Reduced pulmonary clearance of endothelin-1 in pulmonary hypertension,☆☆,,★★

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Abstract

Objective 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. Methods and Results 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±152pg/min, p = 0.037). Conclusion PHT is associated with a reduced pulmonary clearance of ET-1 that contributes to the increase in circulating levels. (Am Heart J 1998;135:614-20.)

Section snippets

Patients

Study protocol and the consent form were designed in accordance with the research and ethics committees of the Montreal Heart Institute. The patients with PHT (n=17) were recruited among patients awaiting diagnostic cardiac catheterization for the following conditions: mitral stenosis (n = 12), congestive heart failure (n = 4), and primary PHT (n = 1). The only criteria for inclusion was the presence of a pulmonary artery systolic pressure of ≥40 mm Hg evaluated by echocardiography within the

Patient characteristics and hemodynamics

The mean age in the control group (59.3 ± 2.9 years) was not different from the PHT group (57.8 ± 2.2 years). Table I shows the hemodynamic parameters for the two groups.

. Systemic and pulmonary hemodynamic parameters

Empty CellControl groupPHT
Heart rate (beats/min)65 ± 270 ± 2
Mean arterial pressure (mm Hg)96 ± 292 ± 3
SVR (dynes · sec · cm-5)890 ± 481105 ± 123
Mean pulmonary artery pressure (mm Hg)16 ± 128 ± 2*
PVR (dynes · sec · cm-5)72 ± 9148 ± 29
Cardiac index (L/min/m2)2.81 ± 0.152.41 ± 0.13

SVR, Systemic

Discussion

We used the indicator-dilution technique combined with measurements of immunoreactive ET-1 levels to quantify precisely any alteration in the pulmonary metabolism of circulating ET-1 in patients with PHT.

Acknowledgements

We thank Nathalie Ruel for her expert technical assistance, the staff of the hemodynamic laboratory for their collaboration, and Caroll Boyer and Diane Campeau for preparing the manuscript.

References (21)

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From the Department of aMedicine, Montreal Heart Institute; b Department of Medicine, Royal Victoria Hospital, Montreal; and c Department of Medicine, St. Michael's Hospital, Toronto.

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Supported by the Medical Research Council of Canada, the Fonds de la Recherche en Santé du Québec, and the Quebec Heart and Stroke Foundation.

Reprint requests: Jocelyn Dupuis, MD, Research Center, Montreal Heart Institute, 5000 Bélanger Street East, Montreal, Quebec, Canada, H1T 1C8., E-mail: [email protected]

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