Rolland PH, de Lagausie P, Stathopoulos E, Lepretre O, Viudes G, Gorincour G, Hery G, de Magnee C, Paut O, Guys JM. Phasic hemodynamics and reverse blood flows in the aortic isthmus and pulmonary arteries of preterm lambs with pulmonary vascular dysfunction. Am J Physiol Heart Circ Physiol 295: H2231-H2241, 2008. First published September 26, 2008; doi: 10.1152/ajpheart.00410.2008. Time-domain representations of the fetal aortopulmonary circulation were carried out in lamb fetuses to study hemodynamic consequences of congenital diaphragmatic hernia (CDH) and the effects of endothelin-receptor antagonist tezosentan (3 mg/45 min). From the isthmic aortic and left pulmonary artery (PA) flows (Q) and isthmic aortic, PA, and left auricle pressures (P) on day 135 in 10 controls and 7 CDH fetuses (28 ewes), discrete-triggered P and Q waveforms were modelized as P(t) and Q(t) functions to obtain basic hemodynamic profiles, pulsatile waves [P, Q, and entry impedance (Z(e))], and P and Q hysteresis loops. In the controls, blood propelling energy was accounted for by biventricular ejection flow waves (kinetic energy) with low Z(e) and by flow-driven pressure waves (potential energy) with low Z(e). Weak fetal pulmonary perfusion was ensured by reflux (reverse flows) from PA branches to the ductus anteriosus and aortic isthmus as reverse flows. Endothelin-receptor antagonist blockade using tezosentan slightly increased the forward flow but largely increased diastolic backward flow with a diminished left auricle pre-and postloading. In CHD fetuses, the static component overrode phasic flows that were detrimental to reverse flows and the direction of the diastolic isthmic flow changed to forward during the diastole period. Decreased cardiac output, flattened pressure waves, and increased forward Z(e) promoted backward flow to the detriment of forward flow (especially during diastole). Additionally, the intrapulmonary arteriovenous shunting was ineffective. The slowing of cardiac output, the dampening of energetic pressure waves and pulsatility, and the heightening of phasic impedances contributed to the lowering of aortopulmonary blood flows. We speculate that reverse pulmonary flow is a physiological requirement to protect the fetal pulmonary circulation from the prominent right ventricular stream and to enhance blood flow to the fetal heart and brain.