endothelin-1 and Mitral-Valve-Stenosis

Topics: Adult; Aged; Capillaries; Catheterization; Endothelin-1; Heart Valve Prosthesis Implantation; Humans; Hypertension, Pulmonary; Middle Aged; Mitral Valve Stenosis; Predictive Value of Tests; Pulmonary Circulation; Remission Induction

Increased plasma endothelin (ET)-1 concentrations have been observed in patients with rheumatic mitral stenosis (MS). However, the mechanisms of increased circulating ET-1 in patients with MS remain unclear.. We measured plasma concentrations of ET-1 in blood samples from the femoral vein and artery, and right and left atria obtained from 20 patients with moderate-to-severe rheumatic MS before and after percutaneous transluminal mitral valvuloplasty (PTMV) [group 1; 16 patients in chronic atrial fibrillation and 4 patients in sinus rhythm]. In addition, we measured plasma concentrations of ET-1 in the peripheral venous blood samples obtained from 22 control patients (including 14 healthy volunteers in sinus rhythm [group 2] and 8 patients in chronic lone atrial fibrillation [group 3]). Plasma ET-1 concentrations were measured by solid-phase, sandwich enzyme-linked immunosorbent assay.. The peripheral venous plasma concentrations of ET-1 were significantly higher in group 1 patients (2.46 +/- 0.90 pg/mL) than in group 2 and group 3 patients (0.74 +/- 0.42 pg/mL and 0.99 +/- 0.41 pg/mL, respectively [mean +/- SD]; p < 0.0001). However, there was no significant difference in the peripheral venous concentrations of ET-1 between group 2 and group 3 patients. In group 1 patients, the plasma ET-1 concentration in the femoral vein (2.46 +/- 0.90 pg/mL) was significantly higher than that in the right atrium (2.02 +/- 0.69 pg/mL), left atrium (2.11 +/- 0.99 pg/mL), and femoral artery (2.05 +/- 0.75 pg/mL) [p = 0.0001]. The plasma ET-1 concentration in the femoral vein was not correlated with the mean left atrial pressure (r = 0.05; p = 0.838) and mean pulmonary artery pressure (r = 0.07; p = 0.757). The plasma ET-1 concentration in the left atrium was also not correlated with the mean left atrial pressure (r = 0.11; p = 0.656), mean pulmonary artery pressure (r = 0.06; p = 0.788), or mitral valve area (r = 0.02; p = 0.936). Although the area of mitral valve increased significantly (1.06 +/- 0.17 cm(2) vs 1.48 +/- 0.32 cm(2); p < 0.0001), and the mean left atrial pressure (23.0 +/- 5.1 mm Hg vs 17.6 +/- 5.9 mm Hg; p < 0.0001) and mean pulmonary arterial pressure (31.0 +/- 7.9 mm Hg vs 25.5 +/- 7.0 mm Hg; p < 0.001) fell significantly and immediately after PTMV, there were no significant changes in the plasma ET-1 concentrations in the femoral vein, right atrium, left atrium, and femoral artery immediately after PTMV.. Increased production of ET-1 in the pulmonary circulation in response to increased pulmonary artery pressure was not the mechanism of increased circulating ET-1 concentration in patients with MS. We proposed that one of the mechanisms of increased ET-1 concentration in the femoral vein was increased peripheral ET-1 release due to increased systemic venous pressure and mechanical damage of the endothelium.

Topics: Adult; Age Factors; Aged; Analysis of Variance; Biomarkers; Case-Control Studies; Catheterization; Cohort Studies; Echocardiography, Doppler; Endothelin-1; Female; Follow-Up Studies; Hemodynamics; Humans; Logistic Models; Male; Middle Aged; Mitral Valve Stenosis; Postoperative Period; Preoperative Care; Probability; Reference Values; Rheumatic Heart Disease; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome; Vascular Resistance

Increased plasma endothelin-1 concentrations have been observed in patients with rheumatic mitral stenosis. Endothelin-1 levels have never been investigated in patients with mitral stenosis and history of cerebral thromboembolism.. We measured plasma concentrations of endothelin-1 in the peripheral venous blood samples obtained from 20 patients with moderate to severe rheumatic mitral stenosis (16 with permanent atrial fibrillation and 4 with sinus rhythm). Six patients had history of thromboembolism. The remaining 14 patients did not have history of thromboembolism. Plasma endothelin-1 concentrations were measured using solid phase sandwich enzyme linked-immuno-sorbent assay.. The peripheral venous concentrations of endothelin-1 of the six patients with history of thromboembolism did not differ from the concentrations of the 14 patients without history of thromboembolism (2.40 +/- 1.39 pg/ml vs. 2.49 +/- 0.66 pg/ml, p = 0.9).. Although plasma endothelin-1 concentrations were increased in patients with mitral stenosis, plasma endothelin-1 concentrations were not further elevated in patients with mitral stenosis and history of thromboembolism.

