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J Thorac Cardiovasc Surg 1995;110:148-156
© 1995 Mosby, Inc.
GENERAL THORACIC SURGERY |
Worcester, Mass.
Supported in part by a grant from the National Institutes of Health (No. DE-07444) (Sandy C. Marks, Jr.) and the James E. Liston Fund at the University of Illinois at Chicago.
Received for publication June 23, 1994. Accepted for publication Oct. 24, 1994. Address for reprints: Dean E. Schraufnagel, MD, Section of Respiratory and Critical Care Medicine, Department of Medicine M/C 787, University of Illinois at Chicago, 840 S. Wood St., Chicago, IL 60612-7323.
Abstract
Serum endothelin levels increase during sepsis, ischemia, reperfusion, pulmonary operations, and systemic hypertension after surgery. Despite extensive study, the site and extent of action of endothelin on the pulmonary microcirculation are not well established. To assess the effect of endothelin on the pulmonary vasculature, especially the veins, the circulation of the lung was cast with methyl methacrylate 10 minutes after endothelin-1 was given intravenously to rats. Endothelin-1, at concentrations of 0.1, 1.0, and 10.0µg/kg of body weight, increased the mean systemic arterial blood pressure 8%, 7%, and 17% (p < 0.01) and mean pulmonary arterial blood pressure 15%, 28%, and 53%, respectively (p < 0.01). The proportional increases in the pulmonary pressures were greater than those of the systemic pressures (p < 0.01). Scanning electron microscopy of cast blood vessels showed more contraction of the veins than the arteries. For doses of 0, 0.1, 1.0, and 10.0µg/kg, the respective focal contraction of small veins was 6.7% (±4.4), 15.4% (±9.1), 23.3% (±10.1), and 14.4% (±9.0) of the vessel diameter (p < 0.01). In addition, the diameters of capillaries increased (p < 0.01) and the capillary interspaces decreased (p < 0.01) after endothelin administration, but not in a linear dose-dependent manner. The dose of endothelin correlated with the change in the mean systemic (r = 0.82, p < 0.01) and the mean pulmonary (r = 0.80, p < 0.01) blood pressures. The mean pulmonary pressure change correlated with the focal venous contraction on the casts (r = 0.35, p < 0.01), capillary diameter (r = 0.64, p < 0.01), and capillary interspace distance (r = -0.34, p < 0.01). The venous contraction was related to the capillary diameter (r = 0.26, p < 0.01). The most notable effect of endothelin-1 in rat pulmonary microcirculation is focal constriction of small veins. Because this effect may lead to pulmonary edema, endothelin antagonists may be of benefit in a variety of clinical situations. (J THORAC CARDIOVASC SURG 1995;110:148-56)
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