which endothelial dysfunction may play a part. CAS patients with MB usually present mixed chest pain and positive stress tests as well as reversal redistribution on myocardial scintigraphy whereas CAS patients without MB displayed chest pain at rest, negative stress test and reversal redistribution.

Topics: Acetylcholine; Adult; Aged; Biomarkers; Case-Control Studies; Chest Pain; Coronary Angiography; Coronary Vasospasm; Electrocardiography; Endothelin-1; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Bridging; Myocardial Perfusion Imaging; Nitric Oxide; Predictive Value of Tests; Retrospective Studies

The association of endothelin 1 (ET-1) and endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms (G5665T and T8002C, VNTR and T-786C respectively) with the occurrence of acute chest syndrome and painful vaso-occlusive crises was evaluated in homozygous SS children. This retrospective study reveals that ET-1 T8002 and ecNOS C-786 alleles are associated with, respectively, an increased and a decreased risk of acute chest syndrome.

Topics: Adolescent; Anemia, Sickle Cell; Chest Pain; Child; Endothelin-1; Female; Genetic Predisposition to Disease; Humans; Male; Nitric Oxide Synthase Type III; Pain; Polymorphism, Genetic; Vascular Diseases

To compare the accuracy of biomarkers for identifying acute chest syndrome (ACS) in patients with sickle cell disease presenting to a pediatric emergency department (ED).. We conducted a 13-month-long (2002-2003) cohort study with nested case-control in patients with sickle cell disease presenting to the pediatric ED with vaso-occlusive crises or fever in which we compared levels of secretory phospholipase A2 (sPLA2), endothelin-1, interleukin-6 (IL-6), and peripheral white blood cell count (WBC) in cases that were complicated by ACS and in control subjects with uncomplicated illnesses. For diagnosis, a test was considered to be accurate when the area under its receiver operator characteristic curve (AUC) was >0.70. Laboratory tests with AUC values > or =0.70 were entered into a binary recursive partitioning model for diagnosis.. For the period of study, samples from 72 visits were obtained from 51 patients who presented with vaso-occlusive crises (range: 1-4 visits per patient; 15 were enrolled more than once). ACS complicated 19 of 72 visits (26%, 95% confidence interval: 17%-38%). At an AUC value of 0.79, only the sPLA2 test was accurate for diagnosing ACS. AUC values for peripheral WBC, endothelin-1, and IL-6 were 0.68, 0.51, and 0.52, respectively. Binary recursive partitioning retained only sPLA2 at a cutoff of 13.7 ng/mL to be accurate for diagnosis. This cutoff had a sensitivity of 74% (14 of 19), a specificity of 87% (46 of 53), a positive likelihood ratio of 5.6, and a negative likelihood ratio of 0.18.. Secretory phospholipase A2 but not endothelin-1, IL-6, or WBC is an accurate test for identifying present or incipient ACS in young patients who present to the ED with sickle cell pain crises.

Topics: Acute Disease; Adolescent; Anemia, Sickle Cell; Area Under Curve; Biomarkers; Chest Pain; Child; Endothelin-1; Female; Humans; Interleukin-6; Leukocyte Count; Lung Diseases; Male; Phospholipases A; Phospholipases A2; Sensitivity and Specificity; Syndrome

Previous reports have indicated that hypertensive patients who have angina-like chest pain and normal coronary arteriograms have reduced coronary flow velocity reserve (CFVR) levels. In addition, elevated plasma endothelin-1 (ET-1) levels have been reported to be associated with microvascular angina. The purpose of this study was to evaluate the plasma ET-1 levels and CFVR in patients with chest pain but without coronary artery disease (CAD). A total of 66 patients were included in this study. CAD was ruled out by exercise stress test or coronary angiogram. Plasma ET-1 and CFVR measurements were performed in patients with (n=35) and without (n=31) a history of angina-like chest pain. CFVR was measured using adenosine-triphosphate stress transthoracic Doppler echocardiography. The mean ET-1 level was significantly higher and the CFVR was significantly lower in patients in the symptomatic group than in those in the asymptomatic group (ET-1: 3.85 +/- 1.24 pg/ml vs. 2.98 +/- 1.27 pg/ml, CFVR: 2.26 +/- 0.48 vs. 2.77 +/- 0.11, respectively). Plasma ET-1 level and CFVR were significantly correlated with each other (-r = 0.265, p = 0.033). Age, blood pressure, cardiovascular risk factors, and left ventricular mass index were similar between the two groups. The results of multiple regression analysis indicate that age (p = 0.008) and plasma ET-1 concentration (p = 0.031) had statistically independent associations with CFVR. Attenuated CFVR in the symptomatic hypertensive patients was associated with endothelial dysfunction, which results in elevated plasma ET-1 levels. The link between these two parameters may play a role in the genesis of chest pain in hypertensive patients without CAD.