Topics: Adult; Aged; Atrial Fibrillation; Endothelin-1; Female; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Mitral Valve Stenosis; Rheumatic Heart Disease

The rise of pressure in the pulmonary circulation during the course of mitral stenosis leads to pathomorphological changes and a reduction in vascular compliance. Endothelial dysfunction is also promoted, with increased expression of endothelin. This aim of this study was to evaluate whether the increase in endothelin-1 levels in pulmonary hypertension due to advanced mitral stenosis is reversible after valve replacement.. Thirty-nine patients with isolated, longlasting post-rheumatic mitral stenosis were enrolled. During preoperative Swan-Ganz catheterization blood samples were withdrawn from the pulmonary artery and capillaries for measurement of endothelin-1 (ET-1). Similar examinations were performed six months after mitral valve replacement. Hemodynamic parameters were measured also during 25-W exercise effort.. The mean preoperative hemodynamic parameters of the pulmonary circulation were moderately increased. Mean plasma levels of ET-1 were about three-fold higher than normal. Capillary levels of ET-1 were significantly higher than those in the pulmonary artery (1.78+/-1.22 versus 1.03+/-1.16 pg/ml, p <0.05). There was no significant correlation between ET-1 level and any hemodynamic or clinical parameters, except NYHA functional class. After surgery, pulmonary capillary levels of ET-1 fell significantly, but were still high (1.78+/-1.22 versus 1.41+/-1.00 pg/ml); ET-1 levels in the pulmonary artery were unchanged. Patients with persistently high ET-1 levels had significantly worse exercise hemodynamic parameters, especially of pulmonary arterial compliance.. In patients with long-lasting, severe mitral stenosis, ET-1 levels remained increased and the ET-1 concentration gradient across the pulmonary circulation persisted for six months after valve replacement. High ET-1 capillary levels are correlated with poor exercise tolerance and poor exercise compliance of the pulmonary vessels.

Topics: Endothelin-1; Endothelium, Vascular; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mitral Valve; Mitral Valve Stenosis; Prospective Studies

Pulmonary hypertension (PHT) is associated with increased endothelin-1 (ET-1) levels that correlate with the severity of the disease. The pulmonary circulation is an important site for ET-1 metabolism and may modulate plasma ET-1 through an increase in production, a reduction in removal, or a combination of both. We measured and compared pulmonary metabolism of circulating ET-1 in controls and in patients with PHT.. The indicator-dilution technique was combined with measurements of ET-1 levels to quantify pulmonary metabolism of ET-1 in controls (n = 13) and in patients with PHT (n = 17). ET-1 levels doubled in PHT (p < 0.05) and, although there was no difference between aortic and pulmonary artery levels in controls (0.68+/-0.09 and 0.61+/-0.08 pg/ml, respectively, p = 0.22), they tended to be higher in PHT (1.23+/-0.26 vs 1.07+/-0.19 pg/ml, p = 0.08). Pulmonary extraction of tracer iodine-125-ET-1 was reduced from 47%+/-2.0% in the controls to 34%+/-3.6% in PHT (p = 0.005) and inversely correlated with the severity of pulmonary hypertension (r = -0.524, p = 0.03). Consequently, circulating ET-1 clearance was reduced by PHT from 1424+/-77 ml/min to 892+/-119 ml/min (p < 0.001). Pulmonary production of circulating ET-1 (in picograms per minute) was not different but the quantity of ET-1 that survives passage through the lungs was increased by PHT (1860+/-359 pg/min vs 992+/-152 pg/min, p = 0.037).. PHT is associated with a reduced pulmonary clearance of ET-1 that contributes to the increase in circulating levels.

Topics: Aorta, Thoracic; Biomarkers; Blood Pressure; Cardiac Catheterization; Echocardiography; Endothelin-1; Heart Failure; Humans; Hypertension, Pulmonary; Iodine Radioisotopes; Middle Aged; Mitral Valve Stenosis; Pulmonary Artery; Pulmonary Wedge Pressure; Severity of Illness Index; Spectrophotometry; Vascular Resistance