POST-CARDIOPULMONARY BYPASS PULMONARY-HYPERTENSION IN LAMBS WITH INCREASED PULMONARY BLOOD-FLOW - A ROLE FOR ENDOTHELIN-I

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 f low. Although post-CPB pulmonary hypertension is well described, its m echanisms 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 threefo ld: to characterize the changes in pulmonary vascular resistance and v ascular reactivity induced by hypothermic CPB; to investigate the effe cts of preexisting increased pulmonary blood flow on these changes; an d to better define the role of endothelin 1 in the pathogenesis of pos t-CPB pulmonary hypertension. Methods and Results Vascular pressures a nd blood hows were monitored in 14 1-month-old lambs with increased pu lmonary blood flow (after in utero placement of an aortopulmonary shun t) and 6 age-matched control lambs. During the 2-hour study period aft er 105.3+/-0.6 minutes of hypothermic CPB, the increase in pulmonary v ascular resistance was significantly augmented in lambs with increased pulmonary blood flow compared with control lambs (P<.05). Pretreatmen t with PD 145065 (a nonselective endothelin receptor blocker; 50 mu g . kg(-1). min(-1)) completely blocked this increase in pulmonary vascu lar resistance and blocked the increase in pulmonary vascular resistan ce in response to acute alveolar hypoxia after CPB (96.3+/-88.5% versu s -9.7+/-16.4%,; P<.05). Plasma endothelin 1 levels increased after CP B 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 augmen ted in lambs with increased pulmonary blood flow. Pretreatment with en dothelin 1 receptor blockers eliminated the increase in pulmonary vasc ular resistance and the pulmonary vasoconstricting response to alveola r hypoxia, suggesting a role for endothelin 1 in post-CPB pulmonary hy pertension, Endothelin 1 receptor blockers may decrease morbidity in c hildren at risk for pulmonary hypertension after surgical repair with CPB and warrants further study.