Maternal beta-adrenoceptor blockade reduces fetal tolerance to asphyxia. A study in pregnant sheep.
Maternal and fetal beta 1-adrenoceptor blockade was induced in sheep by infusing i.v. 11 pregnant ewes with metoprolol in doses producing maternal plasma concentrations of metoprolol comparable to those obtained in clinical use. Ten other ewes and their fetuses served as controls. Under acute anaesthesia the fetus was exteriorized and subjected to two levels of controlled asphyxia by intermittent, complete obstruction of the maternal placental blood flow. Fetal haemodynamic reactions were assessed by measuring fetal heart rate, cardiac contractility, cardiac output and cerebral blood flow. The metabolic reactions were evaluated from blood gases, pH, lactate and hypoxanthine concentrations, while the electrophysiological status of the brain was evaluated from the somatosensory evoked EEG potentials (SEP). Already during the period of moderate asphyxia the beta-blocked fetuses demonstrated a blunted haemodynamic response, in comparison with the control fetuses, resulting in an accelerating lactic acidosis, signs of a breakdown of intra-cellular energy-rich phosphates and an impaired cerebral function. During the period of severe asphyxia, both groups of fetuses exhibited signs of extensive cerebral deterioration. During the ensuing recovery phase, 80% of the control fetuses regained their brain function, as assessed by SEP, whereas this was true for only 30% of the beta 1-blocked fetuses. It is concluded that the ovine fetus relies heavily on greatly increased sympatho-adrenal activity to adapt itself to asphyxia and that blockade of the fetal beta 1-adrenoreceptors by maternal medication is a hazard to the potentially asphyctic fetus.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005260:Female; D005318:Fetal Heart / Q000187:drug effects; D005311:Fetal Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008790:Metoprolol / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply; D011247:Pregnancy; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D007042:Hypoxanthines; D007773:Lactates; D019271:Hypoxanthine; D019344:Lactic Acid; D008790:Metoprolol