Post-cardiopulmonary bypass pulmonary hypertension in lambs with increased pulmonary blood flow. A role for endothelin 1.
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.


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 micrograms.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.
Reddy
V M
VM
Department of Cardiothoracic Surgery, University of California, San Francisco 94143-0106, USA.
Hendricks-Munoz
K D
KD
Rajasinghe
H A
HA
Petrossian
E
E
Hanley
F L
FL
Fineman
J R
JR
D000818:Animals; D001794:Blood Pressure; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002648:Child; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D005333:Fetus; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D009842:Oligopeptides / Q000494:pharmacology*; D011183:Postoperative Complications; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000196:embryology / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D019332:Endothelin-1; D009842:Oligopeptides; C082887:PD 145065