Topics: Aged; Blood Flow Velocity; Chest Pain; Coronary Circulation; Echocardiography; Endothelin-1; Female; Humans; Hypertension; Male; Middle Aged

Endothelin-1 (ET-1) is a potent positive inotrope in vitro, but its physiological effects on intrinsic myocardial contractile function in humans in vivo are unknown. Plasma ET-1 levels are elevated in heart failure, and ET-1 may be involved in the pathophysiology of this condition. However, its effects on contractile function of the failing human heart are also unknown.. A specific ET(A) receptor antagonist, BQ123, was infused (40 nmol/min, 16 minutes) into the left coronary artery in 8 patients with atypical chest pain (normal left ventricular ¿LV function and coronary arteries) and 8 patients with nonischemic dilated cardiomyopathy (DCM) who were undergoing diagnostic catheterization. In normal subjects, BQ123 rapidly induced a significant reduction in LV dP/dt(max) (-270+/-71 mm Hg/s after 16 minutes; P<0.05) and in LV dP/dt at a developed pressure of 40 mm Hg (LV dP/dt(40)) (-179+/-54 mm Hg/s; P<0.05). In DCM patients, however, BQ123 caused no reductions in LV dP/dt(max) (62+/-49 mm Hg/s after 16 minutes) or LV dP/dt(40) (83+/-51 mm Hg/s;P<0.05 compared with normal subjects). BQ123 had no effect on heart rate, LV relaxation, LV end-diastolic pressure, right atrial pressure, or pulmonary pressure in either patient group.. Endogenous ET-1 has a tonic positive inotropic effect in normal subjects, independent of effects on the peripheral vasculature and unmasked by inhibition of ET(A) receptors. However, the effect of short-term ET(A) blockade in DCM patients was opposite to that in normal subjects, which suggests that ET-1 may cause negative inotropic effects in the failing heart.

Topics: Adult; Cardiac Output, Low; Cardiomyopathy, Dilated; Chest Pain; Coronary Vessels; Endothelin Receptor Antagonists; Endothelin-1; Female; Humans; Injections; Male; Middle Aged; Myocardial Contraction; Peptides, Cyclic; Receptor, Endothelin A; Reference Values

Vasospastic angina as a result of alcohol ingestion has been reported, but the mechanism of alcohol-induced coronary artery spasm is presently unknown. This report presents 2 cases of alcohol-induced variant angina (VA) with elevated levels of plasma endothelin-1 after alcohol ingestion. In case 1, the plasma endothelin-1 concentration was 3.15 pg/ml before drinking (normal <2.30 pg/ml) and increased to 4.09 pg/ml when measured 5 h after alcohol ingestion. After 2 months of abstinence, the plasma endothelin-1 concentration was 2.88 pg/ml and 6 months after abstinence, it decreased to 2.03 pg/ml (normal range). In case 2, the plasma endothelin-1 concentration was 2.44 pg/ml before drinking and increased to 4.36 pg/ml when measured 5 h after alcohol ingestion. After 2 months of abstinence, the plasma endothelin-1 concentration was 3.04 pg/ml and 6 months after abstinence, it decreased to 2.09 pg/ml (normal range). These 2 cases suggest that a relationship may exist between alcohol-induced VA and elevation in the plasma endothelin-1 concentration after alcohol ingestion.

Topics: Aged; Alcoholic Beverages; Angina Pectoris, Variant; Chest Pain; Coronary Angiography; Coronary Vasospasm; Electrocardiography; Endothelin-1; Ethanol; Humans; Male; Temperance; Time Factors