Increased circulating endothelin-1 in rheumatic mitral stenosis: irrelevance to left atrial and pulmonary artery pressures.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Chen
Mien-Cheng
MC
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Sung Hsiang, Kaohsiung Hsien 83301, Taiwan, Republic of China. chenmien@ms76.hinet.net
Wu
Chiung-Jen
CJ
Yip
Hon-Kan
HK
Chang
Hsueh-Wen
HW
Chen
Chien-Jen
CJ
Yu
Teng-Hung
TH
Hung
Wei Chin
WC
D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002404:Catheterization / Q000379:methods; D015331:Cohort Studies; D015150:Echocardiography, Doppler; D019332:Endothelin-1 / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008946:Mitral Valve Stenosis / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D011184:Postoperative Period; D011300:Preoperative Care; D011336:Probability; D012016:Reference Values; D012214:Rheumatic Heart Disease / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014655:Vascular Resistance
D015415:Biomarkers; D019332:Endothelin-1