title: Phasic hemodynamics and reverse blood flows in the aortic isthmus and pulmonary arteries of preterm lambs with pulmonary vascular dysfunction.
abstract: 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 Pt and Qt functions to obtain basic hemodynamic profiles, pulsatile waves [P, Q, and entry impedance (Ze)], and P and Q hysteresis loops. In the controls, blood propelling energy was accounted for by biventricular ejection flow waves (kinetic energy) with low Ze and by flow-driven pressure waves (potential energy) with low Ze. 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 Ze 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.
authors.affiliation: Physiopathology and Vascular Therapeutics, School of Medicine, University of the Mediterranean Sea, 27 Blvd. Jean-Moulin, and Department of Pediatric Surgery, LaTimone-Hospital, Marseilles, France. pierre-henri.rolland@univmed.fr
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Rolland
authors.forename: Pascal
authors.initials: P
authors.lastname: de Lagausie
authors.forename: Euletheris
authors.initials: E
authors.lastname: Stathopoulos
authors.forename: Olivier
authors.initials: O
authors.lastname: Leprètre
authors.forename: Gilles
authors.initials: G
authors.lastname: Viudes
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gorincour
authors.forename: Géraldine
authors.initials: G
authors.lastname: Hery
authors.forename: Catherine
authors.initials: C
authors.lastname: de Magnée
authors.forename: Olivier
authors.initials: O
authors.lastname: Paut
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Guys
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000196:embryology / Q000503:physiopathology*; D001794:Blood Pressure; D002302:Cardiac Output; D065128:Endothelin Receptor Antagonists; D005333:Fetus / Q000098:blood supply; D005865:Gestational Age; D006439:Hemodynamics / Q000187:drug effects; D006548:Hernia, Diaphragmatic / Q000473:pathology / Q000503:physiopathology*; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000098:blood supply* / Q000196:embryology / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D011651:Pulmonary Artery / Q000187:drug effects / Q000196:embryology / Q000503:physiopathology* / Q000648:ultrastructure; D011652:Pulmonary Circulation / Q000187:drug effects; D011673:Pulsatile Flow; D011725:Pyridines / Q000494:pharmacology; D012039:Regional Blood Flow; D012756:Sheep; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D013777:Tetrazoles; D014665:Vasodilator Agents; C120582:tezosentan