Placental and fetal hemodynamics after labetalol or pindolol in a sheep model of increased placental vascular resistance and maternal hypertension

Reprod Sci. 2009 Aug;16(8):749-57. doi: 10.1177/1933719109335068. Epub 2009 Apr 20.

Abstract

We investigated the effects of labetalol and pindolol on uterine, placental, and fetal hemodynamics following norepinephrine-induced maternal hypertension in a sheep model of increased placental vascular resistance. Also, we examined fetal and placental hemodynamic responses to acute hypoxemia after antihypertensive medication. Norepinephrine increased maternal heart rate (HR), mean arterial pressure (MAP) and uterine vascular resistance (R(UtA)), and decreased uterine volume blood flow (Q(UtA)). Both labetalol and pindolol decreased maternal HR, MAP, and R(UtA), but did not restore Q(UtA). Fetal MAP was unaffected while fetal HR and placental volume blood flow (Q(UA)) decreased and placental vascular resistance increased. During hypoxemia, which was induced by decreasing maternal inspiratory oxygen fraction, all these parameters remained unchanged in the labetalol group while fetal HR increased and Q(UA) further decreased in the pindolol group. We conclude that labetalol and pindolol may compromise uterine and placental hemodynamics. Hypoxemic stress provokes divergent hemodynamic responses in fetuses exposed to these differently acting adrenoceptor antagonists.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects
  • Disease Models, Animal
  • Female
  • Fetal Hypoxia / physiopathology
  • Fetus / blood supply*
  • Heart Rate, Fetal / drug effects
  • Hemodynamics / drug effects*
  • Hypertension / chemically induced
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Labetalol / adverse effects
  • Labetalol / pharmacology*
  • Norepinephrine
  • Pindolol / adverse effects
  • Pindolol / pharmacology*
  • Placenta / blood supply*
  • Placental Circulation / drug effects
  • Pregnancy
  • Regional Blood Flow / drug effects
  • Sheep
  • Uterus / blood supply
  • Vascular Resistance / drug effects*

Substances

  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Pindolol
  • Labetalol
  • Norepinephrine