ABSTRACT
OBJECTIVE: Cardiac surgery for congenital heart defects is commonly complicated by shunt-induced chronic pulmonary hypertension and associated acute hypertensive crises. To investigate the effects of vasodilators in chronic and acute pulmonary hypertension, we used the innominate artery to create a growing aortopulmonary shunt in young piglets. METHODS: Pulmonary hemodynamics and right ventricular function and their responses to hypoxia, intravenous prostacyclin, and inhaled nitric oxide were investigated after closure of the shunt by using pulmonary flow-pressure relationships, pulmonary vascular resistance partitioning, pulmonary vascular impedance, and ventriculoarterial coupling expressed as the ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance. RESULTS: Shunt-induced pulmonary hypertension was associated with medial hypertrophy of pulmonary arteries, increased resistance, increased elastance, increased wave reflection, and preserved ventriculoarterial coupling. Hypoxic pulmonary vasoconstriction was blunted in the shunt group. Compared with prostacyclin, inhaled nitric oxide was a more effective vasodilator in the shunt group and in hypoxia. Effective pulmonary arterial elastance and right ventricular end-systolic elastance increased in chronic (shunt) and acute (hypoxic) hypertension and decreased with vasodilators, preserving a normal coupling. CONCLUSIONS: A growing aortopulmonary shunt in the young pig is a reliable model of chronic pulmonary hypertension, with medial hypertrophy, increased resistance, and increased elastance. In this model inhaled nitric oxide is a better pulmonary vasodilator than intravenous prostacyclin, with neither drug having a specific inotropic effect, and normal coupling is preserved in chronic and acute pulmonary hypertension.
Subject(s)
Epoprostenol/administration & dosage , Hypertension, Pulmonary/drug therapy , Nitric Oxide/pharmacology , Administration, Inhalation , Analysis of Variance , Animals , Blood Gas Analysis , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Hemodynamics , Hypoxia/drug therapy , Infusions, Intravenous , Male , Probability , Pulmonary Gas Exchange , Random Allocation , Sensitivity and Specificity , Swine , Vasodilation/drug effectsABSTRACT
OBJECTIVE: To investigate the effects of endogenous endothelins on pulmonary haemodynamics and gas exchange in oleic acid lung injury. DESIGN: Prospective experimental study in dogs. SETTING: Animal research laboratory in a university teaching hospital. SUBJECTS. Seventeen anaesthetised and ventilated mongrel dogs. INTERVENTIONS: Nine pretreated dogs received an infusion of the endothelin A and B receptor antagonist bosentan (10 mg/kg) started before oleic acid. Eight treated dogs received bosentan started 90 min after oleic acid. Cardiac index (CI) was manipulated by inflating an inferior vena caval balloon or by opening a femoral arterio-venous bypass. MEASUREMENTS AND RESULTS: Pulmonary vascular resistance was defined by measuring the gradient between mean pulmonary artery pressure (MPAP) and occluded PAP (PAOP) at five levels of CI. Intrapulmonary shunt was measured using the inert gas SF(6). Pretreatment with bosentan prevented the oleic acid-induced shift of (MPAP-PAOP)/CI plots to higher pressures, but did not affect the increase in intrapulmonary shunt. Treatment of established oleic acid lung injury with bosentan had no effect. CONCLUSIONS: Pretreatment, but not treatment, with bosentan, in the dose used, blunted the oleic acid-induced increase in pulmonary vascular resistance, suggesting that endothelins contribute to the increase in pulmonary vascular tone in the early stages of oleic acid lung injury.
