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(Circulation. 1997;95:1054-1061.)
© 1997 American Heart Association, Inc.

Articles

Post–Cardiopulmonary Bypass Pulmonary Hypertension in Lambs With Increased Pulmonary Blood Flow

A Role for Endothelin 1

V. Mohan Reddy, MD; Karen D. Hendricks-Munoz, MD; Hiranya A. Rajasinghe, MD; Edwin Petrossian, MD; Frank L. Hanley, MD; Jeffrey R. Fineman, MD

the Departments of Cardiothoracic Surgery (V.M.R., H.A.R., E.P., F.L.H.) and Pediatrics (J.R.F.), University of California, San Francisco, and the Department of Pediatrics (K.D.H.-M.), New York University.

Correspondence to Jeffrey R. Fineman, MD, University of California, San Francisco, 505 Parnassus Ave, Box 0106, M-680, San Francisco, CA 94143-0106.

Background After cardiopulmonary bypass (CPB), pulmonary hypertension and its associated increased vascular reactivity are a major source of morbidity, particularly for children with increased pulmonary blood flow. Although post-CPB pulmonary hypertension is well described, its mechanisms remain incompletely understood. Plasma levels of endothelin 1, a potent vasoactive substance implicated in pulmonary hypertension, are increased after CPB. The purpose of the present study was threefold: to characterize the changes in pulmonary vascular resistance and vascular reactivity induced by hypothermic CPB; to investigate the effects of preexisting increased pulmonary blood flow on these changes; and to better define the role of endothelin 1 in the pathogenesis of post-CPB pulmonary hypertension.

Methods and Results Vascular pressures and blood flows were monitored in 14 1-month-old lambs with increased pulmonary blood flow (after in utero placement of an aortopulmonary shunt) and 6 age-matched control lambs. During the 2-hour study period after 105.3±20.6 minutes of hypothermic CPB, the increase in pulmonary vascular resistance was significantly augmented in lambs with increased pulmonary blood flow compared with control lambs (P<.05). Pretreatment with PD 145065 (a nonselective endothelin receptor blocker; 50 µg·kg^-1·min^-1) completely blocked this increase in pulmonary vascular resistance and blocked the increase in pulmonary vascular resistance in response to acute alveolar hypoxia after CPB (96.3±88.5% versus -9.7±16.4%; P<.05). Plasma endothelin 1 levels increased after CPB in all lambs.

Conclusions Preexisting increased pulmonary blood flow alters the response of the pulmonary circulation to hypothermic CPB; the increase in pulmonary vascular resistance induced by CPB is augmented in lambs with increased pulmonary blood flow. Pretreatment with endothelin 1 receptor blockers eliminated the increase in pulmonary vascular resistance and the pulmonary vasoconstricting response to alveolar hypoxia, suggesting a role for endothelin 1 in post-CPB pulmonary hypertension. Endothelin 1 receptor blockers may decrease morbidity in children at risk for pulmonary hypertension after surgical repair with CPB and warrants further study.

Key Words: hypertension, pulmonary • cardiopulmonary bypass • endothelin

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