title: In utero ventilation augments the left ventricular response to isoproterenol and volume loading in fetal sheep.
abstract: In its normal circulatory environment, the fetal left ventricle can maximally increase output less than 2-fold, in contrast to the nearly 3-fold increase that occurs at birth. Several studies have attributed this finding to fetal myocardial "immaturity," and speculated that there is a rapid maturation of the myocardium in the perinatal period. We investigated the importance of the circulatory environment itself, rather than myocardial immaturity, by measuring left ventricular output (LVO) during in utero oxygen ventilation and isoproterenol infusion. We studied seven near-term fetal sheep greater than or equal to 2 d after placement of intravascular catheters, an endotracheal tube, and an electromagnetic flow transducer around the ascending aorta. We measured hemodynamic variables in the presence and absence of all combinations of oxygen ventilation, isoproterenol infusion, and volume infusion. Baseline LVO was normal (133 +/- 27 mL.kg-1.min-1). Individually, oxygen ventilation (136 +/- 11 mL.kg-1.min-1, p less than 0.001) and isoproterenol (48 +/- 11 mL.kg-1.min-1, p less than 0.05) increased LVO significantly; volume infusion did not. Their cumulative effect increased LVO nearly 3-fold (to 387 +/- 98 mL.kg-1.min-1), similar to levels seen in the newborn lamb. Mean left atrial pressure increased above right during oxygen ventilation (from 0.05 +/- 0.54 kPa to 0.82 +/- 0.39 kPa, p less than or equal to 0.0001). We conclude that the previously observed limitation in maximal LVO in the near-term fetus is primarily caused by its circulatory environment rather than relative myocardial immaturity, and speculate that a prominent Starling response is uncovered by decreases in left ventricular afterload and right ventricular constraint.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco 94143.
authors.forename: D F
authors.initials: DF
authors.lastname: Teitel
authors.forename: M
authors.initials: M
authors.lastname: Dalinghaus
authors.forename: S C
authors.initials: SC
authors.lastname: Cassidy
authors.forename: B D
authors.initials: BD
authors.lastname: Payne
authors.forename: A M
authors.initials: AM
authors.lastname: Rudolph
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume; D002302:Cardiac Output / Q000187:drug effects*; D005260:Female; D005318:Fetal Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D012121:Respiration, Artificial; D012756:Sheep / Q000196:embryology*; D016276:Ventricular Function
chemical_list: D007545:Isoproterenol; D010100:Oxygen